An evaluation of the effects of intensity and duration on outcomes across treatment domains for children with autism spectrum disorder.

Applied behavior analysis (ABA) is considered an effective treatment for individuals with autism spectrum disorder (ASD), and many researchers have further investigated factors associated with treatment outcomes. However, few studies have focused on whether treatment intensity and duration have differential influences on separate skills. The aim of the current study was to investigate how treatment intensity and duration impact learning across different treatment domains, including academic, adaptive, cognitive, executive function, language, motor, play, and social. Separate multiple linear regression analyses were used to evaluate these relationships. Participants included 1468 children with ASD, ages 18 months to 12 years old, M=7.57 years, s.d.=2.37, who were receiving individualized ABA services. The results indicated that treatment intensity and duration were both significant predictors of mastered learning objectives across all eight treatment domains. The academic and language domains showed the strongest response, with effect sizes of 1.68 and 1.85 for treatment intensity and 4.70 and 9.02 for treatment duration, respectively. These findings are consistent with previous research that total dosage of treatment positively influences outcomes. The current study also expands on extant literature by providing a better understanding of the differential impact that these treatment variables have across various treatment domains.

Distinct post-translational features of type I collagen are conserved in mouse and human periodontal ligament.

BACKGROUND AND OBJECTIVE: Specifics of the biochemical pathways that modulate collagen cross-links in the periodontal ligament (PDL) are not fully defined. Better knowledge of the collagen post-translational modifications that give PDL its distinct tissue properties is needed to understand the pathogenic mechanisms of human PDL destruction in periodontal disease. In this study, the post-translational phenotypes of human and mouse PDL type I collagen were surveyed using mass spectrometry. PDL is a highly specialized connective tissue that joins tooth cementum to alveolar bone. The main function of the PDL is to support the tooth within the alveolar bone while under occlusal load after tooth eruption. Almost half of the adult population in the USA has periodontal disease resulting from inflammatory destruction of the PDL, leading to tooth loss. Interestingly, PDL is unique from other ligamentous connective tissues as it has a high rate of turnover. Rapid turnover is believed to be an important characteristic for this specialized ligament to function within the oral-microbial environment. Like other ligaments, PDL is composed predominantly of type I collagen. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including hydroxylation, glycosylation and cross-linking. The chemistry, placement and quantity of intermolecular cross-links are believed to be important regulators of tissue-specific structural and mechanical properties of collagens. MATERIAL AND METHODS: Type I collagen was isolated from several mouse and human tissues, including PDL, and analyzed by mass spectrometry for post-translational variances. RESULTS: The collagen telopeptide cross-linking lysines of PDL were found to be partially hydroxylated in human and mouse, as well as in other types of ligament. However, the degree of hydroxylation and glycosylation at the helical Lys87 cross-linking residue varied across species and between ligaments. These data suggest that different types of ligament collagen, notably PDL, appear to have evolved distinctive lysine/hydroxylysine cross-linking variations. Another distinguishing feature of PDL collagen is that, unlike other ligaments, it lacks any of the known prolyl 3-hydroxylase 2-catalyzed 3-hydroxyproline site modifications that characterize tendon and ligament collagens. This gives PDL a novel modification profile, with hybrid features of both ligament and skin collagens. CONCLUSION: This distinctive post-translational phenotype may be relevant for understanding why some individuals are at risk of rapid PDL destruction in periodontal disease and warrants further investigation. In addition, developing a murine model for studying PDL collagen may be useful for exploring potential clinical strategies for promoting PDL regeneration.

Effect of bone morphogenetic protein-2, demineralized bone matrix and systemic parathyroid hormone (1-34) on local bone formation in a rat calvaria critical-size defect model.

AIM: To determine the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) soak-loaded on to an absorbable collagen sponge (ACS) to induce local bone formation compared with the clinical reference demineralized bone matrix (DBM) and to investigate potential additive/synergistic effects of exogenous parathyroid hormone (PTH). METHODS: Critical-size (8 mm), through-through calvaria osteotomy defects in 160 adult male Sprague-Dawley rats were randomized to receive one of eight interventions: rhBMP-2/ACS, DBM, ACS, or serve as controls (empty defects) combined or not with systemic PTH. Ten animals from each group were followed for 4 and 8 wks for radiographic and histometric analysis. Multivariable analysis was used to assess the effect of experimental intervention and healing time on local bone formation. RESULTS: In the multivariable analysis, rhBMP-2/ACS exhibited significantly greater histologic bone formation than control (ß ± SE: 54.76 ± 5.85, p < 0.001) and ACS (ß ± SE: 9.14 ± 3.31, p = 0.007) whereas DBM showed significantly less bone formation than control (ß ± SE: -32.32 ± 8.23, p < 0.001). Overall, PTH did not show a significant effect on bone formation (ß ± SE: 2.72 ± 6.91, p = 0.70). No significant differences in histological defect closure were observed between 4 and 8 wks for all but the control group without PTH. CONCLUSION: rhBMP-2/ACS significantly stimulates local bone formation whereas bone formation appears significantly limited by DBM. Systemic application of PTH provided no discernible additive/synergistic effects on local bone formation.

Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides.

Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered.

The anti-endotoxic effects of the KSL-W decapeptide on Escherichia coli O55:B5 and various oral lipopolysaccharides.

BACKGROUND AND OBJECTIVE: Host responses following the recognition of bacterial lipopolysaccharide can range from acute inflammation to septic shock. The aim of this study was to evaluate the ability of the KSL-W decapeptide to bind to and block the endotoxic effects of lipopolysaccharide. MATERIAL AND METHODS: An enzyme-linked immunosorbent assay-based binding assay using fluorescently labeled KSL-W to detect adsorbed Escherichia coli O55:B5 lipopolysaccharide was employed. A commercially available recombinant Factor C lipopolysaccharide detection assay, hemagglutination of rabbit erythrocytes as well as E-selectin expression in human umbilical vein endothelial cells were used to assess the anti-endotoxic effects after KSL-W exposure to E. coli lipopolysaccharide as well as to oral lipopolysaccharide samples. RESULTS: Lipopolysaccharide-binding assays using E. coli O55:B5 lipopolysaccharide revealed both a higher maximal binding range (532-713 microM) and a half-maximum binding concentration (70-185 microM) for the KSL-W peptide when compared with its analog control. Significant inhibition of E-selectin expression in human umbilical vein endothelial cells (p < 0.0001) as well as hemagglutination of rabbit erythrocytes occurred after the interaction of KSL-W with E. coli lipopolysaccharide. Recombinant Factor C enzyme detection inhibition revealed dose-dependent inhibition values ranging from 1.0-51.8 microM. which were dependent upon the type of lipopolysaccharide sample tested. CONCLUSION: These results demonstrate that for the concentrations tested, the KSL-W decapeptide was nontoxic to mammalian cells and could bind to and block the host recognition and response towards enteric, as well as oral, lipopolysaccharide samples.

Heat shock protein expression pattern (HSP70) in the hydrothermal vent mussel Bathymodiolus azoricus.

We previously reported evidence of increased levels of DNA damage in the hydrothermal mussel Bathymodiolus azoricus, which suggested that the species was not fully resistant to the natural toxicity of its deep-sea vent environment. In the present study, HSP70 was used as a biomarker of sub-cellular stress. Differences in HSP70 expression pattern were observed between vent sites, typified by different depths/toxicity profiles, and between different mussel tissue types. A comparison of specimens collected by remote operated vehicle (ROV) and acoustically-operated cages showed that less stress (as indicated by changes in HSP70 levels) was induced by the faster cage recovery method. Therefore alternatives to ROV collection should be considered when planning experiments involving live deep sea organisms. Significantly, a positive correlation was found between the levels of DNA strand breakage, as measured using the Comet assay, and HSP70 expression pattern; evidence was also obtained for the constitutive expression of at least one HSP isoform which was located within the cell nucleus.

Scaling filtration time initial dependencies of wastewater sludges.

The filtration time, t(f), during constant pressure dead-end filtration testing of wastewater sludge is dependant on the initial height, h(0), and the initial solids concentration, phi(0). The theoretical dependencies of these initial conditions are explored: t(f) varies with h(0)(2) and cphi(0)(2), where c is a material dependant parameter that is also dependant on phi(0) and the applied pressure. Empirical values for c relative to a given phi(0) are determined from phenomenological filtration theory to give a qualitative scaling method to compare the filtration behaviour of highly compressible materials under differing initial conditions. The method is validated using filtration testing of municipal wastewater sludge. This new scaling method is applied to the filtration results of a range of different wastewater sludges, additives and treatments to illustrate its application for plant comparisons, polyelectrolyte comparisons, dose optimisation of polyelectrolyte and ferric chloride and combinations thereof, and the effects of two physicochemical treatments.

Lipopolysaccharide heterogeneity: innate host responses to bacterial modification of lipid a structure.

The innate host response system is composed of various mechanisms designed to detect and facilitate host responses to microbial components, such as lipopolysaccharides (LPS). To enable this to occur, innate systems contain multiple pattern recognition receptors (i.e., LBP, CD14, and TLRs), which identify certain features within bacterial LPS that are foreign to the host, as well as essential and uniquely specific for bacteria. Innate host identification of unique bacterial components or patterns, therefore, relies on the inability of bacteria to alter these essential or critical components dramatically. Historically, LPS have been viewed as essential outer-membrane molecules containing both a highly variable outer region (O-segment) as well as a relatively conserved inner region (lipid A). However, over the last decade, new evidence has emerged, revealing that increased natural diversity or heterogeneity within specific components of LPS, such as lipid A-resulting in minor to moderate changes in lipid A structure-can produce dramatic host responses. Therefore, examples of natural lipid A heterogeneity, and the mechanisms that control it, represent a novel approach in which bacteria modulate host responses and may thereby confer specific advantages to certain bacterial species under changing environmental host conditions.

The fundamentals of wastewater sludge characterization and filtration.

The move to greater emphasis on the disposal of wastewater sludges through routes such as incineration and the added cost of landfill emplacement puts high demands on dewatering technology for these sludges. A clear problem in this area is that wastewater sludges are slow and difficult to dewater and traditional methods of laboratory measurement for prediction of filtration performance are inadequate. This is highly problematic for the design and operational optimisation of centrifuges, filters and settling devices in the wastewater industry. The behaviour is assessed as being due to non-linear behaviour of these sludges which negates the use of classical approaches. These approaches utilise the linear portion of a t versus V2 plot (where t is the time to filtration and V is the specific filtrate volume) to extract a simple Darcian permeability. Without this parameter, a predictive capacity for dewatering using current theory is negated.

Ultrasonic treatment of Cryptosporidium oocysts.

The effect of 20 kHz ultrasound on the viability of Cryptosporidium oocysts was investigated. More than 90% of the dispersed Cryptosporidium oocysts could be deactivated in about 1.5 min of continuous sonication. In order to apply this technique to large quantities of contaminated water, quantitative filtration and redispersion of Cryptosporidium oocysts were investigated and found to be easily achievable. The estimated cost of sonication showed that the ultrasound treatment of Cryptosporidium oocysts contaminated water could be a very effective means of "deactivating" Cryptosporidium oocysts.

Complete characterisation of thermally treated sludges.

As disposal options for sludges become more difficult to find and more expensive to operate, those relying on some form of thermal treatment are becoming more commercially attractive. The incentive, especially for more heavily populated countries, is the production of treated solids suitable for beneficial application to land. It is the level of treatment required to achieve this cost effectively which has been the focus of much of the research in this field. There are now several commercially available plants designed to thermally treat sludges and many have been in full scale operation for a number of years. One of the auxiliary claims often made by proponents of such treatments, is that the resultant sludges are more amenable to dewatering and therefore easier and cheaper to handle. In this work we have used a novel filtration rig to obtain complete sets of filtration data for different sludges. Historically sludge characterisation has been achieved by measurement of an empirical Capillary Suction Time (CST) parameter, however with the new filtration apparatus it is now possible to obtain fundamental sludge characteristics across a wide range of volume fractions in hours not days. We have applied this technology to characterise different sludge samples before and after thermal treatment under different sets of operating conditions (pH, temperature and pressure) to simulate some of the commercially available thermal treatment technologies. We have also examined the effects of various chemical oxidants (hydrogen peroxide and Fenton's reagent) used as pretreatments to the thermal process and attempted to compare their cost efficiencies. The results show that the physical structure of the sludge is irreversibly altered by decreasing the pH or heating to temperatures in excess of 150 degrees C in a way which significantly enhances the dewaterability of the material. The treated sludge not only has a higher permeability but also has a higher final per cent solids (often in the autothermal region). In contrast the amounts of chemical additives used in pretreatment to achieve similar effects are cost prohibitive.

Fractionation of natural organic matter in drinking water and characterization by 13C cross-polarization magic-angle spinning NMR spectroscopy and size exclusion chromatography.

Natural organic matter from drinking water sources was fractionated, and the fractions were characterized by NMR and SEC with the aim of relating NOM structure to treatability. Organic matter was isolated from two Australian surface waters (Horsham, Moorabool) by reverse osmosis and from a groundwater (Wanneroo) by anion exchange. The isolates were fractionated according to polarity and charge by resin adsorption. 13C NMR spectra of the freeze-dried fractions showed the most hydrophobic fraction to be high in aliphatic and aromatic carbon while slightly hydrophobic organics have more carbonyl and alkoxyl carbon. The Horsham and Wanneroo hydrophilic fractions show strong alkoxyl signals attributed to carbohydrate. Moorabool hydrophilics contain aromatic (phenolic) carbon; the apparent absence of carbohydrate appears to be an artifact. Size-exclusion chromatograms were recorded on the original and fractionated organics with both UV and dissolved organic carbon detection. The Horsham and Moorabool organics have similar molecular size distributions while Wanneroo is dominated by strongly absorbing species having large hydrodynamic radii. The hydrophobic and charged hydrophilic fractions also have high apparent MW, while the neutral fraction is higher in low-MW compounds of relatively low specific absorbance, suggestive of carbohydrates.

Watch what you say and how you say it: differential response to speech by participants with and without head injuries.

Previous research has shown that both prosodic and content variations in speech register are important when addressing all individuals. Motherese speech register has been associated with higher levels of perceived disability and is viewed more negatively by individuals with a history of head injury. This research was conducted to investigate the separate contributions of content and prosody in producing differential response to speech by individuals with and without a history of head injury. Participants included 210 introductory psychology students with and without head injuries. No significant demographic differences were found between these groups. Participants listened to 4 sets of audiotaped instructions from afictitious home economics teacher containing prosodic and content variations. Afterward, they rated the teacher on the following dimensions: liking, positive impact, negative impact, grade level being taught, and whether they would recommend hiring this teacher. Analysis of variance revealed there were no significant group differences between participants rating with normal speech. As expected, both groups favored the normal speech register over motherese. However, the group with head injuries consistently rated the speech with motherese content as more negative, less likable, less likely to hire, and aimed at a lower grade level. Participants with head injuries also rated the speech register with motherese prosody as less likable and less likely to hire. These results suggest that when addressing individuals with head injuries, both what you say and how you say it are important.

The association of isolated mild fetal hydronephrosis with postnatal vesicoureteral reflux.

OBJECTIVE: We evaluated the incidence of vesicoureteral reflux in fetuses with prenatally detected isolated mild fetal hydronephrosis. METHODS: Fetuses with isolated mild fetal hydronephrosis (defined as a fetal renal pelvis anteroposterior diameter of > or = 4 and < 10 mm before 24 weeks' gestational age) were prospectively evaluated with postnatal renal ultrasound and voiding cystourethrography within the first few weeks after delivery. Infants were evaluated regardless of whether or not renal pelvic dilatation was seen on postnatal ultrasound examination. RESULTS: Forty cases of mild fetal hydronephrosis were identified from the 5,432 patients cared for at our institution from February 1996 to December 1998 (overall incidence: 1/136). Cases involving aneuploidy (n = 1) and inadequate follow-up (n = 5) were excluded from the investigation. One fetus with documented mild hydronephrosis early in gestation had spontaneous resolution and did not undergo postnatal evaluation. Of the remaining 33 infants, 32 underwent postnatal renal ultrasound examination and all had voiding cystourethrography. Vesicoureteral reflux was identified in five (15%) of the neonates. Eighty per cent (four out of five) of these infants were male. Resolution of vesicoureteral reflux occurred in 75% (three out of four) of the infants available for follow-up within 2 years of birth. CONCLUSIONS: Isolated mild fetal hydronephrosis is associated with vesicoureteral reflux on postnatal voiding cystourethrography.

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.

OBJECTIVE: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum. STUDY DESIGN: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism. RESULTS: In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum. CONCLUSION: Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.

Prediction of the dewatering of selected inorganic sludges.

There are a number of laboratory techniques traditionally used in the characterisation of sludges for the prediction of the efficient operation of dewatering processes such as centrifugation and filtration. In industry, capillary suction time and specific resistance to filtration measurements are common. Whilst useful in predicting trends, they do not assist in the design and optimisation of devices from first principles. Recent work in our laboratories has developed a technique for the fast measurement of the permeability and compressibility of sludge. This information, when coupled with first-principle models is useful for the prediction of the performance of solid-liquid separation devices. The work has shown that a single volume fraction dependent parameter, namely the solids diffusivity, calculated from permeability and compressibility, is able to fully characterise the dewaterability of sludge. This allows different sludges to be compared in an unequivocal fashion. Data will be presented for a range of sludges from different sources showing vastly different dewatering properties. The dewaterability of the different sludges is easily compared and the true role of flocculants in dewatering is highlighted.

Exploring information technology adoption by family physicians: survey instrument valuation.

As the information needs of family physicians become more complex, there will be a greater need to successfully implement the technologies needed to manage that information. The ability to stratify primary care physicians can enable the implementation process to be more efficient. This research tested a new instrument on 101 family physicians, and was able to stratify physicians into high, intermediate, and low information technology (IT) usage groups. It is expected that this stratification would allow managers of IT implementation to target specific adoption strategies for each group. The instrument is available from ddixon@julian.uwo.ca.

Malignant pleural mesothelioma in pregnancy.

A 37-year-old pregnant woman presented at 18 weeks' gestation with unrelenting chest and shoulder pain, massive pleural effusion, and a large thoracic mass. Biopsy revealed an undifferentiated sarcomatous pleural mesothelioma. Malignant mesothelioma is a rare thoracic malignancy, which has not been described in pregnancy and appears to be minimally affected by the pregnant state.

Universal versus selective gestational diabetes screening: application of 1997 American Diabetes Association recommendations.

OBJECTIVE: We sought to evaluate the impact of the 1997 American Diabetes Association gestational diabetes mellitus screening guidelines applied to a universally screened population. STUDY DESIGN: A retrospective analysis of 18,504 women universally screened for gestational diabetes mellitus at Mayo Clinic, Rochester, between January 1, 1986, and December 31, 1997, was performed. Diabetic screening consisted of plasma glucose determination 1 hour after a 50-g oral glucose challenge. Diagnosis of gestational diabetes mellitus was based on National Diabetes Data Group criteria. RESULTS: Of 564 cases of gestational diabetes mellitus diagnosed during the study period, 17 (3.0%) would have been missed under the 1997 American Diabetes Association selective screening guidelines while exempting only 10% of this predominantly white population from screening. Screening only women >/=25 years old would have detected 90.4% of gestational diabetes mellitus cases, whereas the addition of the remaining 3 screening criteria combined would have detected only an additional 6.6% of cases. CONCLUSIONS: The proportion of patients with gestational diabetes mellitus that would remain undiagnosed under the 1997 American Diabetes Association screening guidelines would be relatively small in our population. However, implementation of these guidelines would decrease the number of screens by only 10% while adding significant complexity to the screening process. Youth appears to be the most significant protective factor for gestational diabetes mellitus in our population.

Anaphase aberrations in the embryos of the marine tubeworm Pomatoceros lamarckii (Polychaeta: Serpulidae): a new in vivo test assay for detecting aneugens and clastogens in the marine environment.

The marine environment receives a wide variety of chemical inputs, many of which have the potential to damage DNA or interfere with the process of cell division. Here we describe a new assay based on the early embryo and larval stages of a planktonic spawning, tube dwelling marine worm, Pomatoceros lamarckii, which for experimental purposes has the advantage of producing large numbers of ripe gametes throughout the majority of the year. One of the most promising end-points is the use of dividing cells to detect anaphase aberrations such as lagging chromosomes, tripolar anaphases, acentric fragments and chromosome bridges. Apart from the reference mutagens mitomycin C and cyclophosphamide and the well-documented spindle poison colchicine, we tested the fungicide carbendazim, a primary metabolite of the fungicide benomyl, and thiabendazole, a pesticide and antihelminthic drug; both of which are known to act as aneugens in other test systems. In addition we tested sodium hypochlorite, a widely used oxidizing agent and disinfectant, di-butylphthalate, a commercial plasticizer and suspected aneugen, and sodium chloride, a recognized non-genotoxin. Significant increases in the frequency of anaphase abnormalities occurred with most test compounds at relatively low concentrations, confirming the sensitivity of the new assay. Sodium chloride yielded a negative response except at the highest non-relevant concentrations, where some chromatid stickiness was observed. In addition, the developmental consequences of exposure to these compounds were assessed in 4-8 cell embryos and at 48 h once the embryos had metamorphosed into free swimming larvae. Mitotic inhibition and anaphase aberrations were found to be a more sensitive indicator of genotoxic exposure than larval development, although there was a suggestion of a possible mechanistic link between aneugenicity/clastogenicity and larval fitness. The new test assay provides a rapid and inexpensive method for screening chemicals and effluents destined for release into the marine environment for potential gamete effects.