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BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Refractory black carbon aerosols (rBC) from biomass burning and fossil fuel combustion are deposited to the Antarctic ice sheet and preserve a history of emissions and long-range transport from low latitudes. Antarctic ice core rBC records may thus provide information with respect to past combustion aerosol emissions and atmospheric circulation. Here, we present six East Antarctic ice core records of rBC concentrations and fluxes covering the last two centuries with approximately annual resolution (cal. yr. 1800 to 2000). The ice cores were drilled in disparate regions of the high East Antarctic ice sheet, at different elevations and net snow accumulation rates. Annual rBC concentrations were log-normally distributed and geometric means of annual concentrations ranged from 0.10 to 0.18 μg kg−1. Average rBC fluxes were determined over the time periods 1800 to 2000 and 1963 to 2000 and ranged from 3.4 to 15.5 μg kg−1 m−2 a−1 and 3.6 to 21.8 μg kg−1 m−2 a−1 respectively. Geometric-mean concentrations spanning 1800 to 2000 increased linearly with elevation at a rate of 0.025 μg kg−1/500 m. Spectral analysis of the records revealed significant decadal scale variability, which at several sites was comparable to decadal ENSO variability.

Although women bear the brunt of gonococcal infection-related morbidity, few large studies of gonorrhea treatment in women have been conducted. In a multicenter, double-blind, placebo-controlled trial, 181 evaluable women with uncomplicated gonorrhea were treated with ciprofloxacin (250 mg orally; 94 women) or ceftriaxone (250 mg intramuscularly; 87 women). Twenty-four percent of the participants were infected with antibiotic-resistant Neisseria gonorrhoeae. Cervical gonorrhea was cured in 100% (93 of 93) of the women treated with ciprofloxacin and 99% (83 of 84) receiving ceftriaxone. All pharyngeal (n = 5) or rectal (n = 20) infections treated with ciprofloxacin were cured, as were ceftriaxone-treated patients with pharyngeal (n = 6) or rectal (n = 21) infection. Geometric mean MICs (range) for 248 pretreatment isolates were: penicillin, 0.28 (0.015 to 8.0); tetracycline, 0.46 (0.06 to 4); ciprofloxacin, 0.003 (0.002 to 0.015); and ceftriaxone, 0.004 (0.001 to 0.125) microgram/ml. Both drugs were well tolerated. Despite the high prevalence of antibiotic-resistant gonococci in these populations, 250 mg of oral ciprofloxacin was as effective as an injection of ceftriaxone.

Laser beam welding is a field of growing importance to the industry. As a result of extensive and continuous development of laser beam technology, pulsed Nd:YAG laser beam sources have been introduced. Pulsed laser welding offers the advantage of very low heat input to the workpiece, resulting in low distortion and the ability to join heat sensitive components. Further improvements to the method consider pulse shape modulation in Nd:YAG laser beam sources resulting in improved weld pool dynamics. Nd:YAG laser beam welding with pulse shape modulation is studied both experimentally and theoretically. Observational results on the interaction between time-dependent heat fluxes and flows in the weld pool as well as on solidification of the molten material are presented. In welds produced with modulated laser beam pulse shape, improved material flow and finer microstructure have been observed. Using an axisymmetric 2D model for heat transfer coupled with surface tension driven flow of molten metals undergoing solid-liquid and evaporation phase transitions in the weld pool, it is shown that the time modulation of the pulse power influences the melting front and flow velocity which together with the predicted undercooling may explain the fine-grain structure of the resolidified welds that have no cracks inside.

Background: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. Methods: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. Results: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. Conclusion: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.

To compare a rapid, office-based test with standard cell culture for screening of women for Chlamydia trachomatis infections.An 8-month prospective crossover trial used alternating screening protocols in two Baltimore (Md) sexually transmitted disease clinics from January 2 through August 14, 1991.Consecutive women attending the two clinics who had no indication for administration of antichlamydial antibiotic therapy (eg, history of recent sexual contact with a partner with a sexually transmitted disease, mucopurulent cervicitis, pelvic inflammatory disease, known gonorrhea, or previously diagnosed Chlamydia infections).Chlamydia screening was offered according to one of two protocols. Use of the two screening protocols was alternated between clinics each month. In the "rapid test clinic," eligible women were screened with both a 30-minute enzyme immunoassay test and tissue culture. Patients screened with the rapid test were asked to remain in the clinic until their rapid assay results were available so that, if positive, the patients could be treated. In the "routine screening clinic," eligible women were screened for Chlamydia by cell culture. Women identified as being infected with Chlamydia by screening culture were later confidentially notified of their test results by health department disease intervention specialists and referred for therapy.Performance of screening tests for bringing infected patients to therapy; time intervals between initial clinic visits and therapy; and pelvic inflammatory disease occurring between initial visits and therapy.Chlamydia cultures were positive in 100 (6.6%) of 1526 women screened with the solid-phase immunoassay, 47 of which were detected and treated on the basis of rapid test results. In contrast, 93 (74%) of 126 women with positive screening cultures returned to the clinic and received therapy. The median interval between testing and therapy for women with positive screening cultures was 14 days, and three (3.2%) developed pelvic inflammatory disease in the interval between testing and return for therapy.Neither cell culture nor a rapid diagnostic test performed well for ensuring therapy of women with Chlamydia infections. The sensitivity of the rapid diagnostic test was low, and nearly one fourth of the women with positive screening cultures did not return for therapy. Evaluation of screening for Chlamydia should consider the utility of strategies for bringing patients to treatment, as well as the more usual measures of test performance, such as sensitivity, specificity, and predictive values.

The paper presented discusses the design of a permanent magnet (PM) excited synchronous generator to be integrated into a modern jet engine. The electrical machine is to replace the mechanical accessory power drive system; thus all secondary power supplied from the engine to the aircraft is supplied by the electrical generator. The generator is also to double as starter motor for the engine, a job which can easily be handled at the required total secondary power level. It has been found that an integrated generator is technically feasible. It is heavier than its conventional counterpart, but offers significant reliability and maintenance benefits. This paper describes part of the work done for a study to investigate the feasibility of integrating a PM generator into a jet engine. IR Force and industry have recognized the potential value of integrating secondary-power-generation devices and engine accessory components into the basic engine structure. The objective of this design approach is to minimize the propulsion system envelope. Provided that a suitable configuration can be defined, the propulsion system should then provide improved installed performance, in two respects: drag will be reduced, and reliability will be improved by eliminating the complex mechanical secondary-power- generating equipment and accessory drive system. A program was undertaken to study the practicality of an integrated jet engine generator and its potential benefits. Experience with conventional aircraft alternators had proven that only solid rotor type electrical machines such as a per- manent magnet (PM) machine would meet the stringent reliability and maintainability requirements which would allow the integration of the alternator into an engine. The program encompassed a detailed study and design effort to determine applicability, location, and configuration of the engine structure. This paper describes the tradeoff and design studies un- dertaken to obtain an electrical machine design suitable for the application. The major goals were to achieve high reliability, low maintenance, and low life cycle costs for the electrical system. These goals can best be served by PM ex- cited electrical machines, since their rotors have a reliability potential which is higher than that for industrial induction motors and only surpassed by solid rotor machines. The PM generator is part of a variable speed constant- frequency-generating system which consists of the high frequency generator and a cycloconverter. The cycloconverter allows power flow in both directions. Thus the cycloconverter generator system is also capable of operating as an elec- tronically commutated motor-drive to start the engine. The cycloconverter will provide for all electrical controls, in- cluding frequency and voltage control, since an ac-PM machine does not allow for a simple reliable voltage control within the machine itself.

Recommendations are presented for quantitatively interpreting spacecraft sterilization requirements. The recommendations resulted from a brief preliminary exploration of the use of system engineering techniques in the control of spacecraft sterilization. Several specific applications of system engineering techniques potentially useful in formulating the over-all sterility assurance and planetary quarantine management system are suggested. These applications have been framed in terms of relative allocations of effort for performing failure analysis and for replicate testing. Examination of the sterilization requirements through the system engineering approach will lead to a realistic apportionment of the estimated contamination contributions by each of the various parts, processes, subsystems, and maneuvers, so that spacecraft sterility can be achieved and maintained.

Permanent magnet synchronous machines and induction motors are often required to operate on‐line starting or inverter‐fed systems, which results in nonsinusoidal stator currents. These, in turn, give rise to undesirable harmonics and power losses which degrade motor performance. In this paper a time‐domain analysis is presented for evaluating the magnetic field distribution in the two‐dimensional cross section of the machine under load conditions. The analysis is applied to a permanent magnet synchronous machine under locked rotor conditions. Although for purposes of this analysis, the iron permeability has been assumed a constant, the method can be easily extended to include iron saturation.

Design of modern electrical machinery to operate at high power densities and optimal efficiency requires accurate performance prediction. To accomplish this objective, magnetic field analysis must be performed taking full account of three‐dimensional effects and iron saturation. In this paper, a three‐dimensional magnetostatic analysis using a hybrid finite‐element formulation is presented. The method employs a combined vector and scalar formulation for representing the magnetic field. The analysis developed in the paper is applied to a permanent‐magnet synchronous machine for evaluating the field distribution on no‐load, in the body of the machine and the end region. Since the operating regime of this particular machine is in the unsaturated region, it was sufficient to implement a finite permeability case. The method described could be easily extended for the full‐load case and the nonlinear algorithm implemented.

A patient is presented who developed a granulomatous hepatitis and pleuritis approximately 7 months after an ileal bypass procedure for morbid obesity. Although the etiological agent was presumed to be Mycobacterium tuberculosis no pathogenic organism was grown from the liver, pleura, bone marrow, sputum, or gastric aspirate. The possibly increased susceptibility of these patients to mycobacterial infections is discussed. The value of obtaining serum levels of ethambutol, isoniazid, and rifampin, in patients with malabsorption is stressed. Although this patient seemed to respond to antituberculous therapy, other possible causes for the granulomatous process are explored.

The SALL genes, similar to the Drosophila gene spalt ,1 encode likely zinc finger transcription factors. In humans, four such genes have been identified to date. Mutations in the gene SALL1 on chromosome 16q12.1 have been associated with Townes-Brocks syndrome and related phenotypes,2,3 and mutations in the gene SALL4 have been shown to be causative in patients with Okihiro syndrome.4,5 SALL2 6 and SALL3 7 remain to be associated with human disease. We previously reported frameshift and nonsense mutations in SALL4 in five of eight families segregating the Okihiro syndrome phenotype.5 A further report4 identified two frameshift mutations and one nonsense mutation in three affected kindreds, including the family reported by Okihiro et al .8 In a recent study of patients with a clinical diagnosis of Holt-Oram syndrome, one additional frameshift mutation and an unclear missense change were reported from a family who turned out to have Okihiro syndrome rather than Holt-Oram.9 Furthermore, we reported one previously identified and three novel SALL4 mutations in patients originally diagnosed as having either Holt-Oram syndrome (later revised to Okihiro syndrome based on the observation of a Duane anomaly in at least one of the affected family members in each family), acro-renal-ocular syndrome, or Holt-Oram syndrome versus thalidomide embryopathy.10 While our findings suggested that acro-renal-ocular syndrome and Okihiro syndrome are allelic, evidence so far has come only from one family in which no gross structural eye defects were seen.11 In order to further substantiate our findings we sought to perform mutation analysis in additional patients diagnosed with acro-renal-ocular syndrome, especially those who presented with structural eye defects. We were also interested in extending our studies to further patients with Okihiro syndrome in order to allow a genotype–phenotype correlation. Here we report five novel …