Diarrhea prevalence in a randomized, controlled prospective trial of point-of-use water filters in homes and schools in the Dominican Republic.

BACKGROUND: Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy. METHODS: We conducted a prospective, randomized, controlled trial whereby 16 villages were selected and randomly assigned to one of four treatment arms based on the installation location of Sawyer® PointONE™ filters (filter in both home and school; filter in home only; filter in school only; control group). Water samples and self-reported information on diarrhea were collected at multiple times throughout the study. RESULTS: Self-reported household prevalence of diarrhea decreased from 25.6 to 9.76% from installation to follow-up (at least 7 days, and up to 200 days post-filter installation). These declines were also observed in diarrhea with economic or educational consequences (diarrhea which led to medical treatment and/or missing school or work) with baseline prevalence of 9.64% declining to 1.57%. Decreases in diarrhea prevalence were observed across age groups. There was no evidence of a loss of efficacy of filters up to 200 days post-filter installation. Installation of filters in schools was not associated with decreases in diarrhea prevalence in school-aged children or family members. Unfiltered water samples both at schools and homes contained potential waterborne bacterial pathogens, dissolved heavy metals and metals associated with particulates. All dissolved metals were detected at levels below World Health Organization action guidelines. CONCLUSIONS: This controlled trial provides strong evidence of the effectiveness of point-of-use, hollow fiber membrane filters at reducing diarrhea from bacterial sources up to 200 days post-installation when installed in homes. No statistically significant reduction in diarrhea was found when filters were installed in schools. Further research is needed in order to explore filter efficacy and utilization after 200 days post-installation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03972618 . Registered 3 June 2019-retrospectively registered.

Phonological pattern frequency and speech production in adults and children.

Recent studies have suggested that both adults and children are sensitive to information about phonological pattern frequency; however, the influence of phonological pattern frequency on speech production has not been studied extensively. The current study examined the effect of phonological pattern frequency on the fluency and flexibility of speech production. Normal- and fast- rate nonsense-word repetitions of three groups of participants (preschool children, school-aged children, and adults) were analyzed. Subjective ratings of the wordlikeness of nonsense words, percentage phonemes correctly repeated, mean duration, and durational variability were measured. In the first experiment, ratings of the wordlikeness of nonsense words were found to correlate with the pattern frequency of sequences embedded in them. In the second analysis, it was found that children, but not adults, repeated infrequent sequences of phonemes less accurately than frequent sequences. In the third experiment, infrequent sequences were produced with longer durations than frequent ones, with children demonstrating a larger difference between frequent and infrequent sequences than adults. Phonological pattern frequency also influenced variability in duration: infrequent sequences of sounds were more variable than frequent ones. Thus, there appears to be an influence of phonological pattern frequency on speech, and, for some measures, a larger effect size is noted for children.

Is processing speed related to severity of language impairment?

Children with specific language impairment (SLI) typically respond more slowly on many tasks than do their typically developing peers. This paper addresses the question of whether speed of response is linearly related to severity of language impairment as measured by standardized test score. To address this question, we performed post hoc analyses of data from a study on lexical processing involving 66 children with SLI (mean age 6 years 9 months) and 66 typically developing children matched for age and nonverbal IQ. Response times derived from a series of tasks were correlated with language test scores. None of the Pearson correlations reached significance when corrected for number of correlations run, nor did a canonical correlation analysis reach significance. If these results are replicated in other studies, then they suggest that there is no direct linear relation between speed of processing and severity of language impairment as it is estimated from scores on standardized tests of language.

The use of deuterium oxide as a mobile phase for structural elucidation by HPLC/UV/ESI/MS

The use of deuterium oxide as a mobile phase in the routine analysis of pharmaceutical compounds was investigated. The deuterium exchange of labile hydrogen atoms aids in structural confirmation and elucidation of unknown impurities and degradation products. Although deuterium oxide as a mobile phase does in some cases change the retention times, the changes in retention times do not interfere with the analysis. A study of the high-performance liquid chromatography system shows that equilibration times for the deuterium-containing mobile phases are similar to equilibration times with changes of other mobile phases. The use of this technique in the analysis of pharmaceutical compounds and other small molecules is presented.

Proton affinities of saturated aliphatic methyl esters

The kinetic method was used to determine the proton affinities of methyl esters of several saturated fatty acids. Decompositions of the proton-bound dimers of the methyl esters, AHB+, were observed under different conditions with two instruments. The proton affinities (PAs) of the methyl esters increase continually with increasing carbon number in the acid. Equilibrium and initial rate experiments were performed with a Fourier transform ion cyclotron resonance mass spectrometer on the methyl ester of the C22 saturated acid (methyl behenate). These experiments give values for PA (methyl behenate) that are perhaps slightly lower than those obtained with the kinetic method. The PAs of the methyl esters of the fatty acids could be correlated with the equation: PA (ester) = (40.0 +/- 2.5)*log(n) + (784.7 +/- 3.9) kJ/mol or PA (ester) = (864 +/- 2) - (479 +/- 41)/n, where n = number of atoms in the molecule. Proton affinities of smaller sets of 1-alkylamines and 1-alkanols can be fit to similar equations.

DNA interaction and photocleavage properties of porphyrins containing cationic substituents at the peripheral position.

A series of mono- and disubstituted cationic porphyrins (1-8) were synthesized and investigated for their ability to bind and cleave DNA in the presence of light. In these porphyrins, the cationic substituents were introduced at various peripheral positions, i.e., the non-meso positions of the porphyrin system. The modes of binding of these porphyrins to DNA were investigated by UV-vis spectroscopy, circular dichroism, and an unwinding assay. The intrinsic binding constants Kb of these porphyrins to calf thymus DNA was found to be in the range 10(4)-10(5) M-1. Two of the zinc(II) complexes of non-meso-substituted cationic porphyrins (5 and 8) were found to bind to DNA via intercalation, which is in contrast to the previously reported outside-binding mode for the Zn(II) complexes of meso-substituted cationic porphyrins. Except for monocationic porphyrin 1 and Ni(II) dicationic porphyrin 6, all the other porphyrins were found to be efficient photocleavers of DNA. The DNA photocleavage characteristics of this series of cationic porphyrins were found to depend on the structural characteristics of the poprhyrins such as (a) length of the side chain of the cationic substituents (2 vs 4), (b) the position of the side chain on the porphyrin ring (4 vs 7), and (c) the presence of the chelating metal in 3, 5, and 8 as compared to the nonmetallo porphyrins 2, 4, and 7, respectively.

Effects of mobile-phase additives, solution pH, ionization constant, and analyte concentration on the sensitivities and electrospray ionization mass spectra of nucleoside antiviral agents.

The effects of various mobile-phase additives, solution pH, pKa, and analyte concentration on electrospray ionization mass spectra of a series of purine and pyrimidine nucleoside antiviral agents were studied in both positive and negative ion models. The use of 1% acetic acid resulted in good HPLC separation and the greatest sensitivity for [M + H]+ ions. In the negative ion mode, 50 mM ammonium hydroxide gave the greatest sensitivity for [M - H]- ions. The sensitivities as [M + H]+ ions were significantly larger than the sensitivities as [M - H]- ions for purine antiviral agents. Vidarabine monophosphate and pyrimidine antiviral agents, however, showed comparable or greater sensitivities as [M - H]- ions. The sensitivity as [M + H]+ showed no systematic variation with pH; however, the sensitivity as [M - H]- did increase with increasing pH. At constant pH, the ion intensity of the protonated species increased with increasing pKa. At higher analyte concentrations, dimer (M2H+) and trimer (M3H+) ions were observed. [M + Na]+ adducts were the dominant ions with 0.5 mM sodium salts for these compounds. The spectra of the more basic purine antiviral agents showed no [M + NH4]+ adduct ions, but [M + NH4]+ ions were the major peaks in the spectra of the less basic pyrimidine antiviral agents with ammonium salts. The ammonium adduct ion was formed preferentially when the proton affinity of the analyte was close to that of NH3. Abundant [M + OAc]- ions were observed for all of the antiviral agents except vidarabine monophosphate from solutions with added HOAc, NaOAc, and NH4OAc. The utility of mobile phases containing 1% HOAc or 50 mM NH4OH was demonstrated for chromatographic separations.

Electrospray ionization mass spectrometry of tetracycline, oxytetracycline, chlorotetracycline, minocycline, and methacycline.

The effects of mobile-phase additives and analyte concentration on electrospray ionization mass spectra of a series of tetracyclines were investigated in both positive and negative ion modes. Only [M + H](+) and [M - H](-) ions were observed. The greatest sensitivity as [M + H](+) ions was obtained with 1% acetic acid and the greatest sensitivity as [M - H](-) ions was obtained using 50 mM ammonium hydroxide. Sensitivities in the positive ion mode were greater than those in the negative ion mode. The sensitivity as [M + H](+) showed no systematic variation with pH; however, the sensitivity as [M - H](-) did increase with increasing pH. A larger linear range was observed for [M - H](-) than for [M + H](+) ions. Both [M + Na](+) and [M + H](+) ions were observed with 0.5 mM sodium acetate and sodium iodide, but no adduct ions were observed with ammonium acetate. Some M(2)H(+) ions were observed at higher concentrations. Cluster ions, Na(NaOAc)(n)(+) or Na(NaI)(n)(+), but no sample ions were observed using 5 mM salts. The data suggest that mechanisms in addition to solution ionization are involved in the formation of the ESI sample ions. The utility of mobile phases containing 1% HOAc or 50 mM NH(4)OH was demonstrated for chromatographic separations.

New payments and incentives in contact capitation: an orthopedics case study.

The purpose of this article is to present a model for equitable distribution of orthopedic contact capitation payments. This model accounts for services covered, patient severity of illness, patient age, and condition prevalence.

Are speech perception deficits associated with developmental dyslexia?

Phonological awareness and phoneme identification tasks were administered to dyslexic children and both chronological age (CA) and reading-level (RL) comparison groups. Dyslexic children showed less sharply defined categorical perception of a bath-path continuum varying voice onset time when compared to the CA but not the RL group. The dyslexic children were divided into two subgroups based on phoneme awareness. Dyslexics with low phonemic awareness made poorer /b/-/p/ distinctions than both CA and RL groups, but dyslexics with normal phonemic awareness did not. Examination of individual profiles revealed that the majority of subjects in each group exhibited normal categorical perception. However, 7 of 25 dyslexics had abnormal identification functions, compared to 1 subject in the CA group and 3 in the RL group. The results suggest that some dyslexic children have a perceptual deficit that may interfere with processing of phonological information. Speech perception difficulties may also be partially related to reading experience.

Cationic porphyrin derivatives as inhibitors of polyamine catabolism.

The effects of six cationic porphyrins on several enzymes involved in polyamine biosynthesis and catabolism have been examined. Both spermidine and spermine synthase were unaffected by the porphyrins at up to 2 mM. By contrast, ornithine and S-adenosylmethionine decarboxylase were inhibited by the nickel and cobalt derivatives of meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin (T4MPyP) with IC50 values in the 10-100 microM region. Spermidine/spermine N1-acetyltransferase (SSAT) and polyamine oxidase (PAO) were highly sensitive to the six meso-substituted cationic porphyrins tested, with Ki values as low as 6 nM for SSAT and 85 nM for PAO. These inhibitors may prove useful in defining the structural features of the active site of these enzymes.

Photosensitized formation of 8-hydroxy-2'-deoxyguanosine and DNA strand breakage by a cationic meso-substituted porphyrin.

Cationic porphyrins, known to have a high affinity for DNA, are useful tools with which to probe a variety of interactions with DNA. In this study we have examined both DNA strand scission and oxidative DNA base damage, measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, using a photoactivated cis-dicationic porphyrin. The data demonstrated a dose-dependent formation for each type of DNA damage. Inhibition of strand scission and 8-OHdG formation with the singlet oxygen scavenger 1,3-diphenylisobenzofuran and with MgCl2 and no apparent effect by D2O suggests that a singlet oxygen mechanism generated in close proximity to the DNA may be responsible for the damage. However, a nearly complete inhibition of 8-hydroxy-2'-deoxyguanosine formation in 75% D2O and the substantial enhancement of 8-hydroxy-2'-deoxyguanosine formation in a helium atmosphere by photoactivated porphyrin rules out singlet oxygen as a primary mechanism for this process. These data indicate that distinct mechanisms lead to 8-OHdG formation and strand scission activity.

DNA intercalation and photosensitization by cationic meso substituted porphyrins.

Several cationic porphyrins are known to bind to DNA by intercalative and outside binding modes. This study identifies the cis and trans isomers of bis(N-methyl-4-phridiniumyl)diphenyl porphyrin as DNA intercalators based on evidence from a DNA topoisomerase I assay. Moreover, both isomers are shown to be potent photosensitizers of DNA, inducing multiple S1 nuclease sensitive breaks in the phosphodiester backbone. Porphyrin-induced photodamage in DNA was also shown to be quantitatively dependent upon ionic strength and to inhibit the action of restriction endonucleases. The results indicate that these porphyrins can be useful probes of DNA structure and have potential as DNA-targeted photosensitizers.

Radiative stabilization of trimethylsilyl adduct ions.

Ketones and phenol react with trimethylsilyl ions to form adduct ions by radiatively or collisionally stabilized addition reactions, in contrast to aliphatic alcohols and ethers, which react with trimethylsilyl ions to form adduct ions by a rapid two-step process. Secondorder rate constants for the addition of trimethylsilyl ions to acetone were independent of pressure from 3×10(-7) to 50×10(-7) tort at room temperature; consequently, the adduct ions, [M+73](+), are formed primarily by radiatively stabilized addition in these ion cyclotron resonance experiments.

Correlations of relative sensitivities in gas chromatography electron ionization mass spectrometry with molecular parameters.

The relative molar sensitivities for a number of compounds having a variety of functional groups were obtained in gas chromatography electron ionization mass spectrometry. Comparable results were obtained with a quadrupole and with a magnetic mass spectrometer. The present relative molar sensitivities are in good agreement with relative ionization cross sections obtained by different techniques and different instruments for a variety of compounds with molecular weights below about 200 u. For compounds of higher molecular weight, the present experimental sensitivities are significantly larger than estimates extrapolated from earlier data. The relatively molar sensitivities correlate well with molecular polarizability.

Segregation of relaxed replicated dimers when DNA ligase and DNA polymerase I are limited during oriC-specific DNA replication.

An in vitro Escherichia coli oriC-specific DNA replication system was used to investigate the DNA replication pathways of oriC plasmids. When this system was perturbed by the DNA ligase inhibitor nicotinamide mononucleotide (NMN), alterations occurred in the initiation of DNA synthesis and processing of intermediates and DNA products. Addition of high concentrations of NMN soon after initiation resulted in the accumulation of open circular dimers (OC-OC). These dimers were decatenated to open circular monomers (form II or OC), which were then processed to closed circular supercoiled monomers (form I or CC) products. After a delay, limited ligation of the interlinked dimers (OC-OC to CC-OC and CC-CC) also occurred. Similar results were obtained with replication protein extracts from polA mutants. The presence of NMN before any initiation events took place prolonged the existence of nicked template DNA and promoted, without a lag period, limited incorporation into form II molecules. This DNA synthesis was nonspecific with respect to oriC, as judged by DnaA protein dependence, and presumably occurred at nicks in the template DNA. These results are consistent with oriC-specific initiation requiring closed supercoiled molecules dependent on DNA ligase activity. The results also show that decatenation of dimers occurs readily on nicked dimer and represents an efficient pathway for processing replication intermediates in vitro.