Profiles of mathematical deficits in children with dyslexia.

Despite a high rate of concurrent mathematical difficulties among children with dyslexia, we still have limited information regarding the prevalence and severity of mathematical deficits in this population. To address this gap, we developed a comprehensive battery of cognitive tests, known as the UCSF Mathematical Cognition Battery (MCB), with the aim of identifying deficits in four distinct mathematical domains: number processing, arithmetical procedures, arithmetic facts retrieval, and geometrical abilities. The mathematical abilities of a cohort of 75 children referred to the UCSF Dyslexia Center with a diagnosis of dyslexia, along with 18 typically developing controls aged 7 to 16, were initially evaluated using a behavioral neurology approach. A team of professional clinicians classified the 75 children with dyslexia into five groups, based on parents' and teachers' reported symptoms and clinical history. These groups included children with no mathematical deficits and children with mathematical deficits in number processing, arithmetical procedures, arithmetic facts retrieval, or geometrical abilities. Subsequently, the children underwent evaluation using the MCB to determine concordance with the clinicians' impressions. Additionally, neuropsychological and cognitive standardized tests were administered. Our study reveals that within a cohort of children with dyslexia, 66% exhibit mathematical deficits, and among those with mathematical deficits, there is heterogeneity in the nature of these deficits. If these findings are confirmed in larger samples, they can potentially pave the way for new diagnostic approaches, consistent subtype classification, and, ultimately personalized interventions.

SA-SSR: a suffix array-based algorithm for exhaustive and efficient SSR discovery in large genetic sequences.

UNLABELLED: Simple Sequence Repeats (SSRs) are used to address a variety of research questions in a variety of fields (e.g. population genetics, phylogenetics, forensics, etc.), due to their high mutability within and between species. Here, we present an innovative algorithm, SA-SSR, based on suffix and longest common prefix arrays for efficiently detecting SSRs in large sets of sequences. Existing SSR detection applications are hampered by one or more limitations (i.e. speed, accuracy, ease-of-use, etc.). Our algorithm addresses these challenges while being the most comprehensive and correct SSR detection software available. SA-SSR is 100% accurate and detected >1000 more SSRs than the second best algorithm, while offering greater control to the user than any existing software. AVAILABILITY AND IMPLEMENTATION: SA-SSR is freely available at http://github.com/ridgelab/SA-SSR CONTACT: perry.ridge@byu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Differences between chimpanzee and baboon gastrointestinal parasite communities.

Cross-species infection among humans, chimpanzees (Pan troglodytes) and baboons (Papio spp.) is potentially a significant public health issue in Africa, and of concern in the conservation of P. troglodytes. However, to date, no statistical comparisons have been made between the prevalence, richness and composition of parasite communities in sympatric populations of baboons and P. troglodytes. We compared parasite communities in sympatric P. troglodytes and Papio papio living in a wilderness site, in the Republic of Senegal, West Africa. We asked whether, in the absence of humans, there are significant differences between these hosts in their interactions with gastrointestinal parasites. We tested whether host, location, or time of collection accounted for variation in prevalence, richness and community composition, and compared prevalence across six studies. We concluded that, despite being closely related, there are significant differences between these two hosts with respect to their parasite communities. At our study site, prevalence of Balantidium, Trichuris and Watsonius was higher in P. papio. Papio papio harboured more parasites per host, and we found evidence of a positive association between Trichuris and Balantidium in P. troglodytes but not P. papio.

Trypanosomatid prevalence and host habitat choice in woodland Drosophila.

Although trypanosomatids (Trypanosomatidae: Kinetoplastida) are common inhabitants of dipteran guts, prevalence in natural fly populations has not been studied. We investigated factors associated with trypanosomatid prevalence in eight species of woodland Drosophila (Drosophilidae: Diptera) collected from five sites in southwest Ohio. We collected infected flies from every site, over both years of our study, and from every Drosophila species. Prevalence differed with host species, but not between sites or with host sex. Prevalence was highest in the most abundant species, members of the subgenus Sophophora, species using decaying fruit as breeding sites, and those able to use more than one type of substrate for oviposition.

Variable effects of crowding on Drosophila hosts of male-lethal and non-male-lethal spiroplasmas in laboratory populations.

Male-lethal, maternally inherited spiroplasmas occur in four species of Drosophila, and persist in natural populations despite imperfect vertical transmission rates. In the field, larval crowding is thought to be sporadic, but occasionally intense. To determine whether crowding affects host persistence, I compared the population dynamics of infected females (hosts) under crowded conditions to those expected from data collected on uncrowded females. I estimated host fitness components and maternal transmission rates for individual females under uncrowded conditions in both the artificial host D. pseudoobscura (this paper) and the native host D. willistoni (previously reported). Spiroplasma infection had no effect on lifetime production of daughters in D. pseudoobscura; however, as with some D. willistoni lines, hosts may produce more of their daughters earlier in life than nonhosts. Because individual contributions to relative rates of increase calculated from these fitness data were similar for hosts and nonhosts, I expected hosts to persist in laboratory populations. Instead, three patterns were observed: rapid extinction of D. willistoni females infected with male-lethal spiroplasmas, slow decline or persistence of hosts (depending on initial frequency) in both D. pseudoobscura infected with male-lethal spiroplasmas, and D. willistoni infected with non-male-lethal spiroplasmas. Population dynamics, then, depend on host species and bacterial isolate. Fitness estimates change with host line in uncrowded D. willistoni, but host genetic background did not affect population dynamics. These and previously published results show that the interaction phenotype changes with host and parasite isolate, and that host fitness can be affected by crowding. Crowding in natural populations may therefore decrease host fitness but, in expanding populations, early reproduction in hosts may be to their advantage. Possible effects of seasonal fluctuations in population density on the fitness of infected Drosophila are discussed.

In vitro pharmacology of R 80122, a novel phosphodiesterase inhibitor.

The cardiac in vitro effects of R 80122, a novel phosphodiesterase (PDE) inhibitor, were investigated and compared with those of the reference compound milrinone and of the calcium-sensitizer adibendan. In guinea pig left atria, both milrinone and R 80122 increased contractile force; 10 microM milrinone was equieffective to 1 microM R 80122. The rate of spontaneously beating atria was not altered by R 80122 in the concentration range of 0.01-0.3 microM. Higher concentrations (1-10 microM) led to a statistically insignificant increase of 20%. Milrinone's effect on frequency was more pronounced and amounted to 21% at 10 microM and to 40% at 100 microM. Adibendan increased heart rate (HR) by 10% at a concentration of only 0.03 microM. This effect was not enhanced any further by increasing the concentration. In papillary muscle, the positive inotropic effects of both milrinone and R 80122 were inhibited by carbachol, indicating involvement of cyclic AMP. Further indications for a cyclic AMP-dependent action were obtained by induction of slow action potentials and synergism with isoprenaline. In electrophysiologic measurements, milrinone reduced action potential duration (APD) in a high concentration whereas R 80122 had no effect. Action potential changes elicited by a toxic concentration of ouabain were reduced by R 80122. Relaxation of rat aortic rings contracted by KCl and relaxation of guinea pig aortic rings contracted by norepinephrine (NE) was comparable for both milrinone and R 80122. R 80122 also caused relaxation of canine coronary arteries constricted with prostaglandin F2 alpha (PGF2 alpha) both with and without endothelium. NE-induced contractions in canine gastrosplenic arteries were not affected by R 80122. Cardiac contractility that had been impaired to various degrees by pentobarbital or by aging was restored to control values by both milrinone and R 80122. R 80122 enhanced cardiac contractility at lower concentrations than milrinone with no concomitant increase in frequency or shortening of the action potential, which may be advantageous for treatment of heart failure.

The incidence and clinical significance of intravenous fat emulsion contamination during infusion.

So that the actual contamination rate of intravenous fat emulsions, as well as the type of microbial contamination, could be quantified, 103 bottles of 10% fat emulsion were collected near infusion completion from patients' bedsides. All samples were cultured and compared according to actual hanging time, in addition to the amount and type of microbial contamination. Recovered organisms included Escherichia coli, Staphylococcus epidermidis, diphtheroids, and Micrococcus. Sample analysis failed to demonstrate significant differences in extrinsic microbial contamination rate or organism multiplication between samples infusing for less than or equal to 12 hr and those infusing longer. Although these products support microbial growth, the contaminants introduced into the infusate by environmental or touch contamination yielded minimal colony growth. No patient developed signs or symptoms of bacteremia during the study period. Therefore, infusion of intravenous fat emulsion products over extended periods of time in this study did not increase the risk of developing infectious complications.

Providing 24-hour nutrient infusions to critically ill patients.

The outcome of critically ill patients receiving total parenteral nutrient (TPN) therapy was evaluated, and the percentage of wasted TPN solutions administered as one-per-day (2- or 3-L) or multiple-per-day (750-mL or 1-L) infusions was determined. Between March 31 and June 1, 1984, all patients who were treated by the nutritional support service (NSS) and who met the study criteria were included in the study. The 24-hour nutrient content of each TPN solution was determined using a published method. Patient outcome was determined using TPN therapy data that were collected from the patients' medical charts and NSS records. To determine waste, all discarded TPN solutions were recorded. A total of 20 patients (10 men and 10 women) were included, representing 23.6% of the 76 patients who received TPN therapy during the study period. Study patients received 24-hour nutrient solutions for a mean of 16.4 +/- 12.9 days and required a mean of 3.9 +/- 4.6 days to reach sufficient metabolic stability to qualify for 24-hour infusions. During the study period, 56 (2.8 +/- 2.5 per patient) orders were changed. The percentage of wasted TPN solutions was low; 4.3% (17 of 1326) multiple-per-day and 1.7% (5 of 292) one-per-day solutions were wasted. Twenty-four-hour TPN solutions can be used successfully in critically ill patient populations.

Retinol-binding protein and prealbumin: useful measures of protein repletion in critically ill, malnourished infants.

Plasma prealbumin (PA) and retinol-binding protein (RBP) concentrations were serially measured in 25 critically ill, malnourished infants requiring parenteral nutrition to determine if these visceral protein markers are useful in assessing acute protein repletion. Significant increases in both proteins (p less than 0.05) were noted as early as 5 to 7 days after institution of parenteral nutrition and continued significantly above baseline values through 2 weeks of observation. Gestational development (in infants less than 4 weeks old) and mean protein intake influenced visceral protein responses. Appropriate for gestational age neonates had more rapid and quantitatively greater PA responses (p less than 0.05) than small for gestational age neonates. Small for gestational age neonates never exceeded baseline RBP responses. Average protein intake of less than or equal to 2 g/kg/day resulted in PA and RBP concentrations below baseline and significantly lower than infants on higher protein intakes (p less than 0.05), at the end of 2 weeks. Average calorie intake of greater than 100 cal/kg/day had no differential influence on PA or RBP when compared with infants on less calories. Prealbumin values correlated with RBP values observed simultaneously (r = 0.588, p less than 0.0001). We conclude that PA and RBP are useful measures of protein repletion in critically ill infants requiring parenteral nutrition.

Relative reactivity of DTPA, immunoreactive antibody-DTPA conjugates, and nonimmunoreactive antibody-DTPA conjugates toward indium-111.

Anti-human serum albumin antibody (Ab) was reacted with cyclic DTPA dianhydride (cDTPAA) at various cDTPAA/Ab molar ratios between 1 and 40. Using a carrier In titration method for DTPA and DTPA-antibody conjugate (Ab-DTPA), we determined that the above reactions produced between 0.1 and 11 DTPA molecules per either immunoreactive antibody (sAb) or nonimmunoreactive antibody (nAb). The percentage of sAb remaining after the above reactions was between 88 and 62%. The reaction of no-carrier-added 111In with the reaction mixture from cDTPAA/Ab molar ratios of 1 to 40 gave radiochemical yields less than or equal to 25% for the respective Ab-DTPA. The rest of the 111In activity was associated with free DTPA. Our results indicate that Ab-DTPA containing greater than 1 DTPA molecule per Ab is more reactive than that containing less than 1 DTPA but is about as reactive as free DTPA. This allows us to label in the presence of free DTPA and consequently prevent colloid formation. The percentage of 111In activity incorporated into sAb-DTPA from the reactions at these molar ratios was similar to that found from the uv analysis. This indicates that the reactivity of sAb-DTPA and nAB-DTPA from the same conjugation reaction is similar. As a result, we were able to conjugate about one DTPA molecule to the Ab without causing deactivation of the Ab and label it with 111In in the presence of excess DTPA. We obtained a specific activity of 6 muCi 111In per microgram of Ab using research grade 111In without further purification.

Clinical effect of nonthrombotic total parenteral nutrition catheters.

Radiographic evidence of subclavian vein thrombosis has been shown to occur in 33% of total parenteral nutrition patients. This incidence can be significantly reduced to 8% when heparin is administered concomitantly in total parenteral nutrition solutions. To evaluate the thrombotic risk of a newly developed polyurethane catheter, 20 concurrent patient pairs were prospectively cannulated with either a standard polyethylene catheter plus heparin or a polyurethane catheter without heparin in a sequential statistical study. Radionuclide venograms (Tc99m) were performed within 72 hr of catheterization, at biweeky intervals, and at termination of total parenteral nutrition administration. No patient in either group developed clinical (pain, arm swelling, collateral veins) or venogram evidence of thrombosis after catheterization during an overall cannulation period of 820 days. Use of polyurethane catheters and elimination of heparin in total parenteral solutions may be particularly important since contraindications to heparin use are common. Additionally, heparin elimination can decrease admixture work and confusion (ie, subcutaneous heparin double dosing) without increasing the risk of subclavian vein thrombosis.

Nutritional support of patients with renal disease.

Current concepts in the nutritional support of patients with renal disease are reviewed. In chronic renal failure, alterations in fat, carbohydrate, and glycogen metabolism usually occur and may be worsened by acute illness. Total parenteral nutrient (TPN) therapy is rarely required unless complications occur. In contrast, acute renal failure is generally associated with hypovolemia, sepsis, soft tissue injury, and coagulation defects, all of which influence metabolism and extracellular fluid volume; the gluconeogenesis that often occurs in these patients masks the metabolic effects of uremia. Nutritional support of patients with renal disease aims at providing adequate nutrients while limiting accumulation of nitrogenous waste. Current concepts concerning essential amino acids (EAAs), nonessential amino acids (NEAAs), and urea recycling are reviewed. The caloric needs of patients with renal failure are assumed to be similar to those of other hospitalized patients. There is no clinically important advantage of using an EAA formulation rather than mixed (EAA and NEAA) amino acids. Since fluid restriction is recommended and protein use is improved with diets with a high calorie-to-nitrogen ratio, the use of TPN solutions with dextrose 350 g is recommended. If glucose intolerance is severe, fat should be considered as a calorie source. Recommendations for monitoring the metabolic status of patients with renal failure receiving nutritional support are reviewed. Monitoring the metabolic status of patients with renal disease is crucial to providing safe and effective nutritional therapy. There appears to be no clinically important advantage to amino acid products specially formulated for use in renal disease.

Labeling monoclonal antibodies and F(ab')2 fragments with (111In) indium using cyclic DTPA anhydride and their in vivo behavior in mice bearing human tumor xenografts.

Monoclonal antibodies (MAb) and their F(ab')2 fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2 fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The 111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with 131I. F(ab')2 labeled with 111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with 131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using 131I-labeled F(ab')2 3 days after injection, it was difficult to visualize tumor grafts with 111In-labeled F(ab')2 due to persistently high renal, liver, and background activity. Increased catabolism of the 131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity for in vivo imaging studies before firm conclusions can be drawn.

Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with a practical concentration (300 micrograms/ml) of antibody to human albumin (Ab) and 1083 17-1A monoclonal colorectal antibody (MAb-17-1A) via an acylation reaction using cyclic DTPA anhydride (cDTPAA). The conjugation reaction was favored as pH increased. Bicarbonate buffer at pH 8.2 was chosen for studies of the effect of the cDTPAA-to-antibody ratio on DTPA conjugation with antibody because of its good buffer capacity at that pH. The reaction of cDTPAA with Ab at molar ratios of 2000, 1000, 500, and 100 in the bicarbonate buffer gave rise to 11, 9, 8, and 2 indium atoms incorporated per Ab with 47%, 55%, 59%, and 77% retention of the binding activity. For the conjugation reaction of MAb-17-1A, 29, 28, 31, 11, 4, and 1 indium atoms were incorporated, with the retention of less than 5%, less than 5%, less than 5%, 12%, 60%, and 93% of binding activity when the molar ratio was 5000, 2000, 1000, 500, 100, and 50.