Accumulation of anthropogenic litter (i.e. garbage; AL) and its ecosystem effects in marine environments are well documented. Rivers receive AL from terrestrial habitats and represent a major source ...of AL to marine environments, but AL is rarely studied within freshwater ecosystems. Our objectives were to 1) quantify AL density in urban freshwaters, 2) compare AL abundance among freshwater, terrestrial, and marine ecosystems, and 3) characterize the activity and composition of AL biofilms in freshwater habitats. We quantified AL from the Chicago River and Chicago's Lake Michigan shoreline, and found that AL abundance in Chicago freshwater ecosystems was comparable to previously reported data for marine and terrestrial ecosystems, although AL density and composition differed among habitats. To assess microbial interactions with AL, we incubated AL and natural substrates in 3 freshwater ecosystems, quantified biofilm metabolism as gross primary production (GPP) and community respiration (CR), and characterized biofilm bacterial community composition via high-throughput sequencing of 16S rRNA genes. The main driver of biofilm community composition was incubation location (e.g., river vs pond), but there were some significant differences in biofilm composition and metabolism among substrates. For example, biofilms on organic substrates (cardboard and leaves) had lower GPP than hard substrates (glass, plastic, aluminum and tiles). In addition, bacterial communities on organic substrates were distinct in composition from those on hard substrates, with higher relative abundances of bacteria associated with cellulose decomposition. Finally, we used our results to develop a conceptual diagram designed to unite the study of AL in terrestrial and freshwater environments with the well-established field of marine debris research. We suggest this broad perspective will be useful for future studies which synthesize AL sources, ecosystem effects, and fate across multiple ecosystem types, and will benefit management and reduction of global AL accumulations.
Water quality data representing 44 New Jersey rivers have been factor analyzed using oblique rotation. The fixed sampling sites include 62 maintained by the U.S. Geological Survey and 14 maintained ...by the Passaic Valley Water Commission (PVWC) in Little Falls, New Jersey. Nominal periods of record are 1970–1996 and 1963–89 respectively. Analyzed variates include inorganic chemical species, temperature, streamflow, BOD, and bacterial counts. Comparison of analysis series employing different data sets and analysis options show that 36 of 323 extracted factors (11.1%) are unstable, which recommends some type of validation procedure for factor reliability. Each analysis series produced some uninterpretable factors. Factors are spatially and temporally invariant in groups ranging from 2 to 58 stations, though some factors have several variants. Factor replication has been judged via inspection and quantified through congruence indices. Matrix-level comparisons have not been shown to be useful in watershed categorization. There is sometimes no discernible geographic or geologic pattern to factor occurrence. The most commonly-extracted factors appear to represent baseflow. Most streams show an inverse correlation between chemical concentrations and flow, but one in the Outer Coastal Plain shows a direct relation, and more than a dozen show no correlation. The second most commonly-extracted factors are interpreted to represent degradation. There is evidence that natural degradation and STP point sources can produce similar factors. High factor loadings (“salients”) do not always appear in patterns that are easily recognized as representing the processes which generate them. It is demonstrated that “missing salients” can be caused by multiple inputs of given variates in a phenomenon for which the term “factor interference” is suggested. Therefore, factor loadings can be sensitive to variance magnitude, even though they are insensitive to concentration means. Comparison of similar factors from many stations and time periods (to express degree of “invariance”) is useful in assigning meaning to factors which are difficult to interpret if examined in isolation. It is demonstrated that the proportion of explained variance accounted for by given factors is highly dependent on the arbitrary field of analyzed variables, so that, in general, it is erroneous to equate relative proportions of factor variance with relative degrees of influence of watershed processes on water quality. It is empirically shown that the effect of log transformation of raw data pursuant to normalization has minimal effect on loadings and is unlikely to affect factor interpretation. Extreme factor scores, by station, have high descriptive correlation with known watershed characteristics, but moderate scores are not useful for identifying characteristics.
Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies.
To examine the ...efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED.
We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively.
Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose.
We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight.
At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares LS mean SE change, -1.49 0.066; P = .008) and 70-mg/d (LS mean SE change, -1.57 0.067; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean SE change, -1.24 0.067; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% P = .01) and 70-mg/d (50.0% P < .001) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis).
The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing.
clinicaltrials.gov Identifier: NCT01291173.
Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace ...environment.
After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.
Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P <or= .0017 for each time point) and change from predose (P < .001 for each time point) PERMP total scores were greater at all postdose time points from 2 to 14 h for adults while receiving LDX vs placebo. LDX demonstrated efficacy vs placebo (P < .0001) by the difference in LS mean (95% CI) for ADHD-RS-IV total scores: -11.5 (-14.2, -8.9). TEAEs (>or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX.
LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD.
ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1.
To improve our understanding of reproductive health and sexual function in women with cloacal malformations and other anorectal malformations (ARMs)
An observational cross-sectional survey was ...administered to individuals assigned female at birth aged 12 to 55 with ARMs and cloacal malformations cared for at our institution. Data included age of thelarche/menarche and questions on body image, gynecologic anatomy, sexual function, and pregnancy.
Twenty-one patients responded in the ARM group and 30 in the cloacal malformation group. There were no differences in median age of thelarche/menarche in patients with ARMs (11/12.5 years) compared with patients with cloacal malformation (11/12 years). Patients with ARMs were more likely to have native vaginal tissue than those with cloacal malformations (n = 18, 82% vs n = 12, 40%; P = .03). There were no differences between groups regarding concerns about dyspareunia and functionality of their vagina (P > .05). Forty-two percent of patients with cloacal malformations and 30% of patients with ARMs reported having been sexually active. Two patients with cloacal malformations and 2 with ARMs reported having been pregnant. Patients with cloacal malformations reported a lower quality of life score (80.4) compared with those with ARMs (87.0) (difference > 4.5).
Patients with a cloacal malformation were less likely to have native vaginal tissue and reported a lower quality of life than those with ARMs. Despite this, patients with a cloacal malformation had similar reproductive health and sexual function compared with patients with ARMs. Our results reinforce the need for comprehensive sexual and reproductive health care for all women with ARMs.
An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on ...intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.
Protocadherin-19 (PCDH19)-clustering epilepsy is a distinct developmental and epileptic encephalopathy characterized by early-onset seizures that are often treatment refractory. Caused by a mutation ...of the PCDH19 gene on the X chromosome, this rare epilepsy syndrome primarily affects females with seizure onset commonly in the first year of life. A global, randomized, double-blind, placebo-controlled, phase 2 trial was conducted to evaluate the efficacy, safety, and tolerability of ganaxolone compared with placebo as adjunctive therapy to a standard antiseizure medication regimen in patients with PCDH19-clustering epilepsy (VIOLET; NCT03865732).
Females aged 1–17 years with a molecularly confirmed pathogenic or likely pathogenic PCDH19 variant who were experiencing ≥12 seizures during a 12-week screening period were stratified by baseline allopregnanolone sulfate (Allo-S) levels (low: ≤2.5 ng/mL; high: >2.5 ng/mL) at screening and randomized 1:1 within each strata to receive ganaxolone (maximum daily dose of 63 mg/kg/day if ≤28 kg or 1800 mg/day if >28 kg) or matching placebo in addition to their standard antiseizure treatment for the 17-week double-blind phase. The primary efficacy endpoint was the median percentage change in 28-day seizure frequency from baseline to the 17-week double-blind phase. Treatment-emergent adverse events (TEAEs) were tabulated by overall, system organ class, and preferred term.
Of the 29 patients screened, 21 (median age, 7.0 years; IQR, 5.0–10.0 years) were randomized to receive either ganaxolone (n = 10) or placebo (n = 11). After the 17-week double-blind phase, the median (IQR) percentage change in 28-day seizure frequency from baseline was − 61.5% (−95.9% to −33.4%) among patients in the ganaxolone group and − 24.0% (−88.2% to −4.9%) among patients in the placebo group (Wilcoxon rank-sum test, p = 0.17). TEAEs were reported by 7 of 10 (70.0%) patients in the ganaxolone group and 11 of 11 (100%) patients in the placebo group. Somnolence was the most common TEAE (40.0% ganaxolone vs 27.3% placebo); serious TEAEs were more common in the placebo group (10.0% ganaxolone vs 45.5% placebo); and 1 (10.0%) patient in the ganaxolone group discontinued the study versus none in the placebo group.
Ganaxolone was generally well tolerated and led to a greater reduction in the frequency of PCDH19-clustering seizures compared to placebo; however, the trend did not reach statistical significance. Novel trial designs are likely needed to evaluate the effectiveness of antiseizure treatments for PCDH19-clustering epilepsy.
●Ganaxolone led to a median 61.5% reduction in seizure frequency.●Ganaxolone was generally well tolerated; most common adverse event was somnolence.●PCDH19-clustering epilepsy poses unique challenges in studying potential treatments.
A series of helquat molecules with increasing number of rings n was studied by electrochemical and break junction methods to provide redox characteristics and single molecule conductance properties. ...Even though selected species do not contain anchoring groups the molecular junction conductance was observed experimentally and depends strongly on the solvent used. Single molecule conductance G is almost two orders of magnitude higher in water environment compared to mesitylene, whereas the distribution of G values is narrow in water and wide in mesitylene solvent. In the non‐polar environment, G increases with increasing n, contrary to generally accepted notion of decreasing tunneling current with increasing molecular length. This behavior is, however, consistent with electrochemical properties, which showed that longer helquats are reduced more easily than the shorter ones. Furthermore, theoretical computations provided most probable molecular junction configurations of helquats in water solvent with excellent agreement between theoretical and experimental G values.
Closing the ring: Helquats represent fast electron‐transfer systems that can be reduced in two one‐ electron steps. Single molecule conductance G of a series of helquats lacking anchoring groups is reported in water and mesitylene solvents. G in water is higher and independent of molecular length, whereas G increases with molecular length in mesitylene and correlates with redox potentials for helquat reduction.
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