<i>Vibrio neptunius</i> sp. nov., <i>Vibrio brasiliensis</i> sp. nov. and <i>Vibrio xuii</i> sp. nov., isolated from the marine aquaculture environment (bivalves, fish, rotifers and shrimps)

The fluorescent amplified fragment length polymorphism (FAFLP) groups A5 (21 isolates), A8 (6 isolates) and A23 (3 isolates) distinguished in an earlier paper (Thompson et al., Syst Appl Microbiol 24, 520-538, 2001) were examined in more depth. These three groups were phylogenetically related to Vibrio tubiashii, but DNA-DNA hybridization experiments proved that the three AFLP groups are in fact novel species. Chemotaxonomic and phenotypic analyses further revealed several differences among the 30 isolates and known Vibrio species. It is proposed to accommodate these isolates in three novel species, namely Vibrio neptunius (type strain LMG 20536T; EMBL accession no. AJ316171; G + C content of the type strain 46·0 mol%), Vibrio brasiliensis (type strain LMG 20546T; EMBL accession no. AJ316172; G + C content of the type strain 45·9 mol%) and Vibrio xuii (type strain LMG 21346T; EMBL accession no. AJ316181; G + C content of the type strain 46·6 mol%). These species can be differentiated on the basis of phenotypic features, including fatty acid composition (particularly 14 : 0 iso, 14 : 0 iso 3-OH, 16 : 0 iso, 16 : 0, 17 : 0 and 17 : 1?8c), enzyme activities and utilization and fermentation of various carbon sources

Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study

L-asparaginase is a frequently used drug in the treatment of canine malignant lymphoma. Since production and availability of native E. coli-derived L-asparaginase are limited, PEG-L-asparaginase (PEG-ASP) is an alternative. However, recommended doses and dosing intervals are mainly empirically determined. A multi-phase clinical dose-finding study with seven healthy Beagle dogs was conducted to find the minimum effective dose and, potentially, a dosing interval for PEG-ASP in dogs. Plasma concentrations of amino acids and PEG-ASP activity were measured at various time points after administration of different doses of PEG-ASP. Anti-PEG and anti-asparaginase antibody titres were measured. Administration of 10 IU/kg PEG-ASP resulted in asparagine depletion in all dogs, albeit for various durations: for 9 days in all dogs, 15 days in five dogs, 21 days in three dogs and 29 days in one dog. Asparagine suppression occurred at PEG-ASP plasma concentrations < 25 IU/L. Subsequent administrations of a second and third dose of 20 IU/kg and 40 IU/kg PEG-ASP resulted in asparagine suppression at < 9 days in five dogs, accompanied by the development of antibodies against PEG and L-asparaginase. Two dogs with prolonged asparagine suppression after the second and third administration did not develop antibodies. Marked individual variation in the mechanism and duration of response to PEG-ASP was noted. Antibody formation against PEG-ASP was frequently observed and sometimes occurred after one injection. This study suggests that PEG-ASP doses as high as the currently used dose of 40 IU/kg might not be needed in treatment of canine malignant lymphoma

Adding a treatment arm to an ongoing clinical trial: a review of methodology and practice

Incorporating an emerging therapy as a new randomisation arm in a clinical trial that is open to recruitment would be desirable to researchers, regulators and patients to ensure that the trial remains current, new treatments are evaluated as quickly as possible, and the time and cost for determining optimal therapies is minimised. It may take many years to run a clinical trial from concept to reporting within a rapidly changing drug development environment; hence, in order for trials to be most useful to inform policy and practice, it is advantageous for them to be able to adapt to emerging therapeutic developments. This paper reports a comprehensive literature review on methodologies for, and practical examples of, amending an ongoing clinical trial by adding a new treatment arm. Relevant methodological literature describing statistical considerations required when making this specific type of amendment is identified, and the key statistical concepts when planning the addition of a new treatment arm are extracted, assessed and summarised. For completeness, this includes an assessment of statistical recommendations within general adaptive design guidance documents. Examples of confirmatory ongoing trials designed within the frequentist framework that have added an arm in practice are reported; and the details of the amendment are reviewed. An assessment is made as to how well the relevant statistical considerations were addressed in practice, and the related implications. The literature review confirmed that there is currently no clear methodological guidance on this topic, but that guidance would be advantageous to help this efficient design amendment to be used more frequently and appropriately in practice. Eight confirmatory trials were identified to have added a treatment arm, suggesting that trials can benefit from this amendment and that it can be practically feasible; however, the trials were not always able to address the key statistical considerations, often leading to uninterpretable or invalid outcomes. If the statistical concepts identified within this review are considered and addressed during the design of a trial amendment, it is possible to effectively assess a new treatment arm within an ongoing trial without compromising the original trial outcomes

A Cmos 13-b Cyclic Rsd A/d Converter

A 13-b CMOS cyclic A/D converter that does not need trimming nor digital calibration is presented. The effects associated with the error on the gain factor 2 as well as the offset errors are corrected by taking full advantage of the redundant signed digit (RSD) principle. The gain error resulting from mismatches among switched capacitors is corrected by a novel strategy that implements an exact multiplication by four after two cycles. As a result, offset errors do not affect the integral or the differential linearities from the RSD algorithm. The remaining overall shift caused by offsets is reduced under the LSB level by a proper choice of capacitor switching sequence. The converter achieves 1/2 LSB integral and differential linearity at 25 kS/s; harmonic distortion is less than -83 dB. Chip area is 2.9 mm2 in a standard CMOS 3-mu-m technology, including control logic and the serial-to-parallel output shift register. Power consumption is 45 mW under +/-5-V supplies

Adhesive capsulitis of the hip: three case reports.

PURPOSE: To describe the diagnosis and treatment of adhesive capsulitis of the hip (ACH). METHOD: A literature review and consideration of three case reports. DISCUSSION: Adhesive capsulitis of the hip is a supposedly rare but probably underestimated condition which predominantly affects middle-aged women. Clinical assessment reveals a painful limitation of joint mobility. The diagnosis is confirmed by arthrography, where the crucial factor is a joint capacity below 12ml. Osteoarthritis and complex regional pain syndrome type 1 are the two main differential diagnoses. Whether the treatment is pharmacological, physical or surgical depends on the aetiology of the condition. Physiotherapy is essential for limiting residual deficits and functional impairments. CONCLUSION: Adhesive capsulitis of the hip is probably more common than suggested by the limited medical literature. The condition is frequently idiopathic but can be secondary to another joint pathology. The first-line treatment consists of sustained-release corticosteroid intra-articular injections and physical therapy. Arthroscopy and manipulation under anaesthesia may be useful in cases of ACH which are refractory to treatment

Neural Networks for High-Storage ContentAddressable Memory: VLSI Circuit and Learning Algorithm

Abstract —Neural networks used as content-addressable memories show unequaled retrieval and speed capabilities in problems srreh as vision and pattern recognition. We propose a new implementation of a VLSI fully interconnected neural network with only two binary memory points per synapse. The small area of single synaptic cells allows implementation of neural networks with hundreds of neurons. Classical learning algorithms like the Hebb’s rule show a poor storage capacity, especially in VLSI neural networks where the range of the synapse weights is limited by the number of memory points contained in each connectiorq we propose a new algorithm for programming a Hopfield neuraf network as a high-storage content-addressable memory. The storage capacity obtained with this algorithm is very promising for pattern recognition applications. I

Transfer of Pantoea citrea, Pantoea punctata and Pantoea terrea to the genus Tatumella emend. as Tatumella citrea comb. nov., Tatumella punctata comb. nov and Tatumella terrea comb. nov and description of Tatumella morbirosei sp nov.

Pantoea citrea, Pantoea punctata and Pantoea terrea were described for strains isolated from fruit and soil originating in Japan. These three 'Japanese' species have been shown to be phylogenetically distant from other species of the genus Pantoea. It has been observed previously that, using multilocus sequence analysis (MLSA), the 'Japanese' species consistently formed a distinct clade with an extended branch length, casting doubt on the inclusion of these species within the genus Pantoea. Furthermore, the 'Japanese' species are closely related to Tatumella ptyseos, strains of which originate from human clinical specimens. DNA DNA hybridization and phenotypic tests confirmed the observed phylogenetic distance of P. citrea, P. punctata and P. terrea from the genus Pantoea and the affiliation of these species with Tatumella. In addition, strains causing pink disease of pineapple, identified previously as P. citrea, were shown to represent a separate species by using 16S rRNA gene sequence analysis, and MLSA and DNA DNA hybridization data. The name Tatumella morbirosei sp. nov. with the type strain LMG 23360(T) (=BD 878(T)=NCPPB 4036(T)=CMC6(T)) is proposed to accommodate these strains. The new combinations Tatumella citrea (Kageyama et al. 1992) comb. nov. (type strain, SHS 2003(T)=ATCC 31623(T)=BD 875(T)=CCUG 30156(T)=CIP 105599(T)=DSM 13699(T)=JCM 8882(T)=LMG 22049(T)), Tatumella punctata (Kiageyama etal. 1992) comb. nov. (type strain, SHS 2006(T)=ATCC 31626(T)= BD 8761=CCUG 30159(T)=CIP 105598(T)=DSM 13700(T)=JCM 8885(T)=LMG 22050(T)) and Tatumella terrea (Kageyama etal. 1992) comb. nov. (type strain, SHS 2008(T)=ATCC 31628(T)=BD 877(T)=CCUG 30161(T)=CIP 105600(T)=DSM 13701(T)=JCM 8887(T)=LMG 22051(T)) are proposed for P. citrea, P. punctata and P. terrea, respectively

Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs : a multi-phase preclinical study

L-asparaginase is a frequently used drug in the treatment of canine malignant lymphoma. Since production and availability of native E. coli-derived L-asparaginase are limited, PEG-L-asparaginase (PEG-ASP) is an alternative. However, recommended doses and dosing intervals are mainly empirically determined. A multi-phase clinical dose-finding study with seven healthy Beagle dogs was conducted to find the minimum effective dose and, potentially, a dosing interval for PEG-ASP in dogs. Plasma concentrations of amino acids and PEG-ASP activity were measured at various time points after administration of different doses of PEG-ASP. Anti-PEG and antiasparaginase antibody titres were measured. Administration of 10 IU/kg PEG-ASP resulted in asparagine depletion in all dogs, albeit for various durations: for 9 days in all dogs, 15 days in five dogs, 21 days in three dogs and 29 days in one dog. Asparagine suppression occurred at PEG-ASP plasma concentrations < 25 IU/L. Subsequent administrations of a second and third dose of 20 IU/kg and 40 IU/kg PEG-ASP resulted in asparagine suppression at < 9 days in five dogs, accompanied by the development of antibodies against PEG and L-asparaginase. Two dogs with prolonged asparagine suppression after the second and third administration did not develop antibodies. Marked individual variation in the mechanism and duration of response to PEG-ASP was noted. Antibody formation against PEG-ASP was frequently observed and sometimes occurred after one injection. This study suggests that PEG-ASP doses as high as the currently used dose of 40 IU/kg might not be needed in treatment of canine malignant lymphoma