Dual arm master controller development

The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape driven manipulators. Studies were performed which addressed to human factor design and performance tradeoffs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented

Development of spasticity with age in a total population of children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>The development of spasticity with age in children with cerebral palsy (CP) has, to our knowledge, not been studied before. In 1994, a register and a health care program for children with CP in southern Sweden were initiated. In the programme the child's muscle tone according to the modified Ashworth scale is measured twice a year until six years of age, then once a year. We have used this data to analyse the development of spasticity with age in a total population of children with cerebral palsy.</p> <p>Methods</p> <p>All measurements of muscle tone in the gastrocnemius-soleus muscle in all children with CP from 0 to 15 years during the period 1995–2006 were analysed. The CP subtypes were classified according to the Surveillance of Cerebral Palsy in Europe network system. Using these criteria, the study was based on 6218 examinations in 547 children. For the statistical analysis the Ashworth scale was dichotomized. The levels 0–1 were gathered in one category and levels 2–4 in the other. The pattern of development with age was evaluated using piecewise logistic regression in combination with Akaike's An Information Criterion.</p> <p>Results</p> <p>In the total sample the degree of muscle tone increased up to 4 years of age. After 4 years of age the muscle tone decreased each year up to 12 years of age. A similar development was seen when excluding the children operated with selective dorsal rhizotomy, intrathecal baclofen pump or tendo Achilles lengthening. At 4 years of age about 47% of the children had spasticity in their gastro-soleus muscle graded as Ashworth 2–4. After 12 years of age 23% of the children had that level of spasticity. The CP subtypes spastic bilateral and spastic unilateral CP showed the same pattern as the total sample. Children with dyskinetic type of CP showed an increasing muscle tone up to age 6, followed by a decreasing pattern up to age 15.</p> <p>Conclusion</p> <p>In children with CP, the muscle tone as measured with the Ashworth scale increases up to 4 years of age and then decreases up to 12 years of age. The same tendency is seen in all spastic subtypes. The findings may have implications both for clinical judgement and for research studies on spasticity treatment.</p

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

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.

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 the feasibility of clinical trial accrual and tolerability using CT for PCa

Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns

ObjectivesTo evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 month follow-up.MethodsThe 1041 infants in this prospective study were born at < 28 weeks gestation, were assessed for 3 indicators of hypotension in the first 24 postnatal hours, had at least one set of protocol cranial ultrasound scans, and were evaluated with a structured neurologic exam at 24 months corrected age. Indicators of hypotension included: 1) lowest mean arterial pressure (MAP) in the lowest quartile for gestational age; 2) treatment with a vasopressor; and 3) blood pressure lability, defined as the upper quartile of the difference between each infant’s lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, i.e. moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound, and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders.ResultsTwenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors, and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24-months follow-up, 6% had developed quadriparesis, 4% diparesis, and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis.ConclusionsThe absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury in ELGANs

The formation and the study of a collection of the Miscanthus resource species gene pool in the conditions of the West Siberian forest steppe

Several species of the genus Miscanthus Anderss. (elephant grass) characterized by a high rate of growth of the aboveground vegetative mass are currently in the focus of attention due to their high practical application as a source of bioethanol and cellulose. The main goals of this study were: (1) molecular genetic identification and (2) histochemical analysis of the genus Miscanthus Anderss. species in the collection of Central Siberian Botanical Garden SB RAS in order to identify the most perspective and technically valuable individuals. To study the collection of Miscanthus samples, a multi-disciplinary approach was applied. To collect the samples of different species from native habitats, traditional systematic and geobotanical methods (comparative morphological and phytocenological) were used. According to the results of the ISSR-analysis, 16 samples of three Miscanthus species were divided into two clades: Sinensis and Sacchariflorus, the former including two subclades. For the samples of M. purpurascens_I and II, a hybrid origin of this species was confirmed by ISSR data. The molecular data obtained from the study allowed us to hypothesize that the samples involved in the subclade I of the Sinensis clade could be used as donors of resistance to adverse environments, and the samples of the subclade II, as donors of high biomass productivity. Based on histochemical analysis, sclerenchyma cells were characterized by the most lignin-rich thickened membranes, so the most appropriate direction in Miscanthus selection should be based on identification and using less lignin-containing samples

Removal of Misincorporated Ribonucleotides from Prokaryotic Genomes: An Unexpected Role for Nucleotide Excision Repair

Stringent steric exclusion mechanisms limit the misincorporation of ribonucleotides by high-fidelity DNA polymerases into genomic DNA. In contrast, low-fidelity Escherichia coli DNA polymerase V (pol V) has relatively poor sugar discrimination and frequently misincorporates ribonucleotides. Substitution of a steric gate tyrosine residue with alanine (umuC_Y11A) reduces sugar selectivity further and allows pol V to readily misincorporate ribonucleotides as easily as deoxynucleotides, whilst leaving its poor base-substitution fidelity essentially unchanged. However, the mutability of cells expressing the steric gate pol V mutant is very low due to efficient repair mechanisms that are triggered by the misincorporated rNMPs. Comparison of the mutation frequency between strains expressing wild-type and mutant pol V therefore allows us to identify pathways specifically directed at ribonucleotide excision repair (RER). We previously demonstrated that rNMPs incorporated by umuC_Y11A are efficiently removed from DNA in a repair pathway initiated by RNase HII. Using the same approach, we show here that mismatch repair and base excision repair play minimal back-up roles in RER in vivo. In contrast, in the absence of functional RNase HII, umuC_Y11A-dependent mutagenesis increases significantly in ΔuvrA, uvrB5 and ΔuvrC strains, suggesting that rNMPs misincorporated into DNA are actively repaired by nucleotide excision repair (NER) in vivo. Participation of NER in RER was confirmed by reconstituting ribonucleotide-dependent NER in vitro. We show that UvrABC nuclease-catalyzed incisions are readily made on DNA templates containing one, two, or five rNMPs and that the reactions are stimulated by the presence of mispaired bases. Similar to NER of DNA lesions, excision of rNMPs proceeds through dual incisions made at the 8th phosphodiester bond 5′ and 4th-5th phosphodiester bonds 3′ of the ribonucleotide. Ribonucleotides misinserted into DNA can therefore be added to the broad list of helix-distorting modifications that are substrates for NER

Controlled ultraviolet (UV) photoinitiated fabrication of monolithic porous layer open tubular (monoPLOT) capillary columns for chromatographic applications

An automated column fabrication technique that is based on a ultraviolet (UV) light-emitting diode (LED) array oven, and provides precisely controlled "in-capillary" ultraviolet (UV) initiated polymerization at 365 nm, is presented for the production of open tubular monolithic porous polymer layer capillary (monoPLOT) columns of varying length, inner diameter (ID), and porous layer thickness. The developed approach allows the preparation of columns of varying length, because of an automated capillary delivery approach, with precisely controlled and uniform layer thickness and monolith morphology, from controlled UV power and exposure time. The relationships between direct exposure times, intensity, and layer thickness were determined, as were the effects of capillary delivery rate (indirect exposure rate), and multiple exposures on the layer thickness and axial distribution. Layer thickness measurements were taken by scanning electron microscopy (SEM), with the longitudinal homogeneity of the stationary phase confirmed using scanning capacitively coupled contactless conductivity detection (sC(4)D). The new automated UV polymerization technique presented in this work allows the fabrication of monoPLOT columns with a very high column-to-column production reproducibility, displaying a longitudinal phase thickness variation within ±0.8% RSD (relative standard deviation)

Pediatric Index of Mortality 3 - an evaluation of function among ICUs in South Africa

OBJECTIVES : To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model. DESIGN : This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay. SETTING : Nine units that care for children within tertiary or quaternary academic hospitals in South Africa. PATIENTS : All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old. INTERVENTIONS : None. MEASUREMENTS AND MAIN RESULTS : There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6–59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79–0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients. CONCLUSIONS : The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.Ann Lake Publications, Getinge, Drager, Biomerieux, Astellas, Fresenius Kabi, the University of Cape Town, Imperial College Press (royalties), Critical Care Society of Southern Africa, N Kelly attorneys.https://journals.lww.com/pccmjournal/pages/default.aspxhj2022Paediatrics and Child Healt