Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.

Science.gov (United States)

Yuan, Ping; Leser, George P; Demeler, Borries; Lamb, Robert A; Jardetzky, Theodore S

2008-09-01

The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

Human hnRNP Q re-localizes to cytoplasmic granules upon PMA, thapsigargin, arsenite and heat-shock treatments

International Nuclear Information System (INIS)

Quaresma, Alexandre J.C.; Bressan, G.C.; Gava, L.M.; Lanza, D.C.F.; Ramos, C.H.I; Kobarg, Joerg

2009-01-01

Eukaryotic gene expression is regulated on different levels ranging from pre-mRNA processing to translation. One of the most characterized families of RNA-binding proteins is the group of hnRNPs: heterogenous nuclear ribonucleoproteins. Members of this protein family play important roles in gene expression control and mRNAs metabolism. In the cytoplasm, several hnRNPs proteins are involved in RNA-related processes and they can be frequently found in two specialized structures, known as GW-bodies (GWbs), previously known as processing bodies: PBs, and stress granules, which may be formed in response to specific stimuli. GWbs have been early reported to be involved in the mRNA decay process, acting as a site of mRNA degradation. In a similar way, stress granules (SGs) have been described as cytoplasmic aggregates, which contain accumulated mRNAs in cells under stress conditions and present reduced or inhibited translation. Here, we characterized the hnRNP Q localization after different stress conditions. hnRNP Q is a predominantly nuclear protein that exhibits a modular organization and several RNA-related functions. Our data suggest that the nuclear localization of hnRNP Q might be modified after different treatments, such as: PMA, thapsigargin, arsenite and heat shock. Under different stress conditions, hnRNP Q can fully co-localize with the endoplasmatic reticulum specific chaperone, BiP. However, under stress, this protein only co-localizes partially with the proteins: GW182 - GWbs marker protein and TIA-1 stress granule component

Control of HIV-1 env RNA splicing and transport: investigating the role of hnRNP A1 in exon splicing silencer (ESS3a) function

International Nuclear Information System (INIS)

Asai, Kengo; Platt, Craig; Cochrane, Alan

2003-01-01

The control of HIV-1 viral RNA splicing and transport plays an important role in the successful replication of the virus. Previous studies have identified both an exon splicing enhancer (ESE) and a bipartite exon splicing silencer (ESS3a and ESS3b) within the terminal exon of HIV-1 that are involved in modulating both splicing and Rev-mediated export of viral RNA. To define the mechanism of ESS3a function, experiments were carried out to better define the cis and trans components required for ESS3a activity. Mutations throughout the 30-nt element resulted in partial loss of ESS function. Combining mutations was found to have an additive effect, suggesting the presence of multiple binding sites. Analysis of interacting factors identified hnRNP A1 as one component of the complex that modulates ESS3a activity. However, subsequent binding analyses determined that hnRNP A1 interacts with only one portion of ESS3a, suggesting the involvement of another host factor. Parallel analysis of the effect of the mutations on Rev-mediated export determined that there is not a direct correlation between the effect of the mutations on splicing and RNA transport. Consistent with this hypothesis, replacement of ESS3a with consensus hnRNP A1 binding sites was found to be insufficient to block Rev-mediated RNA export

AUTOBA: automation of backbone assignment from HN(C)N suite of experiments.

Science.gov (United States)

Borkar, Aditi; Kumar, Dinesh; Hosur, Ramakrishna V

2011-07-01

Development of efficient strategies and automation represent important milestones of progress in rapid structure determination efforts in proteomics research. In this context, we present here an efficient algorithm named as AUTOBA (Automatic Backbone Assignment) designed to automate the assignment protocol based on HN(C)N suite of experiments. Depending upon the spectral dispersion, the user can record 2D or 3D versions of the experiments for assignment. The algorithm uses as inputs: (i) protein primary sequence and (ii) peak-lists from user defined HN(C)N suite of experiments. In the end, one gets H(N), (15)N, C(α) and C' assignments (in common BMRB format) for the individual residues along the polypeptide chain. The success of the algorithm has been demonstrated, not only with experimental spectra recorded on two small globular proteins: ubiquitin (76 aa) and M-crystallin (85 aa), but also with simulated spectra of 27 other proteins using assignment data from the BMRB.

Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients [v1; ref status: indexed, http://f1000r.es/3nv

Directory of Open Access Journals (Sweden)

Sangmin Lee

2014-06-01

Full Text Available Some somatic single nucleotide variants (SNVs are thought to be pathogenic, leading to neurological disease. We hypothesized that heterogeneous nuclear ribonuclear protein A1 (hnRNP A1, an autoantigen associated with multiple sclerosis (MS would contain SNVs. MS patients develop antibodies to hnRNP A1293-304, an epitope within the M9 domain (AA268-305 of hnRNP A1. M9 is hnRNP A1’s nucleocytoplasmic transport domain, which binds transportin-1 (TPNO-1 and allows for hnRNP A1’s transport into and out of the nucleus. Genomic DNA sequencing of M9 revealed nine novel SNVs that resulted in an amino acid substitution in MS patients that were not present in controls. SNVs occurred within the TPNO-1 binding domain (hnRNP A1268-289 and the MS IgG epitope (hnRNP A1293-304, within M9.  In contrast to the nuclear localization of wild type (WT hnRNP A1, mutant hnRNP A1 mis-localized to the cytoplasm, co-localized with stress granules and caused cellular apoptosis. Whilst WT hnRNP A1 bound TPNO-1, mutant hnRNP A1 showed reduced TPNO-1 binding. These data suggest SNVs in hnRNP A1 might contribute to pathogenesis of MS.

Effect of acupuncture on insomnia following stroke: study protocol for a randomized controlled trial.

Science.gov (United States)

Cao, Yan; Yin, Xuan; Soto-Aguilar, Francisca; Liu, Yiping; Yin, Ping; Wu, Junyi; Zhu, Bochang; Li, Wentao; Lao, Lixing; Xu, Shifen

2016-11-16

The incidence, mortality, and prevalence of stroke are high in China. Stroke is commonly associated with insomnia; both insomnia and stroke have been effectively treated with acupuncture for a long time. The aim of this proposed trial is to assess the therapeutic effect of acupuncture on insomnia following stroke. This proposed study is a single-center, single-blinded (patient-assessor-blinded), parallel-group randomized controlled trial. We will randomly assign 60 participants with insomnia following stroke into two groups in a 1:1 ratio. The intervention group will undergo traditional acupuncture that achieves the De-qi sensation, and the control group will receive sham acupuncture without needle insertion. The same acupoints (DU20, DU24, EX-HN3, EX-HN22, HT7, and SP6) will be used in both groups. Treatments will be given to all participants three times a week for the subsequent 4 weeks. The primary outcome will be the Pittsburgh Sleep Quality Index. The secondary outcomes will be: the Insomnia Severity Index; sleep efficacy, sleep awakenings, and total sleep time recorded via actigraphy; the National Institutes of Health Stroke Scale; the Stroke-Specific Quality of Life score; the Hospital Anxiety and Depression Scale. The use of estazolam will be permitted and regulated under certain conditions. Outcomes will be assessed at baseline, 2 weeks after treatment commencement, 4 weeks after treatment commencement, and at the 8-week follow-up. This proposed study will contribute to expanding knowledge about acupuncture treatment for insomnia following stroke. This will be a high-quality randomized controlled trial with strict methodology and few design deficits. It will investigate the effectiveness of acupuncture as an alternative treatment for insomnia following stroke. Chinese Clinical Trial Registry identifier: ChiCTR-IIC-16008382 . Registered on 28 April 2016.

Optimization and shelf life of a low-lactose yogurt with Lactobacillus rhamnosus HN001.

Science.gov (United States)

Ibarra, A; Acha, R; Calleja, M-T; Chiralt-Boix, A; Wittig, E

2012-07-01

Lactose intolerance results in gastrointestinal discomfort and the malabsorption of certain nutrients, such as calcium. The replacement of milk with low-lactose and probiotic-enriched dairy products is an effective strategy of mitigating the symptoms of lactose intolerance. Lactobacillus rhamnosus HN001 (HN001) is a safe, immunity-stimulating probiotic. We have developed a process to increase the hydrolysis of lactose and HN001 growth in yogurt versus β-galactosidase (βG) concentration and enzymatic hydrolysis time (EHT) before bacterial fermentation. The objective of this study was to optimize the conditions by which yogurt is processed as a function of βG and EHT using a multifactorial design, with lactose content, HN001 growth, process time, and sensory quality as dependent variables. Further, the shelf life of the optimized yogurt was evaluated. In the optimization study, polynomials explained the dependent variables. Based on Pearson correlation coefficients, HN001 growth correlated positively with the hydrolysis of lactose. However, low lactose content and high HN001 count increased the fermentation time and lowered the sensory quality. The optimized conditions-using polynomials to obtain yogurt with >1 × 10(7) cfu of HN001/mL, yogurt to which HN001 has been added for lactose-intolerant persons who wish to strengthen their immune system. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Singlet-triplet energy differences in divalent five membered cyclic conjugated Arduengo-type carbenes XC2HN2M (M = C, Si, Ge, Sn, and Pb; X = F, Cl, Br, and I)

Science.gov (United States)

Vessally, Esmail; Dehbandi, Behnam; Ahmadi, Elaheh

2016-09-01

Singlet-triplet energy differences in Arduengo-type carbenes XC2HN2C compared and contrasted with their sila, germa, stana and plumba analogues; at B3LYP/6-311++G** level of theory. Free Gibbs energy differences between triplet (t) and singlet (s) states (Δ G(t-s)) change in the following order: plumbylenes > stannylenes > germylenes > silylenes > carbenes. The singlet states in XC2HN2C are generally more stable when the electron withdrawing groups such as-F was used at β-position. However, the singlet states in XC2N2HM (M = Si, Ge, Sn, and Pb) are generally more stable when the withdrawing groups such as-F was placed. The puckering energy is investigated for each the singlet and triplet states. The DFT calculations found the linear correlation to size of the group 14 divalent element (M), the ∠N-M-N angle, and the Δ(LUMO-HOMO) of XC2HN2M.

Value of supranormal function (SP) and renogram on Tc-99m MAG3 scan in relation to the extent of hydronephrosis (HN) for predicting Ureteropelvic Junction Obstruction (UPO) in the newborn

Energy Technology Data Exchange (ETDEWEB)

Lee, Won Woo; Moon, D. H.; Park, Y. S.; Jun, N. L.; Kim, K. S.; Yoon, C. H.; Kang, W.; Lee, H. K. [Ulsan University, Seoul (Korea, Republic of)

2002-07-01

We studied MAG3 scan in relation to HN for predicting UPO in the newborn. Forty-eight neonates with prenatally diagnosed unilateral HN of anteroposterior pelvic diameter (APPD){>=}10 mm and renal function > 40% were included. SP({>=}55%) and renogram (1:non-obstructive, 2:indeterminate, 3:obstructive, 4:delayed transit) were determined on 1-mon MAG3 scan. APPD of the 19 with UPO(UPO+) was larger than that of the 29 without UPO(UPO-) (24.3{+-}9.2 vs 17.5{+-}11.2, p<0.05). The society for fetal urology grading(SFU) of UPO+(gr 1-4 in 0, 0, 2, 17) were also higher than UPO-(gr 1-4 in 1, 6, 10, 12, p<0.01). SP was present only in 4 UPO+(p<0.001). Renogram of the 19 UPO+ showed higher grades (1-4 in 0, 4, 8, 7 pts) than that of 29 UPO- (p<0.001). Multivariate analysis revealed that addition of SP or renogram increased likelihood ratio({chi}2=7.73, 9.99, p<0.01). Of the 29 with SFU=4, SP or renogram 4 had a positive predictive value of 90%(9/10). MAG3 at 1 month has value in relation to the HN in predicting UPO in pts with prenatally diagnosed unilateral HN.

The effect of O-GlcNAcylation on hnRNP A1 translocation and interaction with transportin1

Energy Technology Data Exchange (ETDEWEB)

Roth, Shira; Khalaila, Isam, E-mail: isam@bgu.ac.il

2017-01-01

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a major pre-mRNA binding protein involved in transcription and translation. Although predominantly nuclear, hnRNP A1 shuttles rapidly between the nucleus and the cytosol, delivering its anchored pre-mRNA for further processing. Translocation is important for hnRNP A1 to accomplish its transcriptional and translational roles. Transportin1 (Trn1), a translocation protein, facilitates the translocation of hnRNP A1 back to the nucleus. Moreover, phosphorylation of serine residues at hnRNP A1 C-terminal domain affects its translocation. In this study, we found that phosphorylation is not the only modification that hnRNP A1 undergoes, but also O-linked N-acetylglucosaminylation (O-GlcNAcylation) could occur. Several putative novel O-GlcNAcylation and phosphorylation sites in hnRNP A1 were mapped. Whereas enhanced O-GlcNAcylation increased hnRNP A1 interaction with Trn1, enhanced phosphorylation reduced the interaction between the proteins. In addition, elevated O-GlcNAcylation resulted in hnRNP A1 seclusion in the nucleus, whereas elevated phosphorylation resulted in its accumulation in the cytosol. These findings suggest that a new player, i.e., O-GlcNAcylation, regulates hnRNP A1 translocation and interaction with Trn1, possibly affecting its function. There is a need for further study, to elucidate the role of O-GlcNAcylation in the regulation of the specific activities of hnRNP A1 in transcription and translation. - Highlights: • O-GlcNAcylation regulates hnRNP A1 translocation and interaction with Trn1. • Reciprocity between phosphorylation and O-GlcNAcylation in hnRNP A1 is proposed. • Novel O-GlcNAcylation and phosphorylation sites on hnRNPA1 were identified.

hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.

Science.gov (United States)

Briese, Michael; Saal-Bauernschubert, Lena; Ji, Changhe; Moradi, Mehri; Ghanawi, Hanaa; Uhl, Michael; Appenzeller, Silke; Backofen, Rolf; Sendtner, Michael

2018-03-20

Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance. Copyright © 2018 the Author(s). Published by PNAS.

Molecules for materials: germanium hydride neutrals and anions. Molecular structures, electron affinities, and thermochemistry of GeHn/GeHn- (n = 0-4) and Ge2Hn/Ge2Hn(-) (n = 0-6).

Science.gov (United States)

Li, Qian-Shu; Lü, Rui-Hua; Xie, Yaoming; Schaefer, Henry F

2002-12-01

The GeH(n) (n = 0-4) and Ge(2)H(n) (n = 0-6) systems have been studied systematically by five different density functional methods. The basis sets employed are of double-zeta plus polarization quality with additional s- and p-type diffuse functions, labeled DZP++. For each compound plausible energetically low-lying structures were optimized. The methods used have been calibrated against a comprehensive tabulation of experimental electron affinities (Chemical Reviews 102, 231, 2002). The geometries predicted in this work include yet unknown anionic species, such as Ge(2)H(-), Ge(2)H(2)(-), Ge(2)H(3)(-), Ge(2)H(4)(-), and Ge(2)H(5)(-). In general, the BHLYP method predicts the geometries closest to the few available experimental structures. A number of structures rather different from the analogous well-characterized hydrocarbon radicals and anions are predicted. For example, a vinylidene-like GeGeH(2) (-) structure is the global minimum of Ge(2)H(2) (-). For neutral Ge(2)H(4), a methylcarbene-like HGë-GeH(3) is neally degenerate with the trans-bent H(2)Ge=GeH(2) structure. For the Ge(2)H(4) (-) anion, the methylcarbene-like system is the global minimum. The three different neutral-anion energy differences reported in this research are: the adiabatic electron affinity (EA(ad)), the vertical electron affinity (EA(vert)), and the vertical detachment energy (VDE). For this family of molecules the B3LYP method appears to predict the most reliable electron affinities. The adiabatic electron affinities after the ZPVE correction are predicted to be 2.02 (Ge(2)), 2.05 (Ge(2)H), 1.25 (Ge(2)H(2)), 2.09 (Ge(2)H(3)), 1.71 (Ge(2)H(4)), 2.17 (Ge(2)H(5)), and -0.02 (Ge(2)H(6)) eV. We also reported the dissociation energies for the GeH(n) (n = 1-4) and Ge(2)H(n) (n = 1-6) systems, as well as those for their anionic counterparts. Our theoretical predictions provide strong motivation for the further experimental study of these important germanium hydrides. Copyright 2002 Wiley

The role of hnRPUL1 involved in DNA damage response is related to PARP1.

Directory of Open Access Journals (Sweden)

Zehui Hong

Full Text Available Heterogeneous nuclear ribonucleoprotein U-like 1 (hnRPUL1 -also known as adenovirus early region 1B-associated proteins 5 (E1B-AP5 - plays a role in RNA metabolism. Recently, hnRPUL1 has also been shown to be involved in DNA damage response, but the function of hnRPUL1 in response to DNA damage remains unclear. Here, we have demonstrated that hnRPUL1 is associated with PARP1 and recruited to DNA double-strand breaks (DSBs sites in a PARP1-mediated poly (ADP-ribosyl ation dependent manner. In turn, hnRPUL1 knockdown enhances the recruitment of PARP1 to DSBs sites. Specifically, we showed that hnRPUL1 is also implicated in the transcriptional regulation of PARP1 gene. Thus, we propose hnRPUL1 as a new component related to PARP1 in DNA damage response and repair.

The role of polypyrimidine tract-binding proteins and other hnRNP proteins in plant splicing regulation

Directory of Open Access Journals (Sweden)

Andreas eWachter

2012-05-01

Full Text Available Alternative precursor mRNA splicing is a widespread phenomenon in multicellular eukaryotes and represents a major means for functional expansion of the transcriptome. While several recent studies have revealed an important link between splicing regulation and fundamental biological processes in plants, many important aspects, such as the underlying splicing regulatory mechanisms, are so far not well understood. Splicing decisions are in general based on a splicing code that is determined by the dynamic interplay of splicing-controlling factors and cis-regulatory elements. Several members of the group of heterogeneous nuclear ribonucleoprotein (hnRNP proteins are well-known regulators of splicing in animals and the comparatively few reports on some of their plant homologues revealed similar functions. This also applies to polypyrimidine tract-binding proteins (PTBs, a thoroughly investigated class of hnRNP proteins with splicing regulatory functions in both animals and plants. Further examples from plants are auto- and cross-regulatory splicing circuits of glycine-rich RNA-binding proteins (GRPs and splicing enhancement by oligouridylatebinding proteins. Besides their role in defining splice site choice, hnRNP proteins are also involved in multiple other steps of nucleic acid metabolism, highlighting the functional versatility of this group of proteins in higher eukaryotes.

MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1

International Nuclear Information System (INIS)

Ziaei, Samira; Shimada, Naoko; Kucharavy, Herman; Hubbard, Karen

2012-01-01

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA-binding protein that modulates splice site usage, polyadenylation, and cleavage efficiency. This protein has also been implicated in mRNA stability and transport from the nucleus. We have previously demonstrated that hnRNP A1 had diminished protein levels and showed cytoplasmic accumulation in senescent human diploid fibroblasts. Furthermore, we have shown that inhibition of p38 MAPK, a key regulator of cellular senescence, elevated hnRNP A1 protein levels and inhibited hnRNP A1 cytoplasmic localization. In this study, we have explored the possible involvement of MNK1, one of the downstream effector of p38 MAPK, in the regulation of hnRNP A1. We have demonstrated that pharmacological inhibition of MNK1 by CGP 57380 decreased the phosphorylation levels of hnRNP A1 in young and senescent fibroblast cells and blocked the cytoplasmic accumulation of hnRNP A1 in senescent cells. In addition, MNK1 formed a complex with hnRNP A1 in vivo. The expression levels of MNK1, phospho-MNK1, and phospho-eIF4E proteins were found to be elevated in senescent cells. These data suggest that MNK1 regulates the phosphorylation and the subcellular distribution of hnRNP A1 and that MNK1 may play a role in the induction of senescence. -- Highlights: ► MNK1 and not MAPKAPK2 phosphorylates hnRNP A1. ► MNK1 has elevated levels in senescent cells, this has not been reported previously. ► MNK1 activity induces cytoplasmic accumulation of hnRNP A1 in senescent cells. ► Altered cytoplasmic localization of hnRNP A1 may alter gene expression patterns. ► Our studies may increase our understanding of RNA metabolism during cellular aging.

hnRNP-U is a specific DNA-dependent protein kinase substrate phosphorylated in response to DNA double-strand breaks

International Nuclear Information System (INIS)

Berglund, Fredrik M.; Clarke, Paul R.

2009-01-01

Cellular responses to DNA damage are orchestrated by the large phosphoinositol-3-kinase related kinases ATM, ATR and DNA-PK. We have developed a cell-free system to dissect the biochemical mechanisms of these kinases. Using this system, we identify heterogeneous nuclear ribonucleoprotein U (hnRNP-U), also termed scaffold attachment factor A (SAF-A), as a specific substrate for DNA-PK. We show that hnRNP-U is phosphorylated at Ser59 by DNA-PK in vitro and in cells in response to DNA double-strand breaks. Phosphorylation of hnRNP-U suggests novel functions for DNA-PK in the response to DNA damage.

Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

Science.gov (United States)

Berg, J; Fellier, H; Christoph, T; Kremminger, P; Hartmann, M; Blaschke, H; Rovensky, F; Towart, R; Stimmeder, D

2000-04-01

HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited

hnRNP L regulates differences in expression of mouse integrin alpha2beta1.

Science.gov (United States)

Cheli, Yann; Kunicki, Thomas J

2006-06-01

There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains. Decreased alpha2beta1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet alpha2beta1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L-specific siRNA. Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1.

hnRNP L regulates differences in expression of mouse integrin α2β1

Science.gov (United States)

Cheli, Yann; Kunicki, Thomas J.

2006-01-01

There is a 2-fold variation in platelet integrin α2β1 levels among inbred mouse strains. Decreased α2β1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet α2β1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L–specific siRNA. Thus, decreased surface α2β1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1. PMID:16455949

The methylation of the C-terminal region of hnRNPQ (NSAP1) is important for its nuclear localization

International Nuclear Information System (INIS)

Passos, Dario O.; Quaresma, Alexandre J.C.; Kobarg, Joerg

2006-01-01

Protein arginine methylation is an irreversible post-translational protein modification catalyzed by a family of at least nine different enzymes entitled PRMTs (protein arginine methyl transferases). Although PRMT1 is responsible for 85% of the protein methylation in human cells, its substrate spectrum has not yet been fully characterized nor are the functional consequences of methylation for the protein substrates well understood. Therefore, we set out to employ the yeast two-hybrid system in order to identify new substrate proteins for human PRMT1. We were able to identify nine different PRMT1 interacting proteins involved in different aspects of RNA metabolism, five of which had been previously described either as substrates for PRMT1 or as functionally associated with PRMT1. Among the four new identified possible protein substrates was hnRNPQ3 (NSAP1), a protein whose function has been implicated in diverse steps of mRNA maturation, including splicing, editing, and degradation. By in vitro methylation assays we were able to show that hnRNPQ3 is a substrate for PRMT1 and that its C-terminal RGG box domain is the sole target for methylation. By further studies with the inhibitor of methylation Adox we provide evidence that hnRNPQ1-3 are methylated in vivo. Finally, we demonstrate by immunofluorescence analysis of HeLa cells that the methylation of hnRNPQ is important for its nuclear localization, since Adox treatment causes its re-distribution from the nucleus to the cytoplasm

PRMT5 regulates IRES-dependent translation via methylation of hnRNP A1

Science.gov (United States)

Gao, Guozhen; Dhar, Surbhi

2017-01-01

Abstract The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES). Using an IRES-dependent reporter system, we established that PRMT5 facilitates the translation of a subset of IRES-containing genes. The heterogeneous nuclear ribonucleoprotein, hnRNP A1, is an IRES transacting factor (ITAF) that regulates the IRES-dependent translation of Cyclin D1 and c-Myc. We showed that hnRNP A1 is methylated by PRMT5 on two residues, R218 and R225, and that this methylation facilitates the interaction of hnRNP A1 with IRES RNA to promote IRES-dependent translation. This study defines a new role for PRMT5 regulation of cellular protein levels, which goes beyond the known functions of PRMT5 as a transcription and splicing regulator. PMID:28115626

Oxygen Plasma Modification of Poss-Coated Kapton(Registered TradeMark) HN Films

Science.gov (United States)

Wohl, C. J.; Belcher, M. A.; Ghose, S.; Connell, J. W.

2008-01-01

The surface energy of a material depends on both surface composition and topographic features. In an effort to modify the surface topography of Kapton(Registered TradeMark) HN film, organic solutions of a polyhedral oligomeric silsesquioxane, octakis(dimethylsilyloxy)silsesquioxane (POSS), were spray-coated onto the Kapton(Registered TradeMark) HN surface. Prior to POSS application, the Kapton(Registered TradeMark) HN film was activated by exposure to radio frequency (RF)-generated oxygen plasma. After POSS deposition and solvent evaporation, the films were exposed to various durations of RF-generated oxygen plasma to create a topographically rich surface. The modified films were characterized using optical microscopy, attenuated total reflection infrared (ATR-IR) spectroscopy, and high-resolution scanning electron microscopy (HRSEM). The physical properties of the modified films will be presented.

The rotational spectra of HOCO/plus/, HOCN, HN3, and HNCO from quantum mechanical calculations

Science.gov (United States)

Defrees, D. J.; Loew, G. H.; Mclean, A. D.

1982-01-01

Ab initio molecular orbital theory has been used to determine the equilibrium geometries, rotational constants, and rotational spectra of four isoelectronic molecules. Two of these, HOCO(plus) and HOCN, are candidate interstellar molecules. The other two, HNCO and HN3, have known rotational constants. Theoretical rotational constants and spectra for the two unknown species were corrected with the mean experimental to theoretical ratios from the two known species. This procedure resulted in predicted frequencies of 83.75 plus or minus 0.2 GHz for the 4(04) to 3(03) transition in HOCN and 85.08 plus or minus 0.2 GHz for the same transition in HOCO(plus). These are the central lines of triplets whose other members are the 4(14) to 3(13) and 4(13) to 3(12) transitions. The triplet splittings were predicted to be 0.36 plus or minus 0.01 GHz for HOCN and 0.33 plus or minus 0.01 GHz for HOCO(plus). These results indicate that HOCO(plus) is a better candidate for the source of a series of lines reported by Thaddeus, Guelin, and Linke than is HOCN.

Probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM® modifies subpopulations of fecal lactobacilli and Clostridium difficile in the elderly.

Science.gov (United States)

Lahtinen, Sampo J; Forssten, Sofia; Aakko, Juhani; Granlund, Linda; Rautonen, Nina; Salminen, Seppo; Viitanen, Matti; Ouwehand, Arthur C

2012-02-01

Aging is associated with alterations in the intestinal microbiota and with immunosenescence. Probiotics have the potential to modify a selected part of the intestinal microbiota as well as improve immune functions and may, therefore, be particularly beneficial to elderly consumers. In this randomized, controlled cross-over clinical trial, we assessed the effects of a probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM on the intestinal microbiota and fecal immune markers of 31 elderly volunteers and compared these effects with the administration of the same cheese without probiotics. The probiotic cheese was found to increase the number of L. rhamnosus and L. acidophilus NCFM in the feces, suggesting the survival of the strains during the gastrointestinal transit. Importantly, probiotic cheese administration was associated with a trend towards lower counts of Clostridium difficile in the elderly, as compared with the run-in period with the plain cheese. The effect was statistically significant in the subpopulation of the elderly who harbored C. difficile at the start of the study. The probiotic cheese was not found to significantly alter the levels of the major microbial groups, suggesting that the microbial changes conferred by the probiotic cheese were limited to specific bacterial groups. Despite that the administration of the probiotic cheese to the study population has earlier been shown to significantly improve the innate immunity of the elders, we did not observe measurable changes in the fecal immune IgA concentrations. No increase in fecal calprotectin and β-defensin concentrations suggests that the probiotic treatment did not affect intestinal inflammatory markers. In conclusion, the administration of probiotic cheese containing L. rhamnosus HN001 and L. acidophilus NCFM, was associated with specific changes in the intestinal microbiota, mainly affecting specific subpopulations of intestinal lactobacilli and C

Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

International Nuclear Information System (INIS)

Cui, Huaqing; Wu, Feng; Sun, Yanling; Fan, Guocai; Wang, Qingming

2010-01-01

Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed

Antigenic sites on the HN domain of botulinum neurotoxin A stimulate protective antibody responses against active toxin.

Science.gov (United States)

Ayyar, B Vijayalakshmi; Tajhya, Rajeev B; Beeton, Christine; Atassi, M Zouhair

2015-10-28

Botulinum neurotoxins (BoNTs) are the most toxic substances known. BoNT intoxicates cells in a highly programmed fashion initiated by binding to the cell surface, internalization and enzymatic cleavage of substrate, thus, inhibiting synaptic exocytosis. Over the past two decades, immunological significance of BoNT/A C-terminal heavy chain (HC) and light chain (LC) domains were investigated extensively leading to important findings. In the current work, we explored the significance of BoNT/A heavy chain N-terminal (HN) region as a vaccine candidate. Mice were immunized with recombinant HN519-845 generating antibodies (Abs) that were found to be protective against lethal dose of BoNT/A. Immuno-dominant regions of HN519-845 were identified and individually investigated for antibody response along with synthetic peptides within those regions, using in vivo protection assays against BoNT/A. Results were confirmed by patch-clamp analysis where anti-HN antibodies were studied for the ability to block toxin-induced channel formation. This data strongly indicated that HN519-593 is an important region in generating protective antibodies and should be valuable in a vaccine design. These results are the first to describe and dissect the protective activity of the BoNT/A HN domain.

Experimental determination of the real elements of the density matrix of H(n=3) atoms produced in 20--100-keV collisions of H+ on Kr

International Nuclear Information System (INIS)

Seifert, N.; Gibson, N.D.; Risley, J.S.

1995-01-01

In continuation of our previous work, charge transfer processes occurring in protons on rare-gas-atom collisions have been investigated. Diagonal and real off-diagonal coherence elements of the density matrix for H(n=3) atoms produced in 20--100-keV electron-capture collisions with Kr atoms are experimentally determined by analyzing the Balmer-α light from the decay of H atoms from the (n=3) state to the (n=2) state. The intensity and polarization of the emitted light are measured as functions of an axially symmetric electric field in the collision region. These data are fitted to a numerical model of the H atom in an electric field in order to extract density-matrix elements. The results are compared to previous studies of H + on He and Ar. The collisionally produced dipole moment of the H(n=3) atom decreases for increasing atomic number of the rare-gas target atoms, which indicates that the final phase of the collision process is not essential for the formation of the dipole moment. This physical picture is further supported by our alignment data. Absolute cross sections for charge transfer to the 3s, 3p, and 3d levels are presented as well

Some spherical analysis related to the pairs (U (n), Hn) and (U (p, q ...

Indian Academy of Sciences (India)

)-invariant, left invariant differential operators on Hn is commutative. It is generated by. P = p. ∑ j=1. (X2 j + Y2 j ) − n. ∑ j=p+1 (X2 j + Y2 j ) and T = ∂∂t where {T,X1,...,Xn,Y1,...,Yn} denotes the standard basis of the Lie algebra of Hn. That is ...

Vermistatin derivatives with α-glucosidase inhibitory activity from the mangrove endophytic fungus Penicillium sp. HN29-3B1.

Science.gov (United States)

Liu, Yayue; Xia, Guoping; Li, Hanxiang; Ma, Lin; Ding, Bo; Lu, Yongjun; He, Lei; Xia, Xuekui; She, Zhigang

2014-07-01

Three new vermistatin derivatives, 6-demethylpenisimplicissin (1), 5'-hydroxypenisimplicissin (2), and 2''-epihydroxydihydrovermistatin (3), along with five known vermistatin analogues, methoxyvermistatin (4), vermistatin (5), 6-demethylvermistatin (6), hydroxyvermistatin (7), and penisimplicissin (8), were isolated from the culture of the mangrove endophytic fungus Penicillium sp. HN29-3B1 from Cerbera manghas. Their structures were elucidated mainly by nuclear magnetic resonance spectroscopy. The absolute configurations of compounds 1 and 2 were deduced on the basis of circular dichroism data. The absolute structures of compounds 3 and 5 were confirmed by a single-crystal X-ray diffraction experiment using Cu Kα radiation. In the bioactivity assay, compounds 1 and 3 exhibited α-glucosidase inhibitory activity with IC50 values of 9.5 ± 1.2 and 8.0 ± 1.5 µM, respectively. The plausible biosynthetic pathways for all compounds are discussed. Georg Thieme Verlag KG Stuttgart · New York.

Polyketides with α-Glucosidase Inhibitory Activity from a Mangrove Endophytic Fungus, Penicillium sp. HN29-3B1.

Science.gov (United States)

Liu, Yayue; Yang, Qin; Xia, Guoping; Huang, Hongbo; Li, Hanxiang; Ma, Lin; Lu, Yongjun; He, Lei; Xia, Xuekui; She, Zhigang

2015-08-28

Five new compounds, pinazaphilones A and B (1, 2), two phenolic compounds (4, 5), and penicidone D (6), together with the known Sch 1385568 (3), (±)-penifupyrone (7), 3-O-methylfunicone (8), 5-methylbenzene-1,3-diol (9), and 2,4-dihydroxy-6-methylbenzoic acid (10) were obtained from the culture of the endophytic fungus Penicillium sp. HN29-3B1, which was isolated from a fresh branch of the mangrove plant Cerbera manghas collected from the South China Sea. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Structures of compounds 4 and 7 were further confirmed by a single-crystal X-ray diffraction experiment using Cu Kα radiation. The absolute configurations of compounds 1-3 were assigned by quantum chemical calculations of the electronic circular dichroic spectra. Compounds 2, 3, 5, and 7 inhibited α-glucosidase with IC50 values of 28.0, 16.6, 2.2, and 14.4 μM, respectively, and are thus more potent than the positive control, acarbose.

Specific interaction between hnRNP H and HPV16 L1 proteins: Implications for late gene auto-regulation enabling rapid viral capsid protein production

Energy Technology Data Exchange (ETDEWEB)

Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min; Huang, Hui [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhang, Jun; Xia, Ning-Shao [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China); Miao, Ji, E-mail: jmiao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhao, Qinjian, E-mail: qinjian_zhao@xmu.edu.cn [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China)

2013-01-18

Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.

Control groups in recent septic shock trials

DEFF Research Database (Denmark)

Pettilä, Ville; Hjortrup, Peter B; Jakob, Stephan M

2016-01-01

PURPOSE: The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. METHODS: We searched for original articles presenting......, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. RESULTS: A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58...... % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2...

Binding of the heterogeneous ribonucleoprotein K (hnRNP K to the Epstein-Barr virus nuclear antigen 2 (EBNA2 enhances viral LMP2A expression.

Directory of Open Access Journals (Sweden)

Henrik Gross

Full Text Available The Epstein-Barr Virus (EBV -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively. EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2 Type 1. The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3 which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K. Specific binding of the ADMA- antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.

Early enteral feeding in postsurgical cancer patients. Fish oil structured lipid-based polymeric formula versus a standard polymeric formula.

Science.gov (United States)

Kenler, A S; Swails, W S; Driscoll, D F; DeMichele, S J; Daley, B; Babineau, T J; Peterson, M B; Bistrian, B R

1996-01-01

OBJECTIVES: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. SUMMARY BACKGROUND DATA: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption. METHODS: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour. RESULTS: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group. CONCLUSION: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional

Long Noncoding RNA lncSHGL Recruits hnRNPA1 to Suppress Hepatic Gluconeogenesis and Lipogenesis.

Science.gov (United States)

Wang, Junpei; Yang, Weili; Chen, Zhenzhen; Chen, Ji; Meng, Yuhong; Feng, Biaoqi; Sun, Libo; Dou, Lin; Li, Jian; Cui, Qinghua; Yang, Jichun

2018-04-01

Mammalian genomes encode a huge number of long noncoding RNAs (lncRNAs) with unknown functions. This study determined the role and mechanism of a new lncRNA, lncRNA suppressor of hepatic gluconeogenesis and lipogenesis (lncSHGL), in regulating hepatic glucose/lipid metabolism. In the livers of obese mice and patients with nonalcoholic fatty liver disease, the expression levels of mouse lncSHGL and its human homologous lncRNA B4GALT1-AS1 were reduced. Hepatic lncSHGL restoration improved hyperglycemia, insulin resistance, and steatosis in obese diabetic mice, whereas hepatic lncSHGL inhibition promoted fasting hyperglycemia and lipid deposition in normal mice. lncSHGL overexpression increased Akt phosphorylation and repressed gluconeogenic and lipogenic gene expression in obese mouse livers, whereas lncSHGL inhibition exerted the opposite effects in normal mouse livers. Mechanistically, lncSHGL recruited heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) to enhance the translation efficiency of CALM mRNAs to increase calmodulin (CaM) protein level without affecting their transcription, leading to the activation of the phosphatidyl inositol 3-kinase (PI3K)/Akt pathway and repression of the mTOR/SREBP-1C pathway independent of insulin and calcium in hepatocytes. Hepatic hnRNPA1 overexpression also activated the CaM/Akt pathway and repressed the mTOR/SREBP-1C pathway to ameliorate hyperglycemia and steatosis in obese mice. In conclusion, lncSHGL is a novel insulin-independent suppressor of hepatic gluconeogenesis and lipogenesis. Activating the lncSHGL/hnRNPA1 axis represents a potential strategy for the treatment of type 2 diabetes and steatosis. © 2018 by the American Diabetes Association.

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

Science.gov (United States)

Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

2017-12-08

Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Influence of commercial inactivated yeast derivatives on the survival of probiotic bacterium Lactobacillus rhamnosus HN001 in an acidic environment.

Science.gov (United States)

Toh, Mingzhan; Liu, Shao Quan

2017-12-01

This study evaluated the influence of three inactivated yeast derivatives (IYDs) used in wine production, namely OptiRed ® , OptiWhite ® and Noblesse ® , on the viability of the probiotic strain Lactobacillus rhamnosus HN001 in an acidic environment. Addition of the IYDs at 3 g/L significantly enhanced the survival of the probiotic bacteria by 2.75-4.05 log cycles after 10-h exposure in a pH 3.0 buffer. Acid stress assay with IYD components obtained after centrifugation and filtration revealed that water-soluble compounds were responsible for improving the acid tolerance of L. rhamnosus HN001 for all three preparations. Differences in protective effect amongst the IYDs on L. rhamnosus HN001 were observed when permeates and retentates of the water-soluble extracts, obtained through ultrafiltration with a 2 kDa membrane, were assayed against the lactic acid bacterium. Chemical analysis of the water-soluble components suggests that low molecular weight polysaccharides, specific free amino acids and/or antioxidants in the 2 kDa permeates could have contributed to the enhanced survival of L. rhamnosus HN001 during acid stress. The contrast amongst the 2 kDa retentates' viability enhancing property may have been attributed to the differences in size and structure of the higher molecular weight carbohydrates and proteins, as the survival of the probiotic did not relate to the concentration of these compounds. These results suggests that oenological IYDs could potentially be applied to probiotic foods for enhancing the acid tolerance of the beneficial microorganisms, and consequently prolonging the shelf life of these products.

Clinical trial participation. Viewpoints from racial/ethnic groups.

Science.gov (United States)

Roberson, N L

1994-11-01

Racial/ethnic groups' participation in clinical trials is a relatively new area of research that warrants attention. Although racial/ethnic groups have been included in experimental studies since the 1940s, they were not included in significant numbers in clinical trials for cancer. Clinical trials play a dominant role in clinical oncology. Despite this state-of-the-art cancer treatment, however, there is mounting concern that this scientific progress is not being shared equitably by all segments of the U.S. population. There is underrepresentation of members of racial/ethnic groups in cancer clinical trials, which suggests that participation may be a critical issue. Unfortunately, little is known or documented about these groups' participation in clinical trials. This paper discusses racial/ethnic groups' views and opinions about clinical trial participation. Diagnostic research was conducted as a beginning phase to investigate this new area of research. African Americans, Hispanics, and Native Americans in three Buffalo, New York, communities were selected as study subjects. Data were collected via telephone surveys. Qualitative methods were employed for data analysis and reporting. Findings showed that study subjects knew little about cancer clinical trials and basically had no opportunity to participate. They believed that participation in clinical trials could be beneficial. In each of the three groups, however, there were cultural factors believed to influence participation. A primary concern was "mistrust of white people" and the feeling of being treated like "guinea pigs." Based on study findings, it was evident that recruitment for improving participation requires strategic planning that involves participants representative of the study population. To yield results, the plan should be tailored to the target group, presented as a credible study, designed to reflect trust in the medical care team, and implemented through a continuous educational process.

Quality assurance of 3-D conformal radiation therapy for a cooperative group trial - RTOG 3D QA center initial experience

International Nuclear Information System (INIS)

Michalski, Jeff M.; Purdy, James A.; Harms, William B.; Bosch, Walter R.; Oehmke, Frederick; Cox, James D.

1996-01-01

PURPOSE: 3-D conformal radiation therapy (3DCRT) holds promise in allowing safe escalation of radiation dose to increase the local control of prostate cancer. Prospective evaluation of this new modality requires strict quality assurance (QA). We report the results of QA review on patients receiving 3DCRT for prostate cancer on a cooperative group trial. MATERIALS and METHODS: In 1993 the NCI awarded the ACR/RTOG and nine institutions an RFA grant to study the use of 3DCRT in the treatment of prostate cancer. A phase I/II trial was developed to: a) test the feasibility of conducting 3DCRT radiation dose escalation in a cooperative group setting; b) establish the maximum tolerated radiation dose that can be delivered to the prostate; and c) quantify the normal tissue toxicity rate when using 3DCRT. In order to assure protocol compliance each participating institution was required to implement data exchange capabilities with the RTOG 3D QA center. The QA center reviews at a minimum the first five case from each participating center and spot checks subsequent submissions. For each case review the following parameters are evaluated: 1) target volume delineation, 2) normal structure delineation, 3) CT data quality, 4) field placement, 5) field shaping, and 6) dose distribution. RESULTS: Since the first patient was registered on August 23, 1994, an additional 170 patients have been accrued. Each of the nine original approved institutions has participated and three other centers have recently passed quality assurance bench marks for study participation. Eighty patients have been treated at the first dose level (68.4 Gy minimum PTV dose) and accrual is currently ongoing at the second dose level (73.8 Gy minimum PTV dose). Of the 124 cases that have undergone complete or partial QA review, 30 cases (24%) have had some problems with data exchange. Five of 67 CT scans were not acquired by protocol standards. Target volume delineation required the submitting institution

Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study.

Science.gov (United States)

Toscano, Marco; De Grandi, Roberta; Stronati, Laura; De Vecchi, Elena; Drago, Lorenzo

2017-04-21

To evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition. Twenty healthy Italian volunteers, eight males and twelve females, participated in the study. Ten subjects took a sachet containing 4 × 10 9 colony-forming units (CFU) of Bifidobacterium longum BB536 and 10 9 CFU of Lactobacillus rhamnosus HN001, 30 min before breakfast (pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast (post-prandial administration). The ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine. Immediately after 1-mo of probiotic administration, B. longum BB536 and L. rhamnosus HN001 load was increased in the majority of subjects in both pre-prandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in Firmicutes abundance was detected immediately after 1-mo of B. longum BB536 and L. rhamnosus HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of Proteobacteria abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of Blautia producta , Blautia wexlerae and Haemophilus ducrey was observed, together with a reduction of Holdemania filiformis , Escherichia vulneris , Gemmiger formicilis and Streptococcus sinensis abundance. In addition, during follow-up period we observed a further reduction in Escherichia vulneris and Gemmiger formicilis , together with a decrease in Roseburia faecis and

Mechanisms underlying regulation of cell cycle and apoptosis by hnRNP B1 in human lung adenocarcinoma A549 cells.

Science.gov (United States)

Han, Juan; Tang, Feng-ming; Pu, Dan; Xu, Dan; Wang, Tao; Li, Weimin

2014-01-01

Overexpression of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), a nuclear RNA binding protein, has been reported to occur in early-stage lung cancer and in premalignant lesions. DNA-dependent protein kinase (DNA-PK) is known to be involved in the repair of double-strand DNA breaks. Reduced capacity to repair DNA has been associated with the risk of lung cancer. We investigated a link between hnRNP B1 and DNA-PK and their effects on proliferation, cell cycle, and apoptosis in the human lung adenocarcinoma cell line A549. We found that hnRNP B1 and DNA-PK interact with each other in a complex fashion. Reducing hnRNP B1 expression in A549 cells with the use of RNAi led to upregulation of p53 activity through upregulation of DNA-PK activity but without inducing p53 expression. Further, suppression of hnRNP B1 in A549 cells slowed cell proliferation, promoted apoptosis, and induced cell cycle arrest at the G1 stage. The presence of NU7026 reduced the arrest of cells at the G1 stage and reduced the apoptosis rate while promoting cell growth. Taken together, our results demonstrate that by regulating DNA-PK activity, hnRNP B1 can affect p53-mediated cell cycle progression and apoptosis, resulting in greater cell survival and subsequent proliferation.

Downslope föhn winds over the Antarctic Peninsula and their effect on the Larsen Ice Shelves

Science.gov (United States)

Grosvenor, D. P.; King, J. C.; Choularton, T. W.; Lachlan-Cope, T.

2014-03-01

Mesoscale model simulations are presented of a westerly föhn event over the Antarctic Peninsula mountain ridge and onto the Larsen C Ice Shelf, just south of the recently collapsed Larsen B Ice Shelf. Aircraft observations showed the presence of föhn jets descending near to the ice shelf surface with maximum wind speeds at 250-350 m in height. Surface flux measurements suggested that melting was occurring. Simulated profiles of wind speed, temperature and wind direction were very similar to the observations. However, the good match only occurred at a model time corresponding to ˜9 h before the aircraft observations were made since the model föhn jets died down after this. Through comparison to an Automatic Weather Station (AWS) on the ice shelf surface (east side of the ridge) this was attributed to problems with the time evolution of the large scale meteorology of the analysis used to nudge the upper levels of the model. Timing issues aside, the otherwise good comparison between the model and observations gave confidence that the model flow structure was similar to that in reality. Details of the model jet structure are explored and discussed and are found to have ramifications for the placement of AWS stations on the ice shelf in order to detect föhn flow. Cross sections of the flow are also examined and were found to compare well to the aircraft measurements. Gravity wave breaking above the mountain crest likely created a situation similar to hydraulic flow and allowed föhn flow and ice shelf surface warming to occur despite strong upwind blocking, which in previous studies of this region has generally not been considered. The surface energy budget of the model during the melting periods showed that the net downwelling shortwave surface flux was the largest contributor to the melting energy, indicating that the cloud clearing effect of föhn events is likely to be the most important factor for increased melting relative to non-föhn days. The results also

Viability of the Lactobacillus rhamnosus HN001 probiotic strain in Swiss- and Dutch-type cheese and cheese-like products.

Science.gov (United States)

Cichosz, Grażyna; Aljewicz, Marek; Nalepa, Beata

2014-06-01

The objective of this study was to determine the viability of the probiotic Lactobacillus rhamnosus HN001 in Swiss-type and Dutch-type cheese and cheese-like products (milk fat is substituted by stearin fraction of palm fat) during manufacture, ripening, and storage. The use of the probiotic L. rhamnosus HN001 in Dutch-type cheese and cheese-like products significantly (P = 0.1) changed their chemical composition (protein and fat content) and an insignificant increase (approximately 1.6% in cheese-like products and approximately 0.3% in cheese) in yield. L. rhamnosus HN001 did not affect the rate of changes in the pH of ripened cheese and cheese-like products. A minor increase in probiotic counts was observed in initial stages of production and were partially removed with whey. Ripened cheese and cheese-like products were characterized by high survival rates of probiotic bacteria which exceeded 8 log CFU/g after ripening. An insignificant reduction in the number of viable probiotic cells was noted during storage of Swiss-type and Dutch-type cheese, whereas a significant increase in probiotic cell counts was observed in cheese-like products during storage. © 2014 Institute of Food Technologists®

High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.

Science.gov (United States)

Levengood, Jeffrey D; Tolbert, Michele; Li, Mei-Ling; Tolbert, Blanton S

2013-07-01

Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I internal ribosome entry site (IRES) to recruit the 40S ribosomal subunit via a pathway that requires the cytoplasmic localization of hnRNP A1, which acts as an IRES trans-activating factor. The mechanism of how hnRNP A1 trans activates EV71 RNA translation is unknown, however. Here, we report that the UP1 domain of hnRNP A1 interacts specifically with stem loop II (SLII) of the IRES, via a thermodynamically well-defined biphasic transition that involves conserved bulge 5'-AYAGY-3' and hairpin 5'-RY(U/A)CCA-3' loops. Calorimetric titrations of wild-type and mutant SLII constructs reveal these structural elements are essential to form a high-affinity UP1-SLII complex. Mutations that alter the bulge and hairpin primary or secondary structures abrogate the biphasic transition and destabilize the complex. Notably, mutations within the bulge that destabilize the complex correlate with a large reduction in IRES-dependent translational activity and impair EV71 replication. Taken together, this study shows that a conserved SLII structure is necessary to form a functional hnRNP A1-IRES complex, suggesting that small molecules that target this stem loop may have novel antiviral properties.

Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1.

Directory of Open Access Journals (Sweden)

Bruna Baumgarten Krebs

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a fatal neurodegenerative disease that affects the upper and lower motor neurons. 5-10% of cases are genetically inherited, including ALS type 20, which is caused by mutations in the hnRNPA1 gene. The goals of this work are to analyze the effects of non-synonymous single nucleotide polymorphisms (nsSNPs on hnRNPA1 protein function, to model the complete tridimensional structure of the protein using computational methods and to assess structural and functional differences between the wild type and its variants through Molecular Dynamics simulations. nsSNP, PhD-SNP, Polyphen2, SIFT, SNAP, SNPs&GO, SNPeffect and PROVEAN were used to predict the functional effects of nsSNPs. Ab initio modeling of hnRNPA1 was made using Rosetta and refined using KoBaMIN. The structure was validated by PROCHECK, Rampage, ERRAT, Verify3D, ProSA and Qmean. TM-align was used for the structural alignment. FoldIndex, DICHOT, ELM, D2P2, Disopred and DisEMBL were used to predict disordered regions within the protein. Amino acid conservation analysis was assessed by Consurf, and the molecular dynamics simulations were performed using GROMACS. Mutations D314V and D314N were predicted to increase amyloid propensity, and predicted as deleterious by at least three algorithms, while mutation N73S was predicted as neutral by all the algorithms. D314N and D314V occur in a highly conserved amino acid. The Molecular Dynamics results indicate that all mutations increase protein stability when compared to the wild type. Mutants D314N and N319S showed higher overall dimensions and accessible surface when compared to the wild type. The flexibility level of the C-terminal residues of hnRNPA1 is affected by all mutations, which may affect protein function, especially regarding the protein ability to interact with other proteins.

Novel somatic single nucleotide variants within the RNA binding protein hnRNP A1 in multiple sclerosis patients [v2; ref status: indexed, http://f1000r.es/4dh

Directory of Open Access Journals (Sweden)

Sangmin Lee

2014-09-01

Full Text Available Some somatic single nucleotide variants (SNVs are thought to be pathogenic, leading to neurological disease. We hypothesized that heterogeneous nuclear ribonuclear protein A1 (hnRNP A1, an autoantigen associated with multiple sclerosis (MS would contain SNVs. MS patients develop antibodies to hnRNP A1293-304, an epitope within the M9 domain (AA268-305 of hnRNP A1. M9 is hnRNP A1’s nucleocytoplasmic transport domain, which binds transportin-1 (TPNO-1 and allows for hnRNP A1’s transport into and out of the nucleus. Genomic DNA sequencing of M9 revealed nine novel SNVs that resulted in an amino acid substitution in MS patients that were not present in controls. SNVs occurred within the TPNO-1 binding domain (hnRNP A1268-289 and the MS IgG epitope (hnRNP A1293-304, within M9.  In contrast to the nuclear localization of wild type (WT hnRNP A1, mutant hnRNP A1 mis-localized to the cytoplasm, co-localized with stress granules and caused cellular apoptosis. Whilst WT hnRNP A1 bound TPNO-1, mutant hnRNP A1 showed reduced TPNO-1 binding. These data suggest SNVs in hnRNP A1 might contribute to pathogenesis of MS.

Hazelnut meal in diets for seawater farmed rainbow trout (Oncorhynchus mykiss: effects on growth performance and body composition

Directory of Open Access Journals (Sweden)

Soner Bilen

2010-01-01

Full Text Available A 77-day feeding trial was designed in order to assess the effect of partial or total replacement of soybean meal by hazelnut meal (HNM on feed intake, growth performance, nutrient utilization and body composition of rainbow trout (initial mean body weight: 80.0±3.5 g in seawater conditions. A control and three experimental diets were formulated in which soybean meal level (25.5% in the control diet was replaced by hazelnut meal at 39.2 (HN 39, 78.4 (HN 78 and 100% (HN 100 to provide 44% crude protein and 20% crude lipid diets. Diets were fed to 125 rainbow trout to apparent satiation by hand twice daily at 09.00 and 16.00 hours under natural photoperiod conditions. At the end of the feeding trial, fish of all groups almost tripled their body weight and no significant difference (P>0.05 was revealed in final weight or specific growth rate between treatments. However, feed conversion ratio (FCR of the HN100 group was significantly higher than other treatments (P<0.05. There was a slightly decreasing trend in protein efficiency ratio (PER and net protein utilization (NPU with increasing level of dietary hazelnut meal, but it was only significant in groups of fish fed HN100. All groups of fish displayed similar carcass and muscle compositions. According to the results of the present study, it can be stated that hazelnut meal can replace soybean meal at up to 200 g kg-1 in grow-out diets of rainbow trout without any detrimental effects on growth performance.

Paramyxovirus membrane fusion: Lessons from the F and HN atomic structures

International Nuclear Information System (INIS)

Lamb, Robert A.; Paterson, Reay G.; Jardetzky, Theodore S.

2006-01-01

Paramyxoviruses enter cells by fusion of their lipid envelope with the target cell plasma membrane. Fusion of the viral membrane with the plasma membrane allows entry of the viral genome into the cytoplasm. For paramyxoviruses, membrane fusion occurs at neutral pH, but the trigger mechanism that controls the viral entry machinery such that it occurs at the right time and in the right place remains to be elucidated. Two viral glycoproteins are key to the infection process-an attachment protein that varies among different paramyxoviruses and the fusion (F) protein, which is found in all paramyxoviruses. For many of the paramyxoviruses (parainfluenza viruses 1-5, mumps virus, Newcastle disease virus and others), the attachment protein is the hemagglutinin/neuraminidase (HN) protein. In the last 5 years, atomic structures of paramyxovirus F and HN proteins have been reported. The knowledge gained from these structures towards understanding the mechanism of viral membrane fusion is described

Expression of anti-heterogenous nuclear ribonucleoprotein (anti-hnRNP in limited systemic sclerosis patients: Relation to radiographic findings of the hand

Directory of Open Access Journals (Sweden)

Nihal Fathi

2018-01-01

Conclusion: Joint affection in SSc is more frequent than expected. Anti-hnRNP A1 and anti hnRNP A2 antigens may be useful markers for SSc patient although no significant relation was found with radiologic findings.

Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

Science.gov (United States)

Zhou, Yifan; Apai, Dániel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.; Miles-Páez, Paulo A.; Lowrance, Patrick J.; Radigan, Jacqueline; Burgasser, Adam J.

2018-03-01

Time-resolved observations of brown dwarfs’ rotational modulations provide powerful insights into the properties of condensate clouds in ultra-cool atmospheres. Multi-wavelength light curves reveal cloud vertical structures, condensate particle sizes, and cloud morphology, which directly constrain condensate cloud and atmospheric circulation models. We report results from Hubble Space Telescope/Wide Field Camera 3 near-infrared G141 taken in six consecutive orbits observations of HN Peg B, an L/T transition brown dwarf companion to a G0V type star. The best-fit sine wave to the 1.1–1.7 μm broadband light curve has an amplitude of 1.206% ± 0.025% and period of 15.4 ± 0.5 hr. The modulation amplitude has no detectable wavelength dependence except in the 1.4 μm water absorption band, indicating that the characteristic condensate particle sizes are large (>1 μm). We detect significantly (4.4σ) lower modulation amplitude in the 1.4 μm water absorption band and find that HN Peg B’s spectral modulation resembles those of early T type brown dwarfs. We also describe a new empirical interpolation method to remove spectral contamination from the bright host star. This method may be applied in other high-contrast time-resolved observations with WFC3.

Comparative genome analysis identifies two large deletions in the genome of highly-passaged attenuated Streptococcus agalactiae strain YM001 compared to the parental pathogenic strain HN016.

Science.gov (United States)

Wang, Rui; Li, Liping; Huang, Yan; Luo, Fuguang; Liang, Wanwen; Gan, Xi; Huang, Ting; Lei, Aiying; Chen, Ming; Chen, Lianfu

2015-11-04

Streptococcus agalactiae (S. agalactiae), also known as group B Streptococcus (GBS), is an important pathogen for neonatal pneumonia, meningitis, bovine mastitis, and fish meningoencephalitis. The global outbreaks of Streptococcus disease in tilapia cause huge economic losses and threaten human food hygiene safety as well. To investigate the mechanism of S. agalactiae pathogenesis in tilapia and develop attenuated S. agalactiae vaccine, this study sequenced and comparatively analyzed the whole genomes of virulent wild-type S. agalactiae strain HN016 and its highly-passaged attenuated strain YM001 derived from tilapia. We performed Illumina sequencing of DNA prepared from strain HN016 and YM001. Sequencedreads were assembled and nucleotide comparisons, single nucleotide polymorphism (SNP) , indels were analyzed between the draft genomes of HN016 and YM001. Clustered regularly interspaced short palindromic repeats (CRISPRs) and prophage were detected and analyzed in different S. agalactiae strains. The genome of S. agalactiae YM001 was 2,047,957 bp with a GC content of 35.61 %; it contained 2044 genes and 88 RNAs. Meanwhile, the genome of S. agalactiae HN016 was 2,064,722 bp with a GC content of 35.66 %; it had 2063 genes and 101 RNAs. Comparative genome analysis indicated that compared with HN016, YM001 genome had two significant large deletions, at the sizes of 5832 and 11,116 bp respectively, resulting in the deletion of three rRNA and ten tRNA genes, as well as the deletion and functional damage of ten genes related to metabolism, transport, growth, anti-stress, etc. Besides these two large deletions, other ten deletions and 28 single nucleotide variations (SNVs) were also identified, mainly affecting the metabolism- and growth-related genes. The genome of attenuated S. agalactiae YM001 showed significant variations, resulting in the deletion of 10 functional genes, compared to the parental pathogenic strain HN016. The deleted and mutated functional genes all

Viral DNA Replication Orientation and hnRNPs Regulate Transcription of the Human Papillomavirus 18 Late Promoter.

Science.gov (United States)

Wang, Xiaohong; Liu, Haibin; Ge, Hui; Ajiro, Masahiko; Sharma, Nishi R; Meyers, Craig; Morozov, Pavel; Tuschl, Thomas; Klar, Amar; Court, Donald; Zheng, Zhi-Ming

2017-05-30

The life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Although expression of viral early genes is initiated immediately upon virus infection of undifferentiated basal cells, viral DNA amplification and late gene expression occur only in the mid to upper strata of the keratinocytes undergoing terminal differentiation. In this report, we show that the relative activity of HPV18 TATA-less late promoter P 811 depends on its orientation relative to that of the origin (Ori) of viral DNA replication and is sensitive to the eukaryotic DNA polymerase inhibitor aphidicolin. Additionally, transfected 70-nucleotide (nt)-long single-strand DNA oligonucleotides that are homologous to the region near Ori induce late promoter activity. We also found that promoter activation in raft cultures leads to production of the late promoter-associated, sense-strand transcription initiation RNAs (tiRNAs) and splice-site small RNAs (spliRNAs). Finally, a cis -acting AAGTATGCA core element that functions as a repressor to the promoter was identified. This element interacts with hnRNP D0B and hnRNP A/B factors. Point mutations in the core prevented binding of hnRNPs and increased the promoter activity. Confirming this result, knocking down the expression of both hnRNPs in keratinocytes led to increased promoter activity. Taking the data together, our study revealed the mechanism of how the HPV18 late promoter is regulated by DNA replication and host factors. IMPORTANCE It has been known for decades that the activity of viral late promoters is associated with viral DNA replication among almost all DNA viruses. However, the mechanism of how DNA replication activates the viral late promoter and what components of the replication machinery are involved remain largely unknown. In this study, we characterized the P 811 promoter region of HPV18 and demonstrated that its activation depends on the orientation of DNA replication. Using single

Detection of rabies in camel, goat and cattle in Sudan using Fluorescent antibody test (FAT and hemi nested Polymerase Chain Reaction (hnRT-PCR

Directory of Open Access Journals (Sweden)

Baraa Abdalaziz Ahmed

2016-09-01

Full Text Available Objective: The objective of this study was to identify rabies virus in camels and other animals in Sudan. Materials and methods: Four camel samples were collected from Garraht Elzawia, Kab-kabia and North Darfur areas in Sudan. The samples were collected based on clinical signs. In addition, two camel samples were obtained from Khartoum and Tambool, one goat sample was collected from El-Fashir, and one cattle sample was obtained from Atbara. The samples were transported to the Veterinary Research Institute (VRI at Khartoum, Sudan for further studies. The samples were subjected for nested and hemi nested RT-PCR (hnRT-PCR along with the gold standard Fluorescent antibody test (FAT to diagnose rabies. Results: Out of eight samples, seven were found to be positive by both FAT and RT-PCR methods. The remaining one sample was positive by FAT but negative by hnRT-PCR indicating the suitablity of hnRT-PCR along with FAT for accurate diagnosis of rabies in animals. Conclusion: The study concluded that FAT and RT-PCR are useful tools for research and diagnosis of rabies. [J Adv Vet Anim Res 2016; 3(3.000: 274-277

Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data.

Science.gov (United States)

Luo, Jake; Eldredge, Christina; Cho, Chi C; Cisler, Ron A

2016-10-17

than 30 years) until reaching the 60-69 years-old group, which had a diversity level of 54.7 different types of adverse events per trial arm. The 70-100 years-old group showed the highest diversity level of 55.5 events per trial arm, which is approximately 3.44 times more than the 20-29 years-old group (Page-related patterns among different categories. The results show that there is a significant adverse event variance at the population level between different age groups in clinical trials. The data suggest that age-associated adverse events should be considered in planning, monitoring, and regulating clinical trials.

HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy

Directory of Open Access Journals (Sweden)

Xinran Xiang, Mingqian Feng, Mildred Felder, Joseph P. Connor, Yan-gao Man, Manish S. Patankar, Mitchell Ho

2011-01-01

Full Text Available Background: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin.Methodology/Principal Findings: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 µg/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro.Conclusion/Significance: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.

Science.gov (United States)

Dreger, Peter; Döhner, Hartmut; McClanahan, Fabienne; Busch, Raymonde; Ritgen, Matthias; Greinix, Hildegard; Fink, Anna-Maria; Knauf, Wolfgang; Stadler, Michael; Pfreundschuh, Michael; Dührsen, Ulrich; Brittinger, Günter; Hensel, Manfred; Schetelig, Johannes; Winkler, Dirk; Bühler, Andreas; Kneba, Michael; Schmitz, Norbert; Hallek, Michael; Stilgenbauer, Stephan

2012-05-24

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015.

Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1.

Science.gov (United States)

Liebertz, Daniel J; Lechner, Melissa G; Masood, Rizwan; Sinha, Uttam K; Han, Jing; Puri, Raj K; Correa, Adrian J; Epstein, Alan L

2010-02-22

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.

Recommendations for Collection and Handling of Specimens From Group Breast Cancer Clinical Trials

Science.gov (United States)

Leyland-Jones, Brian R.; Ambrosone, Christine B.; Bartlett, John; Ellis, Matthew J.C.; Enos, Rebecca A.; Raji, Adekunle; Pins, Michael R.; Zujewski, Jo Anne; Hewitt, Stephen M.; Forbes, John F.; Abramovitz, Mark; Braga, Sofia; Cardoso, Fatima; Harbeck, Nadia; Denkert, Carsten; Jewell, Scott D.

2008-01-01

Recommendations for specimen collection and handling have been developed for adoption across breast cancer clinical trials conducted by the Breast International Group (BIG)-sponsored Groups and the National Cancer Institute (NCI)-sponsored North American Cooperative Groups. These recommendations are meant to promote identifiable standards for specimen collection and handling within and across breast cancer trials, such that the variability in collection/handling practices that currently exists is minimized and specimen condition and quality are enhanced, thereby maximizing results from specimen-based diagnostic testing and research. Three working groups were formed from the Cooperative Group Banking Committee, BIG groups, and North American breast cancer cooperative groups to identify standards for collection and handling of (1) formalin-fixed, paraffin-embedded (FFPE) tissue; (2) blood and its components; and (3) fresh/frozen tissue from breast cancer trials. The working groups collected standard operating procedures from multiple group specimen banks, administered a survey on banking practices to those banks, and engaged in a series of discussions from 2005 to 2007. Their contributions were synthesized into this document, which focuses primarily on collection and handling of specimens to the point of shipment to the central bank, although also offers some guidance to central banks. Major recommendations include submission of an FFPE block, whole blood, and serial serum or plasma from breast cancer clinical trials, and use of one fixative and buffer type (10% neutral phosphate-buffered formalin, pH 7) for FFPE tissue across trials. Recommendations for proper handling and shipping were developed for blood, serum, plasma, FFPE, and fresh/frozen tissue. PMID:18955459

TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA.

Science.gov (United States)

Flynn, Rachel Litman; Centore, Richard C; O'Sullivan, Roderick J; Rai, Rekha; Tse, Alice; Songyang, Zhou; Chang, Sandy; Karlseder, Jan; Zou, Lee

2011-03-24

Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres. Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the re-accumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity.

USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics.

Science.gov (United States)

Russell, Sarah M; Lechner, Melissa G; Gong, Lucy; Megiel, Carolina; Liebertz, Daniel J; Masood, Rizwan; Correa, Adrian J; Han, Jing; Puri, Raj K; Sinha, Uttam K; Epstein, Alan L

2011-09-01

Head and neck squamous cell carcinomas (HNSCC) are common and aggressive tumors that have not seen an improvement in survival rates in decades. These tumors are believed to evade the immune system through a variety of mechanisms and are therefore highly immune modulatory. In order to elucidate their interaction with the immune system and develop new therapies targeting immune escape, new pre-clinical models are needed. A novel human cell line, USC-HN2, was established from a patient biopsy specimen of invasive, recurrent buccal HNSCC and characterized by morphology, heterotransplantation, cytogenetics, phenotype, gene expression, and immune modulation studies and compared to a similar HNSCC cell line; SCCL-MT1. Characterization studies confirmed the HNSCC origin of USC-HN2 and demonstrated a phenotype similar to the original tumor and typical of aggressive oral cavity HNSCC (EGFR(+)CD44v6(+)FABP5(+)Keratin(+) and HPV(-)). Gene and protein expression studies revealed USC-HN2 to have highly immune-modulatory cytokine production (IL-1β, IL-6, IL-8, GM-CSF, and VEGF) and strong regulatory T and myeloid derived suppressor cell (MDSC) induction capacity in vitro. Of note, both USC-HN2 and SCCL-MT1 were found to have a more robust cytokine profile and MDSC induction capacity when compared to seven previously established HNSCC cell lines. Additionally, microarray gene expression profiling of both cell lines demonstrate up-regulation of antigen presenting genes. Because USC-HN2 is therefore highly immunogenic, it also induces strong immune suppression to evade immunologic destruction. Based upon these results, both cell lines provide an excellent model for the development of new suppressor cell-targeted immunotherapies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Group sequential designs for stepped-wedge cluster randomised trials.

Science.gov (United States)

Grayling, Michael J; Wason, James Ms; Mander, Adrian P

2017-10-01

The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into

Trénink hněvu: Smrtelný hřích v temperamentní profesi Coaching anger: A deadly sin in a lively profession

Directory of Open Access Journals (Sweden)

Jeffrey P. Fry

2006-02-01

Full Text Available Podle křesťanské tradice je hněv jedním ze "sedmi smrtelných hříchů". Ve východním náboženském myšlení je hněv považován za jedovatý a návykový. Tyto pohledy poukazují na problémovou povahu hněvu. Jiní se však domnívají, že hněv může nabývat vhodného výrazu a pozitivní funkce. Vzhledem k tomu, že hněv se ve sportu projevuje často, je důležité vyhodnotit význam hněvu také v této oblasti lidského života. Zvláště často projevují hněv trenéři. S ohledem na tuto skutečnost se v tomto příspěvku zaměřuji na povahu hněvu a jeho roli v profesi trenéra. Je na roli, kterou trenér zastává, něco, co by trenérům poskytovalo zvláštní svobodu ve vyjadřování hněvu? "Trénink hněvu" se nezabývá výhradně projevy hněvu trenérů, ale také praktickými kroky vedoucími k účinnému a přiměřenému ovládání této složité emoce. According to Christian tradition, anger comprises one of the "seven deadly sins". In Eastern religious thought anger is held to be poisonous and addictive. These views point to the problematic nature of anger. Some hold, however, that anger can have an appropriate expression and a positive function. Since anger is often vented in sport, it is important to assess the significance of anger in this area of life. Coaches, in particular, frequently display anger. Given this fact, in this paper I focus on the nature of anger and its role in the coaching profession. Is there something distinctive about the role of the coach such that coaches should be granted special leeway in the expression of anger? "Coaching anger" refers not merely to the manifestation of coaches’ anger, but also to practical steps towards effective and appropriate dealing with this complex emotion.

Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells

Science.gov (United States)

Chun, Younghwa; Kim, Raehyung; Lee, Soojin

2016-01-01

Background Recent studies have shown that heterogeneous nuclear ribonucleoprotein U (hnRNP U), a component of the hnRNP complex, contributes to stabilize the kinetochore-microtubule interaction during mitosis. CENP-W was identified as an inner centromere component that plays crucial roles in the formation of a functional kinetochore complex. Results We report that hnRNP U interacts with CENP-W, and the interaction between hnRNP U and CENP-W mutually increased each other’s protein stability by inhibiting the proteasome-mediated degradation. Further, their co-localization was observed chiefly in the nuclear matrix region and at the microtubule-kinetochore interface during interphase and mitosis, respectively. Both microtubule-stabilizing and microtubule-destabilizing agents significantly decreased the protein stability of CENP-W. Furthermore, loss of microtubules and defects in microtubule organization were observed in CENP-W-depleted cells. Conclusion Our data imply that CENP-W plays an important role in the attachment and interaction between microtubules and kinetochore during mitosis. PMID:26881882

The EC randomised controlled trial of prophylactic ethamsylate for very preterm neonates: early mortality and morbidity. The EC Ethamsylate Trial Group.

Science.gov (United States)

1994-05-01

Immature infants are at increased risk of death and disability, often related to haemorrhagic and ischaemic brain damage. Two controlled trials have suggested that a policy of prophylactic ethamsylate may reduce this damage. The aim of the trial reported here was to assess the effects of such a policy in respect of death, disability, and the use of health service resources up to 2 years of age. Short term findings are reported here. Three hundred and thirty four immature (ethamsylate group received the drug, compared with one of the 169 infants in the control group. By about 3 months of age the trial groups were similar in terms of death (20% in the two groups), any diagnosis of periventricular or intraventricular haemorrhage (35% in the ethamsylate v 37% in the control group), or major cerebral abnormality assessed by ultrasound (13% v 12%). The trial provides little evidence to support the use of ethamsylate for routine prophylaxis. The confidence intervals are wide, however, and so these results alone cannot rule out a clinically useful benefit or a harmful effect. A follow up study of the surviving children at the age of 2 years is in progress.

Pragmatic randomised controlled trial of group psychoeducation versus group support in the maintenance of bipolar disorder

Directory of Open Access Journals (Sweden)

Roberts Christopher

2011-07-01

Full Text Available Abstract Background Non-didactically delivered curriculum based group psychoeducation has been shown to be more effective than both group support in a specialist mood disorder centre in Spain (with effects lasting up to five years, and treatment as usual in Australia. It is unclear whether the specific content and form of group psychoeducation is effective or the chance to meet and work collaboratively with other peers. The main objective of this trial is to determine whether curriculum based group psychoeducation is more clinically and cost effective than unstructured peer group support. Methods/design Single blind two centre cluster randomised controlled trial of 21 sessions group psychoeducation versus 21 sessions group peer support in adults with bipolar 1 or 2 disorder, not in current episode but relapsed in the previous two years. Individual randomisation is to either group at each site. The groups are carefully matched for the number and type of therapists, length and frequency of the interventions and overall aim of the groups but differ in content and style of delivery. The primary outcome is time to next bipolar episode with measures of the therapeutic process, barriers and drivers to the effective delivery of the interventions and economic analysis. Follow up is for 96 weeks after randomisation. Discussion The trial has features of both an efficacy and an effectiveness trial design. For generalisability in England it is set in routine public mental health practice with a high degree of expert patient involvement. Trial Registration ISRCTN62761948 Funding National Institute for Health Research, England.

Lipase production from a wild (LPF-5) and a mutant (HN1) strain of ...

African Journals Online (AJOL)

Lipase production from a wild (LPF-5) and a mutant (HN1) strain of Aspergillus niger. ... Several physical parameters (carbon source, nitrogen source, pH, ... for the development of industrial biotechnology for production of extracellular lipase.

SU-F-J-186: Enabling Adaptive IMPT with CBCT-Based Dose Recalculation for H&N and Prostate Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Kurz, C [Ludwig-Maximilians-Universitaet Muenchen, Garching b. Muenchen (Germany); LMU Munich, Munich (Germany); Park, Y; Winey, B; Sharp, G [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Kamp, F; Reiner, M; Nijhuis, R; Ganswindt, U; Thieke, C; Belka, C [LMU Munich, Munich (Germany); Rit, S [University Lyon, Lyon (France); Hansen, D [Aarhus University Hospital, Aarhus (Denmark); Parodi, K; Landry, G [Ludwig-Maximilians-Universitaet Muenchen, Garching b. Muenchen (Germany)

2016-06-15

Purpose: To enable adaptive intensity modulated proton therapy for sites sensitive to inter-fractional changes on the basis of accurate CBCT-based proton dose calculations. To this aim two CBCT intensity correction methods are considered: planning CT (pCT) to CBCT DIR and projection correction based on pCT DIR prior. Methods: 3 H&N and 3 prostate cancer patients with CBCT images and corresponding projections were used in this study, in addition to pCT and re-planning CT (rpCT) images (H&N only). A virtual CT (vCT) was generated by pCT to CBCT DIR. In a second approach, the vCT was used as prior for scatter correction of the CBCT projections to yield a CBCTcor image. BEV 2D range maps of SFUD IMPT plans were compared. For the prostate cases, the geometric accuracy of the vCT was also evaluated by contour comparison to physician delineation of the CBCTcor and original CBCT. Results: SFUD dose calculations on vCT and CBCTcor were found to be within 3mm for 97% to 99% of 2D range maps. Median range differences compared to rpCT were below 0.5mm. Analysis showed that the DIR-based vCT approach exhibits inaccuracies in the pelvic region due to the very low soft-tissue contrast in the CBCT. The CBCTcor approach yielded results closer to the original CBCT in terms of DICE coefficients than the vCT (median 0.91 vs 0.81) for targets and OARs. In general, the CBCTcor approach was less affected by inaccuracies of the DIR used during the generation of the vCT prior. Conclusion: Both techniques yield 3D CBCT images with intensities equivalent to diagnostic CT and appear suitable for IMPT dose calculation for most sites. For H&N cases, no considerable differences between the two techniques were found, while improved results of the CBCTcor were observed for pelvic cases due to the reduced sensitivity to registration inaccuracies. Deutsche Forschungsgemeinschaft (MAP); Bundesministerium fur Bildung und Forschung (01IB13001)

Radiation Therapy Oncology Group clinical trials with misonidazole

International Nuclear Information System (INIS)

Wasserman, T.H.; Stetz, J.; Phillips, T.L.

1981-01-01

This paper presents a review of the progressive clinical trials of the hypoxic cell radiosensitizer, misonidazole, in the Radiation Therapy Oncology Group (RTOG). Presentation is made of all the schemas of the recently completed and currently active RTOG Phase II and Phase III studies. Detailed information is provided on the clinical toxicity of the Phase II trials, specifically regarding neurotoxicity. With limitations in drug total dose, a variety of dose schedules have proven to be tolerable, with a moderate incidence of nausea and vomiting and mild peripheral neuropathy or central neuropathy. No other organ toxicity has been seen, specifically no liver, renal or bone marrow toxicities. An additional Phase III malignant glioma trial in the Brain Tumor Study Group is described

The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

Science.gov (United States)

Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

2017-06-01

The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic

hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

Energy Technology Data Exchange (ETDEWEB)

Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

2014-01-20

The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

Science.gov (United States)

Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

2013-09-01

Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

HN Peg B: A Test of Models of the L to T Dwarf Transition

Science.gov (United States)

Leggett, S. K.; Saumon, D.; Albert, Loic; Cushing, Michael C.; Liu, Michael C.; Luhman, K. L.; Marley, M. S.; Kirkpatrick, J. Davy; Roellig, Thomas L.; Allers, K. N.

2008-08-01

Luhman and collaborators recently discovered an early-T dwarf companion to the G0 dwarf star HN Peg, using Spitzer Infrared Array Camera (IRAC) images. Companionship was established on the basis of the common proper motion inferred from 1998 Two Micron All Sky Survey images and the 2004 IRAC images. In this paper we present new near-infrared imaging data which confirm the common proper motion of the system. We also present new 3-4 μm spectroscopy of HN Peg B, which provides tighter constraints on both the bolometric luminosity determination and the comparison to synthetic spectra. New adaptive optics imaging data are also presented, which show the T dwarf to be unresolved, providing limits on the multiplicity of the object. We use the age, distance, and luminosity of the solar-metallicity T dwarf to determine its effective temperature and gravity, and compare synthetic spectra with these values, and a range of grain properties and vertical mixing, to the observed 0.8-4.0 μm spectra and mid-infrared photometry. We find that models with temperature and gravity appropriate for the older end of the age range of the system (0.5 Gyr) can do a reasonable job of fitting the data, but only if the photospheric condensate cloud deck is thin, and if there is significant vertical mixing in the atmosphere. Dwarfs such as HN Peg B, with well-determined metallicity, radius, gravity, and temperature, will allow development of dynamical atmosphere models, leading to the solution of the puzzle of the L to T dwarf transition. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. Some data were also obtained at the Canada-France-Hawaii Telescope (CFHT), which is operated by the National

A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

Science.gov (United States)

Lemieux, Bruno; Blanchette, Marco; Monette, Anne; Mouland, Andrew J; Wellinger, Raymund J; Chabot, Benoit

2015-01-01

The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

A Function for the hnRNP A1/A2 Proteins in Transcription Elongation.

Directory of Open Access Journals (Sweden)

Bruno Lemieux

Full Text Available The hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes.

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

Energy Technology Data Exchange (ETDEWEB)

Cui Yunfeng [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania (United States); Parker, William [Department of Medical Physics, McGill University Health Center, Montreal, QC (Canada); Breen, Stephen [Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); Yin Fangfang; Cai Jing [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Papiez, Lech S. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Bednarz, Greg [Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Chen Wenzhou [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Xiao Ying, E-mail: ying.xiao@jefferson.edu [Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania (United States)

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is established at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA

Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty.

Science.gov (United States)

Karlsen, Anders P; Mathiesen, Ole; Dahl, Jørgen B

2018-03-01

Postoperative analgesic interventions are often tested adjunct to basic non-opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and possible assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities vary between different control groups in analgesic trials. Control groups from RCTs investigating analgesic interventions after total hip and knee arthroplasty were categorized based on standardized basic analgesic treatment. Morphine consumption 0 to 24 hours postoperatively, and resting pain scores at 6 and 24 hours for subgroups of basic treatments, were compared with ANOVA. In an additional analysis, we compared pain and opioid requirements in trials where a non-steroidal anti-inflammatory drug (NSAID) was administered as an intervention with trial where NSAID was administered in a control group. We included 171 RCTs employing 28 different control groups with large variability in pain scores and opioid requirements. Four types of control groups (comprising 78 trials) were eligible for subgroup comparisons. These subgroups received "opioid" alone, "NSAID + opioid", "acetaminophen + opioid", or "NSAID + acetaminophen + opioid", respectively. Morphine consumption and pain scores varied substantially between these groups, with no consistent superior efficacy in any subgroup. Additionally, trials administering NSAID as an intervention demonstrated lower pain scores and opioid requirements than trials where NSAID was administered in a control group. Analgesic treatment in RCT control groups varies considerably. Control groups receiving various combinations of opioid, NSAID and acetaminophen did not differ consistently in pain and opioid requirements. Pain and opioid requirements were lower in trials administering NSAID as an intervention compared with trials administering NSAID in a control group.

Genetic analysis of human parainfluenza virus type 3 obtained in Croatia, 2011-2015.

Science.gov (United States)

Košutić-Gulija, Tanja; Slovic, Anamarija; Ljubin-Sternak, Sunčanica; Mlinarić-Galinović, Gordana; Forčić, Dubravko

2017-04-01

This study investigated the HPIV3 circulating strains in Croatia and whether the other parts of HPIV3 genome (F gene and HN 582 nucleotides fragment) could be equally suitable for genetic and phylogenetic analysis. Clinical materials were collected in period 2011-2015 from children suffering from respiratory illnesses. In positive HPIV3 samples viral genome was partially amplified and sequenced for HN and F genes. Obtained sequences were analysed by phylogenetic analysis and genetic characterization was performed. All samples from this study belonged to subcluster C and over a short period of time, genetic lineage C3a gained prevalence over the other C genetic lineages, from 39 % in 2011 to more than 90 % in 2013 and 2014. Phylogenetic classifications of HPIV3 based on the entire HN gene, HN 582 nt fragment and entire fusion (F) gene showed identical classification results for Croatian strains and the reference strains. Molecular analysis of the F and HN glycoproteins, showed their similar nucleotide diversity (Fcds P=0.0244 and HNcds P=0.0231) and similar Ka/Ks ratios (F Ka/Ks=0.0553 and HN Ka/Ks=0.0428). Potential N-glycosylation sites, cysteine residues and antigenic sites are generally strongly conserved in HPIV3 glycoproteins from both our and the reference samples. The HPIV3 subclaster C3 (genetic lineage C3a) became the most detected circulating HPIV3 strain in Croatia. The results indicated that the HN 582 nt and the entire F gene sequences were as good for phylogenetic analysis as the entire HN gene sequence.

The impact of probiotics and n-3 long-chain polyunsaturated fatty acids on intestinal permeability in pregnancy: a randomised clinical trial.

Science.gov (United States)

Mokkala, K; Pussinen, P; Houttu, N; Koivuniemi, E; Vahlberg, T; Laitinen, K

2018-02-27

A disruption in intestinal barrier integrity may predispose individuals to metabolic aberrations, particularly during the vulnerable period of pregnancy. We investigated whether intestinal permeability, as measured by serum zonulin concentration, changes over the duration of pregnancy and whether this change is reflected in lipopolysaccharide (LPS) activity. Second, we tested in a randomised double-blind placebo controlled clinical trial the impact of consuming dietary probiotics and/or long chain polyunsaturated fatty acid (LC-PUFA) supplements in lowering serum zonulin concentration and LPS activity. The probiotic supplement was a combination of two bacteria, Bifidobacterium animalis ssp. lactis 420 and Lactobacillus rhamnosus HN001. This study included 200 overweight pregnant women participating in an on-going study; participants were randomised to consume either (1) probiotics, (2) LC-PUFA, (3) probiotics and LC-PUFA, or (4) placebo for each supplement. Blood samples were obtained at early, the baseline, and late pregnancy (mean 14 and 35 weeks of gestation, respectively). Serum zonulin concentration increased from early (mean (standard deviation): 62.7 (12.9) ng/ml) to late pregnancy by 5.3 (95%CI 3.7-6.9) ng/ml, and LPS activity increased from (0.16 (0.04) EU/ml) by 0.04 (95%CI 0.03-0.05) EU/ml. No differences among the intervention groups were detected in the change from early to late pregnancy in serum zonulin concentration (P=0.8) or LPS activity (P=0.2). The change in serum zonulin concentration during the pregnancy was associated with the weeks of follow up (r=0.25, Pzonulin concentration or LPS activity.

A Mythic- Philosophic Analysis of the First Line of Ferdowsi’s Shāhnāma as Compared with Ancient Beliefs and “Khosravāni” Wisdom

OpenAIRE

فرزاد قائمی

2013-01-01

Ferdowsi’s Shāhnāma has a monotheistic context and its narrative deep structure has been demythologized throughout history at religious, ritual and mythic levels. However, an analytical approach can spot traces of the ancient beliefs reflected in the symbolic implications of the narratives as well as the language and imagery of the Shāhnāma. The first line in the Preface of the Shāhnāma, “In the name of God of wisdom and spirit”, best advances a divine ontology. Drawing on historical studies ...

Comparison of Toxicity Associated With Early Morning Versus Late Afternoon Radiotherapy in Patients With Head-and-Neck Cancer: A Prospective Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (HN3)

International Nuclear Information System (INIS)

Bjarnason, Georg A.; MacKenzie, Robert G.; Nabid, Abdenour; Hodson, Ian D.; El-Sayed, Samy; Grimard, Laval; Brundage, Michael; Wright, James; Hay, John; Ganguly, Pradip; Leong, Carson; Wilson, Jane; Jordan, Richard C.K.; Walker, Melanie; Tu Dongsheng; Parulekar, Wendy

2009-01-01

Purpose: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G 1 phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. Methods and Materials: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. Results: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). Conclusion: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving ≥66 Gy and in patients who smoked during therapy

The Rules of Engagement: CTTI Recommendations for Successful Collaborations Between Sponsors and Patient Groups Around Clinical Trials.

Science.gov (United States)

Bloom, Diane; Beetsch, Joel; Harker, Matthew; Hesterlee, Sharon; Moreira, Paulo; Patrick-Lake, Bray; Selig, Wendy; Sherman, Jeffrey; Smith, Sophia K; Valentine, James E; Roberts, Jamie N

2018-03-01

To identify the elements necessary for successful collaboration between patient groups and academic and industry sponsors of clinical trials, in order to develop recommendations for best practices for effective patient group engagement. In-depth interviews, informed by a previously reported survey, were conducted to identify the fundamentals of successful patient group engagement. Thirty-two respondents from 3 sectors participated: patient groups, academic researchers, and industry. The findings were presented to a multistakeholder group of experts in January 2015. The expert group came to consensus on a set of actionable recommendations for best practices for patient groups and research sponsors. Interview respondents acknowledged that not all patient groups are created equal in terms of what they can contribute to a clinical trial. The most important elements for effective patient group engagement include establishing meaningful partnerships, demonstrating mutual benefits, and collaborating as partners from the planning stage forward. Although there is a growing appreciation by sponsors about the benefits of patient group engagement, there remains some resistance and some uncertainty about how best to engage. Barriers include mismatched expectations and a perception that patient groups lack scientific sophistication and that "wishful thinking" may cloud their recommendations. Patient groups are developing diverse skillsets and acquiring assets to leverage in order to become collaborators with industry and academia on clinical trials. Growing numbers of research sponsors across the clinical trials enterprise are recognizing the benefits of continuous and meaningful patient group engagement, but there are still mindsets to change, and stakeholders need further guidance on operationalizing a new model of clinical trial conduct.

Growth and adhesion to HT-29 cells inhibition of Gram-negatives by Bifidobacterium longum BB536 e Lactobacillus rhamnosus HN001 alone and in combination.

Science.gov (United States)

Inturri, R; Stivala, A; Furneri, P M; Blandino, G

2016-12-01

The aim of this study was to test the inhibitory effect of supernatants of broth cultures of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001, both individually and in combination, against Gram-negative strains (uropathogens, enteropathogens and a reference strain). Moreover, in vitro protection of B. longum BB536 and L. rhamnosus HN001, both individually and in combination, against pathogen adhesion to HT-29 cell line, was investigated. The inhibitory activity was performed by the agar diffusion test and in vitro antagonistic activity against pathogen adhesion to human epithelial intestinal HT-29 cells was performed using standardized culture techniques. The study showed that B. longum BB536 and L. rhamnosus HN001, individually and in combination have inhibitory activity against the majority of the Gram negative strains tested. Furthermore, the results showed that both probiotic strains have a good capacity to inhibit pathogenic adhesion to HT-29 cells. Moreover, the ability of B. longum BB536 and L. rhamnosus HN001 to inhibit pathogenic adhesion increased when they were used in combination. The combination of B. longum BB536 and L. rhamnosus HN001 showed inhibitory activity against Gram-negatives and an improved ability to reduce their adhesion properties and to compete with them. The simultaneous presence of the two-probiotic strains could promote competitive mechanisms able to reduce the adhesion properties of pathogen strains and have an important ecological role within the highly competitive environment of the human gut.

A ‘just-in-time’ HN(CA)CO experiment for the backbone assignment of large proteins with high sensitivity

Science.gov (United States)

Werner-Allen, Jon W.; Jiang, Ling; Zhou, Pei

2006-07-01

Among the suite of commonly used backbone experiments, HNCACO presents an unresolved sensitivity limitation due to fast 13CO transverse relaxation and passive 13Cα-13Cβ coupling. Here, we present a high-sensitivity 'just-in-time' (JIT) HN(CA)CO pulse sequence that uniformly refocuses 13Cα-13Cβ coupling while collecting 13CO shifts in real time. Sensitivity comparisons of the 3-D JIT HN(CA)CO, a CT-HMQC-based control, and a HSQC-based control with selective 13Cα inversion pulses were performed using a 2H/13C/15N labeled sample of the 29 kDa HCA II protein at 15 °C. The JIT experiment shows a 42% signal enhancement over the CT-HMQC-based experiment. Compared to the HSQC-based experiment, the JIT experiment is 16% less sensitive for residues experiencing proper 13Cα refocusing and 13Cα-13Cβ decoupling. However, for the remaining residues, the JIT spectrum shows a 106% average sensitivity gain over the HSQC-based experiment. The high-sensitivity JIT HNCACO experiment should be particularly beneficial for studies of large proteins to provide 13CO resonance information regardless of residue type.

A Novel Religious/Spiritual Group Psychotherapy Reduces Depressive Symptoms in a Randomized Clinical Trial.

Science.gov (United States)

Chida, Yoichi; Schrempft, Stephanie; Steptoe, Andrew

2016-10-01

This randomized controlled trial aimed to examine the effect of the Happy Science doctrine-based group psychotherapy on depressive symptoms in 118 Japanese mental disorder outpatients. The treatment group (n = 58) took part in five 90-min sessions at one-week intervals, while the control group (n = 60) received standard care including medication. Depressive symptoms were assessed before the intervention, 5 weeks after the intervention, and at 3-month follow-up. Compared to the control group, the treatment group showed a significant reduction in depressive symptoms both at post-intervention and at 3-month follow-up. In conclusion, this group psychotherapy might be of benefit in treating depressive symptoms.

Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial.

Science.gov (United States)

Zeidan, Youssef H; Habib, Joyce G; Ameye, Lieveke; Paesmans, Marianne; de Azambuja, Evandro; Gelber, Richard D; Campbell, Ian; Nordenskjöld, Bo; Gutiérez, Jorge; Anderson, Michael; Lluch, Ana; Gnant, Michael; Goldhirsch, Aron; Di Leo, Angelo; Joseph, David J; Crown, John; Piccart-Gebhart, Martine; Francis, Prudence A

2018-06-01

To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P = .005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P = .02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Our analysis of the BIG 02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. Copyright © 2018 Elsevier Inc. All rights reserved.

Sociodemographic analysis of patients in radiation therapy oncology group clinical trials

International Nuclear Information System (INIS)

Chamberlain, Robert M.; Winter, Kathryn A.; Vijayakumar, Srinivasan; Porter, Arthur T.; Roach, M.; Streeter, Oscar; Cox, James D.; Bondy, Melissa L.

1998-01-01

Purpose: To assess the degree to which the sociodemographic characteristics of patients enrolled in Radiation Therapy Oncology Group (RTOG) clinical trails are representative of the general population. Methods and Materials: Sociodemographic data were collected on 4016 patients entered in 33 open RTOG studies between July 1991 and June 1994. The data analyzed included educational attainment, age, gender, and race. For comparison, we obtained similar data from the U.S. Department of Census. We also compared our RTOG data with Surveillance Epidemiology and End Results (SEER) data for patients who received radiation therapy, to determine how RTOG patients compared with cancer patients in general, and with patients with cancers at sites typically treated with radiotherapy. Results: Overall, the sociodemographic characteristics of patients entered in RTOG trials were similar to those of the Census data. We found that, in every age group of African-American men and at nearly every level of educational attainment, the proportion of RTOG trial participants mirrored the proportion in the census data. Significant differences were noted only in the youngest category of African-American men, where the RTOG accrues more in the lower educational categories and fewer with college experience. For African-American women, we found a similar pattern in every age group and at each level of educational attainment. As with men, RTOG trials accrued a considerably larger proportion of younger, less educated African-American women than the census reported. Using SEER for comparison, the RTOG enrolled proportionately more African-American men to trials all cancer sites combined, and for prostate and head and neck cancer. In head and neck trials, the RTOG enrolled nearly twice as many African-American men than would be predicted by SEER data. In lung cancer trials, RTOG underrepresented African-American men significantly; however, there was no difference for brain cancer trials. There were

Pilot randomized controlled trial of dialectical behavior therapy group skills training for ADHD among college students.

Science.gov (United States)

Fleming, Andrew P; McMahon, Robert J; Moran, Lyndsey R; Peterson, A Paige; Dreessen, Anthony

2015-03-01

ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications.

Review of Recent Methodological Developments in Group-Randomized Trials: Part 2-Analysis.

Science.gov (United States)

Turner, Elizabeth L; Prague, Melanie; Gallis, John A; Li, Fan; Murray, David M

2017-07-01

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.

Group-Sequential Strategies in Clinical Trials with Multiple Co-Primary Outcomes

Science.gov (United States)

Hamasaki, Toshimitsu; Asakura, Koko; Evans, Scott R; Sugimoto, Tomoyuki; Sozu, Takashi

2015-01-01

We discuss the decision-making frameworks for clinical trials with multiple co-primary endpoints in a group-sequential setting. The decision-making frameworks can account for flexibilities such as a varying number of analyses, equally or unequally spaced increments of information and fixed or adaptive Type I error allocation among endpoints. The frameworks can provide efficiency, i.e., potentially fewer trial participants, than the fixed sample size designs. We investigate the operating characteristics of the decision-making frameworks and provide guidance on constructing efficient group-sequential strategies in clinical trials with multiple co-primary endpoints. PMID:25844122

The hypersurfaces with conformal normal Gauss map in Hn+1 and S1n+1

Directory of Open Access Journals (Sweden)

Shuguo Shi

2008-03-01

Full Text Available In this paper, we introduce the fourth fundamental forms for hypersurfaces in Hn+1 and space-like hypersurfaces in S1n+1, and discuss the conformality of the normal Gauss map of the hypersurfaces in Hn+1 and S1n+1. Particularly, we discuss the surfaces with conformal normal Gauss map in H³ and S³1, and prove a duality property. We give a Weierstrass representation formula for space-like surfaces in S³1 with conformal normal Gauss map. We also state the similar results for time-like surfaces in S³1. Some examples of surfaces in S³1 with conformal normal Gauss map are given and a fully nonlinear equation of Monge-Ampère type for the graphs in S³1 with conformal normal Gauss map is derived.Neste artigo, introduzimos a quarta forma fundamental de uma hipersuperfície em Hn+1 de uma hipersuperfície tipo-espaço em S1n+1, e discutimos a conformalidade da aplicação normal de Gauss de tais hipersuperfícies. Em particular, investigamos o caso de superfícies com aplicação normal de Gauss conforme em H³ e S³1, e provamos um teorema de dualidade. Apresentamos uma representação de Weierstrass para superfícies tipo-espaço em S³1 com aplicação de Gauss conforme. Enunciamos também resultados semelhantes para superfícies tipo-tempo em S³1. São dados alguns exemplos de superfícies em S³1 com aplicações de Gauss conformes, e é deduzida uma equação totalmente não-linear do tipo Monge-Ampère para gráficos em S³1 com aplicações de Gauss conformes.

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

Science.gov (United States)

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

hnRNPs H, H' and F behave differently with respect to posttranslational cleavage and subcellular localization

DEFF Research Database (Denmark)

Honoré, B; Vorum, H; Baandrup, U

1999-01-01

cytoplasmic localization in other cells. The different fates may reflect differences in functional roles that so far only have included nuclear functions. The presence of significant quantities of hnRNP F in the cytoplasm of many cells indicates that it also may have a functional role here. Udgivelsesdato...

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, CnHn and closo-boranes [BxHx]2−

Directory of Open Access Journals (Sweden)

Henning Hopf

2011-02-01

Full Text Available The closo-boranes BxHx+2, or their corresponding anions [BxHx]2− (where x = 5 through 12 and polycycloalkanes CnHn (where n represents even numbers from 6 through 20 exhibit a complementary relationship whereby the structures of the corresponding molecules, e.g., [B6H6]2− and C8H8 (cubane, are based on reciprocal polyhedra. The vertices in the closo-boranes correspond to faces in its polycyclic hydrocarbon counterpart and vice versa. The different bonding patterns in the two series are described. Several of these hydrocarbons (cubane, pentagonal dodecahedrane and the trigonal and pentagonal prismanes are known while others still remain elusive. Synthetic routes to the currently known CnHn highly symmetrical polyhedral species are briefly summarized and potential routes to those currently unknown are discussed. Finally, the syntheses of the heavier element analogues of cubane and the prismanes are described.

What Can We Expect from the ISSUE 3 Trial?

Directory of Open Access Journals (Sweden)

Richard Sutton, DSc FRCP FACC FESC FAHA FHRS

2011-01-01

Full Text Available The ISSUE 3 Trial is designed to demonstrate which patients with vasovagal syncope over the age of 40 years will benefit from pacing dual chamber with the rate drop response. The trial has completed its recruitment of 521 patients and 78 have now been randomized in Phase 2, which is the Pacing ON versus Pacing OFF comparison. During this Phase the end-points are recurrence of syncope or two years of follow-up without recurrence. It has been calculated that 27 early end-points will be sufficient to determine a significant difference between the groups. The background, details and design of the trial are explained. Some early findings are presented. Definitive results are expected by the end of 2011.

Uncertainty inequalities for the Heisenberg group

Indian Academy of Sciences (India)

where φ is an admissible wavelet and kφ is an appropriate positive constant. For more on the history and the relevance of the uncertainty inequality, we refer the readers to the survey [5], the books [6,8], and the papers [2,10,11]. For the Heisenberg group Hn, Thangavelu [16] proved the following theorem. Theorem 1.1.

Native SrTiO3 (001) surface layer from resonant Ti L2,3 reflectance spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Valvidares, Manuel; Huijben, Mark; Yu, Pu; Ramesh, Ramamoorthy; Kortright, Jeffrey

2010-11-03

We quantitatively model resonant Ti L2,3 reflectivity Rs,p(q, hn) from several SrTiO3 (001) single crystals having different initial surface preparations and stored in ambient conditions before and between measurements. All samples exhibit unexpected 300 K Rs(hn) - Rp(hn) anisotropy corresponding to weak linear dichroism and tetragonal distortion of the TiO6 octahedra indicating a surface layer with properties different from cubic SrTiO3. Oscillations in Rs(q) confirm a ubiquitous surface layer 2-3 nm thick that evolves over a range of time scales. Resonant optical constant spectra derived from Rs,p(hn) assuming a uniform sample are refined using a single surface layer to fit measured Rs(q). Differences in surface layer and bulk optical properties indicate that the surface is significantly depleted in Sr and enriched in Ti and O. While consistent with the tendency of SrTiO3 surfaces toward non-stoichiometry, this layer does not conform simply to existing models for the near surface region and apparently forms via room temperature surface reactions with the ambient. This new quantitative spectral modeling approach is generally applicable and has potential to study near-surface properties of a variety of systems with unique chemical and electronic sensitivities.

Prebiotic and probiotic fortified milk in prevention of morbidities among children: community-based, randomized, double-blind, controlled trial.

Directory of Open Access Journals (Sweden)

Sunil Sazawal

Full Text Available BACKGROUND: Recent reviews suggest common infectious diseases continue to be a major cause of death among preschool children in developing countries. Identification of feasible strategies to combat this disease burden is an important public health need. We evaluated the efficacy of adding prebiotic oligosaccharide and probiotic Bifidobacterium lactis HN019 to milk, in preventing diarrhea, respiratory infections and severe illnesses, in children aged 1-4 years as part of a four group study design, running two studies simultaneously. METHODS AND FINDINGS: In a community based double-masked, randomized controlled trial, children 1-3 years of age, willing to participate, were randomly allocated to receive either control milk (Co; n = 312 or the same milk fortified with 2.4 g/day of prebiotic oligosaccharide and 1.9x10(7 colony forming unit (c.f.u/day of probiotic Bifidobacterium lactis HN019 (PP; n = 312. Children were followed up for 1 year providing data for 1-4 years. Biweekly household surveillance was conducted to gather information on compliance and morbidity. Both study groups were comparable at baseline; compliance to intervention was similar. Overall, there was no effect of prebiotic and probiotic on diarrhea (6% reduction, 95% Confidence Interval [CI]: -1 to 12%; p = 0.08. Incidence of dysentery episodes was reduced by 21% (95% CI: 0 to 38%; p = 0.05. Incidence of pneumonia was reduced by 24% (95% CI: 0 to 42%; p = 0.05 and severe acute lower respiratory infection (ALRI by 35% (95% CI: 0 to 58%; p = 0.05. Compared to children in Co group, children in PP group had 16% (95% CI: 5 to 26%, p = 0.004 and 5% (95% CI: 0 to 10%; p = 0.05 reduction in days with severe illness and high fever respectively. CONCLUSIONS/SIGNIFICANCE: Milk can be a good medium for delivery of prebiotic and probiotic and resulted in significant reduction of dysentery, respiratory morbidity and febrile illness. Overall, impact of diarrhea was not significant. These

Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Leder, Verena [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lummer, Martina [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Tegeler, Kathrin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Humpert, Fabian [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lewinski, Martin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Schüttpelz, Mark [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Staiger, Dorothee, E-mail: dorothee.staiger@uni-bielefeld.de [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany)

2014-10-10

Highlights: • We use FCS to investigate binding site requirements for the hnRNP-like protein AtGRP7. • We identify three nucleotides critical for AtGRP7 binding to its own intron. • Mutation of the conserved R{sup 49} abolishes binding altogether. • The paralogue AtGRP8 binds to an overlapping motif with different sequence requirement. • The glycine-rich stretch of a plant hnRNP-like protein contributes to binding. - Abstract: Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased K{sub d} value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R{sup 49} that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding.

Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy

International Nuclear Information System (INIS)

Leder, Verena; Lummer, Martina; Tegeler, Kathrin; Humpert, Fabian; Lewinski, Martin; Schüttpelz, Mark; Staiger, Dorothee

2014-01-01

Highlights: • We use FCS to investigate binding site requirements for the hnRNP-like protein AtGRP7. • We identify three nucleotides critical for AtGRP7 binding to its own intron. • Mutation of the conserved R 49 abolishes binding altogether. • The paralogue AtGRP8 binds to an overlapping motif with different sequence requirement. • The glycine-rich stretch of a plant hnRNP-like protein contributes to binding. - Abstract: Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased K d value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R 49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding

Multicomponent interdisciplinary group intervention for self-management of fibromyalgia: a mixed-methods randomized controlled trial.

Directory of Open Access Journals (Sweden)

Patricia Bourgault

Full Text Available This study evaluated the efficacy of the PASSAGE Program, a structured multicomponent interdisciplinary group intervention for the self-management of FMS.A mixed-methods randomized controlled trial (intervention (INT vs. waitlist (WL was conducted with patients suffering from FMS. Data were collected at baseline (T0, at the end of the intervention (T1, and 3 months later (T2. The primary outcome was change in pain intensity (0-10. Secondary outcomes were fibromyalgia severity, pain interference, sleep quality, pain coping strategies, depression, health-related quality of life, patient global impression of change (PGIC, and perceived pain relief. Qualitative group interviews with a subset of patients were also conducted. Complete data from T0 to T2 were available for 43 patients.The intervention had a statistically significant impact on the three PGIC measures. At the end of the PASSAGE Program, the percentages of patients who perceived overall improvement in their pain levels, functioning and quality of life were significantly higher in the INT Group (73%, 55%, 77% respectively than in the WL Group (8%, 12%, 20%. The same differences were observed 3 months post-intervention (Intervention group: 62%, 43%, 38% vs Waitlist Group: 13%, 13%, 9%. The proportion of patients who reported ≥ 50% pain relief was also significantly higher in the INT Group at the end of the intervention (36% vs 12% and 3 months post-intervention (33% vs 4%. Results of the qualitative analysis were in line with the quantitative findings regarding the efficacy of the intervention. The improvement, however, was not reflected in the primary outcome and other secondary outcome measures.The PASSAGE Program was effective in helping FMS patients gain a sense of control over their symptoms. We suggest including PGIC in future clinical trials on FMS as they appear to capture important aspects of the patients' experience.International Standard Randomized Controlled Trial Number

'Putting Life in Years' (PLINY) telephone friendship groups research study: pilot randomised controlled trial.

Science.gov (United States)

Mountain, Gail A; Hind, Daniel; Gossage-Worrall, Rebecca; Walters, Stephen J; Duncan, Rosie; Newbould, Louise; Rex, Saleema; Jones, Carys; Bowling, Ann; Cattan, Mima; Cairns, Angela; Cooper, Cindy; Edwards, Rhiannon Tudor; Goyder, Elizabeth C

2014-04-24

Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For

Heterochromatin protein 1 (HP1a positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila.

Directory of Open Access Journals (Sweden)

Lucia Piacentini

2009-10-01

Full Text Available Heterochromatin Protein 1 (HP1a is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases methylate the histone H3 at lysine 9 (H3K9me, creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA-immunoprecipitation on microarrays, and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms

‘Putting Life in Years’ (PLINY) telephone friendship groups research study: pilot randomised controlled trial

Science.gov (United States)

2014-01-01

Background Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Methods Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. Results We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Conclusions Recruitment and retention of participants to a definitive trial with a

n-th Roots in finite polyhedral and centro-polyhedral groups

Indian Academy of Sciences (India)

Probability in finite groups; roots of elements; polyhedral groups; centro- polyhedral groups. 2010 Mathematics ... An element g of a finite group G is said to have an n-th root if there exists an element h ∈ G such that g = hn (n is a ..... For the proof of the fourth part, we must consider two cases: (i) m is odd and 4|d,. (ii) m, d are ...

Estimation After a Group Sequential Trial.

Science.gov (United States)

Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Kenward, Michael G; Tsiatis, Anastasios A; Davidian, Marie; Verbeke, Geert

2015-10-01

Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al (2012) and Milanzi et al (2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, N = n or N = 2 n . In this paper, we consider the more practically useful setting of sample sizes in a the finite set { n 1 , n 2 , …, n L }. It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why

Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL.

Science.gov (United States)

Cui, Yunxi; Koirala, Deepak; Kang, HyunJin; Dhakal, Soma; Yangyuoru, Philip; Hurley, Laurence H; Mao, Hanbin

2014-05-01

Minute difference in free energy change of unfolding among structures in an oligonucleotide sequence can lead to a complex population equilibrium, which is rather challenging for ensemble techniques to decipher. Herein, we introduce a new method, molecular population dynamics (MPD), to describe the intricate equilibrium among non-B deoxyribonucleic acid (DNA) structures. Using mechanical unfolding in laser tweezers, we identified six DNA species in a cytosine (C)-rich bcl-2 promoter sequence. Population patterns of these species with and without a small molecule (IMC-76 or IMC-48) or the transcription factor hnRNP LL are compared to reveal the MPD of different species. With a pattern recognition algorithm, we found that IMC-48 and hnRNP LL share 80% similarity in stabilizing i-motifs with 60 s incubation. In contrast, IMC-76 demonstrates an opposite behavior, preferring flexible DNA hairpins. With 120-180 s incubation, IMC-48 and hnRNP LL destabilize i-motifs, which has been previously proposed to activate bcl-2 transcriptions. These results provide strong support, from the population equilibrium perspective, that small molecules and hnRNP LL can modulate bcl-2 transcription through interaction with i-motifs. The excellent agreement with biochemical results firmly validates the MPD analyses, which, we expect, can be widely applicable to investigate complex equilibrium of biomacromolecules. © 2014 The Author(s). Published by Oxford University Press [on behalf of Nucleic Acids Research].

Photosensitized oxygenation of alkenes in the presence of bisazafullerene (C59N)2 and hydroazafullerene C59HN

International Nuclear Information System (INIS)

Tagmatarchis, Nikos; Shinohara, Hisanori

2001-01-01

Bisazafullerene (C 59 N) 2 and hydroazafullerene C 59 HN photosensitize the reaction of alkenes with oxygen. 2-methyl 2-butene and α-terpinene undergo ene and Diels-Alder photooxygenation reactions, respectively, in the presence of minute amounts of azafullerenes to produce the corresponding peroxides

Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study.

Science.gov (United States)

Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

2018-06-01

To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

A cluster randomized controlled platform trial comparing group MEmory specificity training (MEST) to group psychoeducation and supportive counselling (PSC) in the treatment of recurrent depression.

Science.gov (United States)

Werner-Seidler, Aliza; Hitchcock, Caitlin; Bevan, Anna; McKinnon, Anna; Gillard, Julia; Dahm, Theresa; Chadwick, Isobel; Panesar, Inderpal; Breakwell, Lauren; Mueller, Viola; Rodrigues, Evangeline; Rees, Catrin; Gormley, Siobhan; Schweizer, Susanne; Watson, Peter; Raes, Filip; Jobson, Laura; Dalgleish, Tim

2018-06-01

Impaired ability to recall specific autobiographical memories is characteristic of depression, which when reversed, may have therapeutic benefits. This cluster-randomized controlled pilot trial investigated efficacy and aspects of acceptability, and feasibility of MEmory Specificity Training (MEST) relative to Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N = 62). A key aim of this study was to determine a range of effect size estimates to inform a later phase trial. Assessments were completed at baseline, post-treatment and 3-month follow-up. The cognitive process outcome was memory specificity. The primary clinical outcome was symptoms on the Beck Depression Inventory-II at 3-month follow-up. The MEST group demonstrated greater improvement in memory specificity relative to PSC at post-intervention (d = 0.88) and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in depressive symptoms at 3-month follow-up (d = 0.67). However, there was no support for a greater improvement in depressive symptoms at 3 months following MEST relative to PSC (d = -0.04). Although MEST generated changes on memory specificity and improved depressive symptoms, results provide no indication that MEST is superior to PSC in the resolution of self-reported depressive symptoms. Implications for later-phase definitive trials of MEST are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A virtual dosimetry audit - Towards transferability of gamma index analysis between clinical trial QA groups.

Science.gov (United States)

Hussein, Mohammad; Clementel, Enrico; Eaton, David J; Greer, Peter B; Haworth, Annette; Ishikura, Satoshi; Kry, Stephen F; Lehmann, Joerg; Lye, Jessica; Monti, Angelo F; Nakamura, Mitsuhiro; Hurkmans, Coen; Clark, Catharine H

2017-12-01

Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity. Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual 'measurements' were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the 'measured' data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ. For the same virtual 'measured' datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment. Copyright © 2017 Elsevier B.V. All rights reserved.

Internet-Based, Randomized Controlled Trial of Omega-3 Fatty Acids for Hyperactivity in Autism

Science.gov (United States)

Bent, Stephen; Hendren, Robert L.; Zandi, Tara; Law, Kiely; Choi, Jae-Eun; Widjaja, Felicia; Kalb, Luther; Nestle, Jay; Law, Paul

2014-01-01

Objective Preliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder (ASD). We sought to examine the feasibility of a novel, internet-based clinical trial design to evaluate the efficacy of this supplement. Method E-mail invitations were sent to parents of children aged 5-8 enrolled in the Interactive Autism Network. All study procedures, including screening, informed consent, and collection of outcome measures took place over the internet. The primary outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist. Results During the 6-week recruitment period, 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks. Outcome assessments were obtained from all 57 participants and 57 teachers, and the study was completed in 3 months. Children in the omega-3 fatty acid group had a greater reduction in hyperactivity (-5.3 points) compared to the placebo group (-2.6 points), but the difference was not statistically significant (1.9 point greater improvement in the omega-3 group, 95% CI -2.2 to 5.2). Side effects were rare and not associated with omega-3 fatty acids. Participant feedback was positive. Conclusion Internet-based randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials. A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids. Clinical trial registration information—Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder; http://clinicaltrials.gov; NCT01694667. PMID:24839884

Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

Science.gov (United States)

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Zhang, Ying; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2011-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients and available treatments are of little benefit. The objective of this trial was to determine if acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3 times/week on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head/Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates (UWSFR; SSFR). Patients were followed for 6 months after the end of radiotherapy. Results XQ scores for acupuncture were statistically significantly lower than controls starting in week 3 through the 6-months(P=0.003 at week3, all other P’s xerostomia and improved QOL. PMID:22072272

A randomized trial assessing the impact of written information on outpatients' knowledge about and attitude toward randomized clinical trials. The Info Trial Group

DEFF Research Database (Denmark)

Kruse, A Y; Kjaergard, L L; Krogsgaard, K

2000-01-01

To improve the patient education process in clinical research, three information materials describing general aspects of design and conduct of randomized clinical trials were developed. The materials varied in length, reading ability level, and reader appeal. Their influence on knowledge about...... and attitude toward randomized clinical trials was assessed in a randomized, parallel group, evaluator-blinded trial among 415 outpatients. The patients were randomized to the following groups: control (no intervention), leaflet, brochure, or booklet. Knowledge was assessed by a 17-item multiple......-choice questionnaire and attitude was assessed by a 32-item Likert questionnaire at entry and 2 weeks after the intervention. The interventions and the questionnaires were pilot tested and power calculations were performed. At entry, the mean knowledge score was 7.9 points. At follow-up, the knowledge scores increased...

Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

International Nuclear Information System (INIS)

Noisakran, Sansanee; Sengsai, Suchada; Thongboonkerd, Visith; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Chen, Shui-Tein; Puttikhunt, Chunya

2008-01-01

Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

Exercise and nutrition for head and neck cancer patients: a patient oriented, clinic-supported randomized controlled trial

Directory of Open Access Journals (Sweden)

Capozzi Lauren C

2012-10-01

Full Text Available Abstract Background Research on physical activity and nutrition interventions aimed at positively impacting symptom management, treatment-related recovery and quality of life has largely excluded head and neck (HN cancer populations. This translates into a lack of clinical programming available for these patient populations. HN cancer patients deal with severe weight loss, with more than 70% attributed to lean muscle wasting, leading to extended recovery times, decreased quality of life (QoL, and impaired physical functioning. To date, interventions to address body composition issues have focused solely on diet, despite findings that nutritional therapy alone is insufficient to mitigate changes. A combined physical activity and nutrition intervention, that also incorporates important educational components known to positively impact behaviour change, is warranted for this population. Our pilot work suggests that there is large patient demand and clinic support from the health care professionals for a comprehensive program. Methods/Design Therefore, the purpose of the present study is to examine the impact and timing of a 12-week PA and nutrition intervention (either during or following treatment for HN cancer patients on body composition, recovery, serum inflammatory markers and quality of life. In addition, we will examine the impact of a 12-week maintenance program, delivered immediately following the intervention, on adherence, patient-reported outcomes (i.e., management of both physical and psychosocial treatment-related symptoms and side-effects, as well as return to work. Discussion This research will facilitate advancements in patient wellness, survivorship, and autonomy, and carve the path for a physical-activity and wellness-education model that can be implemented in other cancer centers. Trial registration Current Controlled Trials NCT01681654

Klimatizace líhně kuřat

OpenAIRE

Petr, Lukáš

2009-01-01

Diplomová práce se zabývá návrhem systému klimatizačního zařízení pro prostory s líhněmi kuřat. Práce v úvodu krátce přibližuje problematiku klimatizace, představuje dispozice objektu a nastiňuje požadavky na mikroklima pro správnou inkubaci vajec a líhnutí kuřat. Praktická část diplomové práce se dělí na dva základní úseky, a to výpočtový a návrhový. Výpočtová část se zabývá stanovením množství přiváděného čerstvého klimatizačního vzduchu, výpočtem tepelných ztrát, tepelné zátěže a psychrome...

How to Evaluate Phase Differences between Trial Groups in Ongoing Electrophysiological Signals

Science.gov (United States)

VanRullen, Rufin

2016-01-01

A growing number of studies endeavor to reveal periodicities in sensory and cognitive functions, by comparing the distribution of ongoing (pre-stimulus) oscillatory phases between two (or more) trial groups reflecting distinct experimental outcomes. A systematic relation between the phase of spontaneous electrophysiological signals, before a stimulus is even presented, and the eventual result of sensory or cognitive processing for that stimulus, would be indicative of an intrinsic periodicity in the underlying neural process. Prior studies of phase-dependent perception have used a variety of analytical methods to measure and evaluate phase differences, and there is currently no established standard practice in this field. The present report intends to remediate this need, by systematically comparing the statistical power of various measures of “phase opposition” between two trial groups, in a number of real and simulated experimental situations. Seven measures were evaluated: one parametric test (circular Watson-Williams test), and three distinct measures of phase opposition (phase bifurcation index, phase opposition sum, and phase opposition product) combined with two procedures for non-parametric statistical testing (permutation, or a combination of z-score and permutation). While these are obviously not the only existing or conceivable measures, they have all been used in recent studies. All tested methods performed adequately on a previously published dataset (Busch et al., 2009). On a variety of artificially constructed datasets, no single measure was found to surpass all others, but instead the suitability of each measure was contingent on several experimental factors: the time, frequency, and depth of oscillatory phase modulation; the absolute and relative amplitudes of post-stimulus event-related potentials for the two trial groups; the absolute and relative trial numbers for the two groups; and the number of permutations used for non-parametric testing

High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women.

Science.gov (United States)

Ashworth, Ann; Mitchell, Klaus; Blackwell, Jamie R; Vanhatalo, Anni; Jones, Andrew M

2015-10-01

Epidemiological studies suggest that green leafy vegetables, which are high in dietary nitrate, are protective against CVD such as stroke. High blood pressure (BP) is a major risk factor for stroke and inorganic nitrate has been shown to reduce BP. The objective of the present study was to test the hypothesis that diets containing high-nitrate (HN) vegetables would increase plasma nitrate and nitrite concentrations and reduce BP in healthy women. A randomized, crossover trial, where participants received HN vegetables (HN diet) or avoided HN vegetables (Control diet) for 1 week. Before and after each intervention, resting BP and plasma nitrate and nitrite concentrations were measured. University of Exeter, UK. Nineteen healthy women (mean age 20 (sd 2) years; mean BMI 22·5 (sd 3·8) kg/m2). The HN diet significantly increased plasma nitrate concentration (before HN diet: mean 24·4 (sd 5·6) µmol/l; after HN diet: mean 61·0 (sd 44·1) µmol/l, Pdiet: mean 98 (sd 91) nmol/l; after HN diet: mean 185 (sd 34) nmol/l, Pdiet. The HN diet significantly reduced resting systolic BP (before HN diet: mean 107 (sd 9) mmHg; after HN diet: mean 103 (sd 6) mmHg, Pdiet (before Control diet: mean 106 (sd 8) mmHg; after Control diet: mean 106 (sd 8) mmHg). Consumption of HN vegetables significantly increased plasma nitrate and nitrite concentrations and reduced BP in normotensive women.

Are the Cochrane group registers comprehensive? A case study of Japanese psychiatry trials

Directory of Open Access Journals (Sweden)

McGuire Hugh

2002-04-01

Full Text Available Abstract Background Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. Methods We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. Results The Japanese register contained 56 reports of randomized controlled trials (RCTs of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. Conclusions Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect.

An intervention to reduce HIV risk behavior of substance-using men who have sex with men: a two-group randomized trial with a nonrandomized third group.

Directory of Open Access Journals (Sweden)

Gordon Mansergh

2010-08-01

Full Text Available Substance use during sex is associated with sexual risk behavior among men who have sex with men (MSM, and MSM continue to be the group at highest risk for incident HIV in the United States. The objective of this study is to test the efficacy of a group-based, cognitive-behavioral intervention to reduce risk behavior of substance-using MSM, compared to a randomized attention-control group and a nonrandomized standard HIV-testing group.Participants (n = 1,686 were enrolled in Chicago, Los Angeles, New York City, and San Francisco and randomized to a cognitive-behavioral intervention or attention-control comparison. The nonrandomized group received standard HIV counseling and testing. Intervention group participants received six 2-h group sessions focused on reducing substance use and sexual risk behavior. Attention-control group participants received six 2-h group sessions of videos and discussion of MSM community issues unrelated to substance use, sexual risk, and HIV/AIDS. All three groups received HIV counseling and testing at baseline. The sample reported high-risk behavior during the past 3 mo prior to their baseline visit: 67% reported unprotected anal sex, and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. The three groups significantly (p0.05 from each other at 3-, 6-, and 12-mo follow-up. Outcomes for the 2-arm comparisons were not significantly different at 12-mo follow-up (e.g., unprotected anal sex, odds ratio = 1.14, confidence interval = 0.86-1.51, nor at earlier time points. Similar results were found for each outcome variable in both 2- and 3-arm comparisons.These results for reducing sexual risk behavior of substance-using MSM are consistent with results of intervention trials for other populations, which collectively suggest critical challenges for the field of HIV behavioral interventions. Several mechanisms may contribute to statistically indistinguishable reductions in risk

Cognitive-behavioral group therapy in obsessive-compulsive disorder: a clinical trial

Directory of Open Access Journals (Sweden)

Cordioli Aristides V

2002-01-01

Full Text Available Objective: To develop a cognitive-behavioral group therapy protocol and to verify its efficacy to reduce obsessive-compulsive symptoms. Methods: An open clinical trial with 32 obsessive-compulsive patients was performed, in which a cognitive-behavioral group therapy protocol of 12 weekly sessions of two hours, in 5 consecutive groups, was applied. The severity of symptoms was rated with the Yale-Brown Obsessive-Compulsive (Y-BOCS, Hamilton Anxiety (HAM A and Hamilton Depression (HAM D scales. The patients were followed up for 3 months after the end of the treatment. Results: There was a significant reduction in the scores of Y-BOCS, HAM A and HAM D scales with the treatment regardless the use of anti-obsessive medications. The rate of improved patients (decrease of > or = 35% in Y-BOCS was 78.1%. Two patients (6.25% dropped out from the study. The effect size calculated for the Y-BOCS scale was 1.75. Conclusions: This study suggests that cognitive-behavioral group therapy reduces obsessive-compulsive symptoms. In addition, patients presented good compliance.

The rate coefficients for the processes of (n - n')-mixing in collisions of Rydberg atoms H*(n) with H(1s) atoms

International Nuclear Information System (INIS)

Mihajlov, A A; Ignjatovic, Lj M; Djuric, Z; Ljepojevic, N N

2004-01-01

This paper presents the results of semi-classical calculations of rate coefficients of (n - n')-mixing processes in collisions of Rydberg atoms H*(n) with H(1s) atoms. These processes have been modelled by the mechanism of the resonant energy exchange within the electron component of the H*(n) + H collisional system. The calculations of the rate coefficients, based on this model, were performed for the series of principal quantum numbers, n and n', and atomic, T a , and electronic, T e , temperatures. It was shown that these processes can be of significant influence on the populations of Rydberg atoms in weakly ionized plasmas (ionization degree ∼ -4 ), and therefore have to be included in appropriate models of such plasmas

Phase II trial of paclitaxel and cisplatin in patients with extensive stage small cell lung cancer: Cancer and Leukemia Group B Trial 9430.

Science.gov (United States)

Stinchcombe, Thomas E; Mauer, Ann M; Hodgson, Lydia D; Herndon, James E; Lynch, Thomas J; Green, Mark R; Vokes, Everett E

2008-11-01

Cancer and Leukemia Group B trial 9430 was a randomized phase II trial which investigated the safety and activity of four novel doublets in untreated extensive stage small cell lung cancer. The results of the paclitaxel and cisplatin arm have not been reported. Patients received paclitaxel 230 mg/m followed by cisplatin 75 mg/m on day 1 every 21 days. All patients received granulocyte colony stimulating factor 5 microg/kg/d beginning on day 3 of each cycle. The patient characteristics of the 34 patients assigned to this treatment arm were: median age 61.5 years (range 41-82), male (76%), performance status 0 (41%), 1 (32%), and 2 (26%). An objective response was observed in 23 patients (68%; 95% confidence interval (CI): 49-83%); 2 complete responses (6%) and 21 partial responses (62%). Median progression-free survival time was 5.6 months (95% CI: 4.8-7.1 month), and median overall survival time was 7.7 months (95% CI: 7.2-12.6 months). The 1-year survival rate observed was 29% (95% CI: 15-45%). Grade 3/4 neutropenia and thrombocytopenia was observed in 5 (15%) and 4 (12%) patients, respectively. Two patients developed febrile neutropenia including one patient who died of neutropenic sepsis. Grade 3/4 nonhematologic observed were: sensory neuropathy in eight patients (24%); and hyperglycemia, malaise and nausea were all observed in four patients (12%). Cancer and Leukemia Group B will not pursue further investigation of paclitaxel and cisplatin due to the modest activity and the toxicity observed on this trial.

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

Science.gov (United States)

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

The hnRNP 2H9 gene, which is involved in the splicing reaction, is a multiply spliced gene

DEFF Research Database (Denmark)

Honoré, B

2000-01-01

The hnRNP 2H9 gene products are involved in the splicing process and participate in early heat shock-induced splicing arrest. By combining low/high stringency hybridisation, database search, Northern and Western blotting it is shown that the gene is alternatively spliced into at least six...

Everything moves on: referral trends to a leavers' group in a high secure hospital and trial leave progress of group graduates.

Science.gov (United States)

Adshead, Gwen; Pyszora, Natalie; Wilson, Claire; Gopie, Ramesh; Thomas, Deryk; Smith, Julia; Glorney, Emily; Moore, Estelle; Tapp, James

2017-04-01

Moving on from high secure psychiatric care can be a complex and potentially stressful experience, which may hinder progression. A leavers' group in a UK high secure hospital is offered to support patients with this transition. The aims of this study are to investigate characteristics of patients referred for the leavers' group and compare outcomes for leavers' group graduates with those for patients who never attended a leavers' group for any reason. A retrospective quasi-experimental design was applied to data extracted from various records sources - within and outside the high security hospital. About one-fifth of patients who left the hospital on trial leave during the study were referred to the leavers' group (N = 109). Referred patients were significantly more likely to have either been admitted from another high-security hospital or transferred from prison for treatment and have a diagnosis of paranoid schizophrenia. Patients not referred had a significantly higher rate of previously refusing to participate in groups. There was a tendency for rate of return from trial leave for group graduates to be lower than that of patients who did not attend the leavers' group, but this just failed to reach statistical significance (rate ratio [RR] = 1.04; CI 0.97-1.11). A leavers' group appeared to be a valued therapy option for people who had spent a long time in high secure psychiatric care, or those who continued to require hospital treatment beyond prison tariffs. There was a low return rate from trial leave, which made the evaluation of this outcome difficult. A detailed study into both the reasons for return from trial leave and successes would provide further information on ideal preparation for moving on. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Correlative Studies in Clinical Trials: A Position Statement From the International Thyroid Oncology Group.

Science.gov (United States)

Bible, Keith C; Cote, Gilbert J; Demeure, Michael J; Elisei, Rossella; Jhiang, Sissy; Ringel, Matthew D

2015-12-01

Patients with progressive thyroid cancer in distant metastatic sites represent a population with a need for new therapeutic options. Aspiring to improve the treatment of such patients, the objective of this position statement from the International Thyroid Oncology Group (ITOG) is to clarify the importance of incorporating high-quality correlative studies into clinical trials. ITOG was formed to develop and support high-quality multicenter and multidisciplinary clinical trials for patients with aggressive forms of thyroid cancer. The Correlative Sciences Committee of the ITOG focuses on the quality and types of correlative studies included in ITOG-associated clinical trials. This document represents expert consensus from ITOG regarding this issue based on extensive collective experience in clinical and translational trials informed by basic science. The Correlative Studies Committee identified an international writing group representative of diverse specialties, including basic sciences. Drafts were reviewed by all members of the writing group, the larger committee, and the ITOG board. After consideration of all comments by the writing group and modification of the document, the final document was then approved by the authors and the ITOG board. High-quality correlative studies, which include variety in the types of correlates, should be intrinsic to the design of thyroid cancer clinical trials to offer the best opportunity for each study to advance treatment for patients with advanced and progressive thyroid cancer.

Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge.

Science.gov (United States)

Yang, Xin; Zhou, Yingshun; Li, Jianan; Fu, Li; Ji, Gaosheng; Zeng, Fanya; Zhou, Long; Gao, Wenqian; Wang, Hongning

2016-05-01

Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin-neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV.

Group psychotherapy for eating disorders: A randomized clinical trial and a pre-treatment moderator and mediator analyses

DEFF Research Database (Denmark)

Davidsen, Annika Helgadóttir

disorders in group therapy. We conducted a randomized clinical trial and included 159 adult participants, 156 females and 3 males, diagnosed with bulimia nervosa, binge eating disorder, or eating disorder not otherwise specified according to DSM-IV. Eighty participants were allocated to the experimental...

Design and analysis of group-randomized trials in cancer: A review of current practices.

Science.gov (United States)

Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

2018-06-01

The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9.

Science.gov (United States)

Good, Misty; Sodhi, Chhinder P; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Thomas, Debra L; Vikram, Amit; Bibby, Kyle; Morowitz, Michael J; Firek, Brian; Lu, Peng; Hackam, David J

2014-06-01

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and develops partly from an exaggerated intestinal epithelial immune response to indigenous microbes. There has been interest in administering probiotic bacteria to reduce NEC severity, yet concerns exist regarding infection risk. Mechanisms of probiotic activity in NEC are unknown although activation of the microbial DNA receptor Toll-like receptor-9 (TLR9) has been postulated. We now hypothesize that the Gram-positive bacterium Lactobacillus rhamnosus HN001 can attenuate NEC in small and large animal models, that its microbial DNA is sufficient for its protective effects, and that protection requires activation of the Toll-like receptor 9 (TLR9). We now show that oral administration of live or UV-inactivated Lactobacillus rhamnosus HN001 attenuates NEC severity in newborn mice and premature piglets, as manifest by reduced histology score, attenuation of mucosal cytokine response, and improved gross morphology. TLR9 was required for Lactobacillus rhamnosus-mediated protection against NEC in mice, as the selective decrease of TLR9 from the intestinal epithelium reversed its protective effects. Strikingly, DNA of Lactobacillus rhamnosus HN001 reduced the extent of proinflammatory signaling in cultured enterocytes and in samples of resected human ileum ex vivo, suggesting the therapeutic potential of this probiotic in clinical NEC. Taken together, these findings illustrate that Lactobacillus rhamnosus HN001 is an effective probiotic for NEC via activation of the innate immune receptor TLR9 and that Lactobacillus rhamnosus DNA is sufficient for its protective effects, potentially reducing concerns regarding the infectious risk of this novel therapeutic approach. Copyright © 2014 the American Physiological Society.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

International Nuclear Information System (INIS)

Karlsson, Per; Cole, Bernard F.; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron; Castiglione, Monica; Colleoni, Marco; Gruber, Günther

2016-01-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

Energy Technology Data Exchange (ETDEWEB)

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se [Department of Oncology, Institute of Clinical Sciences, Sahgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Cole, Bernard F. [Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont (United States); Price, Karen N. [International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, Massachusetts (United States); Gelber, Richard D. [International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard T. F. Chan School of Public Health, Boston, Massachusetts (United States); Coates, Alan S. [International Breast Cancer Study Group and University of Sydney, Sydney (Australia); Goldhirsch, Aron [Senior Consultant Breast Cancer, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Castiglione, Monica [International Breast Cancer Study Group, Bern (Switzerland); Colleoni, Marco [Division of Medical Senology, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Gruber, Günther [Institute of Radiotherapy, Klinik Hirslanden, Zürich (Switzerland)

2016-10-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

The rate coefficients for the processes of (n - n')-mixing in collisions of Rydberg atoms H*(n) with H(1s) atoms

Energy Technology Data Exchange (ETDEWEB)

Mihajlov, A A [Institute of Physics, PO Box 57, 11001 Belgrade (Serbia and Montenegro); Ignjatovic, Lj M [Institute of Physics, PO Box 57, 11001 Belgrade (Serbia and Montenegro); Djuric, Z [Silvaco Data Systems, Compass Point, St Ives PE27 5JL (United Kingdom); Ljepojevic, N N [Silvaco Data Systems, Compass Point, St Ives PE27 5JL (United Kingdom)

2004-11-28

This paper presents the results of semi-classical calculations of rate coefficients of (n - n')-mixing processes in collisions of Rydberg atoms H*(n) with H(1s) atoms. These processes have been modelled by the mechanism of the resonant energy exchange within the electron component of the H*(n) + H collisional system. The calculations of the rate coefficients, based on this model, were performed for the series of principal quantum numbers, n and n', and atomic, T{sub a}, and electronic, T{sub e}, temperatures. It was shown that these processes can be of significant influence on the populations of Rydberg atoms in weakly ionized plasmas (ionization degree {approx}<10{sup -4}), and therefore have to be included in appropriate models of such plasmas.

Electronic and atomic structure of the AlnHn+2 clusters

DEFF Research Database (Denmark)

Martinez, Jose Ignacio; Alonso, J.A.

2008-01-01

The electronic and atomic structure of the family of hydrogenated Al clusters AlnHn+2 with n=4-11 has been studied using the density functional theory with the generalized gradient approximation (GGA) for exchange and correlation. All these clusters have substantial gaps between the highest...... a polyhedron of n vertices and n H atoms form strong H-Al terminal bonds; one pair of electrons is involved in each of those bonds. The remaining n+1 electron pairs form a delocalized cloud over the surface of the Al cage. The clusters fulfilling the Wade-Mingos rule have wider HOMO-LUMO gaps...... and are chemically more stable. The trends in the gap have some reflections in the form of the photoabsorption spectra, calculated in the framework of time-dependent density functional theory using the GGA single-particle energies and orbitals and a local density approximation exchange-correlation kernel....

A randomized controlled trial of group Stepping Stones Triple P: a mixed-disability trial.

Science.gov (United States)

Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

2013-09-01

Stepping Stones Triple P (SSTP) is a parenting program designed for families of a child with a disability. The current study involved a randomized controlled trial of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group. Participants were 52 families of children diagnosed with an Autism Spectrum Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The results demonstrated significant improvements in parent-reported child behavior, parenting styles, parental satisfaction, and conflict about parenting. Results among participants were similar despite children's differing impairments. The intervention effect was maintained at 6-month follow-up. The results indicate that GSSTP is a promising intervention for a mixed-disability group. Limitations of the study, along with areas for future research, are also discussed. © FPI, Inc.

Group therapy task training versus individual task training during inpatient stroke rehabilitation: a randomised controlled trial.

Science.gov (United States)

Renner, Caroline Ie; Outermans, Jacqueline; Ludwig, Ricarda; Brendel, Christiane; Kwakkel, Gert; Hummelsheim, Horst

2016-07-01

To compare the efficacy of intensive daily applied progressive group therapy task training with equally dosed individual progressive task training on self-reported mobility for patients with moderate to severe stroke during inpatient rehabilitation. Randomized controlled clinical trial. In-patient rehabilitation center. A total of 73 subacute patients with stroke who were not able to walk without physical assistance at randomisation. Patients were allocated to group therapy task training (GT) or individual task training (IT). Both interventions were intended to improve walking competency and comprised 30 sessions of 90 minutes over six weeks. Primary outcome was the mobility domain of the Stroke Impact Scale (SIS-3.0). Secondary outcomes were the other domains of SIS-3.0, standing balance, gait speed, walking distance, stair climbing, fatigue, anxiety and depression. No adverse events were reported in either arm of the trial. There were no significant differences between groups for the SIS mobility domain at the end of the intervention (Z= -0.26, P = 0.79). No significant differences between groups were found in gait speed improvements (GT:0.38 ±0.23; IT:0.26±0.35), any other gait related parameters, or in non-physical outcomes such as depression and fatigue. Inpatient group therapy task training for patients with moderate to severe stroke is safe and equally effective as a dose-matched individual task training therapy. Group therapy task training may be delivered as an alternative to individual therapy or as valuable adjunct to increase time spent in gait-related activities. © The Author(s) 2015.

Evaluation of comorbidity in 9388 head and neck cancer patients: A national cohort study from the DAHANCA database

DEFF Research Database (Denmark)

Bøje, Charlotte Rotbøl; Dalton, Susanne O; Primdahl, Hanne

2014-01-01

diagnosed from 1992 to 2008 was identified from the DAHANCA-database. Data on comorbidity prior to HNSCC-diagnosis was obtained from the National Patient Registry and adapted to the CCI. RESULTS: By dividing the patients into two groups, we tested and validated which type of comorbidities within the CCI...... in randomized trials to avoid bias. Re-evaluation of the CCI revealed that only six conditions had an impact on survival, and a new modified index to assess comorbidity for HNSCC-patients was developed. The performance of HN-CCI to stratify patients on survival was good and HN-CCI is highly recommended...

The effect of participatory women's groups on birth outcomes in Bangladesh: does coverage matter? Study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Fottrell Edward F

2011-09-01

Full Text Available Abstract Background Progress on neonatal survival has been slow in most countries. While there is evidence on what works to reduce newborn mortality, there is limited knowledge on how to deliver interventions effectively when health systems are weak. Cluster randomized trials have shown strong reductions in neonatal mortality using community mobilisation with women's groups in rural Nepal and India. A similar trial in Bangladesh showed no impact. A main hypothesis is that this negative finding is due to the much lower coverage of women's groups in the intervention population in Bangladesh compared to India and Nepal. For evidence-based policy making it is important to examine if women's group coverage is a main determinant of their impact. The study aims to test the effect on newborn and maternal health outcomes of a participatory women's group intervention with a high population coverage of women's groups. Methods A cluster randomised trial of a participatory women's group intervention will be conducted in 3 districts of rural Bangladesh. As we aim to study a women's group intervention with high population coverage, the same 9 intervention and 9 control unions will be used as in the 2005-2007 trial. These had been randomly allocated using the districts as strata. To increase coverage, 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial. An open cohort of women who are permanent residents in the union in which their delivery or death was identified, is enrolled. Women and their newborns are included after birth, or, if a woman dies during pregnancy, after her death. Excluded are women who are temporary residents in the union in which their birth or death was identified. The primary outcome is neonatal mortality in the last 24 months of the study. A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population. Data on home

Phase 3 trial of domiciliary humidification to mitigate acute mucosal toxicity during radiation therapy for head-and-neck cancer: first report of Trans Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM study.

Science.gov (United States)

Macann, Andrew; Fua, Tsien; Milross, Chris G; Porceddu, Sandro V; Penniment, Michael; Wratten, Chris; Krawitz, Hedley; Poulsen, Michael; Tang, Colin I; Morton, Randall P; Hay, K David; Thomson, Vicki; Bell, Melanie L; King, Madeleine T; Fraser-Browne, Carol L; Hockey, Hans-Ulrich P

2014-03-01

To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H&N) cancer. From June 2007 through June 2011, 210 patients with H&N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher & Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2. There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance. TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility. Copyright © 2014 Elsevier Inc. All rights reserved.

The Effectiveness of Picture Exchange Communication System (PECS) Training for Teachers of Children with Autism: A Pragmatic, Group Randomised Controlled Trial

Science.gov (United States)

Howlin, Patricia; Gordon, R. Kate; Pasco, Greg; Wade, Angie; Charman, Tony

2007-01-01

Objective: To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System (PECS). Method: Design: Group randomised, controlled trial (3 groups: immediate treatment, delayed treatment, no treatment). Participants: 84 elementary school…

[Post-stroke speech disorder treated with acupuncture and psychological intervention combined with rehabilitation training: a randomized controlled trial].

Science.gov (United States)

Wang, Ling; Liu, Shao-ming; Liu, Min; Li, Bao-jun; Hui, Zhen-liang; Gao, Xiang

2011-06-01

To assess the clinical efficacy on post-stroke speech disorder treated with acupuncture and psychological intervention combined with rehabilitation training. The multi-central randomized controlled study was adopted. One hundred and twenty cases of brain stroke were divided into a speech rehabilitation group (control group), a speech rehabilitation plus acupuncture group (observation group 1) and a speech rehabilitation plus acupuncture combined with psychotherapy group (observation group 2), 40 cases in each one. The rehabilitation training was conducted by a professional speech trainer. In acupuncture treatment, speech function area in scalp acupuncture, Jinjin (EX-HN 12) and Yuye (EX-HN 13) in tongue acupuncture and Lianquan (CV 23) were the basic points. The supplementary points were selected according to syndrome differentiation. Bloodletting method was used in combination with acupuncture. Psychotherapy was applied by the physician in psychiatric department of the hospital. The corresponding programs were used in each group. Examination of Aphasia of Chinese of Beijing Hospital was adopted to observe the oral speech expression, listening comprehension and reading and writing ability. After 21-day treatment, the total effective rate was 92.5% (37/40) in observation group 1, 97.5% (39/40) in observation group 2 and 87.5% (35/40) in control group. The efficacies were similar in comparison among 3 groups. The remarkable effective rate was 15.0% (6/40) in observation group 1, 50.0% (20/40) in observation group 2 and 2.5% (1/40) in control group. The result in observation group 2 was superior to the other two groups (Prehabilitation training is obviously advantageous in the treatment of post-stroke speech disorder.

Cognitive Behavioral Analysis System of Psychotherapy as group psychotherapy for chronically depressed inpatients: a naturalistic multicenter feasibility trial.

Science.gov (United States)

Sabaß, Lena; Padberg, Frank; Normann, Claus; Engel, Vera; Konrad, Carsten; Helmle, Kristina; Jobst, Andrea; Worlitz, Andrew; Brakemeier, Eva-Lotta

2017-09-27

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is a relatively new approach in the treatment of chronic depression (CD). Adapted as group psychotherapy for inpatients, CBASP is attracting increasing attention. In this naturalistic multicenter trial, we investigated its feasibility after 10 sessions of CBASP group therapy over a treatment time of at least 5 to a maximum of 10 weeks. Treatment outcome was additionally assessed. Across four centers, 116 inpatients with CD (DSM-IV-TR) attended CBASP group psychotherapy. Feasibility was focused on acceptance, and evaluated for patients and therapists after five (t1) and ten sessions (t2) of group psychotherapy. Observer- and self-rating scales (Hamilton Depression Rating Scale-24 items, HDRS 24 ; Beck Depression Inventory-II, BDI-II; World Health Organization Quality of Life assessment, WHOQOL-BREF) were applied before group psychotherapy (t0) and at t2. Dropouts were low (10.3%). Patients' evaluation improved significantly from t1 to t2 with a medium effect size (d = 0.60). Most of the patients stated that the group had enriched their treatment (75.3%), that the size (74.3%) and duration (72.5%) were 'optimal' and 37.3% wished for a higher frequency. Patients gave CBASP group psychotherapy an overall grade of 2 ('good'). Therapists' evaluation was positive throughout, except for size of the group. Outcome scores of HDRS 24 , BDI-II, and WHOQOL-BREF were significantly reduced from t0 to t2 with medium to large effect sizes (d = 1.48; d = 1.11; d = 0.67). In this naturalistic open-label trial, CBASP, when applied as inpatient group psychotherapy, was well accepted by patients and therapists. The results point towards a clinically meaningful effect of inpatient treatment with CBASP group psychotherapy on depression and quality of life. Other potential factors that could have promoted symptom change were discussed. A future controlled study could investigate the safety and efficacy of CBASP

Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years.

Science.gov (United States)

Lemieux, Julie; Brundage, Michael D; Parulekar, Wendy R; Goss, Paul E; Ingle, James N; Pritchard, Kathleen I; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J

2018-02-20

Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor-positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.

Group schema therapy versus group cognitive behavioral therapy for social anxiety disorder with comorbid avoidant personality disorder: study protocol for a randomized controlled trial.

Science.gov (United States)

Baljé, Astrid; Greeven, Anja; van Giezen, Anne; Korrelboom, Kees; Arntz, Arnoud; Spinhoven, Philip

2016-10-08

Social anxiety disorder (SAD) with comorbid avoidant personality disorder (APD) has a high prevalence and is associated with serious psychosocial problems and high societal costs. When patients suffer from both SAD and APD, the Dutch multidisciplinary guidelines for personality disorders advise offering prolonged cognitive behavioral therapy (CBT). Recently there is increasing evidence for the effectiveness of schema therapy (ST) for personality disorders such as borderline personality disorder and cluster C personality disorders. Since ST addresses underlying personality characteristics and maladaptive coping strategies developed in childhood, this treatment might be particularly effective for patients with SAD and comorbid APD. To our knowledge, there are no studies comparing CBT with ST in this particular group of patients. This superiority trial aims at comparing the effectiveness of these treatments. As an additional goal, predictors and underlying mechanisms of change will be explored. The design of the study is a multicentre two-group randomized controlled trial (RCT) in which the treatment effect of group cognitive behavioral therapy (GCBT) will be compared to that of group schema therapy (GST) in a semi-open group format. A total of 128 patients aged 18-65 years old will be enrolled. Patients will receive 30 sessions of GCBT or GST during a period of approximately 9 months. Primary outcome measures are the Liebowitz Social Anxiety Scale Self-Report (LSAS-SR) for social anxiety disorder and the newly developed Avoidant Personality Disorder Severity Index (AVPDSI) for avoidant personality disorder. Secondary outcome measures are the MINI section SAD, the SCID-II section APD, the Schema Mode Inventory (SMI-2), the Inventory of Depressive Symptomatology Self-Report (IDS-SR), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Difficulties in Emotion Regulation Scale (DERS), the Rosenberg Self-Esteem Scale (RSES) and the Acceptance and Action

Cloud Atlas: Rotational Modulations in the L/T Transition Brown Dwarf Companion HN Peg B

Science.gov (United States)

Zhou, Yifan; Apai, Daniel; Metchev, Stanimir; Lew, Ben W. P.; Schneider, Glenn; Marley, Mark S.; Karalidi, Theodora; Manjavacas, Elena; Bedin, Luigi R.; Cowan, Nicolas B.;

Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial

Directory of Open Access Journals (Sweden)

Chen Yuan-Fang

2013-01-01

Full Text Available Abstract Background More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que and KID-6 (Zhao Hai, which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu with BL-23 (Shen Shu and BL-19 (Dan Shu with N-HN-54 (An Mian. The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. Methods/design In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQIand the Hamilton rating scale(HAMD for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. Discussion A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. Trial registration The trial was registered in

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

Science.gov (United States)

Nishi, Daisuke; Su, Kuan-Pin; Usuda, Kentaro; Chiang, Yi-Ju Jill; Guu, Tai-Wei; Hamazaki, Kei; Nakaya, Naoki; Sone, Toshimasa; Sano, Yo; Tachibana, Yoshiyuki; Ito, Hiroe; Isaka, Keiich; Hashimoto, Kenji; Hamazaki, Tomohito; Matsuoka, Yutaka J

2016-09-15

Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. Clinicaltrials.gov: NCT

Personality disorder moderates outcome in short- and long-term group analytic psychotherapy: A randomized clinical trial.

Science.gov (United States)

Lorentzen, Steinar; Ruud, Torleif; Fjeldstad, Anette; Høglend, Per A

2015-06-01

In a randomized clinical trial, short- and long-term psychodynamic group psychotherapy (STG and LTG, respectively) schedules were equally effective for the 'typical' patient during a 3-year study period. Although several studies have reported good effects for patients with personality disorders (PD) in diverse forms of psychotherapy, the significance of treatment duration is unclear. Therefore, we tested the hypothesis that PD patients would improve more during and after LTG than STG. A randomized, longitudinal, prospective study contrasting the outcomes during and after short- and long-term dynamic group psychotherapies. One hundred and sixty-seven outpatients with mood disorders, anxiety disorders, or PD were randomized to STG or LTG (respectively, 20 or 80 weekly sessions of 90 min each). Outcome measures are as follows: symptoms (SCL-90-R), interpersonal problems (IIP-C), and psychosocial functioning (GAF split version: GAF-Symptom and GAF-Function). PD pathology (number of PD criteria items) was selected a priori as a putative moderator of treatment effects. Change during the 3-year study period was assessed using linear mixed models. The study was registered at ClinicalTrials.gov as NCT 00021417. Our hypothesis was supported, as patients with PD improved significantly more regarding all outcome variables in LTG than STG. For patients without PD, the rate of change was similar across 3 years; however, the rate of change in symptoms and interpersonal problems was higher in STG during the first 6 months. The effectiveness of LTG is higher for patients with co-morbid PD. Patients without PD do not appear to experience additional gain from LTG. Clinical implications: LTG demonstrates better effectiveness than STG for patients with personality disorder co-morbidity (PD). Patients without PD do not appear to experience additional gain from attending LTG. Correct initial allocation to treatment duration may prevent disruptive breaks in relationships and lead to both

The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up.

Science.gov (United States)

Castiglione-Gertsch, M; Johnsen, C; Goldhirsch, A; Gelber, R D; Rudenstam, C M; Collins, J; Lindtner, J; Hacking, A; Cortes-Funes, H; Forbes, J

1994-10-01

Adjuvant systemic therapy prolongs disease-free and overall survival in both pre- and postmenopausal patients. Available data shown benefit from multi-agent chemotherapy, prolonged tamoxifen treatment, and ovarian ablation, and that the combination of chemo- and endocrine therapy might be advantageous. In 1978 the International (Ludwig) Breast Cancer Study Group (IBCSG) initiated four complementary randomized controlled clinical trials to evaluate the roles of chemo-endocrine combinations or endocrine therapy alone in specific populations defined by risk (for pre- and perimenopausal patients) or by age (for postmenopausal patients). The results at 10 and 13 years' median follow-up for these trials are summarized in this report and are compared to those of the Overview meta-analysis with regard to chemo-endocrine or endocrine therapy combinations. Furthermore, types of first relapses by sites and second malignant diseases are reported. 1601 evaluable patients with node positive disease were included into the studies I-IV. In Trial I (491 premenopausal patients with 1-3 positive axillary nodes) we studied the addition of low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate-fluorouracil (CMF) combination. In Trial II 327 premenopausal patients with four or more positive axillary nodes were randomized to one year CMFp or to a surgical oophorectomy followed by CMFp. In Trial III (463 postmenopausal patients 65 years old or younger), combined chemoendocrine therapy (one year of CMFp plus tamoxifen (T)) was compared to endocrine therapy (1 year of p + T) or to surgery alone. In Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by surgery alone or by surgery followed by 1 year prednisone and tamoxifen. In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be administered compared with CMF alone. Despite this increased dose intensity, 13-year disease-free survival (DFS) and overall survival (OS) were similar

Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

Directory of Open Access Journals (Sweden)

Ghoreishi Zohreh

2012-08-01

Full Text Available Abstract Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN. Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70% of the group taking omega-3 fatty acid supplement (n = 30 did not develop PN while it was 40.7%( 11 patients in the placebo group(n = 27. A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88, p = 0.029. There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02, p = 0.054. Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295

Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

Directory of Open Access Journals (Sweden)

Mehmet Yabas

Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

Does intermittent pneumatic compression reduce the risk of post stroke deep vein thrombosis? The CLOTS 3 trial: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Dennis Martin

2012-03-01

Full Text Available Abstract Background Approximately 80,000 patients each year are admitted to UK hospitals with an acute stroke and are immobile. At least 10% will develop a proximal Deep Vein Thrombosis in the first month and 1.5% a pulmonary embolus. Although hydration, antiplatelet treatment and early mobilisation may reduce the risk of deep vein thrombosis, there are currently no preventive strategies which have been clearly shown to be both effective and safe. Anticoagulation increases the risks of bleeding and compression stockings are ineffective. Systematic reviews of small randomized trials of intermittent pneumatic compression have shown that this reduces the risk of deep vein thrombosis in patients undergoing surgery, but that there are few data concerning its use after stroke. The CLOTS trial 3 aims to determine whether, compared with best medical care, best medical care plus intermittent pneumatic compression in immobile stroke patients reduces the risk of proximal deep vein thrombosis. Methods/Design CLOTS Trial 3 is a parallel group multicentre trial; with centralized randomisation (minimisation to ensure allocation concealment. Over 80 centres in the UK will recruit 2800 immobile stroke patients within the first 3 days of their hospital admission. Patients will be allocated to best medical care or best medical care plus intermittent pneumatic compression. Ultrasonographers will perform a Compression Duplex Ultrasound Scan to detect deep vein thrombosis in each treatment group at about 7-10 days and 25-30 days. The primary outcome cluster includes symptomatic or asymptomatic deep vein thrombosis in the popliteal or femoral veins detected on either scan. Patients are then followed up by postal or telephone questionnaire at 6 months from randomisation to detect later symptomatic deep vein thrombosis and pulmonary emboli and to establish their functional outcome (Oxford handicap scale and quality of life (EQ5D-3 L. The ultrasonographers performing the

Genome sequence of foot-and-mouth disease virus outside the 3A region is also responsible for virus replication in bovine cells.

Science.gov (United States)

Ma, Xueqing; Li, Pinghua; Sun, Pu; Lu, Zengjun; Bao, Huifang; Bai, Xingwen; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

2016-07-15

The deletion of residues 93-102 in non-structure protein 3A of foot-and-mouth disease virus (FMDV) is associated with the inability of FMDV to grow in bovine cells and attenuated virulence in cattle.Whereas, a previously reported FMDV strain O/HKN/21/70 harboring 93-102 deletion in 3A protein grew equally well in bovine and swine cells. This suggests that changes inFMDV genome sequence, in addition to 93-102 deletion in 3A, may also affectthe viral growth phenotype in bovine cellsduring infection and replication.However, it is nuclear that changes in which region (inside or outside of 3A region) influences FMDV growth phenotype in bovine cells.In this study, to determine the region in FMDV genomeaffecting viral growth phenotype in bovine cells, we constructed chimeric FMDVs, rvGZSB-HKN3A and rvHN-HKN3A, by introducing the 3A coding region of O/HKN/21/70 into the context of O/SEA/Mya-98 strain O/GZSB/2011 and O Cathay topotype strain O/HN/CHA/93, respectively, since O/GZSB/2011 containing full-length 3A protein replicated well in bovine and swine cells, and O/HN/CHA/93 harboring 93-102 deletion in 3A protein grew poorly in bovine cells.The chimeric virusesrvGZSB-HKN3A and rvHN-HKN3A displayed growth properties and plaque phenotypes similar to those of the parental virus rvGZSB and rv-HN in BHK-21 and primary fetal porcine kidney (FPK) cells. However, rvHN-HKN3A and rv-HN replicated poorly in primary fetal bovine kidney (FBK) cells with no visible plaques, and rvGZSB-HKN3A exhibited lower growth rate and smaller plaque size phenotypes than those of the parental virus in FBK cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the difference present in FMDV genome sequence outside the 3A coding region also have influence on FMDV replication ability in bovine cells. Copyright © 2016 Elsevier B.V. All rights reserved.

CULTIVATION OF THE EDIBLE MUSHROOM OUDEMANSIELLA CANARII (JUNGH. HÖHN. IN LIGNOCELLULOSIC SUBSTRATES Cultivo do cogumelo comestível Oudemansiella canarii (Jungh. Höhn. em substratos lignocelulósicos

Directory of Open Access Journals (Sweden)

Marcelo José Silveira Ruegger

2001-10-01

Full Text Available The edible mushroom Oudemansiella canarii (Jungh. Höhn is common in the Brazilian territory, being found in different biomas, where they colonize several plant species. In this study, the O. canarii cultivation was evaluated in polypropilene bags containing sugar-cane bagasse (200 g or eucalyptus sawdust (200 g supplemented with wheat bran (50 g. The composts were sterilized at 121ºC for 1 hour, after cooling they were inoculated with 3 g of spawn and then remained incubated at 25ºC until the basidiomata primordia formation. The mushrooms, harvested after the pilei opening, presented varied sizes reaching 9 cm of diameter and 10 cm of height. The fresh mushrooms presented mild taste and soft consistency. When kept at 4ºC, they maintained good appearance and good consistency for 7 days. In a period of 60 days, the largest basidiomata production was obtained in the compost with sugar-cane bagasse, showing greater productivity (4.47% ± 1.34, biological efficiency (55.66% ± 20.41 and compost consumption (38.78% ± 4.59 averages. Wilcoxon's non-parametric statistical analysis used to compare the biomass production in the two composts, showed significant differences at 5% significance level.O cogumelo comestível Oudemansiella canarii (Jungh. Höhn., é comum no território brasileiro, sendo encontrado em diferentes biomas, onde colonizam várias espécies vegetais. Neste estudo, o cultivo deste basidiomiceto foi realizado em sacos plásticos contendo bagaço de cana-de-açúcar (200 g ou serragem de eucalipto (200 g suplementados com farelo de trigo (50 g. Os substratos foram esterilizados a 121ºC por 1 hora, inoculados com 3 g de grãos de trigo colonizados por micélio do fungo e permaneceram incubados a 25ºC até a formação dos primórdios dos basidiomas. Os cogumelos, colhidos após a abertura do píleo, apresentaram tamanhos variados chegando a atingir 9 cm de diâmetro por 10 cm de altura. Os cogumelos frescos apresentaram paladar

Estimates of Intraclass Correlation Coefficients from Longitudinal Group-Randomized Trials of Adolescent HIV/STI/Pregnancy Prevention Programs

Science.gov (United States)

Glassman, Jill R.; Potter, Susan C.; Baumler, Elizabeth R.; Coyle, Karin K.

2015-01-01

Introduction: Group-randomized trials (GRTs) are one of the most rigorous methods for evaluating the effectiveness of group-based health risk prevention programs. Efficiently designing GRTs with a sample size that is sufficient for meeting the trial's power and precision goals while not wasting resources exceeding them requires estimates of the…

Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial.

Science.gov (United States)

Lipton, Jeffrey H; Chuah, Charles; Guerci-Bresler, Agnès; Rosti, Gianantonio; Simpson, David; Assouline, Sarit; Etienne, Gabriel; Nicolini, Franck E; le Coutre, Philipp; Clark, Richard E; Stenke, Leif; Andorsky, David; Oehler, Vivian; Lustgarten, Stephanie; Rivera, Victor M; Clackson, Timothy; Haluska, Frank G; Baccarani, Michele; Cortes, Jorge E; Guilhot, François; Hochhaus, Andreas; Hughes, Timothy; Kantarjian, Hagop M; Shah, Neil P; Talpaz, Moshe; Deininger, Michael W

2016-05-01

Ponatinib has shown potent activity against chronic myeloid leukaemia that is resistant to available treatment, although it is associated with arterial occlusion. We investigated whether this activity and safety profile would result in superior outcomes compared with imatinib in previously untreated patients with chronic myeloid leukaemia. The Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) study was a randomised, open-label, phase 3 trial designed to assess the efficacy and safety of ponatinib, compared with imatinib, in newly diagnosed patients with chronic-phase chronic myeloid leukaemia. Patients from 106 centres in 21 countries were randomly assigned (1:1, with stratification by Sokal score at diagnosis) using an interactive voice and web response system to receive oral ponatinib (45 mg) or imatinib (400 mg) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met. Eligible patients were at least 18 years of age, within 6 months of diagnosis, and Philadelphia chromosome-positive by cytogenetic assessment, with Eastern Cooperative Oncology Group performance status of 0-2, and had not previously been treated with tyrosine kinase inhibitors. The primary endpoint was major molecular response at 12 months. Patients who remained on study and had molecular assessments at specified timepoints were studied at those timepoints. Safety analyses included all treated patients, as per study protocol. This trial is registered with ClinicalTrials.gov, number NCT01650805. Between Aug 14, 2012, and Oct 9, 2013, 307 patients were randomly assigned to receive ponatinib (n=155) or imatinib (n=152). The trial was terminated early, on Oct 17, 2013, following concerns about vascular adverse events observed in patients given ponatinib in other trials. Trial termination limited assessment of the primary endpoint of major molecular response at 12 months, as only 13 patients in the imatinib group and ten patients in the

Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years

Science.gov (United States)

Brundage, Michael D.; Parulekar, Wendy R.; Goss, Paul E.; Ingle, James N.; Pritchard, Kathleen I.; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J.

2018-01-01

Purpose MA.17R was a Canadian Cancer Trials Group–led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor–positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL. PMID:29328860

Theoretical study of stability and superconductivity of ScHn (n =4 -8 ) at high pressure

Science.gov (United States)

Qian, Shifeng; Sheng, Xiaowei; Yan, Xiaozhen; Chen, Yangmei; Song, Bo

2017-09-01

The synthesis of hydrogen sulfides, with the potential of high-temperature superconductivity, was recently proposed at high Tc = 203 K. It motivated us to employ an ab initio approach for the predictions of crystal structures to find the stable scandium hydrides. In addition to the earlier predicted three stoichiometries of ScH, ScH2, and ScH3, we identify three other metallic stoichiometries of ScH4, ScH6, and ScH8, which show superconductivity at significantly higher temperatures. The phases of ScH4 and ScH6, whose stability does not require extremely high pressures (ZPE), are primarily ionic compounds containing exotic quasimolecular H2 arrangements. The present electron-phonon calculations revealed the superconductive potential of ScH4 and ScH6 with estimated Tc of 98 K and 129 K at 200 GPa and 130 GPa, respectively. The superconductivity of ScHn stems from the large electron-phonon coupling associated with the wagging, bending, and intermediate-frequency modes attributed mainly to the hydrogen atoms.

Methodology Series Module 4: Clinical Trials.

Science.gov (United States)

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

[Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

Science.gov (United States)

Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

2010-08-01

The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

Evolution of L -shell photoabsorption of the molecular-ion series Si Hn + (n =1 ,2 ,3 ): Experimental and theoretical studies

Science.gov (United States)

Kennedy, E. T.; Mosnier, J.-P.; van Kampen, P.; Bizau, J.-M.; Cubaynes, D.; Guilbaud, S.; Carniato, S.; Puglisi, A.; Sisourat, N.

2018-04-01

We report on complementary laboratory and theoretical investigations of the 2 p photoexcitation cross sections for the molecular-ion series Si Hn + (n =1 ,2 ,3 ) near the L -shell threshold. The experiments used an electron cyclotron resonance (ECR) plasma molecular-ion source coupled with monochromatized synchrotron radiation in a merged-beam configuration. For all three molecular ions, the S i2 + decay channel appeared dominant, suggesting similar electronic and nuclear relaxation patterns involving resonant Auger and dissociation processes, respectively. The total yields of the S i2 + products were recorded and put on absolute cross-section scales by comparison with the spectrum of the S i+ parent atomic ion. Interpretation of the experimental spectra ensued from a comparison with total photoabsorption cross-sectional profiles calculated using ab initio configuration interaction theoretical methods inclusive of vibrational dynamics and contributions from inner-shell excitations in both ground and valence-excited electronic states. The spectra, while broadly similar for all three molecular ions, moved towards lower energies as the number of screening hydrogen atoms increased from one to three. They featured a wide and shallow region below ˜107 eV due to 2 p →σ* transitions to dissociative states, and intense and broadened peaks in the ˜107 -113 -eV region merging into sharp Rydberg series due to 2 p →n δ ,n π transitions converging on the LII ,III limits above ˜113 eV . This overall spectral shape is broadly replicated by theory in each case, but the level of agreement does not extend to individual resonance structures. In addition to the fundamental interest, the work should also prove useful for the understanding and modeling of astronomical and laboratory plasma sources where silicon hydride molecular species play significant roles.

CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials

DEFF Research Database (Denmark)

Moher, David; Hopewell, Sally; Schulz, Kenneth F

2010-01-01

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate...... that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed......, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials....

Group sequential and confirmatory adaptive designs in clinical trials

CERN Document Server

Wassmer, Gernot

2016-01-01

This book provides an up-to-date review of the general principles of and techniques for confirmatory adaptive designs. Confirmatory adaptive designs are a generalization of group sequential designs. With these designs, interim analyses are performed in order to stop the trial prematurely under control of the Type I error rate. In adaptive designs, it is also permissible to perform a data-driven change of relevant aspects of the study design at interim stages. This includes, for example, a sample-size reassessment, a treatment-arm selection or a selection of a pre-specified sub-population. Essentially, this adaptive methodology was introduced in the 1990s. Since then, it has become popular and the object of intense discussion and still represents a rapidly growing field of statistical research. This book describes adaptive design methodology at an elementary level, while also considering designing and planning issues as well as methods for analyzing an adaptively planned trial. This includes estimation methods...

Group hypnosis vs. relaxation for smoking cessation in adults: a cluster-randomised controlled trial

Science.gov (United States)

2013-01-01

Background Despite the popularity of hypnotherapy for smoking cessation, the efficacy of this method is unclear. We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers. Methods This was a cluster-randomised, parallel-group, controlled trial. A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers (median size = 11). Participants were 223 smokers consuming ≥ 5 cigarettes per day, willing to quit and not using cessation aids (47.1% females, M = 37.5 years [SD = 11.8], 86.1% Swiss). Nicotine withdrawal, smoking abstinence self-efficacy, and adverse reactions were assessed at a 2-week follow-up. The main outcome, self-reported 30-day point prevalence of smoking abstinence, was assessed at a 6-month follow up. Abstinence was validated through salivary analysis. Secondary outcomes included number of cigarettes smoked per day, smoking abstinence self-efficacy, and nicotine withdrawal. Results At the 6-month follow up, 14.7% in the hypnosis group and 17.8% in the relaxation group were abstinent. The intervention had no effect on smoking status (p = .73) or on the number of cigarettes smoked per day (p = .56). Smoking abstinence self-efficacy did not differ between the interventions (p = .14) at the 2-week follow-up, but non-smokers in the hypnosis group experienced reduced withdrawal (p = .02). Both interventions produced few adverse reactions (p = .81). Conclusions A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session. Trial registration Current Controlled Trials ISRCTN72839675. PMID:24365274

Mandibular advancement appliance for obstructive sleep apnoea: results of a randomised placebo controlled trial using parallel group design

DEFF Research Database (Denmark)

Petri, N.; Svanholt, P.; Solow, B.

2008-01-01

The aim of this trial was to evaluate the efficacy of a mandibular advancement appliance (MAA) for obstructive sleep apnoea (OSA). Ninety-three patients with OSA and a mean apnoea-hypopnoea index (AHI) of 34.7 were centrally randomised into three, parallel groups: (a) MAA; (b) mandibular non......). Eighty-one patients (87%) completed the trial. The MAA group achieved mean AHI and Epworth scores significantly lower (P group and the no-intervention group. No significant differences were found between the MNA group and the no-intervention group. The MAA group had...

Standard versus prosocial online support groups for distressed breast cancer survivors: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Golant Mitch

2011-08-01

Full Text Available Abstract Background The Internet can increase access to psychosocial care for breast cancer survivors through online support groups. This study will test a novel prosocial online group that emphasizes both opportunities for getting and giving help. Based on the helper therapy principle, it is hypothesized that the addition of structured helping opportunities and coaching on how to help others online will increase the psychological benefits of a standard online group. Methods/Design A two-armed randomized controlled trial with pretest and posttest. Non-metastatic breast cancer survivors with elevated psychological distress will be randomized to either a standard facilitated online group or to a prosocial facilitated online group, which combines online exchanges of support with structured helping opportunities (blogging, breast cancer outreach and coaching on how best to give support to others. Validated and reliable measures will be administered to women approximately one month before and after the interventions. Self-esteem, positive affect, and sense of belonging will be tested as potential mediators of the primary outcomes of depressive/anxious symptoms and sense of purpose in life. Discussion This study will test an innovative approach to maximizing the psychological benefits of cancer online support groups. The theory-based prosocial online support group intervention model is sustainable, because it can be implemented by private non-profit or other organizations, such as cancer centers, which mostly offer face-to-face support groups with limited patient reach. Trial Registration ClinicalTrials.gov: NCT01396174

Group treatments for sensitive health care problems: a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence

Directory of Open Access Journals (Sweden)

Clark MD

2009-09-01

Full Text Available Abstract Background The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment. Methods A pragmatic, multi-centre randomised controlled trial in five British National Health Service physiotherapy departments. 174 women with stress and/or urge incontinence were randomised to receive treatment from a physiotherapist delivered in a group or individual setting over three weekly sessions. Outcome were measured as Symptom Severity Index; Incontinence-related Quality of Life questionnaire; National Health Service costs, and out of pocket expenses. Results The majority of women expressed no preference (55% or preference for individual treatment (36%. Treatment attendance was good, with similar attendance with both service delivery models. Overall, there were no statistically significant differences in symptom severity or quality of life outcomes between the models. Over 85% of women reported a subjective benefit of treatment, with a slightly higher rating in the individual compared with the group setting. When all health care costs were considered, average cost per patient was lower for group sessions (Mean cost difference £52.91 95%, confidence interval (£25.82 - £80.00. Conclusion Indications are that whilst some women may have an initial preference for individual treatment, there are no substantial differences in the symptom, quality of life outcomes or non-attendance. Because of the significant difference in mean cost, group treatment is recommended. Trial Registration Trial Registration number: ISRCTN 16772662

Effectiveness of group music therapy versus recreational group singing for depressive symptoms of elderly nursing home residents: pragmatic trial.

Science.gov (United States)

Werner, Jasmin; Wosch, Thomas; Gold, Christian

2017-02-01

Several studies have suggested positive effects of music therapy in dementia, but research on age-related depression has been limited and of insufficient quality. The aim of this study was to examine the effect of interactive group music therapy versus recreational group singing on depressive symptoms in elderly nursing home residents. Residents of two German nursing homes with sufficient length of stay who were not bedridden were invited to participate in a pragmatic trial. A total of 117 participants, grouped into four clusters (based on their wards), were randomised to interactive group music therapy (n = 62; 20 units of 40 minutes, 2×/week) or recreational group singing (n = 55; 10 units of 90 minutes, 1×/week). The level of depressive symptoms was assessed using the Montgomery-Åsberg Depression Rating Scale at baseline (47% with at least mild depression) and follow-up in the 6th and 12th weeks. There was no blinding of assessors. The level of depressive symptoms improved significantly more in those assigned to music therapy (n = 60) than in recreational singing (n = 53), both in 6th week (mean difference 3.0 scores, 95% CI 1.21 to 4.79, p = 0.001) and 12th week (mean difference 4.50 scores, 95% CI 2.51 to 6.50, p elderly people in nursing homes more effectively than recreational singing.

Synthesis IR spectra and crystal structure of N-(4-bromophenyl)-1,1,1-trifluoroacetyl-acetonimine HN(C6H4Br)xC(Me)xCHxC(CF3)xO(HL) and its molecular complex with tungstene(4) oxotetrachloride WOCl4xHL

International Nuclear Information System (INIS)

Sergienko, V.S.; Ilyukhin, A.B.; Abramenko, V.L.

1997-01-01

Synthesis, IR spectroscopic and X-ray diffraction studies of compound HN(C 6 H 4 Br)xC(Me)xCHxC(CF 3 )xO(HL) (1) and of molecular complex WOCl 4 xHL(2) have been conducted. In 1 and 2 HL molecule exists in ketoamine tautomeric form (acid proton is localized at nitrogen atom). The results of 1 and 2 study are compared with literature data on structures of HL type molecules and Mo(6) molecular complexes with β-enaminevinylketone, as well as with the structure of chelate compound WOCl 3 L 1 , where L 1 - anion of N-phenylacetylacetonimine

Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

NARCIS (Netherlands)

de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

Sustained and "sleeper" effects of group metacognitive training for schizophrenia: a randomized clinical trial.

Science.gov (United States)

Moritz, Steffen; Veckenstedt, Ruth; Andreou, Christina; Bohn, Francesca; Hottenrott, Birgit; Leighton, Lucy; Köther, Ulf; Woodward, Todd S; Treszl, András; Menon, Mahesh; Schneider, Brooke C; Pfueller, Ute; Roesch-Ely, Daniela

2014-10-01

Cognitive interventions increasingly complement psychopharmacological treatment to enhance symptomatic and functional outcome in schizophrenia. Metacognitive training (MCT) is targeted at cognitive biases involved in the pathogenesis of delusions. To examine the long-term efficacy of group MCT for schizophrenia in order to explore whether previously established effects were sustained. A 2-center, randomized, controlled, assessor-blind, parallel group trial was conducted. A total of 150 inpatients or outpatients with DSM-IV diagnoses of schizophrenia spectrum disorders were enrolled. All patients were prescribed antipsychotic medication. The second follow-up assessment took place 3 years later after the intervention phase was terminated. Group MCT targeting cognitive biases vs neuropsychological training (COGPACK). Patients received a maximum of 16 sessions. The primary outcome measure was a delusion score derived from the Positive and Negative Syndrome Scale (PANSS). The PANSS positive syndrome and total scores, the Psychotic Symptom Rating Scales, the jumping to conclusions bias, self-esteem, and quality of life served as secondary outcome measures. The intention-to-treat analyses demonstrated that patients in the MCT group had significantly greater reductions in the core PANSS delusion score, after 3 years compared with the control group (η2partial = .037; P = .05). Among the secondary outcomes, the intention-to-treat analyses also demonstrated that patients in the MCT group had significantly greater reductions in the PANSS positive syndrome score (η2partial = .055; P = .02) and the Psychotic Symptom Rating Scales delusion score (η2partial = .109; P = .001). Significant group differences at the 3-year follow-up were also found on measures of self-esteem and quality of life, which did not distinguish groups at earlier assessment points. Attention was improved in the neuropsychological training group relative to the MCT group. The

Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

Science.gov (United States)

O'Neil, Patrick M; Aroda, Vanita R; Astrup, Arne; Kushner, Robert; Lau, David C W; Wadden, Thomas A; Brett, Jason; Cancino, Ana-Paula; Wilding, John P H

2017-11-01

Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m 2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no

Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

Science.gov (United States)

Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

2017-01-01

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

Methodology series module 4: Clinical trials

Directory of Open Access Journals (Sweden)

Maninder Singh Setia

2016-01-01

Full Text Available In a clinical trial, study participants are (usually divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care. We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1 parallel study design, (2 cross-over design, (3 factorial design, and (4 withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials. Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials: The OMERACT Safety Working Group.

Science.gov (United States)

Klokker, Louise; Tugwell, Peter; Furst, Daniel E; Devoe, Dan; Williamson, Paula; Terwee, Caroline B; Suarez-Almazor, Maria E; Strand, Vibeke; Woodworth, Thasia; Leong, Amye L; Goel, Niti; Boers, Maarten; Brooks, Peter M; Simon, Lee S; Christensen, Robin

2017-12-01

Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved. Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions. The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

Effectiveness of group reminiscence for improving wellbeing of institutionalized elderly adults: study protocol for a randomized controlled trial.

Science.gov (United States)

Gaggioli, Andrea; Scaratti, Chiara; Morganti, Luca; Stramba-Badiale, Marco; Agostoni, Monica; Spatola, Chiara A M; Molinari, Enrico; Cipresso, Pietro; Riva, Giuseppe

2014-10-25

Group reminiscence therapy is a brief and structured intervention in which participants share personal past events with peers. This approach has been shown to be promising for improving wellbeing and reducing depressive symptoms among institutionalized older adults. However, despite the considerable interest in reminiscence group therapy, controlled studies to determine its specific benefits as compared to generic social interactions with peers (group conversations about everyday subjects) are still lacking. We have designed a randomized controlled trial aimed at comparing the effects of group reminiscence therapy with those of group recreational activity on the psychological wellbeing of an institutionalized sample of older adults. The study includes two groups of 20 hospitalized elderly participants: the experimental group and the control group. Participants included in the experimental group will receive six sessions of group reminiscence therapy, while the control group will participate in a recreational group discussion. A repeated-measures design will be used post-intervention and three months post-intervention to evaluate changes in self-reported outcome measures of depressive symptoms, self-esteem, life satisfaction, and quality of life from baseline. The protocol of a study aimed at examining the specific effects of group reminiscence therapy on psychological wellbeing, depression, and quality of life among institutionalized elderly people is described. It is expected that the outcomes of this trial will contribute to our knowledge about the process of group reminiscence, evaluate its effectiveness in improving psychological wellbeing of institutionalized individuals, and identify the best conditions for optimizing this approach. This trial was registered with ClinicalTrials.gov (registration number: NCT02077153) on 31 January 2014.

Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

Science.gov (United States)

Badings, E A; Remkes, W S; Dambrink, J-H E; The, S H K; Van Wijngaarden, J; Tjeerdsma, G; Rasoul, S; Timmer, J R; van der Wielen, M L J; Lok, D J A; van 't Hof, A W J

2016-03-01

To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early ( 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line.

Science.gov (United States)

Priesnitz, Christian; Niklas, Jens; Rose, Thomas; Sandig, Volker; Heinzle, Elmar

2012-03-01

This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth. Copyright © 2012 Elsevier Inc. All rights reserved.

Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

Science.gov (United States)

Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

2014-01-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

Informed consent in oncology clinical trials: A Brown University Oncology Research Group prospective cross-sectional pilot study.

Directory of Open Access Journals (Sweden)

Andrew Schumacher

Full Text Available Informed consent forms (ICFs for oncology clinical trials have grown increasingly longer and more complex. We evaluated objective understanding of critical components of informed consent among patients enrolling in contemporary trials of conventional or novel biologic/targeted therapies.We evaluated ICFs for cancer clinical trials for length and readability, and patients registered on those studies were asked to complete a validated 14-question survey assessing their understanding of key characteristics of the trial. Mean scores were compared in groups defined by trial and patient characteristics.Fifty patients, of whom half participated in trials of immunotherapy or biologic/targeted agents and half in trials of conventional therapy, completed the survey. On average, ICFs for industry-originated trials (N = 9 trials were significantly longer (P < .0001 and had lower Flesch ease-of-reading scores (P = .003 than investigator-initiated trials (N = 11. At least 80% of patients incorrectly responded to three key questions which addressed the experimental nature of their trial therapy, its purported efficacy and potential risks relative to alternative treatments. The mean objective understanding score was 76.9±8.8, but it was statistically significantly lower for patients who had not completed high school (P = .011. The scores did not differ significantly by type of cancer therapy (P = .12 or trial sponsor (P = .38.Many participants enrolled on cancer trials had poor understanding of essential elements of their trial. In order to ensure true informed consent, innovative approaches, such as expanded in-person counseling adapted to the patient's education level or cultural characteristics should be evaluated across socio-demographic groups.Clinicaltrials.gov NCT01772511.

Efficacy of group psychotherapy for social anxiety disorder: A meta-analysis of randomized-controlled trials.

Science.gov (United States)

Barkowski, Sarah; Schwartze, Dominique; Strauss, Bernhard; Burlingame, Gary M; Barth, Jürgen; Rosendahl, Jenny

2016-04-01

Group psychotherapy for social anxiety disorder (SAD) is an established treatment supported by findings from primary studies and earlier meta-analyses. However, a comprehensive summary of the recent evidence is still pending. This meta-analysis investigates the efficacy of group psychotherapy for adult patients with SAD. A literature search identified 36 randomized-controlled trials examining 2171 patients. Available studies used mainly cognitive-behavioral group therapies (CBGT); therefore, quantitative analyses were done for CBGT. Medium to large positive effects emerged for wait list-controlled trials for specific symptomatology: g=0.84, 95% CI [0.72; 0.97] and general psychopathology: g=0.62, 95% CI [0.36; 0.89]. Group psychotherapy was also superior to common factor control conditions in alleviating symptoms of SAD, but not in improving general psychopathology. No differences appeared for direct comparisons of group psychotherapy and individual psychotherapy or pharmacotherapy. Hence, group psychotherapy for SAD is an efficacious treatment, equivalent to other treatment formats. Copyright © 2016 Elsevier Ltd. All rights reserved.

TEACCH-based group social skills training for children with high-functioning autism: a pilot randomized controlled trial.

Science.gov (United States)

Ichikawa, Kayoko; Takahashi, Yoshimitsu; Ando, Masahiko; Anme, Tokie; Ishizaki, Tatsuro; Yamaguchi, Hinako; Nakayama, Takeo

2013-10-01

Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted. Eleven children with HFA, aged 5-6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent-child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS). Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers' satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not. We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses. UMIN000004560.

Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial.

Science.gov (United States)

Chi, Kim N; Higano, Celestia S; Blumenstein, Brent; Ferrero, Jean-Marc; Reeves, James; Feyerabend, Susan; Gravis, Gwenaelle; Merseburger, Axel S; Stenzl, Arnulf; Bergman, Andries M; Mukherjee, Som D; Zalewski, Pawel; Saad, Fred; Jacobs, Cindy; Gleave, Martin; de Bono, Johann S

2017-04-01

Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer. SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries. Patients were eligible for participation if they had: metastatic castration-resistant prostate cancer and had received no previous chemotherapy; prostate-specific antigen greater than 5 ng/mL; and a Karnofsky performance score of 70% or higher. Patients were randomly assigned 1:1 centrally to either the docetaxel, prednisone, and custirsen combination or docetaxel and prednisone alone. Patients were not masked to treatment allocation. Randomisation was stratified by opioid use for cancer-related pain and radiographic evidence of progression. All patients received docetaxel 75 mg/m 2 intravenously with 5 mg of prednisone orally twice daily. Patients assigned docetaxel, prednisone, and custirsen received weekly doses of custirsen 640 mg intravenously after three loading doses of 640 mg. The primary endpoint was overall survival analysed in the intention-to-treat population. Patients who received at least one study dose were included in the safety analysis set. This trial is registered with ClinicalTrials.gov, number NCT01188187. The trial is completed and final analyses are reported here. Between Dec 10, 2010, and Nov 7, 2012, 1022 patients were enrolled to the trial, of whom 510 were assigned docetaxel, prednisone, and custirsen and 512 were allocated docetaxel and prednisone. No difference in overall survival was recorded between the two groups (median survival 23·4 months [95% CI 20·9-24·8] with docetaxel, prednisone, and custirsen vs

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

Science.gov (United States)

Paoletti, X; Ezzalfani, M; Le Tourneau, C

2015-09-01

More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bioconversion potential of Trichoderma viride HN1 cellulase for a lignocellulosic biomass Saccharum spontaneum.

Science.gov (United States)

Iqtedar, Mehwish; Nadeem, Mohammad; Naeem, Hira; Abdullah, Roheena; Naz, Shagufta; Qurat ul Ain Syed; Kaleem, Afshan

2015-01-01

The industrialisation of lignocellulose conversion is impeded by expensive cellulase enzymes required for saccharification in bioethanol production. Current research undertakes cellulase production from pretreated Saccharum spontaneum through Trichoderma viride HN1 under submerged fermentation conditions. Pretreatment of substrate with 2% NaOH resulted in 88% delignification. Maximum cellulase production (2603 ± 16.39 U/mL/min carboxymethyl cellulase and 1393 ± 25.55 U/mL/min FPase) was achieved at 6% substrate at pH 5.0, with 5% inoculum, incubated at 35°C for 120 h of fermentation period. Addition of surfactant, Tween 80 and metal ion Mn(+2), significantly enhanced cellulase yield. This study accounts proficient cellulase yield through process optimisation by exploiting cheaper substrate to escalate their commercial endeavour.

Intensive versus conventional blood pressure monitoring in a general practice population. The Blood Pressure Reduction in Danish General Practice trial: a randomized controlled parallel group trial.

Science.gov (United States)

Klarskov, Pia; Bang, Lia E; Schultz-Larsen, Peter; Gregers Petersen, Hans; Benee Olsen, David; Berg, Ronan M G; Abrahamsen, Henrik; Wiinberg, Niels

2018-01-17

To compare the effect of a conventional to an intensive blood pressure monitoring regimen on blood pressure in hypertensive patients in the general practice setting. Randomized controlled parallel group trial with 12-month follow-up. One hundred and ten general practices in all regions of Denmark. One thousand forty-eight patients with essential hypertension. Conventional blood pressure monitoring ('usual group') continued usual ad hoc blood pressure monitoring by office blood pressure measurements, while intensive blood pressure monitoring ('intensive group') supplemented this with frequent home blood pressure monitoring and 24-hour ambulatory blood pressure monitoring. Mean day- and night-time systolic and diastolic 24-hour ambulatory blood pressure. Change in systolic and diastolic office blood pressure and change in cardiovascular risk profile. Of the patients, 515 (49%) were allocated to the usual group, and 533 (51%) to the intensive group. The reductions in day- and night-time 24-hour ambulatory blood pressure were similar (usual group: 4.6 ± 13.5/2.8 ± 82 mmHg; intensive group: 5.6 ± 13.0/3.5 ± 8.2 mmHg; P = 0.27/P = 0.20). Cardiovascular risk scores were reduced in both groups at follow-up, but more so in the intensive than in the usual group (P = 0.02). An intensive blood pressure monitoring strategy led to a similar blood pressure reduction to conventional monitoring. However, the intensive strategy appeared to improve patients' cardiovascular risk profile through other effects than a reduction of blood pressure. Clinical Trials NCT00244660. © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): Results of North Central Cancer Treatment Group trial 98-72-51

International Nuclear Information System (INIS)

Rao, Ravi D.; Krishnan, Sunil; Fitch, Tom R.; Schomberg, Paula J.; Dinapoli, Robert P.; Nordstrom, Kathleen; Scheithauer, Bernd; O'Fallon, Judith R.; Maurer, Matthew J. M.S.; Buckner, Jan C.

2005-01-01

Purpose: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Methods and materials: Therapy consisted of carmustine (40 mg/m 2 /d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m 2 /d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. Results: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Conclusion: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma

Intensive versus conventional blood pressure monitoring in a general practice population. The Blood Pressure Reduction in Danish General Practice trial: a randomized controlled parallel group trial

DEFF Research Database (Denmark)

Klarskov, Pia; Bang, Lia E; Schultz-Larsen, Peter

2018-01-01

To compare the effect of a conventional to an intensive blood pressure monitoring regimen on blood pressure in hypertensive patients in the general practice setting. Randomized controlled parallel group trial with 12-month follow-up. One hundred and ten general practices in all regions of Denmark....... One thousand forty-eight patients with essential hypertension. Conventional blood pressure monitoring ('usual group') continued usual ad hoc blood pressure monitoring by office blood pressure measurements, while intensive blood pressure monitoring ('intensive group') supplemented this with frequent...... a reduction of blood pressure. Clinical Trials NCT00244660....

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

Science.gov (United States)

le Roux, Carel W; Astrup, Arne; Fujioka, Ken; Greenway, Frank; Lau, David C W; Van Gaal, Luc; Ortiz, Rafael Violante; Wilding, John P H; Skjøth, Trine V; Manning, Linda Shapiro; Pi-Sunyer, Xavier

2017-04-08

Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m 2 , or at least 27 kg/m 2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, pprediabetes. Novo Nordisk, Denmark. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial.

Science.gov (United States)

Isacsson, Göran; Nohlert, Eva; Fransson, Anette M C; Bornefalk-Hermansson, Anna; Wiman Eriksson, Eva; Ortlieb, Eva; Trepp, Livia; Avdelius, Anna; Sturebrand, Magnus; Fodor, Clara; List, Thomas; Schumann, Mohamad; Tegelberg, Åke

2018-05-16

The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA. To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective. In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy. Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively). The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive. In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude. Registered with ClinicalTrials

The effectiveness of an online support group for members of the community with depression: a randomised controlled trial.

Directory of Open Access Journals (Sweden)

Kathleen M Griffiths

Full Text Available BACKGROUND: Internet support groups (ISGs are popular, particularly among people with depression, but there is little high quality evidence concerning their effectiveness. AIM: The study aimed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program. METHOD: Volunteers with elevated psychological distress were identified using a community-based screening postal survey. Participants were randomised to one of four 12-week conditions: depression Internet Support Group (ISG, automated depression Internet Training Program (ITP, combination of the two (ITP+ISG, or a control website with delayed access to e-couch at 6 months. Assessments were conducted at baseline, post-intervention, 6 and 12 months. RESULTS: There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG. However, both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group. The ITP program was effective relative to control at post-intervention but not at 6 months. CONCLUSIONS: ISGs for depression are promising and warrant further empirical investigation. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN65657330.

The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

Energy Technology Data Exchange (ETDEWEB)

Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M. Tanaka; Gavis, Elizabeth R. (Princeton); (NIH)

2017-04-01

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

Pilot trial of a dissonance-based cognitive-behavioral group depression prevention with college students.

Science.gov (United States)

Rohde, Paul; Stice, Eric; Shaw, Heather; Gau, Jeff M

2016-07-01

Conduct a pilot trial testing whether a new cognitive-behavioral (CB) group prevention program that incorporated cognitive-dissonance change principles was feasible and appeared effective in reducing depressive symptoms and major depressive disorder onset relative to a brochure control condition in college students with elevated depressive symptoms. 59 college students (M age = 21.8, SD = 2.3; 68% female, 70% White) were randomized to the 6-session Change Ahead group or educational brochure control condition, completing assessments at pretest, posttest, and 3-month follow-up. Recruitment and screening methods were effective and intervention attendance was high (86% attended all 6 sessions). Change Ahead participants showed medium-large reductions in depressive symptoms at posttest (M d = 0.64), though the effect attenuated by 3-month follow-up. Incidence of major depression onset at 3-month follow-up was 4% for Change Ahead participants versus 13% (difference ns). Change Ahead appears highly feasible and showed positive indications of reduced acute phase depressive symptoms and MDD onset relative to a minimal intervention control in this initial pilot. Given the brevity of the intervention, its apparent feasibility, and the lack of evidence-based depression prevention programs for college students, continued evaluation of Change Ahead appears warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness of 3 methods of anchorage reinforcement for maximum anchorage in adolescents: A 3-arm multicenter randomized clinical trial.

Science.gov (United States)

Sandler, Jonathan; Murray, Alison; Thiruvenkatachari, Badri; Gutierrez, Rodrigo; Speight, Paul; O'Brien, Kevin

2014-07-01

The objective of this 3-arm parallel randomized clinical trial was to compare the effectiveness of temporary anchorage devices (TADs), Nance button palatal arches, and headgear for anchorage supplementation in the treatment of patients with malocclusions that required maximum anchorage. This trial was conducted between August 2008 and February 2013 in 2 orthodontic departments in the United Kingdom. The study included 78 patients (ages, 12-18 years; mean age, 14.2 years) who needed maximum anchorage. Eligibility criteria included no active caries, exemplary oral hygiene, and maximum anchorage required. The primary outcome was mesial molar movement during the period in which anchorage supplementation was required. The secondary outcomes were duration of anchorage reinforcement, number of treatment visits, number of casual and failed appointments, total treatment time, dento-occlusal change, and patients' perceptions of the method of anchorage supplementation. Treatment allocation was implemented by contacting via the Internet the randomization center at the University of Nottingham, Clinical Trials Unit. The randomization was based on a computer-generated pseudo-random code with random permuted blocks of randomly varying size. A research assistant who was blinded to the group allocation recorded all data. The patients were randomly allocated to receive anchorage supplementation with TADs, a Nance button on a palatal arch, or headgear. They were all treated with maxillary and mandibular preadjusted edgewise fixed appliances with 0.022-in slot prescription brackets. They were followed until orthodontic treatment was complete. Seventy-eight patients were randomized in a 1:1:1 ratio among the 3 groups. The baseline characteristics were similar in the groups, and they were treated for an average of 27.4 months (SD, 7.1 months); 71 completed orthodontic treatment. The data were analyzed on a per-protocol basis and showed no differences in the effectiveness of anchorage

Set-up improvement in head and neck radiotherapy using a 3D off-line EPID-based correction protocol and a customised head and neck support

International Nuclear Information System (INIS)

Lin, Emile N.J. Th. van; Vight, Lisette van der; Huizenga, Henk; Kaanders, Johannes H.A.M.; Visser, Andries G.

2003-01-01

Purpose: First, to investigate the set-up improvement resulting from the introduction of a customised head and neck (HN) support system in combination with a technologist-driven off-line correction protocol in HN radiotherapy. Second, to define margins for planning target volume definition, accounting for systematic and random set-up uncertainties. Methods and materials: In 63 patients 498 treatment fractions were evaluated to develop and implement a 3D shrinking action level correction protocol. In the comparative study two different HN-supports were compared: a flexible 'standard HN-support' and a 'customised HN-support'. For all three directions (x, y and z) random and systematic set-up deviations (1 S.D.) were measured. Results: The customised HN-support improves the patient positioning compared to the standard HN-support. The 1D systematic errors in the x, y and z directions were reduced from 2.2-2.3 mm to 1.2-2.0 mm (1 S.D.). The 1D random errors for the y and z directions were reduced from 1.6 and 1.6 mm to 1.1 and 1.0 mm (1 S.D.). The correction protocol reduced the 1D systematic errors further to 0.8-1.1 mm (1 S.D.) and all deviations in any direction were within 5 mm. Treatment time per measured fraction was increased from 10 to 13 min. The total time required per patient, for the complete correction procedure, was approximately 40 min. Conclusions: Portal imaging is a powerful tool in the evaluation of the department specific patient positioning procedures. The introduction of a comfortable customised HN-support, in combination with an electronic portal imaging device-based correction protocol, executed by technologists, led to an improvement of overall patient set-up. As a result, application of proposed recipes for CTV-PTV margins indicates that these can be reduced to 3-4 mm

Group versus individual sessions delivered by a physiotherapist for female urinary incontinence: an interview study with women attending group sessions nested within a randomised controlled trial

Directory of Open Access Journals (Sweden)

Smith Jan

2009-09-01

Full Text Available Abstract Background The aim was to explore the concerns and expectations of women invited to attend group physiotherapy sessions for the management of female urinary incontinence and whether the experience changed their views; and to gather recommendations from women attending group sessions on the design and delivery of these sessions Methods An interview study nested within a randomised controlled trial in five British NHS physiotherapy departments, including 22 women who had expressed a preference for an individual physiotherapy session but were randomised to, and attended, group sessions. Results Embarrassment was woven throughout women's accounts of experiencing urinary incontinence and seeking health care. Uncertainty about the nature of group sessions was a source of concern. Attending the first session was seen as a big hurdle by many women. However, a sense of relief was common once the session started, with most women describing some benefit from attendance. Recommendations for design and delivery of the sessions from women focused on reducing embarrassment and uncertainty prior to attendance. Conclusion Taking account of women's embarrassment and providing detailed information about the content of group sessions will enable women to benefit from group physiotherapy sessions for the management of female urinary incontinence. Trial Registration Trial registration number: ISRCTN 16772662

Use of 3D printed models in medical education: A randomized control trial comparing 3D prints versus cadaveric materials for learning external cardiac anatomy.

Science.gov (United States)

Lim, Kah Heng Alexander; Loo, Zhou Yaw; Goldie, Stephen J; Adams, Justin W; McMenamin, Paul G

2016-05-06

Three-dimensional (3D) printing is an emerging technology capable of readily producing accurate anatomical models, however, evidence for the use of 3D prints in medical education remains limited. A study was performed to assess their effectiveness against cadaveric materials for learning external cardiac anatomy. A double blind randomized controlled trial was undertaken on undergraduate medical students without prior formal cardiac anatomy teaching. Following a pre-test examining baseline external cardiac anatomy knowledge, participants were randomly assigned to three groups who underwent self-directed learning sessions using either cadaveric materials, 3D prints, or a combination of cadaveric materials/3D prints (combined materials). Participants were then subjected to a post-test written by a third party. Fifty-two participants completed the trial; 18 using cadaveric materials, 16 using 3D models, and 18 using combined materials. Age and time since completion of high school were equally distributed between groups. Pre-test scores were not significantly different (P = 0.231), however, post-test scores were significantly higher for 3D prints group compared to the cadaveric materials or combined materials groups (mean of 60.83% vs. 44.81% and 44.62%, P = 0.010, adjusted P = 0.012). A significant improvement in test scores was detected for the 3D prints group (P = 0.003) but not for the other two groups. The finding of this pilot study suggests that use of 3D prints do not disadvantage students relative to cadaveric materials; maximally, results suggest that 3D may confer certain benefits to anatomy learning and supports their use and ongoing evaluation as supplements to cadaver-based curriculums. Anat Sci Educ 9: 213-221. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome:a randomized group sequential comparative trial

Science.gov (United States)

2011-01-01

Background In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine ---- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome. Methods A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT). Results A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06. No adverse events were observed in the two groups. Conclusions Zhizhu pills containing IFCA was superior

Immediate versus delayed loading of strategic mini dental implants for the stabilization of partial removable dental prostheses: a patient cluster randomized, parallel-group 3-year trial.

Science.gov (United States)

Mundt, Torsten; Al Jaghsi, Ahmad; Schwahn, Bernd; Hilgert, Janina; Lucas, Christian; Biffar, Reiner; Schwahn, Christian; Heinemann, Friedhelm

2016-07-30

Acceptable short-term survival rates (>90 %) of mini-implants (diameter implants as strategic abutments for a better retention of partial removable dental prosthesis (PRDP) are not available. The purpose of this study is to test the hypothesis that immediately loaded mini-implants show more bone loss and less success than strategic mini-implants with delayed loading. In this four-center (one university hospital, three dental practices in Germany), parallel-group, controlled clinical trial, which is cluster randomized on patient level, a total of 80 partially edentulous patients with unfavourable number and distribution of remaining abutment teeth in at least one jaw will receive supplementary min-implants to stabilize their PRDP. The mini-implant are either immediately loaded after implant placement (test group) or delayed after four months (control group). Follow-up of the patients will be performed for 36 months. The primary outcome is the radiographic bone level changes at implants. The secondary outcome is the implant success as a composite variable. Tertiary outcomes include clinical, subjective (quality of life, satisfaction, chewing ability) and dental or technical complications. Strategic implants under an existing PRDP are only documented for standard-diameter implants. Mini-implants could be a minimal invasive and low cost solution for this treatment modality. The trial is registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00007589 ( www.germanctr.de ) on January 13(th), 2015.

The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.

Science.gov (United States)

Jia, Yue; Ohanyan, Aikoui; Lue, Yan-He; Swerdloff, Ronald S; Liu, Peter Y; Cohen, Pinchas; Wang, Christina

2015-04-01

Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: (1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; (2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; (3) self-dimerization or binding to IGFBP-3 may not be involved in HN's effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects.

The effectiveness of a Housing First adaptation for ethnic minority groups: findings of a pragmatic randomized controlled trial

Directory of Open Access Journals (Sweden)

Vicky Stergiopoulos

2016-10-01

Full Text Available Abstract Background Little is known about the effectiveness of Housing First (HF among ethnic minority groups, despite its growing popularity for homeless adults experiencing mental illness. This randomized controlled trial tests the effectiveness of a HF program using rent supplements and intensive case management, enhanced by anti-racism and anti-oppression practices for homeless adults with mental illness from diverse ethnic minority backgrounds. Methods This unblinded pragmatic field trial was carried out in community settings in Toronto, Canada. Participants were 237 adults from ethnic minority groups experiencing mental illness and homelessness, who met study criteria for moderate needs for mental health services. Participants were randomized to either adapted HF (n = 135 or usual care (n = 102 and followed every 3 months for 24 months. The primary study outcome was housing stability; secondary outcomes included physical and mental health, social functioning, quality of life, arrests and health service use. Intention to treat statistical analyses examined the effectiveness of the intervention compared to usual care. Results During the 24-month study period, HF participants were stably housed a significantly greater proportion of time compared to usual care participants, 75 % (95 % CI 70 to 81 vs. 41 % (95 % CI 35 to 48, respectively, for a difference of 34 %, 95 % CI 25 to 43. HF also led to improvements in community integration over the course of the study: the change in the mean difference between treatment groups from baseline to 24-months was significantly greater among HF participants compared to those in usual care (change in mean difference = 2.2, 95 % CI 0.06 to 4.3. Baseline diagnosis of psychosis was associated with reduced likelihood of being housed ≥ 50 % of the study period (OR = 0.37, 95 % CI 0.18 to 0.72. Conclusion Housing First enhanced with anti-racism and anti-oppression practices can

Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

Science.gov (United States)

Faurholt-Jepsen, M; Frost, M; Ritz, C; Christensen, E M; Jacoby, A S; Mikkelsen, R L; Knorr, U; Bardram, J E; Vinberg, M; Kessing, L V

2015-10-01

The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

EtpE Binding to DNase X Induces Ehrlichial Entry via CD147 and hnRNP-K Recruitment, Followed by Mobilization of N-WASP and Actin.

Science.gov (United States)

Mohan Kumar, Dipu; Lin, Mingqun; Xiong, Qingming; Webber, Mathew James; Kural, Comert; Rikihisa, Yasuko

2015-11-03

Obligate intracellular bacteria, such as Ehrlichia chaffeensis, perish unless they can enter eukaryotic cells. E. chaffeensis is the etiological agent of human monocytic ehrlichiosis, an emerging infectious disease. To infect cells, Ehrlichia uses the C terminus of the outer membrane invasin entry-triggering protein (EtpE) of Ehrlichia (EtpE-C), which directly binds the mammalian cell surface glycosylphosphatidyl inositol-anchored protein, DNase X. How this binding drives Ehrlichia entry is unknown. Here, using affinity pulldown of host cell lysates with recombinant EtpE-C (rEtpE-C), we identified two new human proteins that interact with EtpE-C: CD147 and heterogeneous nuclear ribonucleoprotein K (hnRNP-K). The interaction of CD147 with rEtpE-C was validated by far-Western blotting and coimmunoprecipitation of native EtpE with endogenous CD147. CD147 was ubiquitous on the cell surface and also present around foci of rEtpE-C-coated-bead entry. Functional neutralization of surface-exposed CD147 with a specific antibody inhibited Ehrlichia internalization and infection but not binding. Downregulation of CD147 by short hairpin RNA (shRNA) impaired E. chaffeensis infection. Functional ablation of cytoplasmic hnRNP-K by a nanoscale intracellular antibody markedly attenuated bacterial entry and infection but not binding. EtpE-C also interacted with neuronal Wiskott-Aldrich syndrome protein (N-WASP), which is activated by hnRNP-K. Wiskostatin, which inhibits N-WASP activation, and cytochalasin D, which inhibits actin polymerization, inhibited Ehrlichia entry. Upon incubation with host cell lysate, EtpE-C but not an EtpE N-terminal fragment stimulated in vitro actin polymerization in an N-WASP- and DNase X-dependent manner. Time-lapse video images revealed N-WASP recruitment at EtpE-C-coated bead entry foci. Thus, EtpE-C binding to DNase X drives Ehrlichia entry by engaging CD147 and hnRNP-K and activating N-WASP-dependent actin polymerization. Ehrlichia chaffeensis, an

2D vs. 3D imaging in laparoscopic surgery-results of a prospective randomized trial.

Science.gov (United States)

Buia, Alexander; Stockhausen, Florian; Filmann, Natalie; Hanisch, Ernst

2017-12-01

3D imaging is an upcoming technology in laparoscopic surgery, and recent studies have shown that the modern 3D technique is superior in an experimental setting. However, the first randomized controlled clinical trial in this context dates back to 1998 and showed no significant difference between 2D and 3D visualization using the first 3D generation technique, which is now more than 15 years old. Positive results measured in an experimental setting considering 3D imaging on surgical performance led us to initiate a randomized controlled pragmatic clinical trial to validate our findings in daily clinical routine. Standard laparoscopic operations (cholecystectomy, appendectomy) were preoperatively randomized to a 2D or 3D imaging system. We used a surgical comfort scale (Likert scale) and the Raw NASA Workload TLX for the subjective assessment of 2D and 3D imaging; the duration of surgery was also measured. The results of 3D imaging were statistically significant better than 2D imaging concerning the parameters "own felt safety" and "task efficiency"; the difficulty level of the procedures in the 2D and 3D groups did not differ. Overall, the Raw NASA Workload TLX showed no significance between the groups. 3D imaging could be a possible advantage in laparoscopic surgery. The results of our clinical trial show increased personal felt safety and efficiency of the surgeon using a 3D imaging system. Overall of the procedures, the findings assessed using Likert scales in terms of own felt safety and task efficiency were statistically significant for 3D imaging. The individually perceived workload assessed with the Raw NASA TLX shows no difference. Although these findings are subjective impressions of the performing surgeons without a clear benefit for 3D technology in clinical outcome, we think that these results show the capability that 3D laparoscopy can have a positive impact while performing laparoscopic procedures.

Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in recalcitrant wart: A randomized, placebo-controlled, double-blind clinical trial including an extra group of candidates for cryotherapy.

Science.gov (United States)

Amirnia, Mehdi; Khodaeiani, Effat; Fouladi, Daniel F; Masoudnia, Sima

2016-01-01

Due to paucity of randomized clinical trials, intralesional immunotherapy has not been yet accepted as a standard therapeutic method. To examine the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative (PPD) for treating recalcitrant wart. In this randomized, placebo-controlled, double-blind clinical trial, a total of 69 patients with recalcitrant warts received either intralesional PPD antigen (n = 35) or intralesional saline (n = 34) for six times at 2-week intervals. A third group of candidates for cryotherapy (n = 33) was also included. The decrease in lesion size (good: complete response, intermediate: 50-99% improvement, poor: PPD patients; 0%, 14.7% and 85.3% of the placebo patients and 18.2%, 33.3% and 48.5% of the cryotherapy patients, respectively (PPD versus placebo: p PPD versus cryotherapy: p PPD group. The recurrence rate was 8.6%, 5.9% and 24.2% in the PPD, placebo and cryotherapy groups, respectively (p > 0.05). Intralesional immunotherapy with PPD antigen is highly effective and safe for treating recalcitrant warts. IRCT201407089844N3 in the Iranian Registry of Clinical Trials (IRCT).

Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

DEFF Research Database (Denmark)

Hjorthøj, Carsten; Fohlmann, Allan; Larsen, Anne-Mette

2008-01-01

: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical...

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

Science.gov (United States)

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Reducing therapeutic misconception: A randomized intervention trial in hypothetical clinical trials.

Directory of Open Access Journals (Sweden)

Paul P Christopher

Full Text Available Participants in clinical trials frequently fail to appreciate key differences between research and clinical care. This phenomenon, known as therapeutic misconception, undermines informed consent to clinical research, but to date there have been no effective interventions to reduce it and concerns have been expressed that to do so might impede recruitment. We determined whether a scientific reframing intervention reduces therapeutic misconception without significantly reducing willingness to participate in hypothetical clinical trials.This prospective randomized trial was conducted from 2015 to 2016 to test the efficacy of an informed consent intervention based on scientific reframing compared to a traditional informed consent procedure (control in reducing therapeutic misconception among patients considering enrollment in hypothetical clinical trials modeled on real-world studies for one of five disease categories. Patients with diabetes mellitus, hypertension, coronary artery disease, head/neck cancer, breast cancer, and major depression were recruited from medical clinics and a clinical research volunteer database. The primary outcomes were therapeutic misconception, as measured by a validated, ten-item Therapeutic Misconception Scale (range = 10-50, and willingness to participate in the clinical trial.154 participants completed the study (age range, 23-87 years; 92.3% white, 56.5% female; 74 (48.1% had been randomized to receive the experimental intervention. Therapeutic misconception was significantly lower (p = 0.004 in the scientific reframing group (26.4, 95% CI [23.7 to 29.1] compared to the control group (30.9, 95% CI [28.4 to 33.5], and remained so after controlling for education (p = 0.017. Willingness to participate in the hypothetical trial was not significantly different (p = 0.603 between intervention (52.1%, 95% CI [40.2% to 62.4%] and control (56.3%, 95% CI [45.3% to 66.6%] groups.An enhanced educational intervention augmenting

Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

Science.gov (United States)

Malan, Tina; Moodley, Keymanthri

2016-02-01

Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

Effect of park prescriptions with and without group visits to parks on stress reduction in low-income parents: SHINE randomized trial.

Science.gov (United States)

Razani, Nooshin; Morshed, Saam; Kohn, Michael A; Wells, Nancy M; Thompson, Doug; Alqassari, Maoya; Agodi, Amaka; Rutherford, George W

2018-01-01

Exposure to nature may reduce stress in low-income parents. This prospective randomized trial compares the effect of a physician's counseling about nature with or without facilitated group outings on stress and other outcomes among low-income parents. Parents of patients aged 4-18 years at a clinic serving low-income families were randomized to a supported park prescription versus independent park prescription in a 2:1 ratio. Parents in both groups received physician counseling about nature, maps of local parks, a journal, and pedometer. The supported group received additional phone and text reminders to attend three weekly family nature outings with free transportation, food, and programming. Outcomes measured in parents at baseline, one month and three months post-enrollment included: stress (using the 40-point Perceived Stress Scale [PSS10]); park visits per week (self-report and journaling); loneliness (modified UCLA-Loneliness Scale); physical activity (self-report, journaling, pedometry); physiologic stress (salivary cortisol); and nature affinity (validated scale). We enrolled 78 parents, 50 in the supported and 28 in the independent group. One-month follow-up was available for 60 (77%) participants and three-month follow up for 65 (83%). Overall stress decreased by 1.71 points (95% CI, -3.15, -0.26). The improvement in stress did not differ significantly by group assignment, although the independent group had more park visits per week (mean difference 1.75; 95% CI [0.46, 3.04], p = 0.0085). In multivariable analysis, each unit increase in park visits per week was associated with a significant and incremental decrease in stress (change in PSS10-0.53; 95% CI [-0.89, -0.16]; p = 0.005) at three months. While we were unable to demonstrate the additional benefit of group park visits, we observed an overall decrease in parental stress both overall and as a function of numbers of park visits per week. Paradoxically the park prescription without group park visits

Effect of park prescriptions with and without group visits to parks on stress reduction in low-income parents: SHINE randomized trial.

Directory of Open Access Journals (Sweden)

Nooshin Razani

Full Text Available Exposure to nature may reduce stress in low-income parents. This prospective randomized trial compares the effect of a physician's counseling about nature with or without facilitated group outings on stress and other outcomes among low-income parents.Parents of patients aged 4-18 years at a clinic serving low-income families were randomized to a supported park prescription versus independent park prescription in a 2:1 ratio. Parents in both groups received physician counseling about nature, maps of local parks, a journal, and pedometer. The supported group received additional phone and text reminders to attend three weekly family nature outings with free transportation, food, and programming. Outcomes measured in parents at baseline, one month and three months post-enrollment included: stress (using the 40-point Perceived Stress Scale [PSS10]; park visits per week (self-report and journaling; loneliness (modified UCLA-Loneliness Scale; physical activity (self-report, journaling, pedometry; physiologic stress (salivary cortisol; and nature affinity (validated scale.We enrolled 78 parents, 50 in the supported and 28 in the independent group. One-month follow-up was available for 60 (77% participants and three-month follow up for 65 (83%. Overall stress decreased by 1.71 points (95% CI, -3.15, -0.26. The improvement in stress did not differ significantly by group assignment, although the independent group had more park visits per week (mean difference 1.75; 95% CI [0.46, 3.04], p = 0.0085. In multivariable analysis, each unit increase in park visits per week was associated with a significant and incremental decrease in stress (change in PSS10-0.53; 95% CI [-0.89, -0.16]; p = 0.005 at three months.While we were unable to demonstrate the additional benefit of group park visits, we observed an overall decrease in parental stress both overall and as a function of numbers of park visits per week. Paradoxically the park prescription without group park

TU-FG-201-06: Remote Dosimetric Auditing for Clinical Trials Using EPID Dosimetry: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Miri, N; Legge, K; Greer, P [Newcastle University, Newcastle, NSW (Australia); Lehmann, J [Calvary Mater Newcastle, Newcastle, NSW (Australia); Vial, P [Liverpool Hospital, Sydney, NSW (Australia)

2016-06-15

Purpose: To perform a pilot study for remote dosimetric credentialing of intensity modulated radiation therapy (IMRT) based clinical trials. The study introduces a novel, time efficient and inexpensive dosimetry audit method for multi-center credentialing. The method employs electronic portal imaging device (EPID) to reconstruct delivered dose inside a virtual flat/cylindrical water phantom. Methods: Five centers, including different accelerator types and treatment planning systems (TPS), were asked to download two CT data sets of a Head and Neck (H&N) and Postprostatectomy (P-P) patients to produce benchmark plans. These were then transferred to virtual flat and cylindrical phantom data sets that were also provided. In-air EPID images of the plans were then acquired, and the data sent to the central site for analysis. At the central site, these were converted to DICOM format, all images were used to reconstruct 2D and 3D dose distributions inside respectively the flat and cylindrical phantoms using inhouse EPID to dose conversion software. 2D dose was calculated for individual fields and 3D dose for the combined fields. The results were compared to corresponding TPS doses. Three gamma criteria were used, 3%3mm-3%/2mm–2%/2mm with a 10% dose threshold, to compare the calculated and prescribed dose. Results: All centers had a high pass rate for the criteria of 3%/3 mm. For 2D dose, the average of centers mean pass rate was 99.6% (SD: 0.3%) and 99.8% (SD: 0.3%) for respectively H&N and PP patients. For 3D dose, 3D gamma was used to compare the model dose with TPS combined dose. The mean pass rate was 97.7% (SD: 2.8%) and 98.3% (SD: 1.6%). Conclusion: Successful performance of the method for the pilot centers establishes the method for dosimetric multi-center credentialing. The results are promising and show a high level of gamma agreement and, the procedure is efficient, consistent and inexpensive. Funding has been provided from Department of Radiation Oncology

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials (Chinese version)

DEFF Research Database (Denmark)

Moher, David; Hopewell, Sally; Schulz, Kenneth F

2010-01-01

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate...... that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed......, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials....

Role of 3D animation in periodontal patient education: a randomized controlled trial.

Science.gov (United States)

Cleeren, Gertjan; Quirynen, Marc; Ozcelik, Onur; Teughels, Wim

2014-01-01

This randomized controlled parallel trial investigates the effect of 3D animation on the increase and recall of knowledge on periodontitis by patients with periodontitis. The effects of a 3D animation (3D animation group) were compared with narration and drawing (control group) for periodontal patient education. A total of 68 periodontitis patients were stratified according to educational level and then randomly allocated to control or 3D animation groups. All patients received: (1) a pre-test (baseline knowledge), (2) a patient education video (3D animation or control video), (3) a post-test (knowledge immediately after looking at the video), and (4) a follow-up test (knowledge recall after 2 weeks). Each test contained 10 multiple-choice questions. There was no significant difference in baseline knowledge. Patients receiving the 3D animations had significantly higher scores for both the post-test and the follow-up test, when compared with patients receiving sketch animations. 3D animations are more effective than real-time drawings for periodontal patient education in terms of knowledge recall. 3D animations may be a powerful tool for assisting in the information process. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feasibility and acceptability of group music therapy vs wait-list control for treatment of patients with long-term depression (the SYNCHRONY trial): study protocol for a randomised controlled trial.

Science.gov (United States)

Carr, Catherine Elizabeth; O'Kelly, Julian; Sandford, Stephen; Priebe, Stefan

2017-03-29

Depression is of significant global concern. Despite a range of effective treatment options it is estimated that around one in five diagnosed with an acute depressive episode continue to experience enduring symptoms for more than 2 years. There is evidence for effectiveness of individual music therapy for depression. However, no studies have as yet looked at a group intervention within an NHS context. This study aims to assess the feasibility of conducting a randomised controlled trial of group music therapy for patients with long-term depression (symptom durations of 1 year or longer) within the community. This is a single-centre randomised controlled feasibility trial of group music therapy versus wait-list control with a nested process evaluation. Thirty participants will be randomised with unbalanced allocation (20 to receive the intervention immediately, 10 as wait-list controls). Group music therapy will be offered three times per week in a community centre with a focus on songwriting. Data will be collected post-intervention, 3 and 6 months after the intervention finishes. We will examine the feasibility of recruitment processes including identifying the number of eligible participants, participation and retention rates and the intervention in terms of testing components, measuring adherence and estimation of the likely intervention effect. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of process measures and end-of-participation interviews with participants and referring staff. Whilst group music therapy is an option in some community mental health settings, this will be the first study to examine group music therapy for this particular patient group. We will assess symptoms of depression, acceptability of the intervention and quality of life. We anticipate potential challenges in the recruitment and retention of participants. It is unclear whether offering the intervention three times per week will be

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management.

Science.gov (United States)

Pi-Sunyer, Xavier; Astrup, Arne; Fujioka, Ken; Greenway, Frank; Halpern, Alfredo; Krempf, Michel; Lau, David C W; le Roux, Carel W; Violante Ortiz, Rafael; Jensen, Christine Bjørn; Wilding, John P H

2015-07-02

Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; Pweight (Pweight (Pweight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.).

Clinical Trials

Medline Plus

Full Text Available ... protocol affect the trial's results. Comparison Groups In most clinical trials, researchers use comparison groups. This means ... study before you agree to take part. Randomization Most clinical trials that have comparison groups use randomization. ...

Uudised : Vello Pähn Savonlinnas. Eri Klas pärast juubelit. Ain Anger Mirjam Helini konkursil. Türnpu sünnipäevakontsert / Priit Kuusk

Index Scriptorium Estoniae

Kuusk, Priit, 1938-

1999-01-01

V. Pähn dirigeeris Savonlinna ooperifestivalil Gounod" ooperit "Faust". E.Klas erinevate orkestrite ees juuni-september 1999. 8.-20. augustini Helsingis toimunud IV rahvusvahelisest M. Helini konkursist, kus osales A. Anger. 13.augustil tähistati K. Türnpu 134. sünniaastapäeva kontserdiga Tuulna külas Keila vallas

A comparison of the efficacy of three intervention trial types: postal, group, and one-to-one facilitation, prior management and the impact of message framing and repeat messages on the flock prevalence of lameness in sheep.

Science.gov (United States)

Grant, Claire; Kaler, Jasmeet; Ferguson, Eamonn; O'Kane, Holly; Green, Laura Elizabeth

2018-01-01

The aim of this study was to evaluate the effectiveness of three knowledge-transfer intervention trial types (postal, group, one-to-one) to promote best practice to treat sheep with footrot. Further aims were to investigate whether farmer behaviour (i.e. management of lameness) before the trial was associated with uptake of best practice and whether the benefits of best practice framed positively or negatively influenced change in behaviour. The intervention was a message developed from evidence and expert opinion. It was entitled "Six steps to sound sheep" and promoted (1) catch sheep within three days of becoming lame, (2) inspect feet without foot trimming, (3) correctly diagnose the cause, (4) treat sheep lame with footrot or interdigital dermatitis with antibiotic injection and spray without foot trimming, (5) record the identity of treated sheep, (6) cull repeatedly lame sheep. In 2013, 4000 randomly-selected English sheep farmers were sent a questionnaire, those who responded were recruited to the postal (1081 farmers) or one-to-one intervention (32 farmers) trials. A random sample of 400 farmers were invited to join the group trial; 78 farmers participated. A follow-up questionnaire was sent to all participants in summer 2014. There were 72%, 65% and 91% useable responses for the postal, group and one-to-one trials respectively. In both 2013 and 2014, the prevalence of lameness was lower in flocks managed by LC1 farmers than LC2 and LC3 farmers. Between 2013 and 2014, the reduction in geometric mean (95% CI) period prevalence of lameness, proportional between flock reduction in lameness and within flock reduction in lameness was greatest in the one-to-one (7.6% (7.1-8.2%) to 4.3% (3.6-5.0%), 35%, 72%) followed by the group (4.5% (3.9-5.0%) to 3.1% (2.4-3.7%), 27%, 55%) and then the postal trial (from 3.5% (3.3-3.7%) to 3.2% (3.1-3.4%), 21%, 43%). There was a marginally greater reduction in lameness in farmers using most of Six steps but slow to treat lame

Hepatitis C treatment among racial and ethnic groups in the IDEAL trial.

Science.gov (United States)

Muir, A J; Hu, K-Q; Gordon, S C; Koury, K; Boparai, N; Noviello, S; Albrecht, J K; Sulkowski, M S; McCone, J

2011-04-01

Previous studies of chronic hepatitis C virus (HCV) treatment have demonstrated variations in response among racial and ethnic groups including poorer efficacy rates among African American and Hispanic patients. The individualized dosing efficacy vs flat dosing to assess optimaL pegylated interferon therapy (IDEAL) trial enrolled 3070 patients from 118 United States centres to compare treatment with peginterferon (PEG-IFN) alfa-2a and ribavirin (RBV) and two doses of PEG-IFN alfa-2b and RBV. This analysis examines treatment response among the major racial and ethnic groups in the trial. Overall, sustained virologic response (SVR) rates were 44% for white, 22% for African American, 38% for Hispanic and 59% for Asian American patients. For patients with undetectable HCV RNA at treatment week 4, the positive predictive value of SVR was 86% for white, 92% for African American, 83% for Hispanic and 89% for Asian American patients. The positive predictive values of SVR in those with undetectable HCV RNA at treatment week 12 ranged from 72% to 81%. Multivariate regression analysis using baseline characteristics demonstrated that treatment regimen was not a predictor of SVR. Despite wide-ranging SVR rates among the different racial and ethnic groups, white and Hispanic patients had similar SVR rates. In all groups, treatment response was largely determined by antiviral activity in the first 12 weeks of treatment. Therefore, decisions regarding HCV treatment should consider the predictive value of the early on-treatment response, not just baseline characteristics, such as race and ethnicity. © 2010 Blackwell Publishing Ltd.

Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

Energy Technology Data Exchange (ETDEWEB)

Michalski, Jeff M., E-mail: jmichalski@radonc.wustl.edu [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Yan, Yan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [Emory University School of Nursing, Atlanta, Georgia (United States); Bosch, Walter R. [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Department of Radiation Oncology Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, QC (Canada); Morton, Gerard C. [Department of Radiation Oncology Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON (Canada); Parliament, Matthew B. [Department of Oncology Cross Cancer Institute, Edmonton, AB (Canada); Sandler, Howard M. [Department of Radiation Oncology Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California (United States)

2013-12-01

Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

Energy Technology Data Exchange (ETDEWEB)

Rosenthal, Seth A., E-mail: rosents@sutterhealth.org [Radiation Oncology, Sutter Cancer Centers, Roseville, California (United States); Hunt, Daniel [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sartor, A. Oliver [Tulane University Medical Center, New Orleans, Louisiana (United States); Pienta, Kenneth J. [Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Gomella, Leonard [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Grignon, David [Indiana University, Bloomington, Indiana (United States); Rajan, Raghu [McGill University, Montreal, Quebec (Canada); Kerlin, Kevin J. [Community Clinical Oncology Program, Southeast Cancer Control Consortium, Inc, Winston-Salem, North Carolina (United States); Jones, Christopher U. [Radiation Oncology, Sutter Cancer Centers, Roseville, California (United States); Radiological Associates of Sacramento, Sacramento, California (United States); Dobelbower, Michael [University of Alabama at Birmingham Medical Center, Birmingham, Alabama (United States); Shipley, William U. [Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Zeitzer, Kenneth [Albert Einstein Medical Center, Bronx, New York (United States); Hamstra, Daniel A. [University of Michigan Medical Center, Ann Arbor, Michigan (United States); Donavanik, Viroon [Christiana Care Health Services, Inc, Wilmington, Delaware (United States); Rotman, Marvin [State University of New York Health Science Center–Brooklyn, Brooklyn, New York (United States); Hartford, Alan C. [Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire (United States); Michalski, Jeffrey [Washington University, St. Louis, Missouri (United States); Seider, Michael [Akron City Hospital, Akron, Ohio (United States); Kim, Harold [Wayne State University, Detroit, Michigan (United States); and others

2015-10-01

Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for

Group hypnosis vs. relaxation for smoking cessation in adults: a cluster-randomised controlled trial.

Science.gov (United States)

Dickson-Spillmann, Maria; Haug, Severin; Schaub, Michael P

2013-12-23

Despite the popularity of hypnotherapy for smoking cessation, the efficacy of this method is unclear. We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers. This was a cluster-randomised, parallel-group, controlled trial. A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers (median size = 11). Participants were 223 smokers consuming ≥ 5 cigarettes per day, willing to quit and not using cessation aids (47.1% females, M = 37.5 years [SD = 11.8], 86.1% Swiss). Nicotine withdrawal, smoking abstinence self-efficacy, and adverse reactions were assessed at a 2-week follow-up. The main outcome, self-reported 30-day point prevalence of smoking abstinence, was assessed at a 6-month follow up. Abstinence was validated through salivary analysis. Secondary outcomes included number of cigarettes smoked per day, smoking abstinence self-efficacy, and nicotine withdrawal. At the 6-month follow up, 14.7% in the hypnosis group and 17.8% in the relaxation group were abstinent. The intervention had no effect on smoking status (p = .73) or on the number of cigarettes smoked per day (p = .56). Smoking abstinence self-efficacy did not differ between the interventions (p = .14) at the 2-week follow-up, but non-smokers in the hypnosis group experienced reduced withdrawal (p = .02). Both interventions produced few adverse reactions (p = .81). A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session. Current Controlled Trials ISRCTN72839675.

Quality Assurance for Clinical Trials

Science.gov (United States)

Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

2013-01-01

Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

The mucosal Immune Response Induced in Chicks Immunized with LactobaciUus casei anchoring NDV HN Protein%锚定NDVHN蛋白重组干酪乳杆菌诱导雏鸡黏膜免疫应答

Institute of Scientific and Technical Information of China (English)

孙景秀; 王桂华; 侯喜林; 余丽芸; 田斌; 侯瑞峰; 朱娉慧; 周婷婷; 齐浩

2012-01-01

以干酪乳杆菌作为呈递抗原活载体，表达新城疫病毒保护性抗原HN蛋白。重组于酪乳杆菌表达外源蛋白后，经SDS-PAGE、Westernblot及间接免疫荧光分析，表明目的蛋白表达并展示到乳酸菌表面。将重组菌及空质粒菌株分别滴鼻、点眼免疫雏鸡，于不同时间检测血清样品中特异性IgG；于三免后不同时间采集雏鸡的泪液、气管洗液、胆汁和肠洗液样品，采用间接ELISA方法检测样品的特异性sIgA；用MTY法检测免疫鸡脾淋巴细胞增殖情况，结果显示重组干酪乳杆菌表达系统能刺激动物黏膜免疫反应和系统免疫反应。%Neweasfle disease virus （NDV） HN antigen was expressed by the recombinant Lactobacillus casei. The HN protein was surface-displayed on the L.casei verified by Immunofluorescence Microscopy, SDS-PAGE and Western blot. Intranasal and eye dropping immunized chicks was performed with the recombinant strain L. casei harboring pLA-HN or pLA. Specific anti-HN IgG antibody in the serum and specific anti-HN secret immunoglobulin A（sIgA） antibody in the lung and intestine fluid, tear and bile of chicken were detected by indirect ELISA.T-cell proliferation responses were investigated by MTT test. The results demonstrated that the recombinant L.casei could induce the mucosal and systemic immunity.

The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.

Science.gov (United States)

Tamayo, Joel V; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M Tanaka; Gavis, Elizabeth R

2017-04-04

The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

Directory of Open Access Journals (Sweden)

Joel V. Tamayo

2017-04-01

Full Text Available The Drosophila hnRNP F/H homolog, Glorund (Glo, regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3′ untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial.

Science.gov (United States)

Costeloe, Kate; Hardy, Pollyanna; Juszczak, Edmund; Wilks, Mark; Millar, Michael R

2016-02-13

Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth. However, there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely. We aimed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis, late-onset sepsis, and death in preterm infants. In this multicentre, randomised controlled phase 3 study (the PiPS trial), we recruited infants born between 23 and 30 weeks' gestational age within 48 h of birth from 24 hospitals in southeast England. Infants were randomly assigned (1:1) to probiotic or placebo via a minimisation algorithm randomisation programme. The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU; the placebo was dilute infant formula alone. Clinicians and families were masked to allocation. The primary outcomes were necrotising enterocolitis (Bell stage 2 or 3), blood culture positive sepsis more than 72 h after birth; and death before discharge from hospital. All primary analyses were by intention to treat. This trial is registered with ISRCTN, number 05511098 and EudraCT, number 2006-003445-17. Between July 1, 2010, and July 31, 2013, 1315 infants were recruited; of whom 654 were allocated to probiotic and 661 to placebo. Five infants had consent withdrawn after randomisation, thus 650 were analysed in the probiotic group and 660 in the placebo group. Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups. 61 infants (9%) in the probiotic group had necrotising enterocolitis compared with 66 (10%) in the placebo group (adjusted risk ratio 0·93 (95% CI 0·68-1·27); 73 (11%) infants in the probiotics group had sepsis compared with 77 (12%) in the placebo group (0·97 (0·73-1·29); and 54 (8%) deaths occurred before discharge home in the

The FINISH-3 Trial : A Phase 3, International, Randomized, Single-Blind, Controlled Trial of Topical Fibrocaps in Intraoperative Surgical Hemostasis

NARCIS (Netherlands)

Bochicchio, Grant V.; Gupta, Navyash; Porte, Robert J.; Renkens, Kenneth L.; Pattyn, Piet; Topal, Baki; Troisi, Roberto Ivan; Muir, William; Chetter, Ian; Gillen, Daniel L.; Zuckerman, Linda A.; Frohna, Paul A.

BACKGROUND: This Phase 3, international, randomized, single-blind, controlled trial (FINISH-3) compared the efficacy and safety of Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, vs gelatin sponge alone for use as a hemostat for surgical

A feasibility and efficacy trial of a hand-held humidification device in patients undergoing radiotherapy for head and neck cancer.

Science.gov (United States)

Ghosh, Priyanka; Lazar, Ann A; Ryan, William R; Yom, Sue S

2017-08-01

This study aimed to evaluate the effects of warm-mist humidification during and after head and neck radiation therapy (HN RT) on quality of life (QOL), as measured by the M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) HN score. A secondary aim was to compare QOL among compliers (≥60% of protocol-recommended usage) versus non-compliers. Twenty patients self-administered a hand-held, self-sterilizing humidification device for a recommended time of at least 15 min twice daily for 12 weeks. Patients completed the MDASI-HN instrument at RT start, after 6 weeks, and after 12 weeks. Compliance was reported weekly. The average HN score at baseline was 1.7 (SD = 1.8) and increased to 6.0 (SD = 1.6) after 6 weeks; this increase was much higher than anticipated and the primary endpoint could not be reached. However, compliers had an average of nearly two less HN symptoms (-1.8, 95% CI -4 to 0.2; p = 0.08) than non-compliers at 6 weeks and fewer symptoms at 12 weeks as well (-0.9, 95% CI -2.9 to 1.2; p = 0.39). The most common terms patients used to describe humidification were "helpful" and "soothing." Compliance with humidification during RT was associated with fewer reported HN symptoms and a strong trend to better QOL. Improvements were seen from compliance with occasional required use of a portable, inexpensive device. Our findings support continued efforts to reduce barriers to humidification, as an intervention that should be considered for standard HN RT clinical practice.

A 3-armed randomized controlled trial of nurses' continuing education meetings on adverse drug reactions.

Science.gov (United States)

Sarayani, Amir; Naderi-Behdani, Fahimeh; Hadavand, Naser; Javadi, Mohammadreza; Farsad, Fariborz; Hadjibabaie, Molouk; Gholami, Kheirollah

2015-01-01

Nurses' insufficient knowledge of adverse drug reactions is reported as a barrier to spontaneous reporting. Therefore, CE meetings could be utilized to enhance nurses' competencies. In a 3-armed randomized controlled trial, 496 nurses, working in a tertiary medical center, were randomly allocated to a didactic lecture, brainstorming workshop, or the control group (delayed education). Similar instructors (2 clinical pharmacists) prepared and delivered the educational content to all 3 groups. Outcomes were declarative/procedural knowledge (primary outcome), participation rate, and satisfaction. Knowledge was evaluated using a validated researcher-made questionnaire in 3 time points: immediately before, immediately after, and 3 months after each session. Participants' satisfaction was assessed immediately after each meeting via a standard tool. Data were analyzed using appropriate parametric and nonparametric tests. Rate of participation was 37.7% for the lecture group and 47.5% for the workshop group. The workshop participants were significantly more satisfied in comparison with the lecture group (p techniques. © 2015 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education, Association for Hospital Medical Education.

Evaluation of wet-cupping therapy for persistent non-specific low back pain: a randomised, waiting-list controlled, open-label, parallel-group pilot trial

Directory of Open Access Journals (Sweden)

Kim Kun

2011-06-01

Full Text Available Abstract Background Persistent non-specific low back pain (PNSLBP is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP. Methods We recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to100 numerical rating scale (NRS for pain, the McGill Pain Questionnaire for pain intensity (PPI and the Oswestry Disability Questionnaire (ODQ, and we assessed acetaminophen use and safety issues. Results The results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group, but there was no statistical difference between the groups (p = 0.52. However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p Conclusion This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention

Neck collar, "act-as-usual" or active mobilization for whiplash injury? A randomized parallel-group trial

DEFF Research Database (Denmark)

Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge

2007-01-01

practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general......Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion...

Neck collar, "act-as-usual" or active mobilization for whiplash injury? A randomized parallel-group trial

DEFF Research Database (Denmark)

Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge

2007-01-01

Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general...... practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12...

Standard versus prosocial online support groups for distressed breast cancer survivors: a randomized controlled trial.

Science.gov (United States)

Lepore, Stephen J; Buzaglo, Joanne S; Lieberman, Morton A; Golant, Mitch; Davey, Adam

2011-08-25

The Internet can increase access to psychosocial care for breast cancer survivors through online support groups. This study will test a novel prosocial online group that emphasizes both opportunities for getting and giving help. Based on the helper therapy principle, it is hypothesized that the addition of structured helping opportunities and coaching on how to help others online will increase the psychological benefits of a standard online group. A two-armed randomized controlled trial with pretest and posttest. Non-metastatic breast cancer survivors with elevated psychological distress will be randomized to either a standard facilitated online group or to a prosocial facilitated online group, which combines online exchanges of support with structured helping opportunities (blogging, breast cancer outreach) and coaching on how best to give support to others. Validated and reliable measures will be administered to women approximately one month before and after the interventions. Self-esteem, positive affect, and sense of belonging will be tested as potential mediators of the primary outcomes of depressive/anxious symptoms and sense of purpose in life. This study will test an innovative approach to maximizing the psychological benefits of cancer online support groups. The theory-based prosocial online support group intervention model is sustainable, because it can be implemented by private non-profit or other organizations, such as cancer centers, which mostly offer face-to-face support groups with limited patient reach. ClinicalTrials.gov: NCT01396174.

The efficacy of a group Cognitive Behavioural Therapy for war-affected young migrants living in Australia: A cluster randomised controlled trial

Directory of Open Access Journals (Sweden)

Chew Sia Ooi

2016-10-01

Full Text Available BackgroundPreventative and treatment programmes for people at risk of developing psychological problems after exposure to war trauma have mushroomed in the last decade. However, there is still much contention about evidence-based and culturally sensitive interventions for children. The aim of this study was to examine the efficacy of the Teaching Recovery Techniques in improving the emotional and behavioural outcomes of war-affected children resettled in Australia. Methods and findings A cluster randomised controlled trial with pretest, posttest, and 3-month follow-up design was employed. A total of 82 participants (aged 10 to 17 years were randomised by school into the 8-week intervention (n = 45 or the waiting list (WL control condition (n = 37. Study outcomes included symptoms of posttraumatic stress disorder, depression, internalising and externalising problems, as well as psychosocial functioning. A medium intervention effect was found for depression symptoms. Participants in the intervention condition experienced a greater symptom reduction than participants in the WL control condition, F(1,155 = 5.20, p = .024, partial ƞ2 = 0.07. This improvement was maintained at the 3-month follow-up, F(2,122 = 7.24, p = .001, partial ƞ2 = 0.20. ConclusionsThese findings suggest the potential benefit of the school and group-based intervention on depression symptoms but not on other outcomes, when compared to a waiting list control group.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12611000948998

Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial.

Science.gov (United States)

Leurent, Baptiste; Killaspy, Helen; Osborn, David P; Crawford, Mike J; Hoadley, Angela; Waller, Diane; King, Michael

2014-11-01

Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. Secondary analysis of data from a randomised controlled trial of group art therapy as an adjunctive treatment for schizophrenia (n = 140) versus standard care alone (n = 137). Positive and Negative Syndrome Scale scores at 12 months were compared between trial arms. Interaction between intervention effect and different subgroups, including those with more severe negative symptoms of schizophrenia, and those who expressed a preference for art therapy prior to randomisation, was tested using a linear mixed model. The clinical effectiveness of group art therapy did not significantly differ between participants with more or less severe negative symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P = 0.741], or between those who did and did not express a preference for art therapy [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other exploratory subgroups suggested differences in intervention effect. There was no evidence of greater improvement in clinical symptoms of schizophrenia for those with more severe negative symptoms or those with a preference for art therapy. Identification of patients with schizophrenia who may benefit most from group art therapy remains elusive.

Social support and education groups for single mothers: a randomized controlled trial of a community-based program.

Science.gov (United States)

Lipman, Ellen L; Boyle, Michael H

2005-12-06

Members of families headed by single mothers are at increased risk of psychosocial disadvantage and mental health problems. We assessed the effect of a community-based program of social support and education groups for single mothers of young children on maternal well-being and parenting. We recruited 116 single mothers of children 3 to 9 years old through community advertisements. Eligible mothers were randomly assigned either to participate in a 10-week program of group sessions (1.5 hours per week) offering social support and education, with a parallel children's activity group, or to receive a standard list of community resources and the option to participate in group sessions at the end of the follow-up period. Interviewers blinded to the randomization collected assessment data from all mothers at baseline and at 3 follow-up visits (immediately after the intervention and at 3 and 6 months after the intervention). Outcome measures were self-reported mood, self-esteem, social support and parenting. Between February 2000 and April 2003, the program was offered to 9 groups of single mothers. Most of the mothers in the trial reported high levels of financial and mental health problems. In the short term (after the intervention), mothers in the intervention group had improved scores for mood (p effect = 0.55) and self-esteem (p effect = 0.29) compared with mothers in the control group; scores for the other 2 measures did not differ between the groups. Growth curve analysis of program effects over the follow-up period showed improvement in all 4 outcomes, with no significant difference between the intervention and control groups. This community-based program of group sessions offering social support and education to low-income single mothers had positive short-term effects on mood and self-esteem but not on social support and parenting. Longer follow-up showed attenuation of these effects.

Psychiatric symptoms of patients with primary mitochondrial DNA disorders

Directory of Open Access Journals (Sweden)

Inczedy-Farkas Gabriella

2012-02-01

Full Text Available Abstract Background The aim of our study was to assess psychiatric symptoms in patients with genetically proven primary mutation of the mitochondrial DNA. Methods 19 adults with known mitochondrial mutation (MT have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI, the Symptom Check List-90-Revised (SCL-90-R, the Beck Depression Inventory-Short Form (BDI-SF, the Hamilton Depression Rating Scale (HDRS and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II As control, 10 patients with hereditary sensorimotor neuropathy (HN, harboring the peripheral myelin protein-22 (PMP22 mutation were examined with the same tools. Results The two groups did not differ significantly in gender, age or education. Mean HAQ-DI score was 0.82 in the MT (range: 0-1.625 and 0.71 in the HN group (range: 0-1.625. Level of disability between the two groups did not differ significantly (p = 0.6076. MT patients scored significantly higher on the BDI-SF and HDRS than HN patients (12.85 versus 4.40, p = 0.031, and 15.62 vs 7.30, p = 0.043, respectively. The Global Severity Index (GSI of SCL-90-R also showed significant difference (1.44 vs 0.46, p = 0.013 as well as the subscales except for somatization. SCID-I interview yielded a variety of mood disorders in both groups. Eight MT patient (42% had past, 6 (31% had current, 5 (26% had both past and current psychiatric diagnosis, yielding a lifetime prevalence of 9/19 (47% in the MT group. In the HN group, 3 patients had both past and current diagnosis showing a lifetime prevalence of 3/10 (30% in this group. SCID-II detected personality disorder in 8 MT cases (42%, yielding 3 avoidant, 2 obsessive-compulsive and 3 personality disorder not otherwise specified (NOS diagnosis. No personality disorder was identified in the HN group. Conclusions Clinicians should be aware of the high prevalence of psychiatric symptoms in patients with

A comparison of two treatments for childhood apraxia of speech: methods and treatment protocol for a parallel group randomised control trial

Directory of Open Access Journals (Sweden)

Murray Elizabeth

2012-08-01

Full Text Available Abstract Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds (articulation and melody (prosody of speech. These difficulties may persist through life and are detrimental to academic, social, and vocational development. A number of published single subject and case series studies of speech treatments are available. There are currently no randomised control trials or other well designed group trials available to guide clinical practice. Methods/Design A parallel group, fixed size randomised control trial will be conducted in Sydney, Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech: 1 Rapid Syllable Transition Treatment and the 2 Nuffield Dyspraxia Programme – Third edition. Eligible children will be English speaking, aged 4–12 years with a diagnosis of suspected CAS, normal or adjusted hearing and vision, and no comprehension difficulties or other developmental diagnoses. At least 20 children will be randomised to receive one of the two treatments in parallel. Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals. Treatment will be administered in 1-hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week, 1 month and 4 months post-treatment. All post assessments will be completed by blinded assessors. Our hypotheses are: 1 treatment effects at 1 week post will be similar for both treatments, 2 maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3 generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563).

Science.gov (United States)

Foster, Nadine E; Healey, Emma L; Holden, Melanie A; Nicholls, Elaine; Whitehurst, David Gt; Jowett, Susan; Jinks, Clare; Roddy, Edward; Hay, Elaine M

2014-07-27

Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients' short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. This trial will contribute to the

Directions for new developments on statistical design and analysis of small population group trials.

Science.gov (United States)

Hilgers, Ralf-Dieter; Roes, Kit; Stallard, Nigel

2016-06-14

Most statistical design and analysis methods for clinical trials have been developed and evaluated where at least several hundreds of patients could be recruited. These methods may not be suitable to evaluate therapies if the sample size is unavoidably small, which is usually termed by small populations. The specific sample size cut off, where the standard methods fail, needs to be investigated. In this paper, the authors present their view on new developments for design and analysis of clinical trials in small population groups, where conventional statistical methods may be inappropriate, e.g., because of lack of power or poor adherence to asymptotic approximations due to sample size restrictions. Following the EMA/CHMP guideline on clinical trials in small populations, we consider directions for new developments in the area of statistical methodology for design and analysis of small population clinical trials. We relate the findings to the research activities of three projects, Asterix, IDeAl, and InSPiRe, which have received funding since 2013 within the FP7-HEALTH-2013-INNOVATION-1 framework of the EU. As not all aspects of the wide research area of small population clinical trials can be addressed, we focus on areas where we feel advances are needed and feasible. The general framework of the EMA/CHMP guideline on small population clinical trials stimulates a number of research areas. These serve as the basis for the three projects, Asterix, IDeAl, and InSPiRe, which use various approaches to develop new statistical methodology for design and analysis of small population clinical trials. Small population clinical trials refer to trials with a limited number of patients. Small populations may result form rare diseases or specific subtypes of more common diseases. New statistical methodology needs to be tailored to these specific situations. The main results from the three projects will constitute a useful toolbox for improved design and analysis of small

n-3 fatty acid-based parenteral nutrition improves postoperative recovery for cirrhotic patients with liver cancer: A randomized controlled clinical trial.

Science.gov (United States)

Zhang, Binhao; Wei, Gang; Li, Rui; Wang, Yanjun; Yu, Jie; Wang, Rui; Xiao, Hua; Wu, Chao; Leng, Chao; Zhang, Bixiang; Chen, Xiao-Ping

2017-10-01

A new lipid emulsion enriched in n-3 fatty acid has been reported to prevent hepatic inflammation in patients following major surgery. However, the role of n-3 fatty acid-based parenteral nutrition for postoperative patients with cirrhosis-related liver cancer is unclear. We investigated the safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic patients with liver cancer followed hepatectomy. A prospective randomized controlled clinical trial (Registered under ClinicalTrials.gov Identifier no. NCT02321202) was conducted for cirrhotic patients with liver cancer that underwent hepatectomy between March 2010 and September 2013 in our institution. We compared isonitrogenous total parenteral nutrition with 20% Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany) (treatment group) to Structolipid alone (control group) for five days postoperatively, in the absence of enteral nutrition. We enrolled 320 patients, and 312 (97.5%) were included in analysis (155 in the control group and 157 in the treatment group). There was a significant reduction of morbidity and mortality in the treatment group, when compared with the control group (total complications 78 [50.32%] vs. 46 [29.30%]; P parenteral nutrition significantly improved postoperative recovery for cirrhotic patients with liver cancer following hepatectomy, with a significant reduction in overall mortality and length of hospital stay. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Prophecy as a religious language in the Radical Reformation. The prophetic role and authorial voice of HN and his Family of Love

OpenAIRE

Pietsch, Andreas

2017-01-01

The close relationship between prophecy and dissent is clear and well-researched. The example of the sixteenth-century charismatic Hendrik Niclaes, who wrote prophetical texts under the cryptonym HN, simply seems to be another case in point. Yet a close analysis of his language reveals a certain ambivalence. While Niclaes used a prophetical voice as seen in several characteristic elements of authorship to establish a dissenting position of authority, he also remained very close to conventiona...

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

Science.gov (United States)

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis

Directory of Open Access Journals (Sweden)

Gluud Christian

2008-07-01

Full Text Available Abstract Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. Design The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1 specialized addiction treatment plus treatment as usual or 2 treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. Trial registration ClinicalTrials.gov NCT00484302.

Recruitment to publicly funded trials--are surgical trials really different?

Science.gov (United States)

Cook, Jonathan A; Ramsay, Craig R; Norrie, John

2008-09-01

Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.

Return of individual research results and incidental findings in the clinical trials cooperative group setting.

Science.gov (United States)

Ferriere, Michael; Van Ness, Brian

2012-04-01

The National Cancer Institute (NCI)-funded cooperative group cancer clinical trial system develops experimental therapies and often collects samples from patients for correlative research. The cooperative group bank (CGB) system maintains biobanks with a current policy not to return research results to individuals. An online survey was created, and 10 directors of CGBs completed the surveys asking about understanding and attitudes in changing policies to consider return of incidental findings (IFs) and individual research results (IRRs) of health significance. The potential impact of the 10 consensus recommendations of Wolf et al. presented in this issue are examined. Reidentification of samples is often not problematic; however, changes to the current banking and clinical trial systems would require significant effort to fulfill an obligation of recontact of subjects. Additional resources, as well as a national advisory board would be required to standardize implementation.

Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.

Science.gov (United States)

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Piemontese, Matteo; Nieri, Michele

2012-02-01

To compare immediate versus early non-occlusal loading of dental implants placed flapless in a 3-year, parallel group, randomized clinical trial. The study was conducted in a private dental clinic between July 2005 and July 2010. Patients 18 years or older were randomized to receive implants for fixed partial dentures in cases of partial edentulism. The test group was represented by immediate non-occlusal implant loading, whereas the control group was represented by early non-occlusal implant loading. The outcome variables were implant failure, complications and radiographic bone level at implant sites 3 years after loading, measured from the implant-abutment junction to the most coronal point of bone-to-implant contact. Randomization was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes, and the measurer was blinded to group assignment. Sixty patients were randomized: 30 to the immediately loaded group and 30 to the early loaded group. Four patients dropped out; however, the data of all patients were included in the analysis. No implant failure occurred. Two complications occurred in the control group and one in the test group. The mean bone level at 3 years was 1.91 mm for test group and 1.59 mm for control group. The adjusted difference in bone level was 0.26 mm (CI 95% -0.08 to 0.59, p = 0.1232). The null hypothesis of no difference in failure rates, complications and bone level between implants that were loaded immediately or early at 3 years cannot be rejected in this randomized clinical trial. © 2011 John Wiley & Sons A/S.

Personalised normative feedback for preventing alcohol misuse in university students: Solomon three-group randomised controlled trial.

Directory of Open Access Journals (Sweden)

Maria T Moreira

Full Text Available Young people tend to over-estimate peer group drinking levels. Personalised normative feedback (PNF aims to correct this misperception by providing information about personal drinking levels and patterns compared with norms in similar aged peer groups. PNF is intended to raise motivation for behaviour change and has been highlighted for alcohol misuse prevention by the British Government Behavioural Insight Team. The objective of the trial was to assess the effectiveness of PNF with college students for the prevention of alcohol misuse.Solomon three-group randomised controlled trial. 1751 students, from 22 British Universities, allocated to a PNF group, a normal control group, or a delayed measurement control group to allow assessment of any measurement effects. PNF was provided by email. Participants completed online questionnaires at baseline, 6- and 12-months (only 12-months for the delayed measurement controls. Drinking behaviour measures were (i alcohol disorders; (ii frequency; (iii typical quantity, (iv weekly consumption; (v alcohol-related problems; (vi perceived drinking norms; and (vii positive alcohol expectancies. Analyses focused on high-risk drinkers, as well as all students, because of research evidence for the prevention paradox in student drinkers.Follow-up rates were low, with only 50% and 40% responding at 6- and 12-months, respectively, though comparable to similar European studies. We found no evidence for any systematic attrition bias. Overall, statistical analyses with the high risk sub-sample, and for all students, showed no significant effects of the intervention, at either time-point, in a completed case analysis and a multiple imputation analysis.We found no evidence for the effectiveness of PNF for the prevention of alcohol misuse and alcohol-related problems in a UK student population.Controlled-Trials.com ISRCTN30784467.

Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

OpenAIRE

Crawford, MJ; Killaspy, H; Barnes, TR; Barrett, B; Byford, S; Clayton, K; Dinsmore, J; Floyd, S; Hoadley, A; Johnson, T; Kalaitzaki, E; King, M; Leurent, B; Maratos, A; O'Neill, FA

2012-01-01

OBJECTIVE To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. DESIGN A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. SETTING Study partic...

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

Science.gov (United States)

Slow, Sandy; Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

2014-12-15

To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly

Parental presence on neonatal intensive care unit clinical bedside rounds: randomised trial and focus group discussion

Science.gov (United States)

Boswell, Danette; Broom, Margaret; Smith, Judith; Davis, Deborah

2015-01-01

Background There are limited data to inform the choice between parental presence at clinical bedside rounds (PPCBR) and non-PPCBR in neonatal intensive care units (NICUs). Methods We performed a single-centre, survey-based, crossed-over randomised trial involving parents of all infants who were admitted to NICU and anticipated to stay >11 days. Parents were randomly assigned using a computer-generated stratified block randomisation protocol to start with PPCBR or non-PPCBR and then crossed over to the other arm after a wash-out period. At the conclusion of each arm, parents completed the ‘NICU Parental Stressor Scale’ (a validated tool) and a satisfaction survey. After completion of the trial, we surveyed all healthcare providers who participated at least in one PPCBR rounding episode. We also offered all participating parents and healthcare providers the opportunity to partake in a focus group discussion regarding PPCBR. Results A total of 72 parents were enrolled in this study, with 63 parents (87%) partially or fully completing the trial. Of the parents who completed the trial, 95% agreed that parents should be allowed to attend clinical bedside rounds. A total of 39 healthcare providers’ surveys were returned and 35 (90%) agreed that parents should be allowed to attend rounds. Nine healthcare providers and 8 parents participated in an interview or focus group, augmenting our understanding of the ways in which PPCBR was beneficial. Conclusions Parents and healthcare providers strongly support PPCBR. NICUs should develop policies allowing PPCBR while mitigating the downsides and concerns of parents and healthcare providers such as decreased education opportunity and confidentiality concerns. Trial registration number Australia and New Zealand Clinical Trials Register number, ACTRN12612000506897. PMID:25711125

Effect of physical training on urinary incontinence: a randomized parallel group trial in nursing homes

Directory of Open Access Journals (Sweden)

Vinsnes AG

2012-02-01

Full Text Available Anne G Vinsnes1, Jorunn L Helbostad2, Signe Nyrønning3, Gene E Harkless1,4, Randi Granbo5, Arnfinn Seim61Faculty of Nursing, Sør-Trøndelag University College, 2Department of Neuroscience, Norwegian University of Science and Technology, 3Søbstad Community Hospital and Teaching Nursing Home, Trondheim, Norway; 4University of New Hampshire, College of Health and Social Services, Nursing Faculty, Durham, New Hampshire, USA; 5Department of Physiotherapy, Sør-Trøndelag University College, 6Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, NorwayBackground: Residents in nursing homes (NHs are often frail older persons who have impaired physical activity. Urinary incontinence (UI is a common complaint for residents in NHs. Reduced functional ability and residence in NHs are documented to be risk factors for UI.Objective: To investigate if an individualized training program designed to improve activity of daily living (ADL and physical capacity among residents in nursing homes has any impact on UI.Materials and methods: This randomized controlled trial was a substudy of a Nordic multicenter study. Participants had to be >65 years, have stayed in the NH for more than 3 months and in need of assistance in at least one ADL. A total of 98 residents were randomly allocated to either a training group (n = 48 or a control group (n = 50 after baseline registrations. The training program lasted for 3 months and included accommodated physical activity and ADL training. Personal treatment goals were elicited for each subject. The control group received their usual care. The main outcome measure was UI as measured by a 24-hour pad-weighing test. There was no statistically significant difference between the groups on this measure at baseline (P = 0.15. Changes were calculated from baseline to 3 months after the end of the intervention.Results: Altogether, 68 participants were included in the analysis

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial

Energy Technology Data Exchange (ETDEWEB)

Wang, Ling-Wei, E-mail: lwwang@vghtpe.gov.tw [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Chen, Yi-Wei [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Ho, Ching-Yin [National Yang-Ming University, Taiwan (China); Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan (China); Hsueh Liu, Yen-Wan [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Chou, Fong-In [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Liu, Yuan-Hao [Nuclear Science and Engineering Department, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Liu, Hong-Ming; Peir, Jinn-Jer [Nuclear Science and Technology Development Center, National Tsing Hua University, Taiwan (China); Jiang, Shiang-Huei [Institute of Nuclear Engineering and Science, National Tsing Hua University, Taiwan (China); Chang, Chi-Wei [National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Liu, Ching-Sheng [Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan (China); National Yang-Ming University, Taiwan (China); Lin, Ko-Han [Taoyuan Veterans Hospital, Taiwan (China); Wang, Shyh-Jen [National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Chu, Pen-Yuan [National Yang-Ming University, Taiwan (China); Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan (China); Lo, Wen-Liang; Kao, Shou-Yen [National Yang-Ming University, Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taiwan (China); and others

2016-05-01

Purpose: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. Methods and Materials: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA–positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. Results: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. Conclusions: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

HN-NCA heteronuclear TOCSY-NH experiment for {sup 1}H{sup N} and {sup 15}N sequential correlations in ({sup 13}C, {sup 15}N) labelled intrinsically disordered proteins

Energy Technology Data Exchange (ETDEWEB)

Wiedemann, Christoph; Goradia, Nishit; Häfner, Sabine [Leibniz Institute for Age Research, Fritz Lipmann Institute, Research Group Biomolecular NMR Spectroscopy (Germany); Herbst, Christian [Ubon Ratchathani University, Department of Physics, Faculty of Science (Thailand); Görlach, Matthias; Ohlenschläger, Oliver; Ramachandran, Ramadurai, E-mail: raman@fli-leibniz.de [Leibniz Institute for Age Research, Fritz Lipmann Institute, Research Group Biomolecular NMR Spectroscopy (Germany)

2015-10-15

A simple triple resonance NMR experiment that leads to the correlation of the backbone amide resonances of each amino acid residue ‘i’ with that of residues ‘i−1’ and ‘i+1’ in ({sup 13}C, {sup 15}N) labelled intrinsically disordered proteins (IDPs) is presented. The experimental scheme, {HN-NCA heteronuclear TOCSY-NH}, exploits the favourable relaxation properties of IDPs and the presence of {sup 1}J{sub CαN} and {sup 2}J{sub CαN} couplings to transfer the {sup 15}N{sub x} magnetisation from amino acid residue ‘i’ to adjacent residues via the application of a band-selective {sup 15}N–{sup 13}C{sup α} heteronuclear cross-polarisation sequence of ∼100 ms duration. Employing non-uniform sampling in the indirect dimensions, the efficacy of the approach has been demonstrated by the acquisition of 3D HNN chemical shift correlation spectra of α-synuclein. The experimental performance of the RF pulse sequence has been compared with that of the conventional INEPT-based HN(CA)NH pulse scheme. As the availability of data from both the HCCNH and HNN experiments will make it possible to use the information extracted from one experiment to simplify the analysis of the data of the other and lead to a robust approach for unambiguous backbone and side-chain resonance assignments, a time-saving strategy for the simultaneous collection of HCCNH and HNN data is also described.

Go4it; study design of a randomised controlled trial and economic evaluation of a multidisciplinary group intervention for obese adolescents for prevention of diabetes mellitus type 2

Directory of Open Access Journals (Sweden)

Weijs Peter JM

2008-12-01

Full Text Available Abstract Background In the Netherlands, the first adolescents with diabetes mellitus type 2 as a result of obesity have recently been diagnosed. Therefore, it is very important that programs aiming at the prevention of type 2 diabetes of obese adolescents are developed and evaluated. Methods Go4it is a multidisciplinary group treatment that focuses on: 1 increasing awareness of the current dietary and physical activity behaviour (i.e. energy balance behaviour, 2 improving diet, 3 decreasing sedentary behaviour, 4 increasing levels of physical activity, and 5 coping with difficult situations. Go4it consists of 7 sessions with an interval of 2–3 weeks. The effectiveness of the multidisciplinary group treatment compared with usual care (i.e. referral to a dietician was evaluated in a randomised controlled trial. We examined effects on BMI(sds, body composition, energy expenditure, glucose tolerance and insulin resistance (primary outcome measure, as well as dietary and physical activity behaviour and quality of life. An economic evaluation from a societal perspective was conducted alongside the randomised trial to evaluate the cost-effectiveness of the multidisciplinary treatment program vs. usual care. Discussion In this paper we described a multidisciplinary treatment program (Go4it for obese adolescents and the design of a randomised controlled trial and economic evaluation to evaluate its effectiveness and cost-effectiveness. Trial registration Netherlands Trial Register (ISRCTN27626398.

Long noncoding RNA NEAT1 promotes cell proliferation and invasion by regulating hnRNP A2 expression in hepatocellular carcinoma cells

Directory of Open Access Journals (Sweden)

Mang YY

2017-02-01

Full Text Available Yuanyi Mang, Li Li, Jianghua Ran, Shengning Zhang, Jing Liu, Laibang Li, Yiming Chen, Jian Liu, Yang Gao, Gang Ren Department of Hepato-Biliary-Pancreatic Surgery, The Calmette Affiliated Hospital of Kunming Medical University, The First Hospital of Kunming, Kunming, Yunnan, People’s Republic of China Abstract: Growing evidence demonstrates that long noncoding RNAs (lncRNAs are involved in the progression of various cancers, including hepatocellular carcinoma (HCC. The role of nuclear-enriched abundant transcript 1 (NEAT1, an essential lncRNA for the formation of nuclear body paraspeckles, has not been fully explored in HCC. We aimed to determine the expression, roles and functional mechanisms of NEAT1 in the proliferation and invasion of HCC. Based on real-time polymerase chain reaction data, we suggest that NEAT1 is upregulated in HCC tissues compared with noncancerous liver tissues. The knockdown of NEAT1 altered global gene expression patterns and reduced HCC cell proliferation, invasion and migration. RNA immunoprecipitation and RNA pull-down assays confirmed that U2AF65 binds to NEAT1. Furthermore, the study indicated that NEAT1 regulated hnRNP A2 expression and that this regulation may be associated with the NEAT1–U2AF65 protein complex. Thus, the NEAT1-hnRNP A2 regulation mechanism promotes HCC pathogenesis and may provide a potential target for the prognosis and treatment of HCC. Keywords: long noncoding RNA, NEAT1, RNA-binding protein, HCC

VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

LENUS (Irish Health Repository)

Nyhan, Michelle J

2012-01-31

BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

Improving the effectiveness of psychological interventions for depression and anxiety in the cardiac rehabilitation pathway using group-based metacognitive therapy (PATHWAY Group MCT): study protocol for a randomised controlled trial.

Science.gov (United States)

Wells, Adrian; McNicol, Kirsten; Reeves, David; Salmon, Peter; Davies, Linda; Heagerty, Anthony; Doherty, Patrick; McPhillips, Rebecca; Anderson, Rebecca; Faija, Cintia; Capobianco, Lora; Morley, Helen; Gaffney, Hannah; Shields, Gemma; Fisher, Peter

2018-04-03

Anxiety and depression are prevalent among cardiac rehabilitation patients but pharmacological and psychological treatments have limited effectiveness in this group. Furthermore, psychological interventions have not been systematically integrated into cardiac rehabilitation services despite being a strategic priority for the UK National Health Service. A promising new treatment, metacognitive therapy, may be well-suited to the needs of cardiac rehabilitation patients and has the potential to improve outcomes. It is based on the metacognitive model, which proposes that a thinking style dominated by rumination, worry and threat monitoring maintains emotional distress. Metacognitive therapy is highly effective at reducing this thinking style and alleviating anxiety and depression in mental health settings. This trial aims to evaluate the effectiveness and cost-effectiveness of group-based metacognitive therapy for cardiac rehabilitation patients with elevated anxiety and/or depressive symptoms. The PATHWAY Group-MCT trial is a multicentre, two-arm, single-blind, randomised controlled trial comparing the clinical- and cost-effectiveness of group-based metacognitive therapy plus usual cardiac rehabilitation to usual cardiac rehabilitation alone. Cardiac rehabilitation patients (target sample n = 332) with elevated anxiety and/or depressive symptoms will be recruited across five UK National Health Service Trusts. Participants randomised to the intervention arm will receive six weekly sessions of group-based metacognitive therapy delivered by either cardiac rehabilitation professionals or research nurses. The intervention and control groups will both be offered the usual cardiac rehabilitation programme within their Trust. The primary outcome is severity of anxiety and depressive symptoms at 4-month follow-up measured by the Hospital Anxiety and Depression Scale total score. Secondary outcomes are severity of anxiety/depression at 12-month follow-up, health

Cost effectiveness of group follow-up after structured education for type 1 diabetes: a cluster randomised controlled trial

Science.gov (United States)

2014-01-01

Background This study examines the cost effectiveness of group follow-up after participation in the Dose Adjustment for Normal Eating (DAFNE) structured education programme for type 1 diabetes. Methods Economic evaluation conducted alongside a cluster randomised controlled trial involving 437 adults with type 1 diabetes in Ireland. Group follow-up involved two group education ‘booster’ sessions post-DAFNE. Individual follow-up involved two standard one-to-one hospital clinic visits. Incremental costs, quality-adjusted life years (QALYs) gained and cost effectiveness were estimated at 18 months. Uncertainty was explored using sensitivity analysis and by estimating cost effectiveness acceptability curves. Results Group follow-up was associated with a mean reduction in QALYs gained of 0.04 per patient (P value, 0.052; 95% CI, −0.08 to 0.01, intra-class correlation (ICC), 0.033) and a mean reduction in total healthcare costs of €772 (P value, 0.020; 95% CI, −1,415 to −128: ICC, 0.016) per patient. At alternative threshold values of €5,000, €15,000, €25,000, €35,000, and €45,000, the probability of group follow-up being cost effective was estimated to be 1.000, 0.762, 0.204, 0.078, and 0.033 respectively. Conclusions The results do not support implementation of group follow-up as the sole means of follow-up post-DAFNE. Given the reported cost savings, future studies should explore the cost effectiveness of alternative models of group care for diabetes. Trial registration Current Controlled Trials ISRCTN79759174 (assigned: 9 February 2007). PMID:24927851

Clinical Trials

Medline Plus

Full Text Available ... more screening tests to see which test produces the best results. Some companies and groups sponsor clinical trials that test the ... and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

A randomised trial of preoperative radiotherapy for stage T3 adenocarcinoma of rectum (TROG 01.04): a progress report

International Nuclear Information System (INIS)

Ngan, S.; Fisher, R.; McKay, M.J.; McClure, B.; Burmeister, B.H.; Schache, D.; Joseph, D.; Solomon, M.; Ackland, S.P.; Goldstein, D.; McLachlan, S.; Dhillon, H.; Thompson, P.

2003-01-01

To provide a progress report of the conduct of the randomised trial TROG 01.04. This is a randomised Australian and New Zealand multi-centre trial of preoperative radiotherapy for rectal cancer currently being conducted under the auspices of Trans-Tasman Radiation Oncology Group, Australasian Gastrointestinal Trials Group, Colorectal Surgical Society of Australasia, and Royal Australasian College of Surgeons. The trial comprises two studies, each with its own main objective. These objectives are, in patients with T3 clinically resectable carcinoma of the rectum, to demonstrate that (Study 1) the local recurrence rate in patients treated with a long course (LC) of pre-operative radiotherapy with continuous infusion 5-FU is lower than that in patients treated with a short course (SC) of pre-operative radiotherapy with early surgery; and (Study 2) the local recurrence rate in patients given pre-operative radiotherapy and chemotherapy is lower than that in patients treated with initial surgery. Over 150 patients have been accrued from 21 centres in the first 21 months. All patients were enrolled on Study 1, SC versus LC pre-operative radiotherapy. Study 2 has enrolled no patients in 15 months and has been discontinued. There was no obvious difference in rates of serious adverse events of SC and LC. An Independent Data Monitoring Committee is monitoring these and other aspects of the trial. The trial of SC versus LC is progressing well: such a trial is clearly feasible in Australia and New Zealand. It is however not feasible to compare initial surgery with preoperative radiotherapy

Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group

NARCIS (Netherlands)

Kamat, A.M.; Sylvester, R.J.; Bohle, A.; Palou, J.; Lamm, D.L.; Brausi, M.; Soloway, M.; Persad, R.; Buckley, R.; Colombel, M.; Witjes, J.A.

2016-01-01

PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Energy Technology Data Exchange (ETDEWEB)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca [Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta (Canada); Straube, William [Advanced Technology Consortium, Imaged-Guided Therapy QA Center, St. Louis, Missouri (United States); Laurie, Fran [Quality Assurance Review Center, Lincoln, Rhode Island (United States); Followill, David [Radiological Physics Center, University of Texas MD Anderson Cancer Centre, Houston, Texas (United States)

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

International Nuclear Information System (INIS)

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial

DEFF Research Database (Denmark)

Frederiksen, Pernille; Indahl, Aage; Andersen, Lars L

2017-01-01

-randomized controlled trial. METHODS: Publically employed workers (n = 505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non...

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

Science.gov (United States)

Geissler, Edward K.; Schnitzbauer, Andreas A.; Zülke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, René; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, André; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Turrión, Victor Sánchez; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Fändrich, Fred; Becker, Thomas; Söderdahl, Gunnar; Chazouillères, Olivier; Mäkisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Jürgen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Königsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

2016-01-01

Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. PMID:26555945

Clinical, biochemical and histological results of a double-blind trial with 1,25-dihydroxyvitamin D3, estradiol and placebo in post-menopausal osteoporosis.

Science.gov (United States)

Caniggia, A; Delling, G; Nuti, R; Lorè, F; Vattimo, A

1984-01-01

Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aimed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), estradiol valerate (E2) and placebo. Patients were divided into 4 groups: group 1 was given 1,25(OH)2D3 alone, group 2 was given E2 alone, group 3 was given 1,25(OH)2D3 + E2, group 4 received a placebo. The evaluation of the effects of the treatments included clinical examination of patients, the measurement of a number of biochemical parameters, such as plasma and urinary calcium and phosphate, urinary hydroxyproline, serum alkaline phosphatase, the measurement of intestinal calcium absorption and bone mineral content (BMC) and a histomorphometric study of bone biopsies from the iliac crest. The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3, while patients in the placebo group worsened. BMC decreased in the placebo group and increased, although non significantly, in the patients treated with 1,25(OH)2D3 or E2 or both. The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2. Changes in the volume density of trabecular bone paralleled those in BMC. The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis.

Intervention for children with word-finding difficulties: a parallel group randomised control trial.

Science.gov (United States)

Best, Wendy; Hughes, Lucy Mari; Masterson, Jackie; Thomas, Michael; Fedor, Anna; Roncoli, Silvia; Fern-Pollak, Liory; Shepherd, Donna-Lynn; Howard, David; Shobbrook, Kate; Kapikian, Anna

2017-07-31

The study investigated the outcome of a word-web intervention for children diagnosed with word-finding difficulties (WFDs). Twenty children age 6-8 years with WFDs confirmed by a discrepancy between comprehension and production on the Test of Word Finding-2, were randomly assigned to intervention (n = 11) and waiting control (n = 9) groups. The intervention group had six sessions of intervention which used word-webs and targeted children's meta-cognitive awareness and word-retrieval. On the treated experimental set (n = 25 items) the intervention group gained on average four times as many items as the waiting control group (d = 2.30). There were also gains on personally chosen items for the intervention group. There was little change on untreated items for either group. The study is the first randomised control trial to demonstrate an effect of word-finding therapy with children with language difficulties in mainstream school. The improvement in word-finding for treated items was obtained following a clinically realistic intervention in terms of approach, intensity and duration.

32 CFR 1624.3 - Age selection groups.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Age selection groups. 1624.3 Section 1624.3....3 Age selection groups. Age selection groups are established as follows: (a) The age 20 selection group for each calendar year consists of registrants who have attained or will attain the age of 20 in...

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

Directory of Open Access Journals (Sweden)

Freitag Christine M

2013-01-01

Full Text Available Abstract Background Group-based social skills training (SST has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD. To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS compared to treatment as usual (TAU. It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder.

Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR® trial

DEFF Research Database (Denmark)

Dusser, Daniel; Wise, Robert A; Dahl, Ronald

2016-01-01

BACKGROUND: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR(®), the largest...... randomized clinical trial in COPD performed to date. METHODS: A total of 17,135 patients from TIOSPIR(®) were pooled and grouped by GOLD grading (A-D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular...... (CV) and respiratory mortality were assessed. RESULTS: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV...

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

DEFF Research Database (Denmark)

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S

2016-01-01

PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor......-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards......). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age...

Do multimedia based information services increase knowledge and satisfaction in head and neck cancer patients?

Science.gov (United States)

D'Souza, V; Blouin, E; Zeitouni, A; Muller, K; Allison, P J

2013-09-01

To investigate the impact of a Multimode Comprehensive Tailored Information Package (MCTIP) on Head and Neck (H&N) cancer patients' knowledge and satisfaction. A non-randomized controlled trial was conducted at two participating hospitals. One hospital delivered the MCTIP and the second hospital provided normal care. The study was approved by local ethical committees. Patients with Stage III and IV cancer in the H&N region were recruited between their diagnosis and treatment. All participants were evaluated at baseline, 3 and 6months later using the Satisfaction with Cancer Information Profile (SCIP) and a Cancer Knowledge questionnaire. Data were analyzed using descriptive statistics, T tests, chi square tests and finally linear mixed model analyses to test the potential impact of the intervention. A total of 103 participants participated in this study and complete data at all time points were collected for 96. The Test group reported higher levels of Cancer Knowledge and Satisfaction at all time points (pmultimedia based tailored information and higher levels of satisfaction and cancer knowledge compared to those who receive information in ad hoc manner. Exploring patients' informational needs is necessary before planning information services to them. Copyright © 2013 Elsevier Ltd. All rights reserved.

9 CFR 3.7 - Compatible grouping.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Compatible grouping. 3.7 Section 3.7... Cats 1 Animal Health and Husbandry Standards § 3.7 Compatible grouping. Dogs and cats that are housed...; (c) Puppies or kittens 4 months of age or less may not be housed in the same primary enclosure with...

Individual Versus Group Cognitive-Behavioral Therapy for Partner-Violent Men: A Preliminary Randomized Trial.

Science.gov (United States)

Murphy, Christopher M; Eckhardt, Christopher I; Clifford, Judith M; Lamotte, Adam D; Meis, Laura A

2017-04-01

A randomized clinical trial tested the hypothesis that a flexible, case formulation-based, individual treatment approach integrating motivational interviewing strategies with cognitive-behavioral therapy (ICBT) is more efficacious than a standardized group cognitive-behavioral approach (GCBT) for perpetrators of intimate partner violence (IPV). Forty-two men presenting for services at a community domestic violence agency were randomized to receive 20 sessions of ICBT or a 20-week group cognitive-behavioral therapy (CBT) program. Participants and their relationship partners completed assessments of relationship abuse and relationship functioning at baseline and quarterly follow-ups for 1 year. Treatment uptake and session attendance were significantly higher in ICBT than GCBT. However, contrary to the study hypothesis, GCBT produced consistently equivalent or greater benefits than ICBT. Participant self-reports revealed significant reductions in abusive behavior and injuries across conditions with no differential benefits between conditions. Victim partner reports revealed more favorable outcomes for group treatment, including a statistically significant difference in psychological aggression, and differences exceeding a medium effect size for physical assault, emotional abuse, and partner relationship adjustment. In response to hypothetical relationship scenarios, GCBT was associated with greater reductions than ICBT (exceeding a medium effect) in articulated cognitive distortions and aggressive intentions. Treatment competence ratings suggest that flexible, individualized administration of CBT creates challenges in session agenda setting, homework implementation, and formal aspects of relationship skills training. Although caution is needed in generalizing findings from this small-scale trial, the results suggest that the mutual support and positive social influence available in group intervention may be particularly helpful for IPV perpetrators.

Effect of race/ethnicity on participation in HIV vaccine trials and comparison to other trials of biomedical prevention.

Science.gov (United States)

Dhalla, Shayesta; Poole, Gary

2014-01-01

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

Crystallization and preliminary X-ray crystallographic studies of transportin 1 in complex with nucleocytoplasmic shuttling and nuclear localization fragments

International Nuclear Information System (INIS)

Imasaki, Tsuyoshi; Shimizu, Toshiyuki; Hashimoto, Hiroshi; Hidaka, Yuji; Yamada, Michiyuki; Sato, Mamoru

2006-01-01

Transportin 1 was cocrystallized with nucleocytoplasmic shuttling fragments of JKTBP and hnRNP D and a nuclear localization fragment of TAP. X-ray diffraction data were collected using synchrotron radiation at SPring-8. Nucleocytoplasmic transport of proteins with molar masses of larger than 60 000 is mediated by transport receptors. The transport receptor transportin1 (Trn1) transports various kinds of RNA-binding proteins such as JKTBP, hnRNP D and TAP. Trn1 was successfully cocrystallized with nucleocytoplasmic shuttling fragments of JKTBP and hnRNP D and a nuclear localization fragment of TAP. The crystal of the Trn1–JKTBP fragment complex belongs to space group P2 1 2 1 2, with unit-cell parameters a = 131.5, b =171.5, c = 68.2 Å. The crystals of Trn1 in complex with hnRNP D and TAP fragments are orthorhombic, space group P2 1 2 1 2 1 , with unit-cell parameters a = 69.1, b = 119.1, c = 151.1 Å and a = 69.0, b = 119.1, c = 146.0 Å, respectively. The crystals diffracted to beyond 3.0, 3.2 and 2.4 Å resolution, respectively, using synchrotron radiation at SPring-8

Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

Science.gov (United States)

Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Jiang, Shude; Li, Yanping; Mo, Zhaojun; Xia, Jielai; Xie, Zhongping; Che, Yanchun; Yang, Jingsi; Yin, Zhifang; Wang, Jianfeng; Chu, Jiayou; Cai, Wei; Zhou, Jian; Wang, Junzhi; Li, Qihan

2016-12-01

 The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries.  In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol.  Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups.  The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder--study protocol of the randomised, multi-centre controlled SOSTA--net trial.

Science.gov (United States)

Freitag, Christine M; Cholemkery, Hannah; Elsuni, Leyla; Kroeger, Anne K; Bender, Stephan; Kunz, Cornelia Ursula; Kieser, Meinhard

2013-01-07

Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA-FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. The SOSTA - net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. ISRCTN94863788--SOSTA--net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder.

Clinical Trials

Medline Plus

Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...

Effectiveness of a group diabetes education programme in underserved communities in South Africa: pragmatic cluster randomized control trial

Directory of Open Access Journals (Sweden)

Mash Bob

2012-12-01

Full Text Available Abstract Background Diabetes is an important contributor to the burden of disease in South Africa and prevalence rates as high as 33% have been recorded in Cape Town. Previous studies show that quality of care and health outcomes are poor. The development of an effective education programme should impact on self-care, lifestyle change and adherence to medication; and lead to better control of diabetes, fewer complications and better quality of life. Methods Trial design: Pragmatic cluster randomized controlled trial Participants: Type 2 diabetic patients attending 45 public sector community health centres in Cape Town Interventions: The intervention group will receive 4 sessions of group diabetes education delivered by a health promotion officer in a guiding style. The control group will receive usual care which consists of ad hoc advice during consultations and occasional educational talks in the waiting room. Objective: To evaluate the effectiveness of the group diabetes education programme Outcomes: Primary outcomes: diabetes self-care activities, 5% weight loss, 1% reduction in HbA1c. Secondary outcomes: self-efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c, mean total cholesterol, quality of life Randomisation: Computer generated random numbers Blinding: Patients, health promoters and research assistants could not be blinded to the health centre’s allocation Numbers randomized: Seventeen health centres (34 in total will be randomly assigned to either control or intervention groups. A sample size of 1360 patients in 34 clusters of 40 patients will give a power of 80% to detect the primary outcomes with 5% precision. Altogether 720 patients were recruited in the intervention arm and 850 in the control arm giving a total of 1570. Discussion The study will inform policy makers and managers of the district health system, particularly in low to middle income countries, if this programme can

Group treatments for sensitive health care problems : a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence

OpenAIRE

Lamb, S. E. (Sallie E.); Pepper, Jo; Lall, Ranjit; Jørstad-Stein , Ellen C.; Clark, M. D. (Michael D.); Hill, Lesley; Fereday Smith, Jan

2009-01-01

Abstract Background The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms, quality of life, and costs, and to investigate the effect of patient preference on uptake and outcome of treatment. Methods A pragmatic, multi-centre randomised controlled trial in five British National Health Service physiotherapy departments. 174 women with stress and/or urge incontinence were randomised to receive treatment from a physiotherapist delivered in ...

Fracture Surgery of the extremities with the intra-operative use of 3D-RX: A randomized multicenter trial (EF3X-trial

Directory of Open Access Journals (Sweden)

Marmor Meir

2011-07-01

wrist, ankle or calcaneus eligible for surgery will be subjected to additional intra-operative 3D-RX. In half of the patients the surgeon will be blinded to these results, in the other half the surgeon may use the 3D-RX results to further optimize fracture reduction. In both randomization groups a CT-scan will be performed postoperatively. Based on these CT-scans the quality of fracture reduction and fixation will be determined. During the follow-up visits after hospital discharge at 6 and 12 weeks and 1 year postoperatively the patient relevant outcomes will be determined by joint specific, health economic and quality of life questionnaires. In addition a follow up study will be performed to determine the patient relevant outcomes and prevalence of posttraumatic osteoarthritis at 2 and 5 years postoperatively. Discussion The results of the study will provide more information on the effectiveness of the intra-operative use of 3D-imaging during surgical treatment of intra-articular fractures of the wrist, ankle and calcaneus. A randomized design in which patients will be allocated to a treatment arm during surgery will be used because of its high methodological quality and the ability to detect incongruences in the reduction and/or fixation that occur intra-operatively in the blinded arm of the 3D-RX. An alternative, pragmatic design could be to randomize before the start of the surgery, then two surgical strategies would be compared. This resembles clinical practice better, but introduces more bias and does not allow the assessment of incongruences that would have been detected by 3D-RX in the blinded arm. Trial registration Dutch Trial Register NTR 1902

Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial

OpenAIRE

Leurent, Baptiste; Killaspy, Helen; Osborn, David P.; Crawford, Mike J.; Hoadley, Angela; Waller, Diane; King, Michael

2014-01-01

PURPOSE Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. METHODS Secondary analysis of data from a randomised controlled trial of group art therapy ...

Explaining the impact of a women's group led community mobilisation intervention on maternal and newborn health outcomes: the Ekjut trial process evaluation

Directory of Open Access Journals (Sweden)

Sinha Rajesh

2010-10-01

Full Text Available Abstract Background Few large and rigorous evaluations of participatory interventions systematically describe their context and implementation, or attempt to explain the mechanisms behind their impact. This study reports process evaluation data from the Ekjut cluster-randomised controlled trial of a participatory learning and action cycle with women's groups to improve maternal and newborn health outcomes in Jharkhand and Orissa, eastern India (2005-2008. The study demonstrated a 45% reduction in neonatal mortality in the last two years of the intervention, largely driven by improvements in safe practices for home deliveries. Methods A participatory learning and action cycle with 244 women's groups was implemented in 18 intervention clusters covering an estimated population of 114 141. We describe the context, content, and implementation of this intervention, identify potential mechanisms behind its impact, and report challenges experienced in the field. Methods included a review of intervention documents, qualitative structured discussions with group members and non-group members, meeting observations, as well as descriptive statistical analysis of data on meeting attendance, activities, and characteristics of group attendees. Results Six broad, interrelated factors influenced the intervention's impact: (1 acceptability; (2 a participatory approach to the development of knowledge, skills and 'critical consciousness'; (3 community involvement beyond the groups; (4 a focus on marginalized communities; (5 the active recruitment of newly pregnant women into groups; (6 high population coverage. We hypothesize that these factors were responsible for the increase in safe delivery and care practices that led to the reduction in neonatal mortality demonstrated in the Ekjut trial. Conclusions Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to

PUPTH Prehospital Air Medical Plasma (PAMP) Trial

Science.gov (United States)

2014-07-01

for ability to continue. If unable to improve, they may be replaced . Two formal interim analyses of efficacy will be performed when 33% and 67% of...will be entered and maintained on a password protected SSL website designed for this trial. The data entered for the PAMPer trial will be...testing procedure for clinical trials. Biometrics , 1979. 35(3): p. 549‐56. 96. Murray, D.M., ed. The Design and Analysis of Group Randomized Trials

Disappointment and drop-out rate after being allocated to control group in a smoking cessation trial

DEFF Research Database (Denmark)

Lindström, D; Sundberg-Petersson, I; Adami, J

2010-01-01

If a patient agrees to take part in a randomised trial it is reasonable to presume that the patient would prefer to be allocated into the intervention. This study's aim was to investigate how patients react after they have been randomised into control group....

Clinical Trials

Medline Plus

Full Text Available ... needed. For safety purposes, clinical trials start with small groups of patients to find out whether a ... phase I clinical trials test new treatments in small groups of people for safety and side effects. ...

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

Science.gov (United States)

Schönenberg, Michael; Wiedemann, Eva; Schneidt, Alexander; Scheeff, Jonathan; Logemann, Alexander; Keune, Philipp M; Hautzinger, Martin

2017-09-01

and sham neurofeedback. The primary outcome was symptom score on the Conners' adult ADHD rating scale, assessed before treatment, at midtreatment (after 8 weeks), after treatment (after 16 weeks), and 6 months later. All individuals with at least one observation after randomisation were included in the analyses. This trial is registered with ClinicalTrials.gov, number NCT01883765. Between Feb 1, 2013, and Dec 1, 2015, 761 people were assessed for eligibility. 656 (86%) were excluded and 118 (15%) were eligible for participation in this study. Eligible participants were randomly assigned to neurofeedback (38 [32%]), sham neurofeedback (39 [33%]), or meta-cognitive therapy (41 [35%]). 37 (97%) individuals for neurofeedback, 38 (97%) for sham neurofeedback, and 38 (93%) for meta-cognitive therapy were included in analyses. Self-reported ADHD symptoms decreased substantially for all treatment groups (B=-2·58 [95% CI -3·48 to -1·68]; p<0·0001) between pretreatment and the end of 6 month follow-up, independent of treatment condition (neurofeedback vs sham neurofeedback B=-0·89 [95% CI -2·14 to 0·37], p=0·168; neurofeedback vs meta-cognitive therapy -0·30 [-1·55 to 0·95], p=0·639). No treatment-related or trial-related serious adverse events were reported. Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy. All three treatments were equivalently effective in reducing ADHD symptoms. This first randomised, sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults. German Research Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals.

Science.gov (United States)

Nagao, Akihiko; Maoka, Takashi; Ono, Hiroshi; Kotake-Nara, Eiichi; Kobayashi, Miyuki; Tomita, Mie

2015-02-01

We previously found that mice fed lutein accumulated its oxidative metabolites (3'-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3'-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD(+), (3'R,6'R)-3'-hydroxy-β,ε-caroten-3-one and (6RS,3'R,6'R)-3'-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3' and C6' of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy β-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo β-end group. Other xanthophylls such as β-cryptoxanthin and zeaxanthin, which have a 3-hydroxy β-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and β,ε-caroten-3'-one was significantly increased by the ingestion of β-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy β-end group of xanthophylls to a 3-oxo ε-end group. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Automorphism group of nonabelian groups of order p{sup 3}

Energy Technology Data Exchange (ETDEWEB)

Sarmin, Nor Haniza [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru (Malaysia); Barakat, Yasamin [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Malaysia and Islamic Azad University-Ahvaz Branch, Ahvaz (Iran, Islamic Republic of)

2014-06-19

Let G be a nonabelian group of order p{sup 3}, where p is a prime number. Then G is a two generated group that its commutator, centre and Frattini subgroup coincide and are of order p. Hence, the quotient group of G over its centre and also Frattini quotient group of G, both are of order p{sup 2}. However, the first mentioned quotient is isomorphic to the inner group of G, which is a normal subgroup of automorphism group of G. Whereas, Frattini quotient group of G is an abelian elementary group that can be considered as a vector space of dimension two over Z{sub p}, the field of integers modulo p. In this paper, we consider to apply these properties of G to characterize the automorphism group of G.

Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

Science.gov (United States)

Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E

2017-07-01

Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effects of women's groups practising participatory learning and action on preventive and care-seeking behaviours to reduce neonatal mortality: A meta-analysis of cluster-randomised trials.

Directory of Open Access Journals (Sweden)

Nadine Seward

2017-12-01

. Overall, women's groups practising PLA improved behaviours during and after home deliveries, including the use of safe delivery kits (odds ratio [OR] 2.92, 95% CI 2.02-4.22; I2 = 63.7%, 95% CI 4.4%-86.2%, use of a sterile blade to cut the umbilical cord (1.88, 1.25-2.82; 67.6%, 16.1%-87.5%, birth attendant washing hands prior to delivery (1.87, 1.19-2.95; 79%, 53.8%-90.4%, delayed bathing of the newborn for at least 24 hours (1.47, 1.09-1.99; 68.0%, 29.2%-85.6%, and wrapping the newborn within 10 minutes of delivery (1.27, 1.02-1.60; 0.0%, 0%-79.2%. Effects were partly dependent on the proportion of pregnant women attending groups. We did not find evidence of effects on uptake of antenatal care (OR 1.03, 95% CI 0.77-1.38; I2 = 86.3%, 95% CI 73.8%-92.8%, facility delivery (1.02, 0.93-1.12; 21.4%, 0%-65.8%, initiating breastfeeding within 1 hour (1.08, 0.85-1.39; 76.6%, 50.9%-88.8%, or exclusive breastfeeding for 6 weeks after delivery (1.18, 0.93-1.48; 72.9%, 37.8%-88.2%. The main limitation of our analysis is the high degree of heterogeneity for effects on most behaviours, possibly due to the limited number of trials involving women's groups and context-specific effects.This meta-analysis suggests that women's groups practising PLA improve key behaviours on the pathway to neonatal mortality, with the strongest evidence for home care behaviours and practices during home deliveries. A lack of consistency in improved behaviours across all trials may reflect differences in local priorities, capabilities, and the responsiveness of health services. Future research could address the mechanisms behind how PLA improves survival, in order to adapt this method to improve maternal and newborn health in different contexts, as well as improve other outcomes across the continuum of care for women, children, and adolescents.

Two controlled trials to increase participant retention in a randomized controlled trial of mobile phone-based smoking cessation support in the United Kingdom.

Science.gov (United States)

Severi, Ettore; Free, Caroline; Knight, Rosemary; Robertson, Steven; Edwards, Philip; Hoile, Elizabeth

2011-10-01

Loss to follow-up of trial participants represents a threat to research validity. To date, interventions designed to increase participants' awareness of benefits to society of completing follow-up, and the impact of a telephone call from a senior female clinician and researcher requesting follow-up have not been evaluated robustly. Trial 1 aimed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society. Trial 2 aimed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and researcher. Two single-blind randomized controlled trials were nested within a larger trial, Txt2stop. In Trial 1, participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up, or to a control group receiving a simple reminder regarding follow-up. In Trial 2, participants were randomly allocated to receive a telephone call from a senior female clinician and researcher, or to a control group receiving standard Txt2stop follow-up procedures. Trial 1: 33.5% (327 of 976) of the intervention group and 33.8% (329 of 974) of the control group returned the questionnaire within 26 weeks of randomization, risk ratio (RR) 0.99; 95% confidence interval (CI) 0.88-1.12. In all, 83.3% (813 of 976) of the intervention group and 82.2% (801 of/974) of the control group sent back the questionnaire within 30 weeks of randomization, RR 1.01; 95% CI 0.97, 1.05. Trial 2: 31% (20 of 65) of the intervention group and 32% (20 of 62) of the control group completed trial follow-up, RR 0.93; 95%CI 0.44, 1.98. In presence of other methods to increase follow-up neither experimental method (refrigerator magnet and text message emphasizing participation's benefits to society nor a telephone call from study's principal investigator) increased participant follow-up in the Txt2stop trial.

Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Li, Jin; Qin, Shukui; Xu, Ruihua; Yau, Thomas C C; Ma, Brigette; Pan, Hongming; Xu, Jianming; Bai, Yuxian; Chi, Yihebali; Wang, Liwei; Yeh, Kun-Huei; Bi, Feng; Cheng, Ying; Le, Anh Tuan; Lin, Jen-Kou; Liu, Tianshu; Ma, Dong; Kappeler, Christian; Kalmus, Joachim; Kim, Tae Won

2015-06-01

In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without other uncontrolled medical disorders. We randomly allocated patients (2:1; with a computer-generated unicentric randomisation list [prepared by the study funder] and interactive voice response system; block size of six; stratified by metastatic site [single vs multiple organs] and time from diagnosis of metastatic disease [regorafenib 160 mg once daily or placebo on days 1-21 of each 28 day cycle; patients in both groups were also to receive best supportive care. Participants, investigators, and the study funder were masked to treatment assignment. The primary endpoint was overall survival, and we analysed data on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01584830. Between April 29, 2012, and Feb 6, 2013, we screened 243 patients and randomly assigned 204 patients to receive either regorafenib (136 [67%]) or placebo (68 [33%]). After a median follow-up of 7·4 months (IQR 4·3-12·2), overall survival was significantly better with regorafenib

Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590).

Science.gov (United States)

Bhatia, Aarti K; Lee, Ju-Whei; Pinto, Harlan A; Jacobs, Charlotte D; Limburg, Paul J; Rubin, Philip; Arusell, Robert M; Dunphy, Eamonn P; Khandekar, Janardan D; Reiner, Seth A; Baez-Diaz, Luis; Celano, Paul; Li, Shuli; Li, Yi; Burtness, Barbara A; Adams, George L; Pandya, Kishan J

2017-12-01

13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS). In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups. 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis. Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society. © 2017 American Cancer Society.

Controlling Chronic Diseases Through Evidence-Based Decision Making: A Group-Randomized Trial.

Science.gov (United States)

Brownson, Ross C; Allen, Peg; Jacob, Rebekah R; deRuyter, Anna; Lakshman, Meenakshi; Reis, Rodrigo S; Yan, Yan

2017-11-30

Although practitioners in state health departments are ideally positioned to implement evidence-based interventions, few studies have examined how to build their capacity to do so. The objective of this study was to explore how to increase the use of evidence-based decision-making processes at both the individual and organization levels. We conducted a 2-arm, group-randomized trial with baseline data collection and follow-up at 18 to 24 months. Twelve state health departments were paired and randomly assigned to intervention or control condition. In the 6 intervention states, a multiday training on evidence-based decision making was conducted from March 2014 through March 2015 along with a set of supplemental capacity-building activities. Individual-level outcomes were evidence-based decision making skills of public health practitioners; organization-level outcomes were access to research evidence and participatory decision making. Mixed analysis of covariance models was used to evaluate the intervention effect by accounting for the cluster randomized trial design. Analysis was performed from March through May 2017. Participation 18 to 24 months after initial training was 73.5%. In mixed models adjusted for participant and state characteristics, the intervention group improved significantly in the overall skill gap (P = .01) and in 6 skill areas. Among the 4 organizational variables, only access to evidence and skilled staff showed an intervention effect (P = .04). Tailored and active strategies are needed to build capacity at the individual and organization levels for evidence-based decision making. Our study suggests several dissemination interventions for consideration by leaders seeking to improve public health practice.

Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.

Science.gov (United States)

Panwalkar, Pooja; Clark, Jonathan; Ramaswamy, Vijay; Hawes, Debra; Yang, Fusheng; Dunham, Christopher; Yip, Stephen; Hukin, Juliette; Sun, Yilun; Schipper, Matthew J; Chavez, Lukas; Margol, Ashley; Pekmezci, Melike; Chung, Chan; Banda, Adam; Bayliss, Jill M; Curry, Sarah J; Santi, Mariarita; Rodriguez, Fausto J; Snuderl, Matija; Karajannis, Matthias A; Saratsis, Amanda M; Horbinski, Craig M; Carret, Anne-Sophie; Wilson, Beverly; Johnston, Donna; Lafay-Cousin, Lucie; Zelcer, Shayna; Eisenstat, David; Silva, Marianna; Scheinemann, Katrin; Jabado, Nada; McNeely, P Daniel; Kool, Marcel; Pfister, Stefan M; Taylor, Michael D; Hawkins, Cynthia; Korshunov, Andrey; Judkins, Alexander R; Venneti, Sriram

2017-11-01

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Weight Loss Maintenance for 2 Years after a 6-Month Randomised Controlled Trial Comparing Education-Only and Group-Based Support in Japanese Adults

Directory of Open Access Journals (Sweden)

Yoshio Nakata

2014-11-01

Full Text Available Objective: Our previous study, a 6-month randomised controlled trial, demonstrated that a group-based support promoted weight loss as compared to an education-only intervention. The purpose of this study was to examine weight loss maintenance for 2 years. Methods: Originally, 188 overweight Japanese adults, aged 40-65 years, were randomly assigned to 3 groups: control, education-only or group-based support. After the 6-month intervention, 125 participants in the education-only and the group-based support groups were followed up for 2 years. The primary outcome was the amount of weight lost. The participants were retrospectively grouped into quartiles of percent weight loss for secondary analyses. Results: At the end of follow-up, the amount of weight lost in the education-only and the group-based support groups was the same (3.3 kg. Secondary analyses using data of those who completed the study (n = 100 revealed that the participants in the highest quartile of percent weight loss significantly increased their step counts and moderate-to-vigorous physical activity compared with the lowest quartile. No significant differences were observed in the energy intake among the four groups. Conclusion: The effects of group-based support disappear within 2 years. Increasing physical activity may be a crucial factor for successful maintenance of weight loss.

Humanin: a novel central regulator of peripheral insulin action.

Directory of Open Access Journals (Sweden)

Radhika H Muzumdar

2009-07-01

Full Text Available Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM and Alzheimer's disease (AD. A novel mitochondria-associated peptide, Humanin (HN, has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity.Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice.We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM.

Effect of cognitive behavioral group therapy for recovery of self-esteem on community-living individuals with mental illness: Non-randomized controlled trial.

Science.gov (United States)

Kunikata, Hiroko; Yoshinaga, Naoki; Nakajima, Kazuo

2016-10-01

The aim of this study was to examine over a 12-month post-intervention period whether the participation of community-living individuals with mental illness in cognitive behavioral group therapy for recovery of self-esteem (CBGTRS) resulted in improved outcomes. This was a non-randomized controlled trial. The participants were persons with mental illness who resided in communities in the Chugoku region of Japan. In total, 41 were assigned to an experimental group (CBGTRS intervention, 12 group sessions), and 21 to a control group. Outcome indices (self-esteem, moods, cognition, subjective well-being, psychiatric symptoms) were measured for the experimental group prior to intervention (T0), immediately post-intervention (T1), and at 3 (T2) and 12 (T3) months post-intervention. The control group was measured at the same intervals. For the experimental group, self-esteem scores at T1, T2, and T3 were significantly higher than at T0. Moods and cognition scores remained significantly low until T2. Scores for Inadequate Mental Mastery in the subjective well-being index had not decreased by T3. Confidence in Coping remained significantly high until T2. Psychiatric symptoms scores at T0, T1, T2, and T3 were significantly lower than at T0. The means and standard errors for self-esteem and Inadequate Mental Mastery increased until T3, and those for Tension-Anxiety, Depression-Dejection, and Confusion decreased until T2. From within-group trends and between-group differences in self-esteem, we conclude that CBGTRS may have a relatively long-term effect on self-esteem recovery. T2 is the turning point for moods and cognition; thus, follow-up is needed 3 months following the initial program. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Proton transport properties in zwitterion blends with Brønsted acids.

Science.gov (United States)

Yoshizawa-Fujita, Masahiro; Byrne, Nolene; Forsyth, Maria; MacFarlane, Douglas R; Ohno, Hiroyuki

2010-12-16

We describe zwitterion, 3-(1-butyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (Bimps), mixtures with 1,1,1-trifluoro-N-(trifluoromethylsulfonyl)methanesulfoneamide (HN(Tf)(2)) as new proton transport electrolytes. We report proton transport mechanisms in the mixtures based on results from several methods including thermal analyses, the complex-impedance method, and the pulsed field gradient spin echo NMR (pfg-NMR) method. The glass transition temperature (Tg) of the mixtures decreased with increasing HN(Tf)(2) concentration up to 50 mol %. The Tg remained constant at -55 °C with further acid doping. The ionic conductivity of HN(Tf)(2) mixtures increased with the HN(Tf)(2) content up to 50 mol %. Beyond that ratio, the mixtures showed no increase in ionic conductivity (10(-4) S cm(-1) at room temperature). This tendency agrees well with that of Tg. However, the self-diffusion coefficients obtained from the pfg-NMR method increased with HN(Tf)(2) content even above 50 mol % for all component ions. At HN(Tf)(2) 50 mol %, the proton diffusion of HN(Tf)(2) was the fastest in the mixture. These results suggest that Bimps cannot dissociate excess HN(Tf)(2), that is, the excess HN(Tf)(2) exists as molecular HN(Tf)(2) in the mixtures. The zwitterion, Bimps, forms a 1:1 complex with HN(Tf)(2) and the proton transport property in this mixture is superior to those of other mixing ratios. Furthermore, CH(3)SO(3)H and CF(3)SO(3)H were mixed with Bimps for comparison. Both systems showed a similar tendency, which differed from that of the HN(Tf)(2) system. The Tg decreased linearly with increasing acid content for every mixing ratio, while the ionic conductivity increased linearly. Proton transport properties in zwitterion/acid mixtures were strongly affected by the acid species added.

Comparison of group-based outpatient physiotherapy with usual care after total knee replacement: a feasibility study for a randomized controlled trial.

Science.gov (United States)

Artz, Neil; Dixon, Samantha; Wylde, Vikki; Marques, Elsa; Beswick, Andrew D; Lenguerrand, Erik; Blom, Ashley W; Gooberman-Hill, Rachael

2017-04-01

To evaluate the feasibility of conducting a randomized controlled trial comparing group-based outpatient physiotherapy with usual care in patients following total knee replacement. A feasibility study for a randomized controlled trial. One secondary-care hospital orthopaedic centre, Bristol, UK. A total of 46 participants undergoing primary total knee replacement. The intervention group were offered six group-based exercise sessions after surgery. The usual care group received standard postoperative care. Participants were not blinded to group allocation. Feasibility was assessed by recruitment, reasons for non-participation, attendance, and completion rates of study questionnaires that included the Lower Extremity Functional Scale and Knee Injury and Osteoarthritis Outcome Score. Recruitment rate was 37%. Five patients withdrew or were no longer eligible to participate. Intervention attendance was high (73%) and 84% of group participants reported they were 'very satisfied' with the exercises. Return of study questionnaires at six months was lower in the usual care (75%) than in the intervention group (100%). Mean (standard deviation) Lower Extremity Functional Scale scores at six months were 45.0 (20.8) in the usual care and 57.8 (15.2) in the intervention groups. Recruitment and retention of participants in this feasibility study was good. Group-based physiotherapy was acceptable to participants. Questionnaire return rates were lower in the usual care group, but might be enhanced by telephone follow-up. The Lower Extremity Functional Scale had high responsiveness and completion rates. Using this outcome measure, 256 participants would be required in a full-scale randomized controlled trial.

Ab initio anharmonic vibrational frequency predictions for linear proton-bound complexes OC-H(+)-CO and N(2)-H(+)-N(2).

Science.gov (United States)

Terrill, Kasia; Nesbitt, David J

2010-08-01

Ab initio anharmonic transition frequencies are calculated for strongly coupled (i) asymmetric and (ii) symmetric proton stretching modes in the X-H(+)-X linear ionic hydrogen bonded complexes for OCHCO(+) and N(2)HN(2)(+). The optimized potential surface is calculated in these two coordinates for each molecular ion at CCSD(T)/aug-cc-pVnZ (n = 2-4) levels and extrapolated to the complete-basis-set limit (CBS). Slices through both 2D surfaces reveal a relatively soft potential in the asymmetric proton stretching coordinate at near equilibrium geometries, which rapidly becomes a double minimum potential with increasing symmetric proton acceptor center of mass separation. Eigenvalues are obtained by solution of the 2D Schrödinger equation with potential/kinetic energy coupling explicity taken into account, converged in a distributed Gaussian basis set as a function of grid density. The asymmetric proton stretch fundamental frequency for N(2)HN(2)(+) is predicted at 848 cm(-1), with strong negative anharmonicity in the progression characteristic of a shallow "particle in a box" potential. The corresponding proton stretch fundamental for OCHCO(+) is anomalously low at 386 cm(-1), but with a strong alternation in the vibrational spacing due to the presence of a shallow D(infinityh) transition state barrier (Delta = 398 cm(-1)) between the two equivalent minimum geometries. Calculation of a 2D dipole moment surface and transition matrix elements reveals surprisingly strong combination and difference bands with appreciable intensity throughout the 300-1500 cm(-1) region. Corrected for zero point (DeltaZPE) and thermal vibrational excitation (DeltaE(vib)) at 300 K, the single and double dissociation energies in these complexes are in excellent agreement with thermochemical gas phase ion data.

UV cross-linking of polypeptides associated with 3'-terminal exons

International Nuclear Information System (INIS)

Stolow, D.T.; Berget, S.M.

1990-01-01

Association of nuclear proteins with chimeric vertebrate precursor RNAs containing both polyadenylation signals and an intron was examined by UV cross-linking. One major difference in cross-linking pattern was observed between this chimeric precursor RNA and precursors containing only polyadenylation or splicing signals. The heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptide C cross-linked strongly to sequences downstream of the A addition site in polyadenylation precursor RNA containing only the polyadenylation signal from the simian virus 40 (SV40) late transcription unit. In contrast, the hnRNP C polypeptide cross-linked to chimeric RNA containing the same SV40 late poly(A) cassette very poorly, at a level less than 5% of that observed with the precursor RNA containing just the poly(A) site. Observation that cross-linking of the hnRNP C polypeptide to elements within the SV40 late poly(A) site was altered by the presence of an upstream intron suggests differences in the way nuclear factors associate with poly(A) sites in the presence and absence of an upstream intron. Cross-linking of C polypeptide to chimeric RNA increased with RNAs mutated for splicing or polyadenylation consensus sequences and under reaction conditions (high magnesium) that inhibited polyadenylation. Furthermore, cross-linking of hnRNP C polypeptide to precursors containing just the SV40 late poly(A) site was eliminated in the presence of competing poly(U); polyadenylation, however, was unaffected. Correlation of loss of activity with high levels of hnRNP C polypeptide cross-linking raises questions about the specificity of the interaction between the hnRNP C polypeptide and polyadenylation precursor RNAs in vitro

Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial

Science.gov (United States)

Chan, Ching Han Helen; Lai, Chi-Keung Jonah; Chan, Wai Fung Vivian; Wang, Man Ping; Li, Ho Cheung William; Chan, Sophia Siu Chee; Lam, Tai-Hing

2015-01-01

Background Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Objective Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. Methods This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Results Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators’ posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants’ posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. Conclusions The intervention via the WhatsApp social group was effective in reducing

Virtual reality training improves da Vinci performance: a prospective trial.

Science.gov (United States)

Cho, Jae Sung; Hahn, Koo Yong; Kwak, Jung Myun; Kim, Jin; Baek, Se Jin; Shin, Jae Won; Kim, Seon Hahn

2013-12-01

The DV-Trainer™ (a virtual reality [VR] simulator) (Mimic Technologies, Inc., Seattle, WA) is one of several different robotic surgical training methods. We designed a prospective study to determine whether VR training could improve da Vinci(®) Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) performance. Surgeons (n=12) were enrolled using a randomized protocol. Groups 1 (VR training) and 2 (control) participated in VR and da Vinci exercises. Participants' time and moving distance were combined to determine a composite score: VR index=1000/(time×moving distance). The da Vinci exercises included needle control and suturing. Procedure time and error were measured. A composite index (DV index) was computed and used to measure da Vinci competency. After the initial trial with both the VR and da Vinci exercises, only Group 1 was trained with the VR simulator following our institutional curriculum for 3 weeks. All members of both groups then participated in the second trial of the VR and da Vinci exercises and were scored in the same way as in the initial trial. In the initial trial, there was no difference in the VR index (Group 1 versus Group 2, 8.9 ± 3.3 versus 9.4 ± 3.7; P=.832) and the DV index (Group 1 versus Group 2, 3.85 ± 0.73 versus 3.66 ± 0.65; P=.584) scores between the two groups. At the second time point, Group 1 showed increased VR index scores in comparison with Group 2 (19.3 ± 4.5 versus 9.7 ± 4.1, respectively; P=.001) and improved da Vinci performance skills as measured by the DV index (5.80 ± 1.13 versus 4.05 ± 1.03, respectively; P=.028) and by suturing time (7.1 ± 1.54 minutes versus 10.55 ± 1.93 minutes, respectively; P=.018). We found that VR simulator training can improve da Vinci performance. VR practice can result in an early plateau in the learning curve for robotic practice under controlled circumstances.

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

Science.gov (United States)

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness.

Science.gov (United States)

Santer, Miriam; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Rumsby, Kate; Chorozoglou, Maria; Becque, Taeko; Roberts, Amanda; Liddiard, Lyn; Nollett, Claire; Hooper, Julie; Prude, Martina; Wood, Wendy; Thomas, Kim S; Thomas-Jones, Emma; Williams, Hywel C; Little, Paul

2018-05-03

over the 16 week period was 7.5 (SD. 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group. No statistically significant difference was found in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 points higher than in the bath additives group (95% confidence interval -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. The groups did not differ in secondary outcomes, economic outcomes, or adverse effects. This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children. Further research is needed into optimal regimens for leave-on emollient and soap substitutes. Current Controlled Trials ISRCTN84102309. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

Science.gov (United States)

Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting: a randomised trial

Directory of Open Access Journals (Sweden)

Karlsson Andreas

2010-07-01

Full Text Available Abstract Background Internet administered cognitive behaviour therapy (CBT is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internet-and group administered CBT for panic disorder (with or without agoraphobia in a randomised trial within a regular psychiatric care setting. The second aim of the study was to establish the cost-effectiveness of these interventions. Methods Patients referred for treatment by their physician, or self-referred, were telephone-screened by a psychiatric nurse. Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist. A total of 113 consecutive patients were then randomly assigned to 10 weeks of either guided Internet delivered CBT (n = 53 or group CBT (n = 60. After treatment, and at a 6-month follow-up, patients were again assessed by the psychiatrist, blind to treatment condition. Results Immediately after randomization 9 patients dropped out, leaving 104 patients who started treatment. Patients in both treatment conditions showed significant improvement on the main outcome measure, the Panic Disorder Severity Scale (PDSS after treatment. For the Internet treatment the within-group effect size (pre-post on the PDSS was Cohen's d = 1.73, and for the group treatment it was d = 1.63. Between group effect sizes were low and treatment effects were maintained at 6-months follow-up. We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data. Group CBT utilised considerably more therapist time than did Internet CBT. Defining effect as proportion of PDSS responders, the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost

Validation of Progression‐Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

Science.gov (United States)

Wang, Xiaoyi; Hodgson, Lydia; George, Stephen L.; Sargent, Daniel J.; Foster, Nate R.; Ganti, Apar Kishor; Stinchcombe, Thomas E.; Crawford, Jeffrey; Kratzke, Robert; Adjei, Alex A.; Kindler, Hedy L.; Vokes, Everett E.; Pang, Herbert

2017-01-01

Abstract Purpose. The aim of this study was to investigate whether progression‐free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual‐level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary‐level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least‐square (WLS) regression model and the CBCS model. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary‐level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual‐level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. Implications for Practice. For better disease management and for more efficient clinical trial designs, it is important to know if progression‐free survival (PFS) is

Increasing physical activity among young children from disadvantaged communities: study protocol of a group randomised controlled effectiveness trial

Directory of Open Access Journals (Sweden)

Rebecca M. Stanley

2016-10-01

Full Text Available Abstract Background Participation in regular physical activity (PA during the early years helps children achieve healthy body weight and can substantially improve motor development, bone health, psychosocial health and cognitive development. Despite common assumptions that young children are naturally active, evidence shows that they are insufficiently active for health and developmental benefits. Exploring strategies to increase physical activity in young children is a public health and research priority. Methods Jump Start is a multi-component, multi-setting PA and gross motor skill intervention for young children aged 3–5 years in disadvantaged areas of New South Wales, Australia. The intervention will be evaluated using a two-arm, parallel group, randomised cluster trial. The Jump Start protocol was based on Social Cognitive Theory and includes five components: a structured gross motor skill lesson (Jump In; unstructured outdoor PA and gross motor skill time (Jump Out; energy breaks (Jump Up; activities connecting movement to learning experiences (Jump Through; and a home-based family component to promote PA and gross motor skill (Jump Home. Early childhood education and care centres will be demographically matched and randomised to Jump Start (intervention or usual practice (comparison group. The intervention group receive Jump Start professional development, program resources, monthly newsletters and ongoing intervention support. Outcomes include change in total PA (accelerometers within centre hours, gross motor skill development (Test of Gross Motor Development-2, weight status (body mass index, bone strength (Sunlight MiniOmni Ultrasound Bone Sonometer, self-regulation (Heads-Toes-Knees-Shoulders, executive function tasks, and proxy-report Temperament and Approaches to learning scales, and educator and parent self-efficacy. Extensive quantitative and qualitative process evaluation and a cost-effectiveness evaluation will be conducted

The effectiveness of a health promotion with group intervention by clinical trial. Study protocol

Directory of Open Access Journals (Sweden)

Campo Osaba Maria-Antonia

2012-03-01

responsibility for his/her own health. The rhythm of a weekly session during 8 weeks with recommended activities to put into practice, as well as the support of the group is an opportunity to incorporate healthy habits and make a commitment to self-care. The sheets handed out are a Health Manual that can always be consulted after the workshop ends. Trial registration Clinical Trials.gov Identifier: NCT01440738

The unit group of group algebra $F_qSL(2;Z_3$

Directory of Open Access Journals (Sweden)

Swati Maheshwari

2016-01-01

Full Text Available Let $\\F_q$ be a finite field of characteristic $p$ having $q$ elements, where $q = p^k$ and $p\\ge 5$. Let $ SL(2,\\Z_3$ be the special linear group of $2\\times2$ matrices with determinant $1$ over $\\Z_3$. In this note we establish the structure of the unit group of $\\F_q SL(2,\\Z_3$.

Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes

Directory of Open Access Journals (Sweden)

Kyoung-in Cho

2017-05-01

Full Text Available The pathogenic drivers of sporadic and familial motor neuron disease (MND, such amyotrophic lateral sclerosis (ALS, are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of Ranbp2 in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and

[Clinical Trials for Treatment of Stroke Patients with Dysphagia by Vitalstim Electroacupuncture Combined with Swallowing Rehabilitation Training].

Science.gov (United States)

Zhang, Sheng-Yu; Liu, Shao-Bing; Wu, Wei; Chen, Yi-Min; Liao, Kang-Lin; Xiang, Yong; Pan, Dun

2017-04-25

To observe the clinical effect of vitalstim electroacupuncture (EA) combined with swallowing rehabilitation training in the treatment of stroke patients with dysphagia. A total of 80 stroke patients with dysphagia were randomized into treatment and control groups ( n =40 in each group). Patients of the control group were treated by regular medication for anti-platelet aggregation and anti-coagulation, lipid-lowering, neuroprotection, blood glucose control and blood pressure control, etc. and swallowing function rehabilitation training, and those of the treatment group treated by EA stimulation of Fengchi (GB 20), Jinjin (EX-HN 12) and Yuye (EX-HN 13) with a Vitalstim Electrostimulator and manual acupuncture stimulation of Lianquan (CV 23), Tiantu (CV 22) in combination with regular medication plus swallowing function training as those mentioned in the control group. The EA and manual acupuncture stimulation treatment was conducted once daily, 6 times a week and 4 weeks altogether. The therapeutic effect was assessed by using Kubota swallowing ability test (6 levels), dysphagia subscale (0-6 scores) of the neurological deficit degrees, videofluorography (VFG) assessment (markedly effective, effective and invalid, for evaluating the function and symmetry state of the swallowing movements), and the MOS Item Short Form Health Survey (SF-36, 8 minor items of two major aspects in physiological function, mental health, emotional function, social function and overall health) for assessing the patients' daily-life quality. After the treatment, the dysphagia score of the treatment group was signi-ficantly lower than that of the control group ( P dysphagia (showed by dysphagia score and VFG outcomes) and life quality. EA treatment combined with swallowing function rehabilitation training is effective in improving swallowing ability and daily-life quality in stroke patients with dysphagia.

A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals[S

Science.gov (United States)

Nagao, Akihiko; Maoka, Takashi; Ono, Hiroshi; Kotake-Nara, Eiichi; Kobayashi, Miyuki; Tomita, Mie

2015-01-01

We previously found that mice fed lutein accumulated its oxidative metabolites (3′-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3′-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD+, (3′R,6′R)-3′-hydroxy-β,ε-caroten-3-one and (6RS,3′R,6′R)-3′-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3′ and C6′ of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy β-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo β-end group. Other xanthophylls such as β-cryptoxanthin and zeaxanthin, which have a 3-hydroxy β-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and β,ε-caroten-3′-one was significantly increased by the ingestion of β-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy β-end group of xanthophylls to a 3-oxo ε-end group. PMID:25502844

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Science.gov (United States)

Bruix, Jordi; Qin, Shukui; Merle, Philippe; Granito, Alessandro; Huang, Yi-Hsiang; Bodoky, György; Pracht, Marc; Yokosuka, Osamu; Rosmorduc, Olivier; Breder, Valeriy; Gerolami, René; Masi, Gianluca; Ross, Paul J; Song, Tianqiang; Bronowicki, Jean-Pierre; Ollivier-Hourmand, Isabelle; Kudo, Masatoshi; Cheng, Ann-Lii; Llovet, Josep M; Finn, Richard S; LeBerre, Marie-Aude; Baumhauer, Annette; Meinhardt, Gerold; Han, Guohong

2017-01-07

There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50-0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1-12·1) for regorafenib versus 7·8 months (6·3-8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group

Exploring the effects of a universal classroom management training programme on teacher and child behaviour: A group randomised controlled trial and cost analysis

OpenAIRE

O'Neill, Donal

2017-01-01

Teachers frequently struggle to cope with conduct problems in the classroom. The aim of this study was to assess the effectiveness of the Incredible Years Teacher Classroom Management Training Programme for improving teacher competencies and child adjustment. The study involved a group randomised controlled trial which included 22 teachers and 217 children (102 boys and 115 girls). The average age of children included in the study was 5.3 years (standard deviation = 0.89). Teacher...

HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials.

Science.gov (United States)

Press, Michael F; Sauter, Guido; Buyse, Marc; Fourmanoir, Hélène; Quinaux, Emmanuel; Tsao-Wei, Denice D; Eiermann, Wolfgang; Robert, Nicholas; Pienkowski, Tadeusz; Crown, John; Martin, Miguel; Valero, Vicente; Mackey, John R; Bee, Valerie; Ma, Yanling; Villalobos, Ivonne; Campeau, Anaamika; Mirlacher, Martina; Lindsay, Mary-Ann; Slamon, Dennis J

2016-10-10

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]-positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only

A randomised controlled trial of multiple periods of outdoor free-play to increase moderate-to-vigorous physical activity among 3 to 6 year old children attending childcare: study protocol

Directory of Open Access Journals (Sweden)

Luke Wolfenden

2016-09-01

Full Text Available Abstract Background The implementation of physical activity interventions in centre-based childcare services has been recommended to improve child health. This study aims to evaluate the efficacy of scheduling multiple periods of outdoor free play in increasing the time children spend in moderate-to-vigorous physical activity (MVPA during childcare. Methods The study will employ a between group cluster randomised controlled trial design. Fourteen childcare services in the Hunter New England region of New South Wales, Australia, who currently implement a single session of free outdoor play between their core operational hours of 9 am to 3 pm will be recruited into the trial. Childcare services will be randomised to an intervention or a no intervention control group. Childcare services in the intervention group will be supported by an early childhood education specialist to provide three periods of outdoor free play for children between the hours of 9 am to 3 pm. Each period of outdoor free play will be at least 15 min in duration but must equate to their total usual duration of outdoor play. Services in the control group will continue to implement a single period of outdoor play. The primary trial outcome is minutes of time children spend in MVPA whilst in care assessed objectively via accelerometer over 5 days. Outcome assessment will occur at baseline and 3 months post baseline. Generalised Linear Mixed Models (GLMM under an intention to treat framework will be used to compare differences between groups in the primary trial outcome at follow-up. Sensitivity analysis will be conducted to test assumptions of missing data. Per protocol analysis will be performed using services that implemented the intervention as intended and subgroup analysis undertaken by gender and baseline physical activity levels of children. Discussion The study tests a simple ecological intervention that has the potential to increase child physical activity in care

A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.

Science.gov (United States)

Berres, M; Kukull, W A; Miserez, A R; Monsch, A U; Monsell, S E; Spiegel, R

2014-01-01

The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors

Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): protocol for a randomised controlled trial.

Science.gov (United States)

O'Brien, Claire; Bray, Emma P; Bryan, Stirling; Greenfield, Sheila M; Haque, M Sayeed; Hobbs, F D Richard; Jones, Miren I; Jowett, Sue; Kaambwa, Billingsley; Little, Paul; Mant, Jonathan; Penaloza, Cristina; Schwartz, Claire; Shackleford, Helen; Varghese, Jinu; Williams, Bryan; McManus, Richard J

2013-03-23

Self-monitoring of hypertension with self-titration of antihypertensives (self-management) results in lower systolic blood pressure for at least one year. However, few people in high risk groups have been evaluated to date and previous work suggests a smaller effect size in these groups. This trial therefore aims to assess the added value of self-management in high risk groups over and above usual care. The targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR) trial will be a pragmatic primary care based, unblinded, randomised controlled trial of self-management of blood pressure (BP) compared to usual care. Eligible patients will have a history of stroke, coronary heart disease, diabetes or chronic kidney disease and will be recruited from primary care. Participants will be individually randomised to either usual care or self-management. The primary outcome of the trial will be difference in office SBP between intervention and control groups at 12 months adjusted for baseline SBP and covariates. 540 patients will be sufficient to detect a difference in SBP between self-management and usual care of 5 mmHg with 90% power. Secondary outcomes will include self-efficacy, lifestyle behaviours, health-related quality of life and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative analysis will gain insights into patients' views, experiences and decision making processes. The results of the trial will be directly applicable to primary care in the UK. If successful, self-management of blood pressure in people with stroke and other high risk conditions would be applicable to many hundreds of thousands of individuals in the UK and beyond. ISRCTN87171227.

Prospective, Randomized, Double-Blind, Parallel-Group, Comparative Effectiveness Clinical Trial Comparing a Powder Vehicle Compound of Vitamin D With an Oil Vehicle Compound in Adults With Cystic Fibrosis.

Science.gov (United States)

Hermes, Wendy A; Alvarez, Jessica A; Lee, Moon J; Chesdachai, Supavit; Lodin, Daud; Horst, Ron; Tangpricha, Vin

2017-08-01

There is little consensus on the most efficacious vehicle substance for vitamin D supplements. Fat malabsorption may impede the ability of patients with cystic fibrosis (CF) to absorb vitamin D in an oil vehicle. We hypothesized that vitamin D contained in a powder vehicle would be absorbed more efficiently than vitamin D contained in an oil vehicle in patients with CF. In this double-blind, randomized controlled trial, hospitalized adults with CF were given a one-time bolus dose of 100,000 IU of cholecalciferol (D 3 ) in a powder-based or oil-based vehicle. Serum D 3 , 25-hydroxyvitamin D, and parathyroid hormone concentrations were analyzed at 0, 12, 24, and 48 hours posttreatment. The area under the curve for serum D 3 and the 12-hour time point were also assessed as indicators of D 3 absorption. This trial was completed by 15 patients with CF. The median (interquartile range) age, body mass index, and forced expiratory volume in 1 second were 23.7 (19.9-33.2) years, 19.9 (18.6-22.6) kg/m 2 , and 63% (37%-80%), respectively. The increase in serum D 3 and the area under the curve was greater in the powder group ( P = .002 and P = .036, respectively). Serum D 3 was higher at 12 hours in the powder group compared with the oil group ( P = .002), although levels were similar between groups by 48 hours. In adults with CF, cholecalciferol is more efficiently absorbed in a powder compared with an oil vehicle. Physicians should consider prescribing vitamin D in a powder vehicle in patients with CF to improve the absorption of vitamin D from supplements.

Multiqubit Clifford groups are unitary 3-designs

Science.gov (United States)

Zhu, Huangjun

2017-12-01

Unitary t -designs are a ubiquitous tool in many research areas, including randomized benchmarking, quantum process tomography, and scrambling. Despite the intensive efforts of many researchers, little is known about unitary t -designs with t ≥3 in the literature. We show that the multiqubit Clifford group in any even prime-power dimension is not only a unitary 2-design, but also a 3-design. Moreover, it is a minimal 3-design except for dimension 4. As an immediate consequence, any orbit of pure states of the multiqubit Clifford group forms a complex projective 3-design; in particular, the set of stabilizer states forms a 3-design. In addition, our study is helpful in studying higher moments of the Clifford group, which are useful in many research areas ranging from quantum information science to signal processing. Furthermore, we reveal a surprising connection between unitary 3-designs and the physics of discrete phase spaces and thereby offer a simple explanation of why no discrete Wigner function is covariant with respect to the multiqubit Clifford group, which is of intrinsic interest in studying quantum computation.

Feedback versus no feedback to improve patient outcome in group psychotherapy for eating disorders (F-EAT): A randomized clinical trial

DEFF Research Database (Denmark)

Davidsen, Annika Helgadóttir; Waaddegaard, Mette; Poulsen, Stig Bernt

of continuous feedback on adherence and outcome in group psychotherapy. Methods/design: The trial is set up in a randomized design for outpatients diagnosed with bulimia nervosa, binge eating disorder, or eating disorder not otherwise specified (DSM-IV). They are allocated 1:1 to the experimental group...

Acupuncture at Houxi (SI 3) acupoint for acute neck pain caused by stiff neck: study protocol for a pilot randomised controlled trial.

Science.gov (United States)

Sun, Zhong-ren; Yue, Jin-huan; Tian, Hong-zhao; Zhang, Qin-hong

2014-12-23

The use of acupuncture has been suggested for the treatment of acute neck pain caused by stiff neck in China. However, current evidence is insufficient to draw any conclusions about its efficacy. Therefore this pilot study was designed to evaluate the feasibility and efficacy of acupuncture at the Houxi (SI3) acupoint for treatment of acute neck pain. This pilot study will be a two-parallel-group, assessor-blinded, randomised controlled trial. Thirty-six stiff neck participants with acute neck pain will be recruited and randomly divided into two groups in a 1:1 ratio. Participants in the control group will receive massage on the local neck region (5 min each session, three times a day for 3 days). In addition to massage, patients in the treatment group will receive acupuncture (one session a day for 3 days). Measures will be taken at 0, 3 and 15 days. The primary outcome is the Northwick Park Neck Pain Questionnaire (NPQ). The secondary outcome is the Short Form of the McGill Pain Questionnaire (SF-MPQ). The protocol for this pilot randomised clinical trial has undergone ethics scrutiny and been approved by the ethics review boards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine (Permission number: HZYLL201303502). The findings of this study will provide important clinical evidence on the feasibility and efficacy of acupuncture treatment for stiff neck patients with acute neck pain. In addition, it will explore the feasibility of further acupuncture research. ChiCTR-TRC-13003911. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Effectiveness of a Group Triple P with Chinese Parents Who Have a Child with Developmental Disabilities: A Randomized Controlled Trial

Science.gov (United States)

Leung, Cynthia; Fan, Angel; Sanders, Matthew R.

2013-01-01

The study examined the effectiveness of Group Triple P, a Level 4 variant of the Triple P multilevel system of parenting support, with Chinese parents who had a preschool aged child with a developmental disability, using randomized controlled trial design. Participants (Intervention group: 42; Waitlist Control group: 39) completed measures on…

The effect of a 3-month prevention program on the jump-landing technique in basketball: a randomized controlled trial.

Science.gov (United States)

Aerts, Inne; Cumps, Elke; Verhagen, Evert; Wuyts, Bram; Van De Gucht, Sam; Meeusen, Romain

2015-02-01

In jump-landing sports, the injury mechanism that most frequently results in an injury is the jump-landing movement. Influencing the movement patterns and biomechanical predisposing factors are supposed to decrease injury occurrence. To evaluate the influence of a 3-mo coach-supervised jump-landing prevention program on jump-landing technique using the jump-landing scoring (JLS) system. Randomized controlled trial. On-field. 116 athletes age 15-41 y, with 63 athletes in the control group and 53 athletes in the intervention group. The intervention program in this randomized control trial was administered at the start of the basketball season 2010-11. The jump-landing training program, supervised by the athletic trainers, was performed for a period of 3 mo. The jump-landing technique was determined by registering the jump-landing technique of all athletes with the JLS system, pre- and postintervention. After the prevention program, the athletes of the male and female intervention groups landed with a significantly less erect position than those in the control groups (P < .05). This was presented by a significant improvement in maximal hip flexion, maximal knee flexion, hip active range of motion, and knee active range of motion. Another important finding was that postintervention, knee valgus during landing diminished significantly (P < .05) in the female intervention group compared with their control group. Furthermore, the male intervention group significantly improved (P < .05) the scores of the JLS system from pre- to postintervention. Malalignments such as valgus position and insufficient knee flexion and hip flexion, previously identified as possible risk factors for lower-extremity injuries, improved significantly after the completion of the prevention program. The JLS system can help in identifying these malalignments. Therapy, prevention, level 1b.

African Journal of Health Sciences - Vol 13, No 3 (2006)

African Journals Online (AJOL)

Molecular characterization of chromosome 7 in AML and MDS patients · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. HN Abdelrazik, HM Farawila, MA Sherif, M AlAnsary, 33-42. http://dx.doi.org/10.4314/ajhs.v13i3.30834 ...

Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting: a randomised trial

OpenAIRE

Bergstrom, Jan; Andersson, Gerhard; Ljotsson, Brjann; Ruck, Christian; Andreewitch, Sergej; Karlsson, Andreas; Carlbring, Per; Andersson, Erik; Lindefors, Nils

2010-01-01

Background: Internet administered cognitive behaviour therapy (CBT) is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internet- and group administered CBT for panic disorder (with or without agoraphobia) in a randomised trial within a regular psychiatric care setting. The second aim of the...

Determination of arsenic speciation in sulfidic waters by Ion Chromatography Hydride-Generation Atomic Fluorescence Spectrometry (IC-HG-AFS).

Science.gov (United States)

Keller, Nicole S; Stefánsson, Andri; Sigfússon, Bergur

2014-10-01

A method for the analysis of arsenic species in aqueous sulfide samples is presented. The method uses an ion chromatography system connected with a Hydride-Generation Atomic Fluorescence Spectrometer (IC-HG-AFS). With this method inorganic As(III) and As(V) species in water samples can be analyzed, including arsenite (HnAs(III)O3(n-3)), thioarsenite (HnAs(III)S3(n-3)), arsenate (HnAs(V)O4(n-3)), monothioarsenate (HnAs(V)SO3(n-3)), dithioarsenate (HnAs(V)S2O2(n-3)), trithioarsenate (HnAs(V)S3O(n-3)) and tetrathioarsenate (HnAs(V)S4(n-3)). The peak identification and retention times were determined based on standard analysis of the various arsenic compounds. The analytical detection limit was ~1-3 µg L(-1) (LOD), depending on the quality of the baseline. This low detection limit makes this method also applicable to discriminate between waters meeting the drinking water standard of max. 10 µg L(-1) As, and waters that do not meet this standard. The new method was successfully applied for on-site determination of arsenic species in natural sulfidic waters, in which seven species were unambiguously identified. Copyright © 2014 Elsevier B.V. All rights reserved.

Reducing electronic media use in 2-3 year-old children: feasibility and efficacy of the Family@play pilot randomised controlled trial.

Science.gov (United States)

Hinkley, Trina; Cliff, Dylan P; Okely, Anthony D

2015-08-14

Participation in electronic media use among 2-3 year olds is high and associated with adverse health and developmental outcomes. This study sought to test the feasibility and potential efficacy of a family-based program to decrease electronic media (EM) use in 2-3-year-old children. Family@play was a six-session pilot randomised controlled trial delivered to parents of 2-3 year-old children from August to September 2012 in a community environment in the Illawarra region of New South Wales, Australia. Development of program content was guided by Social Cognitive and Family Systems Theories. The primary outcome was children's electronic media use. Secondary outcomes included children's time in sitting, standing and stepping. Data collectors were blinded to group allocation. Parents completed comprehensive process evaluation measures and participated in focus group discussions following completion of the program. Regression analyses were undertaken and effect sizes calculated using principles of intention to treat. Twenty-two participants (n = 12 intervention; n = 10 control) provided complete baseline data; complete data from 16 participants (n = 6 intervention; n = 10 control) were available post-intervention. Process evaluation results were high, showing the acceptability of the program. Compared with children in the control group, there were greater decreases in total EM use among children in the intervention group (adjusted difference [95 % CI] = -31.2 mins/day [-71.0-8.6] Cohen's d = 0.70). Differences for other outcomes were in the hypothesised direction and ranged from small for postural (sitting, standing, stepping) outcomes to moderate to large for individual electronic media (e.g. TV viewing, DVD/video viewing). This is the first family-based study to engage families of 2-3 year old children outside the United States and target multiple EM behaviours. Family@play was shown to be a feasible and acceptable intervention to deliver to

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial.

Science.gov (United States)

Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki S; Ismail, Hussain Imam H J Muhammad; Chotpitayasunondh, Tawee; Chua, Mary Noreen; Luong, Chan Quang; Rusmil, Kusnandi; Wirawan, Dewa Nyoman; Nallusamy, Revathy; Pitisuttithum, Punnee; Thisyakorn, Usa; Yoon, In-Kyu; van der Vliet, Diane; Langevin, Edith; Laot, Thelma; Hutagalung, Yanee; Frago, Carina; Boaz, Mark; Wartel, T Anh; Tornieporth, Nadia G; Saville, Melanie; Bouckenooghe, Alain

2014-10-11

An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children. We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2-14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281. We randomly assigned 10,275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56·5% (95% CI 43·8-66·4) efficacy. We recorded 647 serious adverse

Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial.

Directory of Open Access Journals (Sweden)

Norma Amador-Licona

Full Text Available HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals, and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55% and AZT/3TC/EFV (15% without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04, but oxidative stress markers were not different between groups.

Omega-3 Supplementation and Loneliness-Related Memory Problems: Secondary Analyses Of A Randomized Controlled Trial

Science.gov (United States)

Jaremka, Lisa M.; Derry, Heather M.; Bornstein, Robert; Prakash, Ruchika Shaurya; Peng, Juan; Belury, Martha A.; Andridge, Rebecca R.; Malarkey, William B.; Kiecolt-Glaser, Janice K.

2014-01-01

Objective Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems. Methods Participants (N=138) from a parent randomized controlled trial (RCT) were randomized to the placebo, 1.25 grams/day of omega-3, or 2.50 grams/day of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the RCT. Results Controlling for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory post-supplementation, as measured by immediate (b = −0.28, t(117) = −2.62, p = .010) and long-delay (b = −.06, t(116) = −2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25 grams/day and 2.50 grams/day supplementation groups, all p values > .10. The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests, all p values > .32. Conclusion These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the utility of exploring novel interventions for treating episodic memory problems among lonely people. ClinicalTrials.gov identifier: NCT00385723 PMID:25264972

10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.

Science.gov (United States)

Bone, Henry G; Wagman, Rachel B; Brandi, Maria L; Brown, Jacques P; Chapurlat, Roland; Cummings, Steven R; Czerwiński, Edward; Fahrleitner-Pammer, Astrid; Kendler, David L; Lippuner, Kurt; Reginster, Jean-Yves; Roux, Christian; Malouf, Jorge; Bradley, Michelle N; Daizadeh, Nadia S; Wang, Andrea; Dakin, Paula; Pannacciulli, Nicola; Dempster, David W; Papapoulos, Socrates

2017-07-01

Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis. In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both

Tailored care for somatoform vertigo/dizziness: study protocol for a randomised controlled trial evaluating integrative group psychotherapy.

Science.gov (United States)

Lahmann, Claas; Henningsen, P; Dieterich, M; Radziej, K; Schmid, G

2015-08-01

Vertigo/dizziness (VD) ranks high in lifetime prevalence and clinical relevance. Nearly half of the complex VD disorders presenting at specialised units for vertigo or otoneurological disorders are not fully explained by an identifiable medical illness, but instead are related to anxiety, depressive, or somatoform disorders. Although there is some evidence that psychotherapy may be effective for these patients, therapeutic options remain unsatisfactory. This report describes the objectives, design and methods of a randomised, controlled clinical trial, evaluating the efficacy of manualised, multimodal group psychotherapy, based on integrative psychotherapy (IPT) and tailored to subgroups of mental disorders in medically unexplained VD. This psychotherapeutic approach will be compared to self-help groups (n = 172; n = 86 per study arm). Improvements with regard to handicap due to VD at 12 months follow-up will serve as primary outcome. Additionally, measures of generic quality of life, severity of vertigo, depression, anxiety, somatisation as well as Head Impulse Test and Computerized Static Posturography will be applied. We will also analyse the cost-effectiveness of this trial. The study aims to improve treatment of this therapeutically underserved population who are often severely impaired in their working and daily lives. ClinicalTrials.gov Identifier: NCT02320851. This is an on-going study; recruitment for the study is about to start.

Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

Science.gov (United States)

Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, T A; Kaye, S B; De Bono, J S; Molife, L R; Banerji, U

2015-01-01

Background: PI3K–AKT–mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. Methods: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. Results: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3–4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3–4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. Conclusions: PI3K–AKT–mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. PMID:26554652

S3T working group. Report 1: group aims

International Nuclear Information System (INIS)

Pouey, M.

1983-04-01

The work group S3T which is aimed to designing and developing devices using unconventional holographic optics is presented. These devices find applications that are classified here in four items high resolution spectrometers, high definition imaging, high flux devices, metrology and interferometry. The problems to solve and the aims of the group in each of these cases are presented. Three synthesis of lectures are in this report. The main one concerns stigmatism conditions of concave holographic gratings used in normal incidence. This new process of focusing is very interesting for hot plasma diagnostics [fr

Effects of prenatal multiple micronutrient supplementation on growth and cognition through 2 y of age in rural Bangladesh: the JiVitA-3 Trial.

Science.gov (United States)

Christian, Parul; Kim, Jeongyong; Mehra, Sucheta; Shaikh, Saijuddin; Ali, Hasmot; Shamim, Abu Ahmed; Wu, Lee; Klemm, Rolf; Labrique, Alain B; West, Keith P

2016-10-01

Childhood undernutrition may have prenatal origins, and the impact of prenatal interventions on postnatal growth is not well known. We assessed the effects of prenatal multiple micronutrient (MM) supplementation on child growth and cognitive development. In a cluster-randomized controlled trial in rural Bangladesh, prenatal MM supplementation compared with iron-folic acid (IFA) supplementation was examined for its impact on growth assessed longitudinally from birth up to 24 mo of age (n = 8529) and, in a subsample (n = 734), on cognitive function at 24 mo of age by use of the Bayley scales of infant and toddler development-third edition test. Prevalence of stunting at birth [length for age z score (LAZ): growth. Ponderal and linear growth velocities were somewhat slower from 3 to 12 mo of age in the MM group than in the IFA group, but not from 12 to 24 mo of age. There was no difference between groups on composite scores of cognition, language, and motor performance at 24 mo of age. In this Bangladeshi trial, maternal pre- and postnatal MM supplementation resulted in improvements in LAZ and reduction in stunting through 3 mo of age, but not thereafter and had no impact on cognitive and motor function at 2 y. This trial was registered at clinicaltrials.gov as NCT000860470. © 2016 American Society for Nutrition.

Parent Training with High-Risk Immigrant Chinese Families: A Pilot Group Randomized Trial Yielding Practice-Based Evidence

Science.gov (United States)

Lau, Anna S.; Fung, Joey J.; Ho, Lorinda Y.; Liu, Lisa L.; Gudino, Omar G.

2011-01-01

We studied the efficacy and implementation outcomes of a culturally responsive parent training (PT) program. Fifty-four Chinese American parents participated in a wait-list controlled group randomized trial (32 immediate treatment, 22 delayed treatment) of a 14-week intervention designed to address the needs of high-risk immigrant families.…

Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials.

Science.gov (United States)

Hongell, Kira; Silva, Diego G; Ritter, Shannon; Meier, Daniela Piani; Soilu-Hänninen, Merja

2018-02-01

Low serum levels of 25-hydroxyvitamin D have been associated with worse outcomes in multiple sclerosis (MS) patients treated with interferon-beta. Association of vitamin D nutrition on the outcomes of other MS therapies has been studied less. Whether patients in the phase 3 fingolimod trials using vitamin D supplements have better clinical, MRI and safety outcomes than non-users. Pooled data from phase 3 FREEDOMS trials was analyzed post hoc. Vitamin D use was defined as 'non-users' (n = 562), 'casual users' (n = 157) and 'daily users' (usage 100% time in the study, n = 110). Expanded Disability Status Scale change from baseline to month 24, and annual relapse rate and proportion of patients with relapses were similar across the vitamin D user groups. Proportion of patients free of new/enlarging T2 lesions significantly favored vitamin D 'daily users' versus 'non-users'. Mean number of lesions were lower and proportion of patients free of gadolinium-enhanced T1-lesions were higher in the 'daily users'. At month 12, percent brain volume change was significantly lower in the 'daily users' versus 'non-users' and remained low at month 24 (non-significant). Incidence of depression was lower for vitamin D 'daily users' (non-significant). We observed improved MRI outcomes on percent brain volume change and proportion of patients free of new/enlarging T2 lesions, and a trend of less depression in the 'daily users' of vitamin D supplement in patients in the FREEDOMS trials.

Treatment of radiation enteritis: a comparison study

International Nuclear Information System (INIS)

Loiudice, T.A.; Lang, J.A.

1983-01-01

Twenty-four patients with severe radiation injury to the small bowel seen over a 4-year period were randomized to four treatment groups: 1) methylprednisolone 80 mg intravenously plus Vivonex-HN, 2 L/day po, 2) methylprednisolone 80 mg intravenously plus total parenteral nutrition, 2.5 L/day, 3) total parenteral nutrition, 2.5 L/day, and 4) Vivonex-HN, 2 L/day po. Patients received nothing by mouth except water in groups II and III, and only Vivonex-HN in groups I and IV. Patients were treated for 8-wk periods. Improvement was gauged by overall nutritional assessment measurements, nitrogen balance data and by radiological and clinical parameters. No significant difference between groups I, II, III, and IV could be found for age, sex, mean radiation dosage, time of onset after radiation therapy, or initial nutritional assessment data. Differences statistically could be found between groups II and III and I and IV regarding nutritional assessment data, nitrogen balance, radiographic and clinical parameters after therapy, with marked improvement noted in groups II and III. We conclude that a treatment regimen consisting of total parenteral nutrition and bowel rest is beneficial in the treatment of radiation enteritis. Methylprednisolone appears to enhance this effect and indeed, may be responsible for a longer lasting response

CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

Science.gov (United States)

Verhaart, René F; Fortunati, Valerio; Verduijn, Gerda M; van Walsum, Theo; Veenland, Jifke F; Paulides, Margarethus M

2014-04-01

Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Automatically generated 3D patient models can be introduced in the clinic for H&N HTP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Does participating in a clinical trial affect subsequent nursing management? Post-trial care for participants recruited to the INTACT pressure ulcer prevention trial: A follow-up study.

Science.gov (United States)

Webster, Joan; Bucknall, Tracey; Wallis, Marianne; McInnes, Elizabeth; Roberts, Shelley; Chaboyer, Wendy

2017-06-01

Participation in a clinical trial is believed to benefit patients but little is known about the post-trial effects on routine hospital-based care. To describe (1) hospital-based, pressure ulcer care-processes after patients were discharged from a pressure ulcer prevention, cluster randomised controlled trial; and (2) to investigate if the trial intervention had any impact on subsequent hospital-based care. We conducted a retrospective analysis of 133 trial participants who developed a pressure ulcer during the clinical trial. We compared outcomes and care processes between participants who received the pressure ulcer prevention intervention and those in the usual care, control group. We also compared care processes according to the pressure ulcer stage. A repositioning schedule was reported for 19 (14.3%) patients; 33 (24.8%) had a dressing applied to the pressure ulcer; 17 (12.8) patients were assessed by a wound care team; and 20 (15.0%) were seen by an occupational therapist. Patients in the trial's intervention group were more likely to have the presence of a pressure ulcer documented in their chart (odds ratio (OR) 8.18, 95% confidence intervals (CI) 3.64-18.36); to be referred to an occupational therapist OR 0.92 (95% CI 0.07; 0.54); to receive a pressure relieving device OR 0.31 (95% CI 0.14; 0.69); or a pressure relieving mattress OR 0.44 (95% CI 0.20; 0.96). Participants with Stage 2 or unstageable ulcers were more likely than others to have dressings applied to their wounds (p=pressure ulcer status and care is poor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trial protocol: a parallel group, individually randomized clinical trial to evaluate the effect of a mobile phone application to improve sexual health among youth in Stockholm County.

Science.gov (United States)

Nielsen, Anna; De Costa, Ayesha; Bågenholm, Aspasia; Danielsson, Kristina Gemzell; Marrone, Gaetano; Boman, Jens; Salazar, Mariano; Diwan, Vinod

2018-02-05

Genital Chlamydia trachomatis infection is a major public health problem worldwide affecting mostly youth. Sweden introduced an opportunistic screening approach in 1982 accompanied by treatment, partner notification and case reporting. After an initial decline in infection rate till the mid-90s, the number of reported cases has increased over the last two decades and has now stabilized at a high level of 37,000 reported cases in Sweden per year (85% of cases in youth). Sexual risk-taking among youth is also reported to have significantly increased over the last 20 years. Mobile health (mHealth) interventions could be particularly suitable for youth and sexual health promotion as the intervention is delivered in a familiar and discrete way to a tech savvy at-risk population. This paper presents a protocol for a randomized trial to study the effect of an interactive mHealth application (app) on condom use among the youth of Stockholm. 446 youth resident in Stockholm, will be recruited in this two arm parallel group individually randomized trial. Recruitment will be from Youth Health Clinics or via the trial website. Participants will be randomized to receive either the intervention (which comprises an interactive app on safe sexual health that will be installed on their smart phones) or a control group (standard of care). Youth will be followed up for 6 months, with questionnaire responses submitted periodically via the app. Self-reported condom use over 6 months will be the primary outcome. Secondary outcomes will include presence of an infection, Chlamydia tests during the study period and proxy markers of safe sex. Analysis is by intention to treat. This trial exploits the high mobile phone usage among youth to provide a phone app intervention in the area of sexual health. If successful, the results will have implications for health service delivery and health promotion among the youth. From a methodological perspective, this trial is expected to provide

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; Facon, Thierry; Hajek, Roman; Weisel, Katja; Hungria, Vania; Minuk, Leonard; Feng, Shibao; Zahlten-Kumeli, Anita; Kimball, Amy S; Moreau, Philippe

2017-10-01

The phase 3 ENDEAVOR trial was a head-to-head comparison of two proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Progression-free survival was previously reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis. The aim of this second interim analysis was to compare overall survival between the two treatment groups. ENDEAVOR was a phase 3, open-label, randomised controlled trial in patients with relapsed or refractory multiple myeloma. Patients were recruited from 198 hospitals and outpatient clinics in 27 countries in Europe, North America, South America, and the Asia-Pacific region. Patients were aged 18 years or older, had relapsed or refractory multiple myeloma, and had received between one and three previous lines of therapy. Patients were randomly assigned (1:1) to receive carfilzomib and dexamethasone (carfilzomib group) or bortezomib and dexamethasone (bortezomib group) through a blocked randomisation scheme (block size of four), stratified by International Staging System stage, previous lines of treatment, previous proteasome inhibitor therapy, and planned route of bortezomib delivery if assigned to the bortezomib group. Carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter) was given as a 30-min intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles; bortezomib (1·3 mg/m 2 ) was given as an intravenous bolus or subcutaneous injection on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20 mg oral or intravenous infusion) was given on days 1, 2, 8, 9, 15, 16, 22, and 23 in the carfilzomib group and on days 1, 2, 4, 5, 8, 9, 11, and 12 in the bortezomib group. The primary endpoint of ENDEAVOR, progression-free survival, has been previously reported. A stratified log-rank test was used to compare overall survival between treatment groups for this prospectively planned second interim

The CCT diagrams of ultra low carbon bainitic steels and their impact toughness properties

International Nuclear Information System (INIS)

Lis, A.K.; Lis, J.; Jeziorski, L.

1998-01-01

The CCT diagrams of ULCB N i steels, HN3MV, HN3MVCu having 5.1% Ni and 3.5% Ni and Cu bearing steels; HN3M1.5Cu, HSLA 100 have been determined. The reduced carbon concentration in steel, in order to prevent the formation of cementite, allowed for using nickel, manganese, chromium and molybdenum to enhance hardenability and refinement of the bainitic microstructures by lowering B S temperature. Copper and microadditions of vanadium and niobium are successfully used for precipitation strengthening of steel both in thermomechanically or heat treated conditions. Very good fracture toughness at low temperatures and high yield strength properties of HN3MVCu and HN3MV steels allowed for fulfillment of the requirements for steel plates for pressure vessels and cryogenic applications. (author)

Consensus statement on essential patient characteristics in systemic treatment trials for metastatic colorectal cancer: Supported by the ARCAD Group.

Science.gov (United States)

Goey, Kaitlyn K H; Sørbye, Halfdan; Glimelius, Bengt; Adams, Richard A; André, Thierry; Arnold, Dirk; Berlin, Jordan D; Bodoky, György; de Gramont, Aimery; Díaz-Rubio, Eduardo; Eng, Cathy; Falcone, Alfredo; Grothey, Axel; Heinemann, Volker; Hochster, Howard S; Kaplan, Richard S; Kopetz, Scott; Labianca, Roberto; Lieu, Christopher H; Meropol, Neal J; Price, Timothy J; Schilsky, Richard L; Schmoll, Hans-Joachim; Shacham-Shmueli, Einat; Shi, Qian; Sobrero, Alberto F; Souglakos, John; Van Cutsem, Eric; Zalcberg, John; van Oijen, Martijn G H; Punt, Cornelis J A; Koopman, Miriam

2018-06-21

Patient characteristics and stratification factors are key features influencing trial outcomes. However, there is substantial heterogeneity in reporting of patient characteristics and use of stratification factors in phase 3 trials investigating systemic treatment of metastatic colorectal cancer (mCRC). We aimed to develop a minimum set of essential baseline characteristics and stratification factors to include in such trials. We performed a modified, two-round Delphi survey among international experts with wide experience in the conduct and methodology of phase 3 trials of systemic treatment of mCRC. Thirty mCRC experts from 15 different countries completed both consensus rounds. A total of 14 patient characteristics were included in the recommended set: age, performance status, primary tumour location, primary tumour resection, prior chemotherapy, number of metastatic sites, liver-only disease, liver involvement, surgical resection of metastases, synchronous versus metachronous metastases, (K)RAS and BRAF mutation status, microsatellite instability/mismatch repair status and number of prior treatment lines. A total of five patient characteristics were considered the most relevant stratification factors: RAS/BRAF mutation status, performance status, primary tumour sidedness and liver-only disease. This survey provides a minimum set of essential baseline patient characteristics and stratification factors to include in phase 3 trials of systemic treatment of mCRC. Inclusion of these patient characteristics and strata in study protocols and final study reports will improve interpretation of trial results and facilitate cross-study comparisons. Copyright © 2018 Elsevier Ltd. All rights reserved.