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Premature Termination (premature + termination)
Terms modified by Premature Termination Selected AbstractsPremature termination of treatment in an inpatient eating disorder programmeEUROPEAN EATING DISORDERS REVIEW, Issue 4 2007Philip C. Masson Abstract This retrospective study was conducted to explore rates, timing and predictors of two forms of premature termination of treatment (PTT) in an inpatient eating disorders programme: patient dropout (DO) and administrative discharge (AD). A chart review was conducted to obtain demographic, Eating Disorder Inventory-2 (EDI-2), and Resident Assessment Instrument-Mental Health (RAI-MH) data for 186 patients being treated for bulimia nervosa (BN), anorexia nervosa (AN), or eating disorder not otherwise specified (EDNOS). Overall, of the 37.6% of patients who terminated treatment prematurely, 22.1% of patients dropped out, and 15.5% of patients were administratively discharged. Time at which discharge occurred was found to be associated with the type of premature termination. The presence of DSM-IV Axis-I comorbidity was found to be the only factor associated with an increased risk of being administratively discharged. No factors were predictive of patients dropping out of treatment. The findings support the notion that AD and patient DO are different events that may have different factors influencing their rates and timing. Implications for future research and programme planning are discussed. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: Results of a twelve-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study,ARTHRITIS & RHEUMATISM, Issue 1 2010Oliver Distler Objective To assess the efficacy and safety of terguride, a partial dopamine agonist, in patients with fibromyalgia syndrome (FMS). Methods In a 12-week, multicenter, double-blind, placebo-controlled, parallel-group study, 99 patients were randomized at a ratio of 2 to 1 to receive terguride or placebo. Over 21 days, the dosage was titrated to a maximum daily dose of 3 mg of terguride or placebo, and this fixed dosage was continued over 9 weeks. The primary efficacy variable was the intensity of pain (100-mm visual analog scale). Secondary efficacy variables included the Fibromyalgia Impact Questionnaire (FIQ) score, the tender point score (TPS), and the Hamilton Depression Scale (HDS) score. During the study, patients were evaluated for the presence of cervical spine stenosis by magnetic resonance imaging (MRI). Results No significant differences in the change in pain intensity, FIQ score, TPS, or HDS score between baseline and 12 weeks were observed in the terguride group as compared with the placebo group. Cervical spine stenosis was detected in 22% of the patients. Only patients with cervical spine stenosis responded to terguride treatment. FIQ scores improved significantly (per-protocol analysis), and pain intensity, the TPS score, and the HDS score showed a trend toward improvement in the terguride group as compared with the placebo group. Terguride treatment was safe. Only those adverse events already known to be side effects of terguride were observed. Premature termination of the study in patients receiving terguride (26%) occurred predominantly during up-titration and in the absence of comedication for treatment of nausea. Conclusion Terguride treatment did not improve pain, the FIQ score, the TPS, or the HDS score in the total study population. However, a subgroup of patients with cervical spine stenosis seemed to benefit from terguride treatment. [source] A Follow-up Study of Characteristics of Young People that Dropout and Continue Psychotherapy: Service Implications for a Clinic in the CommunityCHILD AND ADOLESCENT MENTAL HEALTH, Issue 2 2009Geoffrey Baruch Background:, The paper reports the findings from a follow-up study of the factors that contribute to whether young people dropout or continue once-weekly psychotherapy at a voluntary sector psychotherapy service for young people aged 12 to 21 years. Method:, The study uses data from an ongoing audit of the psychotherapy service that started in 1993; 882 young people were included in the study. Premature termination of treatment was defined as dropping out before the 21st session. Continuation in treatment was defined as remaining in therapy after 20 sessions. Measures and areas of interest used in the study include diagnostic measures, the Youth Self Report Form and Young Adult Self Report Form, demographic characteristics and treatment related information. Results:, Young people who continued in treatment were more likely to be older, have anxieties about sexual and relationship issues and have higher scores on self-reported anxiety-depression. Young people who dropped out of treatment were more likely to be younger, have higher self-reported delinquency scores, have a diagnosis of hyperactivity-conduct disorder and be homeless. Conclusions:, The study of treatment termination has demonstrated the value of service audit and has led to a significant change in clinical practice. [source] Reparallelization techniques for migrating OpenMP codes in computational gridsCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 3 2009Michael Klemm Typical computational grid users target only a single cluster and have to estimate the runtime of their jobs. Job schedulers prefer short-running jobs to maintain a high system utilization. If the user underestimates the runtime, premature termination causes computation loss; overestimation is penalized by long queue times. As a solution, we present an automatic reparallelization and migration of OpenMP applications. A reparallelization is dynamically computed for an OpenMP work distribution when the number of CPUs changes. The application can be migrated between clusters when an allocated time slice is exceeded. Migration is based on a coordinated, heterogeneous checkpointing algorithm. Both reparallelization and migration enable the user to freely use computing time at more than a single point of the grid. Our demo applications successfully adapt to the changed CPU setting and smoothly migrate between, for example, clusters in Erlangen, Germany, and Amsterdam, the Netherlands, that use different kinds and numbers of processors. Benchmarks show that reparallelization and migration impose average overheads of about 4 and 2%, respectively. Copyright © 2008 John Wiley & Sons, Ltd. [source] Premature termination of treatment in an inpatient eating disorder programmeEUROPEAN EATING DISORDERS REVIEW, Issue 4 2007Philip C. Masson Abstract This retrospective study was conducted to explore rates, timing and predictors of two forms of premature termination of treatment (PTT) in an inpatient eating disorders programme: patient dropout (DO) and administrative discharge (AD). A chart review was conducted to obtain demographic, Eating Disorder Inventory-2 (EDI-2), and Resident Assessment Instrument-Mental Health (RAI-MH) data for 186 patients being treated for bulimia nervosa (BN), anorexia nervosa (AN), or eating disorder not otherwise specified (EDNOS). Overall, of the 37.6% of patients who terminated treatment prematurely, 22.1% of patients dropped out, and 15.5% of patients were administratively discharged. Time at which discharge occurred was found to be associated with the type of premature termination. The presence of DSM-IV Axis-I comorbidity was found to be the only factor associated with an increased risk of being administratively discharged. No factors were predictive of patients dropping out of treatment. The findings support the notion that AD and patient DO are different events that may have different factors influencing their rates and timing. Implications for future research and programme planning are discussed. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Effect of the G1896A precore mutation on drug sensitivity and replication yield of lamivudine-resistant HBV in vitroHEPATOLOGY, Issue 1 2003Robert Y. M. Chen Hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) is frequently caused by a mutation (G1896A) in the hepatitis B virus (HBV) precore (PC) reading frame that creates a stop codon, causing premature termination of the PC protein. During lamivudine treatment, drug resistance develops at a similar rate in HBeAg positive and HBeAg negative CHB. Lamivudine-resistant HBV mutants have been shown to replicate inefficiently in vitro in the absence of PC mutations, but it is unknown whether the presence of PC mutations affects replication efficiency or antiviral sensitivity. This study utilized the recombinant HBV baculovirus system to address these issues. HBV baculoviruses encoding the G1896A PC stop codon mutation were generated in wild-type (WT) and lamivudine-resistant (rtM204I and rtL180M + rtM204V) backgrounds, resulting in a panel of 6 related recombinant baculoviruses. In vitro assays were performed to compare the sensitivities of the PC mutant viruses with lamivudine and adefovir and to compare relative replication yields. The PC mutation did not significantly affect sensitivities to either adefovir or lamivudine. WT HBV and PC mutant HBV showed similar replication yields, whereas the replication yields of the lamivudine-resistant mutants were greatly reduced in HBeAg positive HBVs, confirming previous observations. However, the presence of the PC mutation was found to compensate for the replication deficiency in each of the lamivudine-resistant mutants, increasing the replication yields of each virus. In conclusion, the PC stop codon mutation appears to increase the replication efficacy of lamivudine-resistant virus but does not affect in vitro drug sensitivity. [source] Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations,HUMAN MUTATION, Issue 1 2010Alessandra Pangrazio Abstract The "Osteopetroses" are genetic diseases whose clinical picture is caused by a defect in bone resorption by osteoclasts. Three main forms can be distinguished on the basis of severity, age of onset and means of inheritance: the dominant benign, the intermediate and the recessive severe form. While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different phenotypes. We report here the characterization of 25 unpublished patients which has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects. Careful analysis of clinical and molecular data led us to several conclusions. First, intermediate osteopetrosis is not homogeneous, since it can comprise both severe dominant forms with an early onset and recessive ones without central nervous system involvement. Second, the appropriateness of haematopoietic stem cell transplantation in CLCN7-dependent ARO patients has to be carefully evaluated and exhaustive CNS examination is strongly suggested, as transplantation can almost completely cure the disease in situations where no primary neurological symptoms are present. Finally, the analysis of this largest cohort of CLCN7-dependent ARO patients together with some ADO II families allowed us to draw preliminary genotype-phenotype correlations suggesting that haploinsufficiency is not the mechanism causing ADO II. The availability of biochemical assays to characterize ClC-7 function will help to confirm this hypothesis. © 2009 Wiley-Liss, Inc. [source] Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia,HUMAN MUTATION, Issue 4 2008Odity Mukherjee Abstract Frontotemporal dementia (FTD) is a clinical term encompassing dementia characterized by the presence of two major phenotypes: 1) behavioral and personality disorder, and 2) language disorder, which includes primary progressive aphasia and semantic dementia. Recently, the gene for familial frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U) linked to chromosome 17 was cloned. In the present study, 62 unrelated patients from the Washington University Alzheimer's Disease Research Center and the Midwest Consortium for FTD with clinically diagnosed FTD and/or neuropathologically characterized cases of FTLD-U with or without motor neuron disease (MND) were screened for mutations in the progranulin gene (GRN; also PGRN). We discovered two pathogenic mutations in four families: 1) a single-base substitution within the 3, splice acceptor site of intron 6/exon 7 (g.5913A>G [IVS6,2A>G]) causing skipping of exon 7 and premature termination of the coding sequence (PTC); and 2) a missense mutation in exon 1 (g.4068C>A) introducing a charged amino acid in the hydrophobic core of the signal peptide at residue 9 (p.A9D). Functional analysis in mutation carriers for the splice acceptor site mutation revealed a 50% decrease in GRN mRNA and protein levels, supporting haploinsufficiency. In contrast, there was no significant difference in the total GRN mRNA between cases and controls carrying the p.A9D mutation. Further, subcellular fractionation and confocal microscopy indicate that although the mutant protein is expressed, it is not secreted, and appears to be trapped within an intracellular compartment, possibly resulting in a functional haploinsufficiency. Hum Mutat 29(4), 512,521, 2008. © 2008 Wiley-Liss, Inc. [source] Functional analysis helps to clarify the clinical importance of unclassified variants in DNA mismatch repair genes,HUMAN MUTATION, Issue 11 2007Jianghua Ou Abstract Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is caused by DNA variations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Many of the mutations identified result in premature termination of translation and thus in loss-of-function of the encoded mutated protein. These DNA variations are thought to be pathogenic mutations. However, some patients carry other DNA mutations, referred to as unclassified variants (UVs), which do not lead to such a premature termination of translation; it is not known whether these contribute to the disease phenotype or merely represent rare polymorphisms. This is a major problem which has direct clinical consequences. Several criteria can be used to classify these UVs, such as: whether they segregate with the disease within pedigrees, are absent in control individuals, show a change of amino acid polarity or size, provoke an amino acid change in a domain that is evolutionary conserved and/or shared between proteins belonging to the same protein family, or show altered function in an in vitro assay. In this review we discuss the various functional assays reported for the HNPCC-associated MMR proteins and the outcomes of these tests on UVs identified in patients diagnosed with or suspected of having HNPCC. We conclude that a large proportion of MMR UVs are likely to be pathogenic, suggesting that missense variants of MMR proteins do indeed play a role in HNPCC. Hum Mutat 28(11), 1047,1054, 2007. © 2007 Wiley-Liss, Inc. [source] Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli,,HUMAN MUTATION, Issue 4 2005Gitana Aceto Abstract The analysis of APC and MYH mutations in adenomatous polyposis coli patients should provide clues about the genetic heterogeneity of the syndrome in human populations. The entire coding region and intron-exon borders of the APC and MYH genes were analyzed in 60 unrelated Italian adenomatous polyposis coli patients. APC analysis revealed 26 point mutations leading to premature termination, one missense variant and one deletion spanning the entire coding region in 32 unrelated patients. Novel truncating point mutations included c.1176_1177insT (p.His393_PhefsX396), c.1354_1355del (p.Val452_SerfsX458), c.2684C>A (p.Ser895X), c.2711_2712del (p.Arg904_LysfsX910), c.2758_2759del (p.Asp920_CysfsX922), c.4192_4193del (p.Ser1398_SerfsX1407), c.4717G>T (p.Glu1573X) and a novel cryptic APC exon 6 splice site. MYH analysis revealed nine different germline variants in nine patients, of whom five were homozygotes or compound heterozygotes. The mutations included 4 novel MYH missense variants (c.692G>A, p.Arg231His; c.778C>T, p.Arg260Trp; c.1121T>C, p.Leu374Pro; and c.1234C>T, p.Arg412Cys) affecting conserved amino acid residues in the ENDO3c or NUDIX domains of the protein and one novel synonymous change (c.672C>T, p.Asn224Asn). Genotype-phenotype correlations were found in carriers of APC mutations but not in carriers of biallelic MYH mutations, except for a negative correlation with low number of polyps. A distinctive characteristic of patients negative for APC and MYH mutations was a significantly (p<0.0001) older age at diagnosis compared to patients with APC mutations. Moreover, the proportion of cases with an attenuated polyposis phenotype was higher (p = 0.0008) among patients negative for APC and MYH mutations than among carriers of APC or biallelic MYH mutations. © 2005 Wiley-Liss, Inc. [source] Mutations in the human ATP-binding cassette transporters ABCG5 and ABCG8 in sitosterolemiaHUMAN MUTATION, Issue 2 2002Susanne Heimer Abstract Phytosterolemia or Sitosterolemia is a rare autosomal recessive disorder characterized by highly elevated plasma levels of plant sterols and cholesterol as a consequence of hyperabsorption and impaired biliary secretion of sterols. The disease is caused by mutations in two half size ATP-binding cassette transporters, ABCG5 and ABCG8. We have analyzed the genomic sequence of ABCG5 and ABCG8 in five well-characterized patients with Sitosterolemia. In the first patient we found a heterozygous mutation in exon 8 of the ABCG5 gene leading to a premature termination of the protein (Arg408Ter). This German patient is the first European showing a mutation of the ABCG5 gene. In a second patient we found a novel heterozygous mutation in exon 5 of ABCG8 (c.584T>A; Leu195Gln). Both patients were heterozygous for the identified mutation, but no mutation could be identified on the other chromosome. In three further analyzed patients we found mutations in exons 7, 9 and 11 of the ABCG8 gene, respectively, of which two result in a premature termination signal for translation products. One of these patients was compound heterozygous (Trp361Ter and Arg412Ter), the other was homozygous for Trp361Ter. The third patient was homozygous for an amino acid exchange (Gly574Arg). In conclusion this report describes one novel mutation affecting a highly conserved amino acid and two previously identified mutations in the ABCG8 gene. In addition, we identified for the first time a mutation in the ABCG5 gene of a European Sitosterolemia patient. © 2002 Wiley-Liss, Inc. [source] Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patientsHUMAN MUTATION, Issue 1 2002Jean L. Johnson Abstract We report twelve novel mutations in patients with isolated sulfite oxidase deficiency. The mutations are in SUOX, the gene that encodes the molybdohemoprotein sulfite oxidase. These include two frameshift mutations, a four-basepair deletion (562del4) and a single-basepair insertion (113insC), both resulting in premature termination. Nonsense mutations predicting Y343X and Q364X substitutions were identified in a homozygous state in three patients, the latter in two sibs. The remaining eight are missense mutations generating single amino acid substitutions. From the position of the substituted residues, seven of these mutations are considered to be causative of the enzyme deficiency: I201L, R211Q, G305S, R309H, K322R, Q339R, and W393R. The eighth, a C>T transition, predicts an R319C substitution, which could affect the binding of the molybdenum cofactor and thus severely reduce sulfite oxidase activity. This mutation, however, is downstream of a frameshift mutation and is therefore not the causative mutation in this individual. © 2002 Wiley-Liss, Inc. [source] Biochemical and mutational analyses of the cathepsin c gene (CTSC) in three North American families with Papillon Lefčvre syndromeHUMAN MUTATION, Issue 1 2002Y. Zhang Abstract Papillon Lefčvre syndrome (PLS) is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and severe periodontitis. The disease is caused by mutations in the cathepsin C gene (CTSC) that maps to chromosome 11q14. CTSC gene mutations associated with PLS have been correlated with significantly decreased enzyme activity. Mutational analysis of the CTSC gene in three North American families segregating PLS identified four mutations, including a novel mutation p.G139R. All mutations were associated with dramatically reduced CTSC protease enzyme activity. A homozygous c.96T>G transversion resulting in a p.Y32X change was present in a Mexican PLS proband, while one Caucasian PLS proband was a compound heterozygote for the p.Y32X and p.R272P (c.815G>C) mutations. The other Caucasian PLS proband was a compound heterozygote for c.415G>A transition and c.1141delC mutations that resulted in a p.G139R and a frameshift and premature termination (p.L381fsX393), respectively. The c.415G>A was not present in more than 300 controls, suggesting it is not a CTSC polymorphism. Biochemical analysis demonstrated almost no detectable CTSC activity in leukocytes of all three probands. These mutations altered restriction enzyme sites in the highly conserved CTSC gene. Sequence analysis of CTSC exon 3 confirmed the previously reported p.T153I polymorphism in 4 of the 5 ethnically diverse populations studied. © 2002 Wiley-Liss, Inc. [source] Young adults' ideas of cure prior to psychoanalytic psychotherapyJOURNAL OF CLINICAL PSYCHOLOGY, Issue 3 2007Björn Philips The study aims to explore systematically the ideas of cure among young adults prior to psychoanalytic psychotherapy. Forty-six individuals aged 18 to 25 years who applied for psychotherapy underwent the Private Theories Interview (PTI). Twenty distinct categories of ideas of cure were identified. Based on these categories, a theoretical model was constructed with the dimensions, Approaching,Distancing and Doing,Receiving. Individuals were classified into types using "ideal type analysis." Seven ideal types were formed: Processing and Understanding, Mastering Through Own Will and Action, Talking, Discordant Ideas, Incoherent Ideas, Getting It Out, and Avoiding or Placing the Solution onto Others. New hypotheses emerged concerning ideas of cure as an important factor for psychotherapy matching, thus potentially predicting premature termination, alliance, and outcome. © 2007 Wiley Periodicals, Inc. J Clin Psychol 63: 213,232, 2007. [source] Reasons for therapy termination in a university psychology clinicJOURNAL OF CLINICAL PSYCHOLOGY, Issue 9 2002Kimberly Renk This study examined the reasons for therapy termination documented by graduate student therapists. The closed case files of individual adult clients who had terminated their therapy experience at a university-based psychology clinic were reviewed. Results indicated that the most frequent reasons for termination documented by graduate student therapists were that clients stopped attending therapy sessions without providing their therapists with notice or reason and that clients reached a satisfactory termination point in their therapy experience. A substantial number of clients terminated therapy because of difficulties unrelated to therapy, seeking services elsewhere, or dissatisfaction with therapy services. Level of depressive symptomatology and the number of sessions attended differed across clients who had different reasons for termination. By addressing such client concerns early in the therapy experience, premature termination may be prevented. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1173,1181, 2002. [source] The vanG glycopeptide resistance operon from Enterococcus faecalis revisitedMOLECULAR MICROBIOLOGY, Issue 3 2003Florence Depardieu Summary Acquired VanG-type resistance to vancomycin (MIC = 16 µg ml,1) but susceptibility to teicoplanin in Enterococcus faecalis BM4518 and WCH9 is due to the inducible synthesis of peptidoglycan precursors ending in d -alanine- d -serine. The vanG cluster, assigned to a chromosomal location, was composed of genes recruited from various van operons. The 3, end encoded VanG, a d -Ala:d -Ser ligase, VanXYG, a putative bifunctional d,d -peptidase and VanTG, a serine racemase: VanG and VanTG were implicated in the synthesis of d -Ala:d -Ser as in VanC- and VanE-type strains. Upstream from the structural genes for these proteins were vanWG with unknown function and vanYG containing a frameshift mutation which resulted in premature termination of the encoded protein and accounted for the lack of UDP-MurNAc-tetrapeptide in the cytoplasm. Without the frameshift mutation, VanYG had homology with Zn2+ dependent d,d -carboxypeptidases. The 5, end of the gene cluster contained three genes vanUG, vanRG and vanSG encoding a putative regulatory system, which were co-transcribed constitutively from the PYG promoter, whereas transcription of vanYG,WG,G,XYG,TG was inducible and initiated from the PYG promoter. Transfer of VanG-type glycopeptide resistance to E. faecalis JH2-2 was associated with the movement, from chromosome to chromosome, of genetic elements of c. 240 kb carrying also ermB -encoded erythromycin resistance. Sequence determination of the flanking regions of the vanG cluster in donor and transconjugants revealed the same 4 bp direct repeats and 22 bp imperfect inverted repeats that delineated the large element. [source] Production of ,-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous ,039 thalassemia patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009Francesca Salvatori In several types of thalassemia (including ,039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying ,-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the ,039-thalassemia globin gene under control of the ,-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of ,-globin by K562 cell clones expressing the ,039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from ,039-thalassemia patients were demonstrated to be able to produce ,-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of ,0 -thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] A sequence mutation in the cinnamyl alcohol dehydrogenase gene associated with altered lignification in loblolly pinePLANT BIOTECHNOLOGY JOURNAL, Issue 4 2003Geoffrey P. Gill Summary Evidence for the molecular basis of a null allele of cinnamyl alcohol dehydrogenase (CAD) has been discovered in the loblolly pine (Pinus taeda L.) clone 7-56. The mutation is a two-base pair adenosine insertion located in exon 5 that causes a frame-shift which is predicted to result in premature termination of the protein. For routine detection of the mutation, a diagnostic assay was developed utilizing Template-directed Dye-terminator Incorporation and Fluorescence Polarization detection (FP-TDI). Loblolly pine is the most important commercial tree species in the USA, being harvested for pulp and solid wood products. Chemical pulping could be increased in efficiency by selecting for trees having a two-base pair adenosine insertion, by use of the rapid diagnostic assay developed in this study. [source] ATG-Fresenius Treatment and Low-Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010C. E. Benítez We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier:NCT00436722. [source] Inpatient multidisciplinary rehabilitation after hip fracture for residents of nursing homes: A randomised trialAUSTRALASIAN JOURNAL ON AGEING, Issue 1 2008Cesar Uy Objective:,To determine the effectiveness of interdisciplinary rehabilitation for women with hip fracture who were residents of nursing homes. Design:,Randomised controlled trial. Subjects:,Eleven cognitively impaired women with hip fracture who were previously ambulant. Methods:,Participants were randomly allocated to usual care (discharge back to the nursing home soon after surgery to the hip fracture) or an inpatient interdisciplinary rehabilitation program. Results:,Participants were severely cognitively impaired and the majority used a walking aid prior to fracturing their hip. There was one early death, and at final follow up (4 months after hip fracture) median (range) Barthel Index was 28 (0,82) for control group and 68 (0,88) for the intervention group. Conclusion:,No definite conclusion can be drawn about the effectiveness of the intervention because of its premature termination. However, the study established that it is feasible to provide an interdisciplinary rehabilitation for older people with hip fracture and severe disablement. [source] Nonsense-mediated decay: paving the road for genome diversificationBIOESSAYS, Issue 10 2008Francisco Sánchez-Sánchez The expression of protein-encoding genes is a complex process culminating in the production of mature mRNA and its translation by the ribosomes. The production of a mature mRNA involves an intricate series of processing steps. The majority of eukaryotic protein-encoding genes contain intron sequences that disrupt the protein-encoding frame, and hence have to be removed from immature mRNA prior to translation into protein. The mechanism involved in the selection of correct splice sites is incompletely understood. A considerable body of evidence suggests that the splicing machinery has suboptimal efficiency and fidelity leading to substantial processing inaccuracy. Here we discuss a recently published article1 that extends observations that cells rely on nonsense- mediated mRNA decay (NMD) to compensate for such suboptimal processing accuracy. Intriguingly these authors provide evidence for a strong selective pressure in favour of premature termination of mRNA translation in the event of intron retention. The analysis presented implies a positive role of NMD in transcript diversification through alternative splicing and suggest that this ancient surveillance mechanism may have co-evolved with intron acquisition born from the need for quality control of splicing patterns. BioEssays 30:926,928, 2008. © 2008 Wiley Periodicals, Inc. [source] Pilot intervention to enhance sexual rehabilitation for couples after treatment for localized prostate carcinoma,CANCER, Issue 12 2005Andrea L. Canada Ph.D. Abstract BACKGROUND The majority of prostate carcinoma survivors experience enduring sexual difficulties and associated distress in the years after definitive treatment. A counseling intervention aimed at improving levels of sexual satisfaction and increasing successful utilization of medical treatment for erectile dysfunction (ED) was developed and pilot-tested for both the survivor of prostate carcinoma and his partner. METHODS All male participants were 3-month to 5-year survivors of localized prostate carcinoma who had been treated with radical prostatectomy or radiation therapy, and were married or in a committed relationship. Couples were randomized to attend four sessions of counseling together or to have the man attend alone. In both groups, partners completed behavioral homework. The sessions included education on prostate carcinoma and sexual function and options to treat ED as well as sexual communication and stimulation skills. Standardized questionnaires at baseline, posttreatment, and at 3-month and 6-month follow-up assessed sexual function, marital adjustment, psychologic distress, and utilization of treatments for ED. RESULTS Fifty-one of 84 couples randomized to treatment completed the intervention (61%). Attendance by the partner did not affect outcomes. Participants completing the intervention demonstrated improvment in male overall distress (P < 0.01), male global sexual function (P < 0.0001), and female global sexual function (P < 0.05) at 3-month follow-up, but regression toward baseline was noted at 6-month follow-up. However, utilization of ED treatments increased from 31% at the time of study entry to 49% at the 6-month follow-up (P = 0.003). CONCLUSIONS The results of this brief pilot counseling intervention demonstrated significant gains in sexual function and satisfaction and increased utilization of treatments for ED. However, modifications are needed in future randomized trials to reduce the rate of premature termination and to improve long-term maintenance of gains. Cancer 2005. © 2005 American Cancer Society. [source] Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis)CLINICAL GENETICS, Issue 2 2004M Faiyaz-Ul-Haque Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature , bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted. [source] | ||||||||||||||||