Clinical experience with non-invasive prenatal screening for single-gene disorders.

OBJECTIVE: To assess the performance of a non-invasive prenatal screening test (NIPT) for a panel of dominant single-gene disorders (SGD) with a combined population incidence of 1 in 600. METHODS: Cell-free fetal DNA isolated from maternal plasma samples accessioned from 14 April 2017 to 27 November 2019 was analyzed by next-generation sequencing, targeting 30 genes, to look for pathogenic or likely pathogenic variants implicated in 25 dominant conditions. The conditions included Noonan spectrum disorders, skeletal disorders, craniosynostosis syndromes, Cornelia de Lange syndrome, Alagille syndrome, tuberous sclerosis, epileptic encephalopathy, SYNGAP1-related intellectual disability, CHARGE syndrome, Sotos syndrome and Rett syndrome. NIPT-SGD was made available as a clinical service to women with a singleton pregnancy at ≥ 9 weeks' gestation, with testing on maternal and paternal genomic DNA to assist in interpretation. A minimum of 4.5% fetal fraction was required for test interpretation. Variants identified in the mother were deemed inconclusive with respect to fetal carrier status. Confirmatory prenatal or postnatal diagnostic testing was recommended for all screen-positive patients and follow-up information was requested. The screen-positive rates with respect to the clinical indication for testing were evaluated. RESULTS: A NIPT-SGD result was available for 2208 women, of which 125 (5.7%) were positive. Elevated test-positive rates were observed for referrals with a family history of a disorder on the panel (20/132 (15.2%)) or a primary indication of fetal long-bone abnormality (60/178 (33.7%)), fetal craniofacial abnormality (6/21 (28.6%)), fetal lymphatic abnormality (20/150 (13.3%)) or major fetal cardiac defect (4/31 (12.9%)). For paternal age ≥ 40 years as a sole risk factor, the test-positive rate was 2/912 (0.2%). Of the 125 positive cases, follow-up information was available for 67 (53.6%), with none classified as false-positive. No false-negative cases were identified. CONCLUSIONS: NIPT can assist in the early detection of a set of SGD, particularly when either abnormal ultrasound findings or a family history is present. Additional clinical studies are needed to evaluate the optimal design of the gene panel, define target populations and assess patient acceptability. NIPT-SGD offers a safe and early prenatal screening option. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Interventions to improve patient understanding of cancer clinical trial participation: a systematic review.

Patient misunderstanding of cancer clinical trial participation is identified as a critical issue and researchers have developed and tested a variety of interventions to improve patient understanding. This systematic review identified nine papers published between 2000 and 2013, to evaluate the effects of interventions to improve patient understanding of cancer clinical trial participation. Types of interventions included audio-visual information, revised written information and a communication training workshop. Interventions were conducted alone or in combination with other forms of information provision. The nine papers, all with methodological limitations, reported mixed effects on a small range of outcomes regarding improved patient understanding of cancer clinical trial participation. The methodological limitations included: (1) the intervention development process was poorly described; (2) only a small element of the communication process was addressed; (3) studies lacked evidence regarding what information is essential and critical to enable informed consent; (4) studies lacked reliable and valid outcome measures to show that patients are sufficiently informed to provide consent; and (5) the intervention development process lacked a theoretical framework. Future research needs to consider these factors when developing interventions to improve communication and patient understanding during the informed consent process.

Norepinephrine and corticosterone in the medial prefrontal cortex and hippocampus predict PTSD-like symptoms in mice.

This study measured changes in brain extracellular norepinephrine (NE) and free corticosterone (CORT) levels in a mouse model of post-traumatic stress disorder and related them to hyperarousal and fear memory retention. To this end, microdialysis in the medial prefrontal cortex (mPFC) and the hippocampus (HPC) of male C57BL/6NCrl mice was performed during an acoustic startle response (ASR) and following an electric foot shock (FS), as well as during an ASR and recall of contextual fear (CF) 1 day later. Changes in ASR-stimulated NE levels in the mPFC corresponded to ASR 34 days after FS. Changes in basal and ASR-stimulated extracellular NE levels in the HPC, in contrast, were related to expression of early (day 2) and late (day 34) CF after FS. The increase in extracellular NE levels correlated in a U-shape manner with arousal levels and CF, thus suggesting a non-direct relationship. Stress of different modalities/strength (ASR, FS and CF) caused a similar relative increase in free CORT levels both in the mPFC and the HPC. One day after FS, ASR-induced increases in the CORT content in the mPFC tended to correlate with the FS-potentiated ASR in a U-shape manner. Taken together, these data show that the intracerebral increase in free CORT was likely related to an immediate response to stress, whereas NE neurotransmission in the forebrain predicted arousal and CF 1 month after trauma.

Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis.

BACKGROUND: Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. OBJECTIVES: The hemostatic activity of Reelin is investigated and defined in this study. METHODS: The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed. RESULTS: Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin ß1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nm, respectively. Reelin-deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. CONCLUSIONS: By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.

The complex interplay among bacterial motility and virulence factors in different Escherichia coli infections.

Motility mediated by the flagella of Escherichia coli is important for the bacteria to move toward host cells. Here, we present the relationship among bacterial motility, virulence factors, antimicrobial susceptibility, and types of infection. A total of 231 clinical E. coli isolates from different infections were collected and analyzed. Higher-motility strains (motility diameter ≥6.6 mm) were more common in spontaneous bacterial peritonitis (SBP) (SBP 59 %, colonization 32 %, urinary tract infection 16 %, urosepsis 34 %, and biliary tract infection 29 %; p < 0.0001). Compared with the higher-motility group, there was a higher prevalence of afa and ompT genes (p = 0.0160 and p = 0.0497, respectively) in E. coli strains with lower motility. E. coli isolates with higher and lower motility were in different phylogenetic groups (p = 0.018), with a lower prevalence of A and B1 subgroups in higher-motility strains. Also, the patterns of virulence factors and antibiotic susceptibility of E. coli isolates derived from various infections were significantly different. This study demonstrates that the prevalence of higher-motility strains was greater in E. coli isolates from SBP compared to other types of infection. Various types of E. coli infection were associated with differences in bacterial motility, virulence factors, and antibiotic susceptibility. More bacterial virulence factors may be necessary for the development of extraintestinal infections caused by E. coli isolates with lower motility.

Clinical and microbiological characteristics of Klebsiella pneumoniae from community-acquired recurrent urinary tract infections.

Understanding the pathogenesis of recurrent urinary tract infection (RUTI) and whether it is attributable to reinfection with a new strain or relapse with the primary infecting strain is of considerable importance. Because previous studies regarding community-acquired Klebsiella pneumoniae RUTI are inconclusive, we undertook this study to evaluate the characteristics of the host and the bacterial agent K. pneumoniae in RUTI. A prospective study was designed, using consecutive patients diagnosed with community-acquired K. pneumoniae-related UTI from January 2007 to December 2009. Of the total 468 consecutive episodes, we found 7 patients with RUTI. All the patients with RUTI were elderly (median, 74 years), with diabetes (100 %, 7 out of 7). Clinical K. pneumoniae isolates derived from the same patients with RUTI revealed identical genomic fingerprints, indicating that K. pneumoniae UTI relapsed despite appropriate antibiotic therapy. The antimicrobial resistance, growth curve and biofilm formation of the recurrent isolates did not change. K. pneumoniae strains causing RUTI had more adhesion and invasiveness than the colonization strains (p < 0.01). When we compared the recurrent strains with the community-acquired UTI strains, the prevalence of diabetes mellitus was significant (100 % vs 53.7 %, p = 0.03) in the RUTI group. Our data suggest that K. pneumoniae strains might be able to persist within the urinary tract despite appropriate antibiotic treatment, and the greater adhesion and invasiveness in the recurrent strains may play an important role in recurrent infections.

Is the proton radius a player in the redefinition of the International System of Units?

It is now recognized that the International System of Units (SI units) will be redefined in terms of fundamental constants, even if the date when this will occur is still under debate. Actually, the best estimate of fundamental constant values is given by a least-squares adjustment, carried out under the auspices of the Committee on Data for Science and Technology (CODATA) Task Group on Fundamental Constants. This adjustment provides a significant measure of the correctness and overall consistency of the basic theories and experimental methods of physics using the values of the constants obtained from widely differing experiments. The physical theories that underlie this adjustment are assumed to be valid, such as quantum electrodynamics (QED). Testing QED, one of the most precise theories is the aim of many accurate experiments. The calculations and the corresponding experiments can be carried out either on a boundless system, such as the electron magnetic moment anomaly, or on a bound system, such as atomic hydrogen. The value of fundamental constants can be deduced from the comparison of theory and experiment. For example, using QED calculations, the value of the fine structure constant given by the CODATA is mainly inferred from the measurement of the electron magnetic moment anomaly carried out by Gabrielse's group. (Hanneke et al. 2008 Phys. Rev. Lett. 100, 120801) The value of the Rydberg constant is known from two-photon spectroscopy of hydrogen combined with accurate theoretical quantities. The Rydberg constant, determined by the comparison of theory and experiment using atomic hydrogen, is known with a relative uncertainty of 6.6×10(-12). It is one of the most accurate fundamental constants to date. A careful analysis shows that knowledge of the electrical size of the proton is nowadays a limitation in this comparison. The aim of muonic hydrogen spectroscopy was to obtain an accurate value of the proton charge radius. However, the value deduced from this experiment contradicts other less accurate determinations. This problem is known as the proton radius puzzle. This new determination of the proton radius may affect the value of the Rydberg constant . This constant is related to many fundamental constants; in particular, links the two possible ways proposed for the redefinition of the kilogram, the Avogadro constant N(A) and the Planck constant h. However, the current relative uncertainty on the experimental determinations of N(A) or h is three orders of magnitude larger than the 'possible' shift of the Rydberg constant, which may be shown by the new value of the size of the proton radius determined from muonic hydrogen. The proton radius puzzle will not interfere in the redefinition of the kilogram. After a short introduction to the properties of the proton, we will describe the muonic hydrogen experiment. There is intense theoretical activity as a result of our observation. A brief summary of possible theoretical explanations at the date of writing of the paper will be given. The contribution of the proton radius puzzle to the redefinition of SI-based units will then be examined.

A cross-ethnic comparison on incidence of suicide.

BACKGROUND: Suicide rates vary widely across nations and ethnic groups. This study aims to explore potential factors contributing to inter-ethnic differences in suicide rates. METHOD: Study subjects came from a case-control psychological autopsy study conducted in Taiwan, including 116 consecutive suicides from two aboriginal groups and Taiwanese Han; 113 of them each matched with two living controls. Gender-, age- and method-specific suicide rates, population attributable fraction (PAF) of suicide for five major risk factors, help-seeking before suicide and emergency medical aid after suicide were compared between the three ethnic groups. RESULTS: One aboriginal group (the Atayal) had significantly higher adjusted rate ratios (RR) of suicide than the other aboriginal group (the Ami) [RR 0.20, 95% confidence intervals (CI) 0.12-0.34] and the Han (RR 0.26, 95% CI 0.16-0.40). Such differences can be explained by higher PAFs of suicide for three major risk factors (substance dependence, PAF 47.6%, 95% CI 25.5-64.2; emotionally unstable personality disorder, PAF 52.7%, 95% CI 32.8-69.0; family history of suicidal behaviour, PAF 43.5%, 95% CI 23.2-60.2) in this group than in the other two groups. This higher suicide rate was substantially reduced from 68.2/100 000 per year to 9.1/100 000 per year, comparable with the other two groups, after stepwise removal of the effects of these three risk factors. Suicide rates by self-poisoning were also significantly higher in this group than in the other two groups. CONCLUSIONS: Higher rates of specific risk factors and use of highly lethal pesticides for suicide contributed to the higher suicide rate in one ethnic group in Taiwan. These findings have implications for developing ethnicity-relevant suicide prevention strategies.

Generation of a novel factor IX with augmented clotting activities in vitro and in vivo.

BACKGROUND: Hemophilia B is an X-linked inherited disorder caused by the lack of functional factor IX (FIX). Currently, treatment of hemophilia B is performed by intravenous infusion of plasma-derived or recombinant FIX. OBJECTIVE: In an effort to reduce factor usage and cost, we investigated the potential use of FIX variants with enhanced specific clotting activity. METHODS: Seven recombinant FIX variants using alanine replacement were generated and assayed for their activity in vitro and in vivo. RESULTS: One variant containing three substitutions (V86A/E277A/R338A, FIX-Triple) exhibited 13-fold higher specific clotting activity and a 10-fold increased affinity for human FVIIIa compared with FIX-wild-type (FIX-WT) and was thus investigated systematically in vivo. Liver-specific FIX-Triple gene expression following hydrodynamic plasmid delivery revealed a 3.5-fold higher specific clotting activity compared with FIX-WT. Human FIX-Triple and FIX-WT knock-in mice were generated and it was confirmed that FIX-Triple has 7-fold higher specific clotting activity than FIX-WT under normal physiological conditions. Protein infusion of FIX-Triple into hemophilia B mice resulted in greater improvement of hemostasis than that achieved with FIX-WT. Moreover, tail-vein administration of a serotype 8 recombinant Adeno-associated vector (AAV8) expressing either FIX-WT or FIX-Triple in hemophilia B mice demonstrated a 7-fold higher specific clotting activity of FIX-Triple than FIX-WT. CONCLUSIONS: Our results indicate that the FIX-Triple variant exhibits significantly enhanced clotting activity relative to FIX-WT due to tighter binding to FVIIIa, as demonstrated both in vitro and in vivo. Therefore, FIX-Triple is a good candidate for further evaluation in protein replacement therapy as well as gene-based therapeutic strategies.

Maize VP1 complements Arabidopsis abi3 and confers a novel ABA/auxin interaction in roots.

The maize Vp1 gene and abi3 gene of Arabidopsis are believed to be orthologs based on similarities of the mutant phenotypes and amino acid sequence conservation. Here we show that expression of VP1 driven by the 35S promoter can partially complement abi3-6, a deletion mutant allele of abi3. The visible phenotype of seed produced from VP1 expression in the abi3 mutant background is nearly indistinguishable from wild type. VP1 fully restores abscisic acid (ABA) sensitivity of abi3 during seed germination and suppresses the early flowering phenotype of abi3. The temporal regulation of C1-beta-glucuronidase (GUS) and chlorophyll a/b binding protein (cab3)-GUS reporter genes in developing seeds of 35S-VP1 lines were similar to wild type. On the other hand, two qualitative differences are observed between the 35S-VP1 line and wild type. The levels of CRC and C1-GUS expression are markedly lower in the seeds of 35S-VP1 lines than in wild type suggesting incomplete complementation of gene activation functions. Similar to ectopic expression of ABI3 (Parcy et al., 1994), ectopic expression of VP1 in vegetative tissue enhances ABA inhibition of root growth. In addition, 35S-VP1 confers strong ABA inducible expression of the normally seed-specific cruciferin C (CRC) gene in leaves. In contrast, ectopic ABA induction of C1-GUS is restricted to a localized region of the root elongation zone. The ABA-dependent C1-GUS expression expanded to a broader area in the root tissues treated with exogenous application of auxin. Interestingly, auxin-induced lateral root formation is completely suppressed by ABA in 35S-VP1 plants but not in wild type. These results indicate VP1 mediates a novel interaction between ABA and auxin signaling that results in developmental arrest and altered patterns of gene expression.

Optical coating designs using the family competition evolutionary algorithm.

A robust evolutionary approach, called the Family Competition Evolutionary Algorithm (FCEA), is described for the synthesis of optical thin-film designs. Based on family competition and adaptive rules, the proposed approach consists of global and local strategies by integrating decreasing mutations and self-adaptive mutations. The method is applied to three different optical coating designs with complex spectral quantities. Numerical results indicate that the proposed approach performs very robustly and is very competitive with other approaches.

Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A.

Hepatitis C virus nonstructural protein, NS5A, is a phosphoprotein produced from the processing of the viral polyprotein precursor. NS5A associates with several cellular proteins in mammalian cells, and the biological consequences of this interaction are currently unknown. To this end, five stable NS5A-expressing murine and human cell lines were established. Tetracycline-regulated NIH3T3 cells and rat liver epithelial cells as well as the constitutive, NS5A-expressing, human Chang liver, HeLa, and NIH3T3 cells all exhibited cell growth retardation compared with the control cells. Cell cycle analysis by flow cytometry indicated that the NS5A-expressing human epitheloid tumor cells had a reduced S phase and an increase in the G(2)/M phase, which could be explained by a p53-dependent induction of p21(Waf1/Cip1) protein and mRNA levels. NS5A interacts with Cdk1 in vivo and in vitro, and a significant portion of the p21(Waf1/Cip1) was found to be in a complex with Cdk2 in the NS5A-expressing human hepatic cell line. Cdk1 and cyclin B1 proteins were also reduced in human Chang liver cells consistent with the increase in G(2)/M phase. Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes.

Efficient evolutionary algorithm for the thin-film synthesis of inhomogeneous optical coatings.

We propose an efficient evolutionary approach for the thin-film synthesis of inhomogeneous optical coatings. The proposed approach consists of global and local strategies by integration of decreasing-based mutations and self-adaptive mutations by means of family competition and adaptive rules. Numerical results indicate that the proposed approach performs robustly and is competitive with other approaches. Our approach, although somewhat slower, is flexible and can easily be adopted to other application domains. Our approach is also able to generate homogeneous solutions with two materials available.

A family competition evolutionary algorithm for automated docking of flexible ligands to proteins.

In this paper, we study an evolutionary algorithm for flexible ligand docking. Based on family competition and adaptive rules, the proposed approach consists of global and local strategies by integrating decreasing mutations and self-adaptive mutations. To demonstrate the robustness of the proposed approach, we apply it to the problems of the first international contests on evolutionary optimization. Following the description of function optimization, our approach is applied to a dihydrofolate reductase enzyme with the anti-cancer drug methotrexate and with two analogs of the antibacterial drug trimethoprim. Our numerical results indicate that the proposed approach is robust. The docked lowest energy structures have rms derivations ranging from 0.72 A to 1.98 A with respect to the corresponding crystal structure.

Prevention of acute and delayed cisplatin-induced nausea and vomiting with intravenous ondansetron plus intravenous dexamethasone.

BACKGROUND: We conducted a prospective study to evaluate the anti-emetic effect of cisplatin-induced nausea and vomiting with intravenous (i.v.) ondansetron plus i.v. dexamethasone. METHODS: One hundred forty-six chemotherapy (CT)-naive patients were enrolled in the study. They were scheduled to receive cisplatin 50 to 100 mg/m2 (mean, 53 mg/m2) on day 1 followed immediately by continuous infusion of 5-fluorouracil with or without other CT agents on the subsequent days. Three 8 mg doses of ondansetron i.v. were given at 4-hour intervals plus 20 mg dexamethasone i.v. infusions from the start of CT, followed by 5 mg dexamethasone i.v. every 12 hours, and the administration of dexamethasone was discontinued after the completion of CT. RESULTS: The rates of complete protection from acute and delayed vomiting/nausea obtained in these patients were 97.3%/93.2% and 71.2%/60.3%, respectively. The rates of complete protection from both acute and delayed nausea were 70.5% and 58.9%, respectively. By comparison, the total control rate of vomiting was less in female patients than in male patients (p = 0.017), and the total control rate of nausea was lower in the age group less than 50 years (p = 0.045). The time from the start of CT to the onset of nausea appeared to be earlier than that for vomiting (log-rank test, p = 0.045). Adverse events tended to be minor, with constipation and hiccups as the most common. CONCLUSION: These results indicate that i.v. ondansetron plus i.v. dexamethasone is a feasible anti-emetic therapy in an inpatient setting. I.v. ondansetron plus i.v. dexamethasone is highly effective in preventing acute cisplatin-induced nausea and vomiting.

Tuberculosis presenting with pelvic mass, peritoneal lesions, and elevation of serum CA125 mimicking malignant tumor: a case report.

Tuberculosis is a curable infective disease which can mimic a malignant tumor. We report on a young woman who presented with abdominal fullness, body weight loss, and microcytic anemia. A pelvic mass and peritoneal lesions were found. The serum CA125 level was high. The initial gynecologic echo and abdominal CT scan revealed bilateral ovarian mass with peritoneal lesions, and malignancy was highly suspected. Diagnostic laparoscopy was performed, and peritoneal tuberculosis was pathologically proven. Combination anti-tuberculosis therapy was prescribed for one year. She was followed up in the outpatient clinic regularly with symptom improvement, body weigh gain, and improvement of anemia. We suggest that in cases of a pelvic mass and peritoneal lesions, with elevation of the serum CA125 level, tuberculosis should always be kept on the list of differential diagnoses. A tissue diagnosis should always be obtained before treatment, regardless of initial image study and laboratory findings.

Tin-protoporphyrin potentiates arsenite-induced DNA strand breaks, chromatid breaks and kinetochore-negative micronuclei in human fibroblasts.

Numerous reports have shown that oxidative stress is involved in arsenite-induced genetic damage. Arsenite is also a potent inducer of heme oxygenase (HO)-1. To understand whether HO-1 could function as a cellular antioxidant and protect cells from arsenite injury, the effects of tin-protoporphyrin (SnPP), a competitive inhibitor of HO-1, on arsenite-induced genetic damage were examined in human skin fibroblasts (HFW). In the present study, we found that SnPP at 100 microM significantly potentiated arsenite-induced cytotoxicity, DNA strand breaks (assayed by alkaline single cell gel electrophoresis(SCGE)), and chromatid breaks. Although arsenite alone mainly induced kinetochore-plus micronuclei (K(+)-MN), SnPP only synergistically enhanced kinetochore-negative micronuclei (K(-)-MN). The increase in K(-)-MN by SnPP cotreatment was consistent with the increase in DNA strand breaks and chromatid breaks caused by SnPP. However, at higher arsenite doses, K(+)-MN was significantly reduced by SnPP. Pretreatment of HFW cells with hemin, an inducer of HO-1, significantly attenuated the cytotoxicity of arsenite. Therefore, the present results suggest that HO-1 induction by arsenite plays certain roles in protecting cells from arsenite-induced injury.

Recombinant polyclonal antibody libraries.

We describe a technology for generating recombinant polyclonal antibody libraries (PCALs) that enables the creation and perpetuation of standardized mixtures of polyclonal whole antibodies specific for a multiantigen (or polyantigen). Therefore, this technology combines the advantages of targeting multiple antigenic determinants -- high avidity, low likelihood of antigen 'escape variants', and efficient mediation of effector functions, with the advantages of using monoclonal antibodies -- unlimited supply of standardized reagents and the availability of the genetic material for desired manipulations. The technology for generating recombinant polyclonal antibody libraries begins with the creation of phage display Fab (antibody) libraries. This is followed by selection of sublibraries with desired antigen specificities, and mass transfer of the variable region gene pairs of the selected sublibraries to a mammalian expression vector for generation of libraries of polyclonal whole antibodies. We review here our experiments for selection of phage display antibody libraries against microbes and tumor cells, as well as the recent literature on the selection of phage display antibody libraries to multiantigen targets.

Control of cisplatin-induced emesis with intravenous ondansetron plus intravenous dexamethasone: a crossover study of triple 8-mg dose of ondansetron.

Two hundred seventy-five patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron intravenous (IV) were given at 4-hour intervals plus dexamethasone 20 mg IV from the start of chemotherapy followed by dexamethasone 5 mg IV every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron IV were given at 24-hour intervals substituted for ondansetron IV given at 4-hour intervals. There were 237 patients in arm A and 223 patients in arm B. Complete protection from acute and delayed vomiting/nausea obtained in arm A was 94.5%/90.3% and 71.3%/57.8%, respectively; protection obtained in arm B was 92.7%/91.0% and 71.7%/60.5%, respectively. No differences were observed in control of acute emesis after the addition of dexamethasone to ondansetron, given as either a triple 8-mg dose at 4-hour intervals or a single 8-mg dose. The triple dose of ondansetron given at 24-hour intervals was also not more effective than ondansetron given at 4-hour intervals in preventing delayed emesis when dexamethasone was added. However, the former improved control of delayed nausea on day 2. Adverse events tended to be minor, with constipation and hiccup the most common.

A genetic algorithm with adaptive mutations and family competition for training neural networks.

In this paper, we present a new evolutionary technique to train three general neural networks. Based on family competition principles and adaptive rules, the proposed approach integrates decreasing-based mutations and self-adaptive mutations to collaborate with each other. Different mutations act as global and local strategies respectively to balance the trade-off between solution quality and convergence speed. Our algorithm is then applied to three different task domains: Boolean functions, regular language recognition, and artificial ant problems. Experimental results indicate that the proposed algorithm is very competitive with comparable evolutionary algorithms. We also discuss the search power of our proposed approach.