bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotemplating rod-like viruses for the synthesis of copper nanorods and nanowires
Authors: Zhou Jing C , Soto Carissa M , Chen Mu-San , Bruckman Michael A , Moore Martin H , Barry Edward , Ratna Banahalli R , Pehrsson Pehr E , Spies Bradley R , Confer Tammie S
Published: May 2012

Background

In the past decade spherical and rod-like viruses have been used for the design and synthesis of new kind of nanomaterials with unique chemical positioning, shape, and dimensions in the nanosize regime. Wild type and genetic engineered viruses have served as excellent templates and scaffolds for the synthesis of hybrid materials with unique properties imparted by the incorporation of biological and organic moieties and inorganic nanoparticles. Although great advances have been accomplished, still there is a broad interest in developing reaction conditions suitable for biological templates while not limiting the material property of the product.

Results

We demonstrate the controlled synthesis of copper nanorods and nanowires by electroless deposition of Cu on three types of Pd-activated rod-like viruses. Our aqueous solution-based method is scalable and versatile for biotemplating, resulting in Cu-nanorods 24–46 nm in diameter as measured by transmission electron microscopy. Cu2+ was chemically reduced onto Pd activated tobacco mosaic virus, fd and M13 bacteriophages to produce a complete and uniform Cu coverage. The Cu coating was a combination of Cu0 and Cu2O as determined by X- ray photoelectron spectroscopy analysis. A capping agent, synthesized in house, was used to disperse Cu-nanorods in aqueous and organic solvents. Likewise, reactions were developed to produce Cu-nanowires by metallization of polyaniline-coated tobacco mosaic virus.

Conclusions

Synthesis conditions described in the current work are scalable and amenable for biological templates. The synthesized structures preserve the dimensions and shape of the rod-like viruses utilized during the study. The current work opens the possibility of generating a variety of nanorods and nanowires of different lengths ranging from 300 nm to micron sizes. Such biological-based materials may find ample use in nanoelectronics, sensing, and cancer therapy.
Gene regulation is governed by a core network in hepatocellular carcinoma
Authors: Gu Zuguang , Zhang Chenyu , Wang Jin
Published: May 2012

Background

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC.

Results

In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways.

Conclusions

Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further experimental validation is worthwhile.
A high-throughput core sampling device for the evaluation of maize stalk composition
Authors: Muttoni German , Johnson James M , Santoro Nicholas , Rhiner Craig J , von Mogel Karl J Haro , Kaeppler Shawn M , de Leon Natalia
Published: May 2012

Background

A major challenge in the identification and development of superior feedstocks for the production of second generation biofuels is the rapid assessment of biomass composition in a large number of samples. Currently, highly accurate and precise robotic analysis systems are available for the evaluation of biomass composition, on a large number of samples, with a variety of pretreatments. However, the lack of an inexpensive and high-throughput process for large scale sampling of biomass resources is still an important limiting factor. Our goal was to develop a simple mechanical maize stalk core sampling device that can be utilized to collect uniform samples of a dimension compatible with robotic processing and analysis, while allowing the collection of hundreds to thousands of samples per day.

Results

We have developed a core sampling device (CSD) to collect maize stalk samples compatible with robotic processing and analysis. The CSD facilitates the collection of thousands of uniform tissue cores consistent with high-throughput analysis required for breeding, genetics, and production studies. With a single CSD operated by one person with minimal training, more than 1,000 biomass samples were obtained in an eight-hour period. One of the main advantages of using cores is the high level of homogeneity of the samples obtained and the minimal opportunity for sample contamination. In addition, the samples obtained with the CSD can be placed directly into a bath of ice, dry ice, or liquid nitrogen maintaining the composition of the biomass sample for relatively long periods of time.

Conclusions

The CSD has been demonstrated to successfully produce homogeneous stalk core samples in a repeatable manner with a throughput substantially superior to the currently available sampling methods. Given the variety of maize developmental stages and the diversity of stalk diameter evaluated, it is expected that the CSD will have utility for other bioenergy crops as well.
A novel five-way translocation t(7;11;9;22;9)(q22;q13;q34;q11.2;q34) involving Ph chromosome in a patient of chronic myeloid leukemia: a case report
Authors: Yokota Sho , Nakamura Yuichi , Bessho Masami
Published: May 2012

About 5-10 % of chronic myelogenous leukemia (CML) patients show variant Philadelphia (Ph) translocations. The formation mechanisms and clinical significance of variant Ph translocations remain unclear. We report a CML case with a novel five-way complex translocation. Although the result of initial G-banding was 46,XY,t(7;11;9)(q22;q13;q34),t(9;22)(q34;q11.2), fluorescence in situ hybridization (FISH) demonstrated t(7;11;9;22;9)(q22;q13;q34;q11.2;q34) consisting of sequential rearrangements involving five chromosomes. The patient was successfully treated by imatinib and obtained a major molecular response. To our knowledge, this is the tenth CML case with a complicated Ph translocation involving five chromosomes and the third one treated by imatinib. Good response with imatinib therapy suggested that a single-event rearrangement was involved in the chromosomal changes.
Evaluation of the imputation performance of the program IMPUTE in an admixed sample from Mexico City using several model designs
Authors: Krithika S , Valladares-Salgado Adán , Peralta Jesus , La Peña Jorge Escobedo-de , Kumate-Rodríguez Jesus , Cruz Miguel , Parra Esteban J
Published: May 2012

Background

We explored the imputation performance of the program IMPUTE in an admixed sample from Mexico City. The following issues were evaluated: (a) the impact of different reference panels (HapMap vs. 1000 Genomes) on imputation; (b) potential differences in imputation performance between single-step vs. two-step (phasing and imputation) approaches; (c) the effect of different posterior genotype probability thresholds on imputation performance and (d) imputation performance in common vs. rare markers.

Methods

The sample from Mexico City comprised 1,310 individuals genotyped with the Affymetrix 5.0 array. We randomly masked 5% of the markers directly genotyped on chromosome 12 (n = 1,046) and compared the imputed genotypes with the microarray genotype calls. Imputation was carried out with the program IMPUTE. The concordance rates between the imputed and observed genotypes were used as a measure of imputation accuracy and the proportion of non-missing genotypes as a measure of imputation efficacy.

Results

The single-step imputation approach produced slightly higher concordance rates than the two-step strategy (99.1% vs. 98.4% when using the HapMap phase II combined panel), but at the expense of a lower proportion of non-missing genotypes (85.5% vs. 90.1%). The 1,000 Genomes reference sample produced similar concordance rates to the HapMap phase II panel (98.4% for both datasets, using the two-step strategy). However, the 1000 Genomes reference sample increased substantially the proportion of non-missing genotypes (94.7% vs. 90.1%). Rare variants (<1%) had lower imputation accuracy and efficacy than common markers.

Conclusions

The program IMPUTE had an excellent imputation performance for common alleles in an admixed sample from Mexico City, which has primarily Native American (62%) and European (33%) contributions. Genotype concordances were higher than 98.4% using all the imputation strategies, in spite of the fact that no Native American samples are present in the HapMap and 1000 Genomes reference panels. The best balance of imputation accuracy and efficiency was obtained with the 1,000 Genomes panel. Rare variants were not captured effectively by any of the available panels, emphasizing the need to be cautious in the interpretation of association results for imputed rare variants.
In vitro the behaviors of metastasis with suppression of VEGF in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line
Authors: Yang Lei , You Shuo , Kumar Vikas , Zhang Chaoyue , Cao Ya
Published: May 2012

Background

Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. VEGF is believed to implicate poor prognosis in various cancers. The overexpression of VEGF may be an early step in the process of metastasis.

Methods

ELISA was used to investigate the levels of VEGF, bFGF and IL8 in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line and its parental cell line, LNCaP and to determine the effect of bevacizumab on reducing the level of VEGF. Cell proliferation assay, invasion assay and in vitro angiogenesis assay were performed under the condition with bevacizumab or control IgG.

Results

Human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line expressed a higher level of VEGF than its parental primary prostate cancer cell line LNCaP. The effect of bevacizumab is dose-dependent and time-dependent: 100 μg/mL of bevacizumab and 3-day treatment was more effective than low-dose and lesser-day treatment for decreasing the level of VEGF. Bevacizumab is able to suppress cell proliferation, angiogenesis and invasion in human bone metastatic C4-2B prostatic cancer cell line.

Conclusions

The overexpression of VEGF can be inhibited by bevacizumab in human bone metastatic cancer cell line. The behaviors of metastasis involving proliferation, angiogenesis and invasion are suppressed by anti-VEGF therapy.
Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?
Authors: Lakota Katja , Wei Jun , Carns Mary , Hinchcliff Monique , Lee Jungwha , Whitfield Michael L , Sodin-Semrl Snezna , Varga John
Published: May 2012

Introduction

Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients with SSc may contribute to progression of fibrosis. Here we evaluated the levels of adiponectin, a sensitive and specific index of PPAR-gamma activity, as a potential fibrogenic biomarker in SSc.

Methods

Adiponectin levels were determined in the sera of 129 patients with SSc and 86 healthy controls, and serial determinations were performed in 27 patients. Levels of adiponectin mRNA in skin biopsies from SSc patients were assessed in an expression profiling microarray dataset. Regulation of adiponectin gene expression in explanted human subcutaneous preadipocytes and fibroblasts was examined by real-time quantitative PCR.

Results

Patients with diffuse cutaneous SSc had reduced serum adiponectin levels. A significant inverse correlation between adiponectin levels and the modified Rodnan skin score was observed. In longitudinal studies changes in serum adiponectin levels were inversely correlated with changes in skin fibrosis. Skin biopsies from a subset of SSc patients showed reduced adiponectin mRNA expression which was inversely correlated with the skin score. An agonist ligand of PPAR-gamma potently induced adiponectin expression in explanted mesenchymal cells in vitro.

Conclusions

Levels of adiponectin, reflecting PPAR-gamma activity, are correlated with skin fibrosis and might have potential utility as a biomarker in SSc.
Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study
Authors: Yao Song , Zirpoli Gary , Bovbjerg Dana H , Jandorf Lina , Hong Chi Chen , Zhao Hua , Sucheston Lara E , Tang Li , Roberts Michelle , Ciupak Gregory , Davis Warren , Hwang Helena , Johnson Candace S , Trump Donald L , McCann Susan E , Ademuyiwa Foluso , Pawlish Karen S , Bandera Elisa V , Ambrosone Christine B
Published: May 2012

Introduction

American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.

Methods

In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.

Results

More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.

Conclusions

These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women.
Neurocognitive problems in epilepsy
Authors: Lodhi Shruti , Agrawal Niruj
Published: May 2012

Cognitive dysfunction is one of the major contributors to the burden of epilepsy. It can significantly disrupt intellectual development in children and functional status and quality of life in adults. Epilepsy affects cognition through a number of mechanisms in complex interrelationship. Cognitive deficits in epilepsy may be treated indirectly through aggressive seizure control using anti-epileptic drugs or surgery, and by treating comorbid conditions such as depression. The beneficial effects of reducing seizures may offset the adverse cognitive side-effects of these therapies. Direct treatment of cognitive impairment in epilepsy mainly involves memory rehabilitation. Other direct treatments are mostly experimental and their evidence base is currently poor.
Use of Health of the Nation Outcome Scales in psychiatry
Authors: Delaffon Vijay , Anwar Zarina , Noushad Fabida , Ahmed Ayesha S. , Brugha Traolach S.
Published: May 2012

Routine outcome measures are essential to chart individual patient progress and evaluate models of service provision. The Health of the Nation Outcome Scales (HoNOS) were commissioned by the Royal College of Psychiatrists as a simple, brief measure for this purpose. It is one of the most widely used outcome measures in mental health services globally and has been translated into at least seven languages. Its use has broadened beyond its original purpose and in several countries collection of HoNOS data is mandatory. We review 585 potential articles to chart the development and evolution of HoNOS, as well as its psychometric properties, qualitative attributes and uses in clinical practice and research. The potential barriers to implementation of HoNOS on a wide scale are considered and its future role in evaluating effectiveness and benchmarking of services are discussed.
Looking north of the border
Authors: Lyons Donald
Published: May 2012

Scottish legislation on incapacity differs significantly from English and Welsh legislation. Clinicians must be aware of the authority of attorneys, especially in relation to welfare and medical treatment. The number of welfare attorneys is growing and they may not be aware of how best to use their powers.
Severe mental illness in 33 588 prisoners worldwide: systematic review and meta-regression analysis
Authors: Fazel Seena , Seewald Katharina
Published: May 2012

Background

High levels of psychiatric morbidity in prisoners have been documented in many countries, but it is not known whether rates of mental illness have been increasing over time or whether the prevalence differs between low–middle-income countries compared with high-income ones.

Aims

To systematically review prevalence studies for psychotic illness and major depression in prisoners, provide summary estimates and investigate sources of heterogeneity between studies using meta-regression.

Method

Studies from 1966 to 2010 were identified using ten bibliographic indexes and reference lists. Inclusion criteria were unselected prison samples and that clinical examination or semi-structured instruments were used to make DSM or ICD diagnoses of the relevant disorders.

Results

We identified 109 samples including 33 588 prisoners in 24 countries. Data were meta-analysed using random-effects models, and we found a pooled prevalence of psychosis of 3.6% (95% CI 3.1–4.2) in male prisoners and 3.9% (95% CI 2.7–5.0) in female prisoners. There were high levels of heterogeneity, some of which was explained by studies in low–middle-income countries reporting higher prevalences of psychosis (5.5%, 95% CI 4.2–6.8;P=0.035 on meta-regression). The pooled prevalence of major depression was 10.2% (95% CI 8.8–11.7) in male prisoners and 14.1% (95% CI 10.2–18.1) in female prisoners. The prevalence of these disorders did not appear to be increasing over time, apart from depression in the USA (P=0.008).

Conclusions

High levels of psychiatric morbidity are consistently reported in prisoners from many countries over four decades. Further research is needed to confirm whether higher rates of mental illness are found in low- and middle-income nations, and examine trends over time within nations with large prison populations.
Strengths and Difficulties Questionnaire scores and mental
health in looked after children
Authors: Goodman Anna , Goodman Robert
Published: May 2012

British local authorities are required to monitor the mental health of
looked after children using mean Strengths and Difficulties Questionnaire
(SDQ) scores from parents or carers. This assumes that differences in mean
SDQ scores reflect genuine differences in child mental health in this group,
something we examined using nationally representative surveys
(n = 1391, age 5–16). We found that the SDQ was a
genuinely dimensional measure of mental health in these children and
provided accurate estimates of disorder prevalence.
Autoimmunity in psychiatry
Authors: Davison Kenneth
Published: May 2012

Current knowledge of the role of autoimmunity in the pathogenesis of the
main psychiatric disorders is briefly outlined. The significance of
immunological effects on synaptic transmission and associated
neuropsychiatric syndromes is emphasised. Clinical psychiatrists are
encouraged to keep abreast of developments in this increasingly important
area.
Reading about … the history of psychiatry
Authors: Beveridge Allan
Published: May 2012

In recent decades ideological battles have raged over how the history of psychiatry should be interpreted. Should the emergence of psychiatry in the late 18th century be seen as the triumph of the Enlightenment, ushering in a rational approach to mental illness and overturning the primitive and often barbaric ideas of previous eras? Or should the rise of psychiatry be seen in a more sinister light? Does it represent the extension of the state into the lives of its citizens, controlling and policing the disaffected and discontented? Are psychiatrists benign humanitarians or agents of oppression? Should the historical narrative be one of progress, as psychiatry steadily extends its knowledge of mental illness and develops more and more effective therapy? Or is the reverse true: has the advent of psychiatry been a calamity for the mad?
Emergency department junior medical staff's knowledge, skills and confidence with psychiatric patients: a survey
Authors: Gordon Jacqueline Therese
Published: May 2012

Aims and method

To determine knowledge, skills and confidence of junior medical emergency department staff in managing mental health patients. Over a 2-year period new emergency department junior doctors were given a questionnaire to complete early on in their post and prior to any mental health training. The questionnaire asked about knowledge, confidence, concerns and skills in the management of mental health patients in accident and emergency services.

Results

More than half of the 32 doctors surveyed said they lacked knowledge, skills and confidence when assessing mental health patients.

Clinical implications

The survey has demonstrated a need for mental health training of new doctors working in the emergency department. Effective training for such doctors can be offered by a liaison psychiatry service. This should be embedded in their teaching programme and be continually responsive to their perceived training needs.
Motivational reserve: does it help our understanding of cognitive impairment? Commentary on … Healthy brain ageing
Authors: Woods Bob
Published: May 2012

Motivational reserve is being proposed as an additional component of reserve capacities which may prevent, or ameliorate the effects of, cognitive impairment in later life. This is consistent with an understanding of the presentation of dementia which goes beyond neuropathological and neuropsychological changes. The construct may help make sense of findings relating to the potentially preventative qualities of a diverse range of ‘cognitive’ activities and of social networks, as well as of education. However, caution is required in relation to how cognitive impairment is evaluated and defined, to avoid confounds such as has been the case with level of education.
Deferasirox Reduces Serum Ferritin and Labile Plasma Iron in RBC Transfusion–Dependent Patients With Myelodysplastic Syndrome
Authors: List Alan F. , Baer Maria R. , Steensma David P. , Raza Azra , Esposito Jason , Martinez-Lopez Noelia , Paley Carole , Feigert John , Besa Emmanuel
Published: May 2012

Purpose

This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1–risk myelodysplastic syndrome (MDS).

Patients and Methods

Eligible patients had serum ferritin ≥ 1,000 μg/L and had received ≥ 20 units of RBCs with ongoing transfusion requirements. The starting dose of deferasirox was 20 mg/kg/d, with dose escalation up to 40 mg/kg/d permitted.

Results

A total of 176 patients were enrolled, and 173 patients received therapy. Median serum ferritin decreased 23% in the 53% of patients who completed 12 months of treatment (n = 91), 36.7% in patients who completed 2 years (n = 49), and 36.5% in patients who completed 3 years (n = 33) despite continued transfusion requirement. Reduction in serum ferritin significantly correlated with ALT improvement (P < .001). Labile plasma iron (LPI) was measured quarterly during the first year of the study. Sixty-eight patients (39.3%) had elevated LPI at baseline. By week 13, LPI levels normalized in all patients with abnormal baseline level. Fifty-one (28%) of 173 patients experienced hematologic improvement by International Working Group 2006 criteria; of these, only seven patients received growth factors or MDS therapy. Over the 3-year study, 138 (79.8%) of 173 patients discontinued therapy, 43 patients (24.8%) because of adverse events or disease progression and 23 patients (13.2%) because of abnormal laboratory values. The most common drug-related adverse events were gastrointestinal disturbances and increased serum creatinine. There were 28 deaths, none of which were considered related to deferasirox.

Conclusion

Deferasirox reduces serum ferritin and LPI in transfusion-dependent patients with MDS. A subset of patients had an improvement in hematologic and hepatic parameters.
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
Authors: Lynch Thomas J. , Bondarenko Igor , Luft Alexander , Serwatowski Piotr , Barlesi Fabrice , Chacko Raju , Sebastian Martin , Neal Joel , Lu Haolan , Cuillerot Jean-Marie , Reck Martin
Published: May 2012

Purpose

Ipilimumab, which is an anti–cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin.

Patients and Methods

Patients (N = 204) with chemotherapy-naive non–small-cell lung cancer (NSCLC) were randomly assigned 1:1:1 to receive paclitaxel (175 mg/m2) and carboplatin (area under the curve, 6) with either placebo (control) or ipilimumab in one of the following two regimens: concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ≤ 18 weeks (induction). Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy. Response was assessed by using immune-related response criteria and modified WHO criteria. The primary end point was immune-related progression-free survival (irPFS). Other end points were progression-free survival (PFS), best overall response rate (BORR), immune-related BORR (irBORR), overall survival (OS), and safety.

Results

The study met its primary end point of improved irPFS for phased ipilimumab versus the control (hazard ratio [HR], 0.72; P = .05), but not for concurrent ipilimumab (HR, 0.81; P = .13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; P = .02). Phased ipilimumab, concurrent ipilimumab, and control treatments were associated with a median irPFS of 5.7, 5.5, and 4.6 months, respectively, a median PFS of 5.1, 4.1, and 4.2 months, respectively, an irBORR of 32%, 21% and 18%, respectively, a BORR of 32%, 21% and 14%, respectively, and a median OS of 12.2, 9.7, and 8.3 months. Overall rates of grade 3 and 4 immune-related AEs were 15%, 20%, and 6% for phased ipilimumab, concurrent ipilimumab, and the control, respectively. Two patients (concurrent, one patient; control, one patient) died from treatment-related toxicity.

Conclusion

Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC.
Chromosomal Instability (CIN) Phenotype, CIN High or CIN Low, Predicts Survival for Colorectal Cancer
Authors: Watanabe Toshiaki , Kobunai Takashi , Yamamoto Yoko , Matsuda Keiji , Ishihara Soichiro , Nozawa Keijiro , Yamada Hideki , Hayama Tamuro , Inoue Eisuke , Tamura Junko , Iinuma Hisae , Akiyoshi Takashi , Muto Tetsuichiro
Published: May 2012

Purpose

To examine whether chromosomal instability (CIN) phenotype, determined by the severity of CIN, can predict survival for stages II and III colorectal cancer (CRC).

Patients and Methods

We determined microsatellite instability (MSI) and loss of heterozygosity (LOH) status in 1,103 patients (training [n = 845] and validation [n = 258] sets with stages II and III CRC). The LOH ratio was defined as the frequency of LOH in chromosomes 2p, 5q, 17p, and 18q. According to the LOH ratio, non–MSI high tumors were classified as CIN high (LOH ratio ≥ 33%) or CIN low (LOH ratio < 33%). CIN-high tumors were subclassified as CIN high (mild type; LOH ratio < 75%) or CIN high (severe type; LOH ratio ≥ 75%). We used microarrays to identify a gene signature that could classify the CIN phenotype and evaluated its ability to predict prognosis.

Results

CIN high showed the worst survival (P < .001), whereas there was no significant difference between CIN low and MSI high. CIN high (severe type) showed poorer survival than CIN high (mild type; P < .001). Multivariate analysis revealed that CIN phenotype was an independent risk factor for disease-free and overall survival, respectively, in both the training (P < .001 and P = .0155) and validation sets (P < .001 and P = .0076). Microarray analysis also revealed that survival was significantly poorer in those with the CIN-high than in the CIN-low gene signature (P = .0203). In a validation of 290 independent CRCs (GSE14333), the CIN-high gene signature showed significantly poorer survival than the CIN-low signature (P = .0047).

Conclusion

The CIN phenotype is a predictive marker for survival and may be used to select high-risk patients with stages II and III CRC.
Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Authors: Krop Ian , Demuth Tim , Guthrie Tina , Wen Patrick Y. , Mason Warren P. , Chinnaiyan Prakash , Butowski Nicholas , Groves Morris D. , Kesari Santosh , Freedman Steven J. , Blackman Samuel , Watters James , Loboda Andrey , Podtelezhnikov Alexei , Lunceford Jared , Chen Cong , Giannotti Maxine , Hing Jeremy , Beckman Robert , LoRusso Patricia
Published: May 2012

Purpose

Aberrant Notch signaling has been implicated in the pathogenesis of many human cancers. MK-0752 is a potent, oral inhibitor of γ-secretase, an enzyme required for Notch pathway activation. Safety, maximum-tolerated dose, pharmacokinetics (PKs), pharmacodynamics, and preliminary antitumor efficacy were assessed in a phase I study of MK-0752.

Patients and Methods

MK-0752 was administered in three different schedules to patients with advanced solid tumors. Hair follicles were collected at higher dose levels to assess a gene signature of Notch inhibition.

Results

Of 103 patients who received MK-0752, 21 patients received a continuous once-daily dosing at 450 and 600 mg; 17 were dosed on an intermittent schedule of 3 of 7 days at 450 and 600 mg; and 65 were dosed once per week at 600, 900, 1,200, 1,500, 1,800, 2,400, 3,200, and 4,200 mg. The most common drug-related toxicities were diarrhea, nausea, vomiting, and fatigue. PKs (area under the concentration-time curve and maximum measured plasma concentration) increased in a less than dose proportional manner, with a half-life of approximately 15 hours. Significant inhibition of Notch signaling was observed with the 1,800- to 4,200-mg weekly dose levels, confirming target engagement at those doses. One objective complete response and an additional 10 patients with stable disease longer than 4 months were observed among patients with high-grade gliomas.

Conclusion

MK-0752 toxicity was schedule dependent. Weekly dosing was generally well tolerated and resulted in strong modulation of a Notch gene signature. Clinical benefit was observed, and rational combination trials are currently ongoing to maximize clinical benefit with this novel agent.
Lxrα Regulates the Androgen Response in Prostate Epithelium
Authors: Viennois Emilie , Esposito Teresa , Dufour Julie , Pommier Aurélien , Fabre Stephane , Kemeny Jean-Louis , Guy Laurent , Morel Laurent , Lobaccaro Jean-Marc , Baron Silvère
Published: May 2012

Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that commonly occurs in older men. We show that liver X receptor (Lxr)-α knockout mice (lxrα−/−) develop ventral prostate hypertrophy, correlating with an overaccumulation of secreted proteins in prostatic ducts and an alteration of vesicular trafficking in epithelial cells. In the fluid of the lxrα−/− prostates, spermine binding protein is highly accumulated and shows a 3000-fold increase of its mRNA. This overexpression is mediated by androgen hypersensitivity in lxrα−/− mice, restricted to the ventral prostate. Generation of chimeric recombinant prostates demonstrates that Lxrα is involved in the establishment of the epithelial-mesenchymal interactions in the mouse prostate. Altogether these results point out the crucial role of Lxrα in the homeostasis of the ventral prostate and suggest lxrα−/− mice may be a good model to investigate the molecular mechanisms of benign prostatic hyperplasia.
Androgen Effects on Adipose Tissue Architecture and Function in Nonhuman Primates
Authors: Varlamov Oleg , White Ashley E. , Carroll Julie M. , Bethea Cynthia L. , Reddy Arubala , Slayden Ov , O'Rourke Robert W. , Roberts Charles T.
Published: May 2012

The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue.
Improving dosing of gentamicin in the obese patient: a 3-cycle drug chart and case note audit
Authors: Manjaly Joseph G , Reece-Smith Alexander M , Sivaloganathan Sivan S , Thuraisamy Christina , Smallwood Katie Lm , Jonas Elizabeth , Longman Robert J
Published: May 2012

Summary

Objectives

To assess the use of an electronic dose calculator to improve accuracy in the use of a complex Gentamicin prescription policy and assess turnaround time of blood sampling to dose delivery in an NHS hospital.

Design

Retrospective review of drug chart, case notes and hospital antibiotic database.

Setting

University Hospitals Bristol, UK

Participants

Patients receiving once daily intravenous gentamicin using the trust protocol, during the same time window for 3 consecutive years.

Main outcome measures

i) Accuracy of dose and frequency prescription of Gentamicin. ii) Time frame for measurement of serum Gentamicin levels.

Results

Following the introduction of the online calculator, prescribing errors in obese patients dropped from 43% to 20%, a similar level as in non-obese patients. Errors in frequency calculations dropped from 12.8% to 4%. On average, drug doses could be administered within 2.5 hours of a blood sample being taken.

Conclusions

Online tools can be used to improve prescribing for the complex dosing policies that will increasingly been required to tailor prescribing in obese patients. Serum gentamicin levels can be measured within a 2.5 hour time frame in the environment of an NHS hospital.
Management of Neonates With Suspected or Proven Early-Onset Bacterial Sepsis
Authors: Polin Richard A. ,   the COMMITTEE ON FETUS AND NEWBORN, Papile Lu-Ann , Baley Jill E. , Bhutani Vinod K. , Carlo Waldemar A. , Cummings James , Kumar Praveen , Tan Rosemarie C. , Wang Kasper S. , Watterberg Kristi L.
Published: May 2012

With improved obstetrical management and evidence-based use of intrapartum antimicrobial therapy, early-onset neonatal sepsis is becoming less frequent. However, early-onset sepsis remains one of the most common causes of neonatal morbidity and mortality in the preterm population. The identification of neonates at risk for early-onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis have a poor positive predictive accuracy. As a result, clinicians often treat well-appearing infants for extended periods of time, even when bacterial cultures are negative. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed). Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality. To reduce these risks, antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the management of infants with suspected or proven early-onset sepsis.
Home Care of Children and Youth With Complex Health Care Needs and Technology Dependencies
Authors: Elias Ellen Roy , Murphy Nancy A. ,   the COUNCIL ON CHILDREN WITH DISABILITIES, Liptak Gregory S. , Adams Richard C. , Burke Robert , Friedman Sandra L. , Houtrow Amy , Kalichman Miriam , Kuo Dennis , Levy Susan E. , Norwood Kenneth W. , Turchi Renee M. , Wiley Susan E.
Published: May 2012

This Clinical Report was reaffirmed May 2017 and December 2022.

Children and youth with complex medical issues, especially those with technology dependencies, experience frequent and often lengthy hospitalizations. Hospital discharges for these children can be a complicated process that requires a deliberate, multistep approach. In addition to successful discharges to home, it is essential that pediatric providers develop and implement an interdisciplinary and coordinated plan of care that addresses the child’s ongoing health care needs. The goal is to ensure that each child remains healthy, thrives, and obtains optimal medical home and developmental supports that promote ongoing care at home and minimize recurrent hospitalizations. This clinical report presents an approach to discharging the child with complex medical needs with technology dependencies from hospital to home and then continually addressing the needs of the child and family in the home environment.
Reflections on the enforcement of the genetic code of Act No. XXI of 2008
Authors: Sótonyi Gergely , Papp Judit
Published: May 2012

The genetic code of Act No. XXI of 2008 is a milestone in the national codification of Hungarian human genetic studies and research. The code is in conformity with international as well as EU legislations. It guarantees full enforcement of both the right to self-determination and the rules of the profession. The criteria of legal functioning are institutional accreditation, regular auditing, decreed government control, and coordinated network structure. Further government and ministerial decrees are necessitated for its enforcement. Orv. Hetil., 2012, 153, 683–689.
Some data on inflammatory bowel diseases in Hungary: analytical data on ulcerative colistis
Authors: Miheller Pál , Nagy Ferenc , Palatka Károly , Altorjay István , Horváth Gábor , Lőrinczy Katalin , Újszászy László , Virányi Zsolt , Szepes Attila , Molnár Tamás , Farkas Klaudia , Szepes Zoltán , Nyári Tibor , Wittmann Tibor , Tulassay Zsolt
Published: May 2012

Prospective data collection seems to be essential in evidence-based medicine. Because of the new therapeutic options, the need for standard data collection and testing has significantly increased. In Hungary, a registry for patients with inflammatory bowel disease has already been set up, which makes it possible for clinicians to collect prospective data on their patients. Aim: Basic characteristics of the database of patients with ulcerative colitis are presented in this paper. Methods: The inflammatory bowel disease registry uses the programme of Microsoft Access database management system. Data are stored in a central server. Results: The incidence of inflammatory bowel diseases has been permanently increasing in Hungary; however, its overall prevalence is still low among the European countries. The frequent administration of immunosuppressive medications (azathioprine and corticosteroids) and their increased doses worsen the estimation of the activity. Conclusions: 1., It would be very useful to gain prospective data from all national centres. This kind of database would be able to give a complete picture regarding the Hungarian therapeutical practice. 2., Medications of patients may alter the clinical value of the laboratory findings in the process of determining the severity of the disease. Orv. Hetil., 2012, 153, 702–712.
Pressure retarded osmosis for energy production: membrane materials and operating conditions
Authors: Kim H. , Choi J.-S. , Lee S.
Published: May 2012

Pressure retarded osmosis (PRO) is a novel membrane process to produce energy. PRO has the potential to convert the osmotic pressure difference between fresh water (i.e. river water) and seawater to electricity. Moreover, it can recover energy from highly concentrated brine in seawater desalination. Nevertheless, relatively little research has been undertaken for fundamental understanding of the PRO process. In this study, the characteristics of the PRO process were examined using a proof-of-concept device. Forward osmosis (FO), reverse osmosis (RO), and nanofiltration (NF) membranes were compared in terms of flux rate and concentration polarization ratio. The results indicated that the theoretical energy production by PRO depends on the membrane type as well as operating conditions (i.e. back pressure). The FO membrane had the highest energy efficiency while the NF membrane had the lowest efficiency. However, the energy production rate was low due to high internal concentration polarization (ICP) in the PRO membrane. This finding suggests that the control of the ICP is essential for practical application of PRO for energy production.
Comparison of surface functional groups and metal uptake efficiency of rice husk harvested from different climatic zones
Authors: Matin Amir Hossein , Khaloo Shokooh Sadat , Akbarzadeh Abbas , Riahi Mohammad
Published: May 2012

Rice husk (RH) is a very effective natural adsorbent for fast removal of heavy metal cations from water solutions. Application of RH for removal of some heavy metal ions, such as Ni, Zn, Mn, Co, Cu, Pb and Cd from water solutions has been studied and different maximum adsorption capacities and a variety of optimized conditions were reported in the literature. In this work, the efficiency of RH harvested from different climatic regions was studied. For this proposal, different RH samples were collected from three different climatic regions of Iran (nominated as RH1 to RH3); their removal efficiencies of heavy metal cations of Ni2+, Cu2+ and Cd2+ were investigated and compared. The adsorption data at optimum conditions could be assessed well by both Langmuir and Freundlich models. Statistical analysis of the results of adsorption isotherms showed that different RH samples have different efficiencies in uptake of these heavy metal ions. The RH samples were characterized using Fourier transform infrared spectroscopy and Boehm titration, which indicated that amounts of functional groups differed between RHs that are grown in different climatic conditions.
Comparison between a moving bed bioreactor and a fixed bed bioreactor for biological phosphate removal and denitrification
Authors: Choi H. J. , Lee A. H. , Lee S. M.
Published: May 2012

Moving bed bioreactors (MBBR) and fixed bed bioreactors (FBBR) were compared for biological phosphorus removal and denitrification. The sorption denitrification P-elimination (S-DN-P) process was selected for this study. Results indicated that all nutrients were removed by the FBBR process compared with the MBBR process: 19.8% (total COD), 35.5% (filtered COD), 27.6% (BOD5), 62.2% (acetate), 78.5% (PO4-P), and 54.2% (NO3-N) in MBBR; 49.7% (total COD), 54.0% (filtered COD), 63.2% (BOD5), 99.6% (acetate), 98.6% (PO4-P), and 75.9% (NO3-N) in FBBR. The phosphate uptake and NO3-N decomposition in the FBBR process during the denitrification phase were much higher than for the MBBR process despite being of shorter duration. Results obtained from this study are helpful in elucidating the practical implications of using MBBR and FBBR for the removal of bio-P and denitrification from wastewater.