bluuebunny/crossref_metadata_2025 huggingface dataset:
ORCHIDS: an Observational Randomized Controlled Trial on Childhood Differential Susceptibility
Authors: Chhangur Rabia R , Weeland Joyce , Overbeek Geertjan , Matthys WalterCHJ , Orobio de Castro Bram
Published: October 2012

Background

A central tenet in developmental psychopathology is that childhood rearing experiences have a major impact on children’s development. Recently, candidate genes have been identified that may cause children to be differentially susceptible to these experiences (i.e., susceptibility genes). However, our understanding of the differential impact of parenting is limited at best. Specifically, more experimental research is needed. The ORCHIDS study will investigate gene-(gene-)environment interactions to obtain more insight into a) moderating effects of polymorphisms on the link between parenting and child behavior, and b) behavioral mechanisms that underlie these gene-(gene-)environment interactions in an experimental design.

Methods/Design

The ORCHIDS study is a randomized controlled trial, in which the environment will be manipulated with an intervention (i.e., Incredible Years parent training). In a screening, families with children aged 4–8 who show mild to (sub)clinical behavior problems will be targeted through community records via two Dutch regional healthcare organizations. Assessments in both the intervention and control condition will be conducted at baseline (i.e., pretest), after 6 months (i.e., posttest), and after 10 months (i.e., follow-up).

Discussion

This study protocol describes the design of a randomized controlled trial that investigates gene-(gene-)environment interactions in the development of child behavior. Two hypotheses will be tested. First, we expect that children in the intervention condition who carry one or more susceptibility genes will show significantly lower levels of problem behavior and higher levels of prosocial behavior after their parent(s) received the Incredible Years training, compared to children without these genes, or children in the control group. Second, we expect that children carrying one or more susceptibility genes will show a heightened sensitivity to changes in parenting behaviors, and will manifest higher emotional synchronization in dyadic interchanges with their parents. This may lead to either more prosocial behavior or antisocial behavior depending on their parents’ behavior.

Trial registration

Dutch Trial Register (NTR3594)
Quantification of multiple infections of Plasmodium falciparum in vitro
Authors: Wacker Mark A , Turnbull Lindsey B , Walker Leah A , Mount Michael C , Ferdig Michael T
Published: October 2012

Background

Human malaria infections caused by the parasite Plasmodium falciparum often contain more than one genetically distinct parasite. Despite this fact, nearly all studies of multiple strain P. falciparum infections have been limited to determining relative densities of each parasite within an infection. In light of this, new methods are needed that can quantify the absolute number of parasites within a single infection.

Methods

A quantitative PCR (qPCR) method was developed to track the dynamic interaction of P. falciparum infections containing genetically distinct parasite clones in cultured red blood cells. Allele-specific primers were used to generate a standard curve and to quantify the absolute concentration of parasite DNA within multi-clonal infections. Effects on dynamic growth relationships between parasites under drug pressure were examined by treating mixed cultures of drug sensitive and drug resistant parasites with the anti-malarial drug chloroquine at different dosing schedules.

Results

An absolute quantification method was developed to monitor the dynamics of P. falciparum cultures in vitro. This method allowed for the observation of competitive suppression, the reduction of parasites numbers due to the presence of another parasite, and competitive release, the improved performance of a parasite after the removal of a competitor. These studies demonstrated that the presence of two parasites led to the reduction in density of at least one parasite. The introduction of drug to a mixed culture containing both a drug resistant and drug sensitive parasites resulted in an increased proportion of the drug resistant parasite. Moreover, following drug treatment, the resistant parasite experienced competitive release by exhibiting a fitness benefit greater than simply surviving drug treatment, due to the removal of competitive suppression by the sensitive parasite.

Conclusions

The newly developed assay allowed for the examination of the dynamics of two distinct clones in vitro; both competitive suppression and release were observed. A deeper understanding of the dynamic growth responses of multiple strain P. falciparum infections, with and without drug pressure, can improve the understanding of the role of parasite interactions in the spread of drug resistant parasites, perhaps suggesting different treatment strategies.
Evaluation of the malaria rapid diagnostic test SDFK90: detection of both PfHRP2 and Pf-pLDH
Authors: Heutmekers Marloes , Gillet Philippe , Cnops Lieselotte , Bottieau Emmanuel , Van Esbroeck Marjan , Maltha Jessica , Jacobs Jan
Published: October 2012

Background

Rapid diagnosis of Plasmodium falciparum infections is important because of the potentially fatal complications. SDFK90 is a recently marketed malaria rapid diagnostic test (RDT) targeting both histidine-rich protein 2 (PfHRP2) and P. falciparum-specific Plasmodium lactate dehydrogenase (Pf-pLDH). The present study evaluated its diagnostic accuracy.

Methods

SDFK90 was tested against a panel of stored whole blood samples (n= 591) obtained from international travellers suspected of malaria, including the four human Plasmodium species and Plasmodium negative samples. Microscopy was used as a reference method, corrected by PCR for species diagnosis. In addition, SDFK90 was challenged against 59 P. falciparum samples with parasite density ≥4% to assess the prozone effect (no or weak visible line on initial testing and a higher intensity upon 10-fold dilution).

Results

Overall sensitivity for the detection of P. falciparum was 98.5% and reached 99.3% at parasite densities >100/μl. There were significantly more PfHRP2 lines visible compared to Pf-pLDH (97.3% vs 86.9%), which was mainly absent at parasite densities <100/μl. Specificity of SDFK90 was 98.8%. No lot-to-lot variability was observed (p = 1.00) and test results were reproducible. A prozone effect was seen for the PfHRP2 line in 14/59 (23.7%) P. falciparum samples tested, but not for the Pf-pLDH line. Few minor shortcomings were observed in the kit’s packaging and information insert.

Conclusions

SDFK90 performed excellent for P. falciparum diagnosis. The combination of PfHRP2 and Pf-pLDH ensures a low detection threshold and counters potential problems of PfHRP2 detection such as gene deletions and the prozone effect.
Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields
Authors: Rulseh Aaron Michael , Keller Jiří , Klener Jan , Šroubek Jan , Dbalý Vladimír , Syrůček Martin , Tovaryš František , Vymazal Josef
Published: October 2012

Glioblastoma multiforme (GBM) is the most common and malignant primary intracranial tumor, and has a median survival of only 10 to 14 months with only 3 to 5% of patients surviving more than three years. Recurrence (RGBM) is nearly universal, and further decreases the median survival to only five to seven months with optimal therapy. Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence.
Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer
Authors: Liu Kun , Qian Tao , Tang Liming , Wang Jie , Yang Haohua , Ren Jun
Published: October 2012

Background

MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC), and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction.

Methods

Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs), using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS) was also investigated.

Results

Let-7i was significantly down-regulated in most tumor tissues (78/86: 91%) compared with paired NATs (P < 0.001), and low levels of let-7i were significantly correlated with local invasion, lymphatic metastasis, and poor pathologic tumor response. Multivariate Cox regression analysis revealed that low let-7i expression was an unfavorable prognostic factor of OS (hazard ratio (HR) = 2.316, P =0.024) independently of other clinicopathological factors, including tumor node metastasis (TNM) stage (HR = 3.226, P = 0.013), depth of infiltration (HR = 4.167, P < 0.001), and lymph node status (HR = 2.245, P = 0.037).

Conclusions

These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.
Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China
Authors: Ji Hong , Li Liang , Liu YanMing , Ge HengMing , Wang XuShan , Hu JianLi , Wu Bin , Fu JianGuang , Zhang ZhenYu , Chen XiaoQin , Zhang MingLei , Ding Qiang , Xu WenBo , Tang FenYang , Zhou MingHao , Wang Hua , Zhu FengCai
Published: October 2012

Background

The major etiology of hand, foot and mouth disease (HFMD) is infection with human enterovirus A (HEV-A). Among subtypes of HEV-A, coxsackievirusA16 (CoxA16) and enterovirus 71 (EV71) are major causes for recurrent HFMD among infants and children in Jiangsu Province, mainland China. Here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human EV71 and CoxA16 infections in infants and children aged 0 to 15 years. The results may facilitate the development of immunization against HFMD.

Methods

This study used cross-section of 40 pairs of pregnant women and neonates and 800 subjects aged 1 month to 15 years old. Micro-dose cytopathogenic effects measured neutralizing antibodies against EV71 and CoxA16. Chi-square test compared seroprevalence rates between age groups and McNemar test, paired-Samples t-test and independent-samples t-test analyzed differences of geometric mean titers.

Results

A strong correlation between titers of neutralizing antibody against EV71 and CoxA16 in prenatal women and neonates was observed (rEV71 = 0.67, rCoxA16 = 0.56, respectively,p < 0.05). Seroprevalence rates of anti-EV71 antibody gradually decreased with age between 0 to 6 months old, remained low between 7 to 11 months (5.0–10.0%), and increased between 1 and 4 years (22.5–87.5%). Age-specific seroprevalence rates of anti-EV71 antibody stabilized in >80% of children between 5 to 15 years of age. However, seroprevalence rates of anti-CoxA16 antibody were very low (0.0–13.0%) between 0 to 6 months of age, gradually increased between 7 months to 4 years (15.0–70.0%), and stabilized at 54.0% (108/200) between 5 to 15 years. Seroprevalence rates against EV71 and CoxA16 were low under 1 year (0.0–10.0%), and showed an age dependent increase with high seroprevalence (52.5–62.5%) between 4 and10 years of age.

Conclusions

Concomitant infection of EV71 and CoxA16 was common in Jiangsu Province. Therefore, development of bivalent vaccine against both EV71 and CoxA16 is critical. The optimal schedule for vaccination may be 4 to11 months of age.
High diversity of genetic lineages and virulence genes in nasal Staphylococcus aureusisolates from donkeys destined to food consumption in Tunisia with predominance of the ruminant associated CC133 lineage
Authors: Gharsa Haythem , Ben Sallem Rym , Ben Slama Karim , Gómez-Sanz Elena , Lozano Carmen , Jouini Ahlem , Klibi Naouel , Zarazaga Myriam , Boudabous Abdellatif , Torres Carmen
Published: October 2012

Background

The objective of this study was to determine the genetic lineages and the incidence of antibiotic resistance and virulence determinants of nasal Staphylococcus aureus isolates of healthy donkeys destined to food consumption in Tunisia.

Results

Nasal swabs of 100 donkeys obtained in a large slaughterhouse in 2010 were inoculated in specific media for S. aureus and methicillin-resistant S. aureus (MRSA) recovery. S. aureus was obtained in 50% of the samples, being all of isolates methicillin-susceptible (MSSA). Genetic lineages, toxin gene profile, and antibiotic resistance mechanisms were determined in recovered isolates. Twenty-five different spa-types were detected among the 50 MSSA with 9 novel spa-types. S. aureus isolates were ascribed to agr type I (37 isolates), III (7), II (4), and IV (2). Sixteen different sequence-types (STs) were revealed by MLST, with seven new ones. STs belonging to clonal clomplex CC133 were majority. The gene tst was detected in 6 isolates and the gene etb in one isolate. Different combinations of enterotoxin, leukocidin and haemolysin genes were identified among S. aureus isolates. The egc-cluster-like and an incomplete egc-cluster-like were detected. Isolates resistant to penicillin, erythromycin, fusidic acid, streptomycin, ciprofloxacin, clindamycin, tetracycline, or chloramphenicol were found and the genes blaZ, erm(A), erm(C), tet(M), fusC were identified.

Conclusions

The nares of donkeys frequently harbor MSSA. They could be reservoirs of the ruminant-associated CC133 lineage and of toxin genes encoding TSST-1 and other virulence traits with potential implications in public health. CC133 seems to have a broader host distribution than expected.
Bovine viral diarrhea virus in free-ranging wild ruminants in Switzerland: low prevalence of infection despite regular interactions with domestic livestock
Authors: Casaubon Julien , Vogt Hans-Rudolf , Stalder Hanspeter , Hug Corinne , Ryser-Degiorgis Marie-Pierre
Published: October 2012

Background

In the frame of an eradication program for bovine viral diarrhea (BVD) in Swiss livestock, the question was raised whether free-ranging wildlife could threaten the success of this sanitary measure. Therefore, we conducted serological and virological investigations on BVD virus (BVDV) infections in the four indigenous wild ruminant species (roe deer, red deer, Alpine chamois and Alpine ibex) from 2009 to 2011, and gathered information on interactions between wild and domestic ruminants in an alpine environment by questionnaire survey.

Results

Thirty-two sera out of 1’877 (1.7%, 95% confidence interval [CI] 1.2-2.4) were seropositive for BVDV, and a BVDV1 sub genotype h virus was found in a seropositive chamois (0.05%, 95% CI 0.001-0.3). The seropositive animals originated from sub-alpine or alpine regions and significantly more seropositive red deer, chamois and ibex than roe deer were found. There were no statistically significant differences between sampling units, age classes, genders, and sampling years. The obtained prevalences were significantly lower than those documented in livestock, and most positive wild ruminants were found in proximity of domestic outbreaks. Additionally, BVDV seroprevalence in ibex was significantly lower than previously reported from Switzerland. The survey on interspecific interactions revealed that interactions expected to allow BVDV transmission, from physical contacts to non-simultaneous use of the same areas, regularly occur on pastures among all investigated ruminant species. Interactions involving cervids were more often observed with cattle than with small ruminants, chamois were observed with all three domestic species, and ibex interacted mostly with small ruminants. Interactions related to the use of anthropogenic food sources were frequently observed, especially between red deer and cattle in wintertime.

Conclusions

To our knowledge, this is the first report of BVDV RNA isolated from an Alpine chamois. Nevertheless, our results suggest that BVDV infections are only sporadic in Swiss wild ruminants, despite regular occurrence of interactions with potentially infected livestock. Overall, serological, virological and ethological data indicate that wildlife is currently an incidental spill-over host and not a reservoir for BVDV in Switzerland.
Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report
Authors: Dell’Edera Domenico , Tinelli Andrea , Capozzi Oronzo , Epifania Annunziata Anna , Malvasi Antonio , Lofrese Dominga , Pacella Elena , Milazzo Giusi Natalia , Mazzone Eleonora , Leo Manuela , Rocchi Mariano
Published: October 2012

Introduction

Premature ovarian failure is defined as the cessation of ovarian activity before the age of 40 years. It is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone and follicle-stimulating hormone).

Case presentation

Our patient, a 22-year-old Caucasian woman under evaluation for infertility, had experienced secondary amenorrhea from the age of 18. No positive family history was noted regarding premature menopause. An examination of our patient’s karyotype showed the presence of a reciprocal translocation, apparently balanced, which had the X chromosome long arm (q13) and the 14 chromosome short arm (p12) with consequent karyotype: 46, X, t(X; 14)(q13;p12).

Conclusions

Our study has underlined that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It highlighted a genetic etiology, in the form of a chromosomal abnormality, as the causal factor in amenorrhea.
Rural Indonesia women’s traditional beliefs about antenatal care
Authors: Agus Yenita , Horiuchi Shigeko , Porter Sarah E
Published: October 2012

Background

The Indonesia Maternal Mortality Rate (MMR) of 420/100.00 live births remains among the highest in East Asia while coverage of births assisted by skilled providers is still low. Traditional beliefs have been a key factor associated with the choice between midwives or traditional birth attendants (TBA) and the low number of antenatal care visits in rural West Sumatra.

Methods

We conducted three focus groups with 16 women from rural West Java to describe their perception regarding issues related to traditional beliefs. Focus group discussions provided data for the content analysis.

Results

The majority of the 16 women interviewed was from Village Dago, West Java and had only an elementary school education. Their ages ranged from 19 to 40 years. Most were multiparous housewives with an income of IDR 918.750 per month, which was lower than the monthly income in West Java (IDR. 1.172.060). Emerging from the focus group discussion were four main themes regarding their pregnancy and traditional beliefs: 1) pregnancy was a normal cycle in women’s life (pregnancy is a natural phenomena, not a sickness; no recognition of danger signs during pregnancy and death of baby or mother during pregnancy was brought about by God’s will); 2) women followed the traditional beliefs (positive motivation to follow the traditional beliefs and fear of not following the traditional beliefs); 3) relying on TBA called paraji rather than midwife (parajis are kind, tolerant and patient and have more experience than midwives; more accessibility than midwives and encouragement of natural birth) and 4) midwives are more secure than paraji; (they use a medical standard of care).

Conclusions

Women’s beliefs grounded in religion and tradition permeated the village culture making it difficult to counter their long held health practices with practices based on recent advances in health care. Use of TBA in this village was still dominant and women believed that following traditional beliefs led to a healthy pregnancy therefore, they also followed all relatives’ suggestions. Understanding the complexities of local culture is the first step to improving women’s awareness of how to preserve their pregnancy and prevent complications.
A study of patient satisfaction after cataract surgery with implantation of different types of intraocular lenses
Authors: Wei Ching-Kuo , Wang Shun-Mu , Lin Jen-Chieh
Published: October 2012

Background

The implementation of capitated payment has driven medical institutions through developing balance billing for medical services. By exploring the patients’ decision-making factors on different self-pay items, a reference for the pricing and sales strategy for the related products can be formed. The major purposes of this study were to analyze the determinants of preoperative selection and postoperative satisfaction with implantation of different types of intraocular lenses in cataract surgery.

Methods

This cross-sectional study consisted of 127 patients that were 50 years of age and older, and who had phacoemulsification with intraocular lens implantation in both eyes. Data were collected by using a structured questionnaire. The following parameters were measured: access to medical care, attitude towards receiving medical products at one’s own expense, overall patient satisfaction and postoperative visual clarity.

Results

The results showed that the patient’s gender, educational level and economic status influenced the type of intraocular lens chosen. Patients in the insurance group cared about access to medical care, and patients in the balance billing group cared about product differentiation. ANOVA results showed no statistically significant differences in the overall satisfaction of the patients among the groups with different types of intraocular lenses. Patients that received cataract surgery with implantation of multifocal intraocular lenses had better vision when trying to view smaller objects and when looking at objects under strong light.

Conclusions

Manufacturers should increase the number of differences between their products, and health care providers can then recommend the appropriate intraocular lens in accordance with the needs or demands of their patients, and also by keeping in mind the financial constraints of their patients.
Control of directional change after mechanical stimulation in Drosophila
Authors: Zhou Yating , Cameron Scott , Chang Wen-Tzu , Rao Yong
Published: October 2012

Background

Proper adjustment of moving direction after external mechanical stimulation is essential for animals to avoid danger (e.g. predators), and thus is vital for survival. This process involves sensory inputs, central processing and motor outputs. Recent studies have made considerable progress in identifying mechanosensitive neurons and mechanosensation receptor proteins. Our understandings of molecular and cellular mechanisms that link mechanosensation with the changes in moving direction, however, remain limited.

Results

In this study, we investigate the control of movement adjustment in Drosophila. In response to gentle touch at the anterior segments, Drosophila larvae reorient and select a new direction for forward movement. The extent of change in moving direction is correlated with the intensity of tactile stimuli. Sensation of gentle touch requires chordotonal organs and class IV da neurons. Genetic analysis indicates an important role for the evolutionarily conserved immunoglobulin (Ig) superfamily protein Turtle (Tutl) to regulate touch-initiated directional change. Tutl is required specifically in post-mitotic neurons at larval stage after the completion of embryonic development. Circuit breaking analysis identified a small subset of Tutl-positive neurons that are involved in the adjustment of moving direction.

Conclusion

We identify Tutl and a small subset of CNS neurons in modulating directional change in response to gentle touch. This study presents an excellent starting point for further dissection of molecular and cellular mechanisms controlling directional adjustment after mechanical stimulation.
Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications
Authors: Fan Hai-Xia , Li Hai-Xia , Chen Dong , Gao Zhong-Xiuzi , Zheng Jin-Hua
Published: October 2012

Background

Type IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis.

Methods

Here, we observed the changes in morphology and distribution of type IV collagen (ColIV) in the basement membrane (BM) surrounding nests of carcinoma in 48 patients with oral tongue squamous cell (OTSCC). We examined the correlation between the expressions of ColIV, MMP-2 and MMP-9 and the prognosis of OTSCC patients. The intensity and patterns of expression were assessed immunohistochemically using anti-human mouse monoclonal MMP-2, MMP-9 and Col IV antibodies. Statistical analyses were performed to determine the prognostic correlations of ColIV, MMP-2, and MMP-9 levels.

Results

MMP-2 and MMP-9 expressions in OTSCC were higher than those in normal oral mucosa and dysplastic oral mucosa group(MMP-2 iOD: 66.40 ± 24.20, 134.69 ± 37.08, and 357.79 ± 116.78; MMP-9 iOD: 88.05 ± 23.85, 307.13 ± 93.22, and 791.31 ± 260.52; in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01); however, ColIV immunoreactivity was lower (ColIV iOD: 406.87 ± 62.95, 247.83 ± 42.30, and 151.92 ± 38.17 in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01). High tumour and stromal MMP-2 and MMP-9 expression was significantly associated with positive lymph node status. Col IV expression was associated with positive lymph node status (P < 0.05), and have negatively correlated with the expression of MMP-2 and MMP-9. Overall survival was significantly shorter in patients with high tumour and stromal MMP-2 and MMP-9 expression, and tended to be shorter in patients with low ColIV expression.

Conclusions

Degradation of ColIV was closely related to increased MMP-2 and MMP-9 expression; MMP-9 have more important function than MMP-2 during the cancer development. Monitoring changes in the expression of ColIV, MMP-2, and MMP-9 may be a useful technique for assessing prognoses in OTSCC patients.
Modular nanotransporters: a versatile approach for enhancing nuclear delivery and cytotoxicity of Auger electron-emitting 125I
Authors: Slastnikova Tatiana A , Koumarianou Eftychia , Rosenkranz Andrey A , Vaidyanathan Ganesan , Lupanova Tatiana N , Sobolev Alexander S , Zalutsky Michael R
Published: October 2012

Background

This study evaluates the potential utility of a modular nanotransporter (MNT) for enhancing the nuclear delivery and cytotoxicity of the Auger electron emitter125I in cancer cells that overexpress the epidermal growth factor receptor (EGFR).

Methods

MNTs are recombinant multifunctional polypeptides that we have developed for achieving selective delivery of short-range therapeutics into cancer cells. MNTs contain functional modules for receptor binding, internalization, endosomal escape and nuclear translocation, thereby facilitating the transport of drugs from the cell surface to the nucleus. The MNT described herein utilized EGF as the targeting ligand and was labeled with125I usingN-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate (SGMIB). Membrane binding, intracellular and nuclear accumulation kinetics, and clonogenic survival assays were performed using the EGFR-expressing A431 epidermoid carcinoma and D247 MG glioma cell lines.

Results

[125I]SGMIB-MNT bound to A431 and D247 MG cells with an affinity comparable to that of native EGF. More than 60% of internalized [125I]SGMIB-MNT radioactivity accumulated in the cell nuclei after a 1-h incubation. The cytotoxic effectiveness of [125I]SGMIB-MNT compared with125I-labeled bovine serum albumin control was enhanced by a factor of 60 for D247 MG cells and more than 1,000-fold for A431 cells, which express higher levels of EGFR.

Conclusions

MNT can be utilized to deliver125I into the nuclei of cancer cells overexpressing EGFR, significantly enhancing cytotoxicity. Further evaluation of [125I]SGMIB-MNT as a targeted radiotherapeutic for EGFR-expressing cancer cells appears warranted.
Effect of doping concentration on absorbance, structural, and magnetic properties of cobalt-doped ZnO nano-crystallites
Authors: Shafique Muhammad Ahsan , Shah Saqlain A , Nafees Muhammad , Rasheed Khalid , Ahmad Riaz
Published: October 2012

Controlled conduction of magnetic spins is desired for data processing in modern spintronic devices. Transition metal-doped ZnO is a potential candidate for this purpose. We studied the effects of cobalt doping on structural, absorbance, and magnetic properties of ZnO nano-particles. Different compositions (Zn0.99Co0.1O, Zn0.97Co0.3O, and Zn0.95Co0.5O) of cobalt-doped ZnO were fabricated using metallic chlorides by co-precipitation method. XRD revealed standard ZnO wurtzite crystal structure without lattice distortion due to impurities but showed presence of additional phases at higher doping ratios. Fourier transformed infrared spectroscopy also confirmed the standard ZnO profiles at lower doping ratios but additional phases at higher doping. Vibrating sample magnetometer showed soft ferromagnetic behavior for low impurity samples and harder ferromagnetic behavior for higher doping at room temperature. A simultaneous differential scanning calorimetry/thermo gravimetric analysis was performed to study the phase variations during crystallization.
Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate
Authors: Lee Sang-Won , Park Hee-Jin , Kim Beom Kyung , Han Kwang-Hyub , Lee Soo-Kon , Kim Seung Up , Park Yong-Beom
Published: October 2012

Introduction

We identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values.

Methods

We consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated.

Results

The median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001).

Conclusions

The cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.
Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children
Authors: Wong Hector R , Cvijanovich Natalie Z , Hall Mark , Allen Geoffrey L , Thomas Neal J , Freishtat Robert J , Anas Nick , Meyer Keith , Checchia Paul A , Lin Richard , Bigham Michael T , Sen Anita , Nowak Jeffrey , Quasney Michael , Henricksen Jared W , Chopra Arun , Banschbach Sharon , Beckman Eileen , Harmon Kelli , Lahni Patrick , Shanley Thomas P
Published: October 2012

Introduction

Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.

Methods

Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.

Results

Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.

Conclusions

Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27.

The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.
Late Budgets
Authors: Andersen Asger Lau , Lassen David Dreyer , Nielsen Lasse Holbøll Westh
Published: October 2012

The budget forms the legal basis for government spending, and timely budgets, enacted before the new fiscal year, are an integral part of good governance. This paper examines the causes of late budgets using a unique dataset of budget completion dates for US state governments 1988–2007, constructed from news reports and state budget office surveys. We find 23 percent of state budgets to be late. We show that changing economic circumstances and divided government are the driving forces behind late budgets, which is consistent with a war-of-attrition bargaining model featuring budget baselines and preferences over deviations from such baselines. (JEL C78, D72, H61, H72)
Poverty Alleviation and Child Labor
Authors: Edmonds Eric V , Schady Norbert
Published: October 2012

Poor women with children in Ecuador were selected at random for a cash transfer that is less than 20 percent of median child labor earnings. Poor families with children in school at the time of the award use the transfer to postpone the child's entry into the labor force. Students in families induced to take up the transfer by the experiment reduce paid employment by 78 percent and unpaid economic activity inside their home by 32 percent. Time in unpaid household services increases, but overall time spent working declines. (JEL I32, I38, J13, J22, J82, O12)
The Heterogeneous Geographic and Socioeconomic Incidence of Cigarette Taxes: Evidence from Nielsen Homescan Data
Authors: Harding Matthew , Leibtag Ephraim , Lovenheim Michael F
Published: October 2012

We use Nielsen Homescan data to examine who bears the economic burden of cigarette taxes. We find cigarette taxes are less than fully passed through to consumer prices, suggesting consumers and producers split the excess burden of these taxes. Using information on consumer location, we show the availability of lower-tax goods across state borders creates significant differences in the pass-through rate. Tax avoidance opportunities also have a sizable effect on purchasing behavior by altering consumer search, prices paid and quantities purchased. Finally, we demonstrate that the incidence of cigarette taxes and the border effect varies by household income and education. (JEL D12, H22, H25, H26, H71, L66)
Spatial Competition and Cross-Border Shopping: Evidence from State Lotteries
Authors: Knight Brian , Schiff Nathan
Published: October 2012

This paper investigates competition between jurisdictions in the context of cross-border shopping for state lottery tickets. Our theoretical model, in which consumers consider both travel costs and lottery payoffs, predicts that per-resident sales should be more responsive to prices in small states with densely populated borders. Using weekly sales data from US lotteries and drawing identification from the roll-over feature of jackpots, we estimate this responsiveness and find large effects that vary significantly across states. Using these estimates, we show that competitive pressures from neighboring states may lead to substantially lower optimal prices. (JEL H27, H71, H73, R51)
Assessing and referring adolescents' health-related social problems: qualitative evaluation of a novel web-based approach
Authors: Wylie Sarah A , Hassan Areej , Krull Emily G , Pikcilingis Aaron B , Corliss Heather L , Woods Elizabeth R , Fleegler Eric W
Published: October 2012

We conducted a qualitative study to examine users' perceptions of a web-based screening and referral system for young adults with health-related social problems. The first 50 patients who used the system also took part in semi-structured interviews. There were 20 patients aged 15–17 years and 30 aged 18–25 years. Completing the web-based screening process took an average of 25 min. Ninety percent of participants reported at least one major health-related social problem and a total of 134 referrals were selected for further assistance. Ninety-six percent of participants said they would recommend the system to a friend or peer, and 80% supported its use for annual screening. Perceived strengths of the system were novelty, privacy, ease of use, relevance, motivation, variety and proximity of referrals, and clinic staff support. Perceived shortcomings were length, sensitivity, navigation challenges and agency availability. The system complemented provider visits and preserved privacy while improving attention to patient needs. Computerized screening and referral tools have potential to improve the quality of care in vulnerable young adults.
User engagement with and attitudes towards an interactive SMS reminder system for patients with tuberculosis
Authors: Mohammed Shama , Siddiqi Osman , Ali Owais , Habib Ali , Haqqi Faraz , Kausar Maimoona , Khan Aamir J
Published: October 2012

We conducted a qualitative study to understand user perceptions, acceptability and engagement with an interactive SMS reminder system designed to improve treatment adherence for patients with tuberculosis (TB). Patients received daily reminders and were asked to respond after taking their medication. Non-responsive patients were sent up to three reminders a day. We enrolled 30 patients with TB who had access to a mobile phone and observed their engagement with the system for a one-month period. We also conducted semi-structured interviews with 24 patients to understand their experience with the system. Most patients found the reminders helpful and encouraging. The average response rate over the study period was 57%. However, it fell from a mean response rate of 62% during the first ten days to 49% during the last ten days. Response rates were higher amongst females, participants with some schooling, and participants who had sent an SMS message the week prior to enrolment. Non-responsiveness was associated with a lack of access to the owner of the mobile phone, problems with the mobile phone itself and literacy. Our pilot study suggests that interactive SMS reminders are an acceptable and appreciated method of supporting patients with TB in taking their medication.
Malpractice claims regarding calls to Swedish telephone advice nursing: what went wrong and why?
Authors: Ernesäter Annica , Winblad Ulrika , Engström Maria , Holmström Inger K
Published: October 2012

We analysed the characteristics of all malpractice claims arising out of telephone calls to Swedish Healthcare Direct (SHD) during 2003–2010 ( n = 33). The National Board of Health and Welfare's (NBHW) investigations describing the causes of the malpractice claims and the healthcare providers' reported measures were analysed using Qualitative Content Analysis. The original telephone calls themselves, which had been recorded, were analysed using the Roter Interaction Analysis System (RIAS). Among the 33 cases, 13 patients died and 12 were admitted to intensive care. Failure to listen to the caller ( n = 12) was the most common reason for malpractice claims, and work-group discussion ( n = 13) was the most common measure taken to prevent future re-occurrence. Male patients ( n = 19) were in the majority, and females ( n = 24) were the most common callers. The most common symptoms were abdominal ( n = 11) and chest pain ( n = 6). Telenurses followed up on caller understanding in six calls, and mainly used closed-ended questions. Despite the severity of these malpractice claims, the measures taken mainly addressed active failure, rather than the latent conditions. Third-party communication should be regarded as a risk. When callers make repeated contacts, telenurses need to re-evaluate their need for care.
A teledermatology care management protocol for tracking completion of teledermatology recommendations
Authors: Eastman Kristin L , Lutton Marie C , Raugi Gregory J , Sakamoto Mandy R , McDowell Jennifer A , McFarland Lynne V , Reiber Gayle E
Published: October 2012

In July 2009 we implemented a 3-year store-and-forward teledermatology project to provide dermatology care to veterans living in rural and underserved areas of the US Pacific Northwest. We also developed a follow-up protocol and tracking system. Information about all completed teledermatology consultations was entered into a database, and major procedures and select medications were tracked. In the first 21 months, 8202 dermatology conditions in 5232 veterans were treated and 3370 major procedures carried out. Ninety-five percent of conditions were associated with no more than two teledermatology consultations, and no condition required more than ten consultations. In total, 1454 conditions were reviewed for clinical pathological correlation, and in 310 (21%) there was a subsequent clinical pathological correlation conference, resulting in a change in final diagnosis for 93 conditions. The follow-up was important in ensuring high quality patient care.
Validity and reliability of the assessment and diagnosis of musculoskeletal elbow disorders using telerehabilitation
Authors: Lade Hannah , McKenzie Stephanie , Steele Leah , Russell Trevor G
Published: October 2012

We examined the validity and reliability of a physiotherapy examination of the elbow, using telerehabilitation. The patho-anatomical diagnoses, systems diagnosis and physical examination findings of face-to-face physiotherapy examinations were compared with telerehabilitation examinations. Ten participants attended a single session, during which they were interviewed, a face-to-face physical examination was performed and a remote physical examination was conducted, guided by an examiner at a different location via a telerehabilitation system. Conventional face-to-face physiotherapy physical examination test results, diagnoses and systems diagnoses were compared to those produced by an examiner using the telerehabiliation system. There was substantial agreement for systems diagnosis (73%; P = 0.013) for validity and almost perfect agreement for intra-rater reliability (90%; P = 0.001). The inter-rater reliability had a weaker and non-significant agreement (64%; P = 0.11). Physical examination data demonstrated >68% agreement across all three datasets, between the examination methods. Performing a telerehabilitation physical examination to determine a musculoskeletal diagnosis of the elbow joint complex is both valid and reliable.
Attitudes of women in midlife to web-based interventions for promoting physical activity
Authors: Im Eun-Ok , Chang Sun Ju , Chee Wonshik , Chee Eunice
Published: October 2012

We explored the attitudes of women at midlife to web-based interventions for promoting physical activity. 145 women volunteered to participate in one of four online forums. The forums were for four major racial/ethnic groups. 90 volunteers were recruited for the online forums (29 Whites, 23 Hispanics, 21 African Americans, and 17 Asians). Two sets of topics on attitudes to physical activity and racial/ethnic contexts were used. Each topic had some introductory questions and related prompts, and these were posted on the online forum sites in a serial fashion during the six-month period. We used a thematic analysis. Four major themes emerged: (1) ‘a matter of the source of the information’; (2) ‘I can pace myself’; (3) ‘lack of interpersonal interactions’; and (4) ‘culture-specificity and low cost.’ The women in all ethnic groups thought that the source of the information was much more important than the medium of the information (e.g. web-based, booklet or face-to-face). They liked the self-controllability in web-based interventions. They preferred web-based interventions to other types of interventions because of easy accessibility, but they were concerned about lack of interpersonal interaction. None of the White or African American women indicated the need for culture-specificity in web-based interventions, but Hispanic and Asian women indicated that culture-specific interventions should be provided. Web-based interventions appear to have several advantages over conventional approaches to promoting physical activity.
Radiography of the Past — Three Dimensional, Virtual Reconstruction of a Roman Town in Lusitania
Authors: Klein Michael , Vermeulen Frank , Corsi Cristina
Published: October 2012

The European project, “RADIO-PAST” was launched in 2009 within the Marie Curie framework “Industry-Academia Partnerships and Pathways”. The project aims to join resources and different skills to tackle each possible aspect connected with “non-destructive” approaches to understand and reconstruct complex archaeological sites. The consortium of 7 partners has chosen an “open laboratory for research and experimentation” in and around the abandoned Roman site of Ammaia in central Portugal, but some research activities are carried out by the partner institutions in different areas of the Mediterranean and continental Europe. This paper describes the various methods and procedures which were used to undertake the three dimensional reconstruction of this Roman urban site in Lusitania.