SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Hebrew numerals

344

Background Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. Methods In a trial conducted at 37 children’s hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. Results The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. Conclusions Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Concepts: Heart, Relative risk, Cardiac arrest, Asystole, Therapeutic hypothermia, Harshad number, Hebrew numerals, Drowning

88

Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. Methods We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. Conclusions Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).

Concepts: Clinical trial, Infection, Antibiotic resistance, Placebo, Antibiotic, Probiotic, Clostridium difficile, Hebrew numerals

5

Our previously presented method for high throughput computational screening of mutant activity (Hediger et al., 2012) is benchmarked against experimentally measured amidase activity for 22 mutants of Candida antarctica lipase B (CalB). Using an appropriate cutoff criterion for the computed barriers, the qualitative activity of 15 out of 22 mutants is correctly predicted. The method identifies four of the six most active mutants with ≥3-fold wild type activity and seven out of the eight least active mutants with ≤0.5-fold wild type activity. The method is further used to screen all sterically possible (386) double-, triple- and quadruple-mutants constructed from the most active single mutants. Based on the benchmark test at least 20 new promising mutants are identified.

Concepts: Scientific method, Enzyme, Test method, Enzymes, Hebrew numerals, Benchmark

2

Our hypothesis is that there are no difference in the injury incidence on artificial turf and natural grass. During the 2011/2012 season, we recorded injuries which occurred to two Italian stadiums equipped with third-generation artificial turf during 36 games (391 players). Data were compared with the injuries which occurred in the same season in two stadiums equipped with natural grass (372 players). We recorded 43 injuries during the playing time (16.7 per 1000 h). About 23 (18.1 per 1000 h) injuries occurred on artificial turf, while 20 (15.2 per 1000 h) on the natural grass with no statistical differences P > 0.05. We recorded 10 (7.87 per 1000 h) contact and 13 (10.23 per 1000 h) non-contact injuries on artificial turf, while 5 (3.8 per 1000 h) contact and 15 (11.4 per 1000 h) non-contact injuries on natural grass P > 0.05. The overall relative risk was 1.15; 95% CI: 0.64-2.07). Our study demonstrates a substantial equivalence in injury risk on natural grass and artificial turf in elite professional soccer athletes during official matches.

Concepts: Injury, Association football, Prime number, Hebrew numerals, Artificial turf, Grass, Major League Baseball, Substantial equivalence

1

When ingested alone, beetroot juice and sodium bicarbonate are ergogenic for high-intensity exercise performance. This study sought to determine the independent and combined effects of these supplements. Eight endurance trained (V̇O2max 65 mL·kg·min(-1)) male cyclists completed four x 4-km time trials (TT) in a double-blind Latin square design supplementing with beetroot crystals (BC) for 3 days (15 g.day(-1) + 15 g 1 h prior to TT, containing 300 mg nitrate per 15 g), bicarbonate (Bi 0.3 g·kg(-1) body mass [BM] in 5 doses every 15 min from 2.5 h prior to TT); BC+Bi or placebo (PLA). Subjects completed TTs on a Velotron cycle ergometer under standardized lab conditions. Plasma nitrite concentrations were significantly elevated only in the BC+Bi trial prior to the TT (1520 ± 786 nmol.L(-1)) compared to baseline (665 ± 535 nmol.L(-1), p = 0.02) and the Bi and PLA conditions (Bi: 593 ± 203 nmol.L(-1), p < 0.01; PLA: 543 ± 369 nmol.L(-1), p< 0.01). Plasma nitrite concentrations were not elevated in the BC trial prior to the TT (1102 ± 218 nmol.L(-1)) compared to baseline (975 ± 607 nmol.L(-1), p > 0.05). Blood bicarbonate concentrations were increased in the BC+Bi and Bi trials prior to the TT (BC+Bi: 30.9 ± 2.8 mmol.L(-1); Bi: 31.7 ± 1.1 mmol.L(-1)). There were no differences in mean power output (386 - 394 W) or the time taken to complete the TT (335.8 - 338.1 s) between any conditions. Under the conditions of this study, supplementation was not ergogenic for 4-km TT performance.

Concepts: Ammonia, Chemistry, Carbonate, Hebrew numerals, Nitrate, Isle of Man TT, Individual time trial, Time trial

0

0

The effects of intravenous fluid therapy on fluid compartments and hemodynamics of the human body remain enigmatic. We therefore tested the efficacy of bioimpedance spectroscopy in a crossover study, where 15 males received 0.5 ml/kg/min ELO-MEL-isoton (osmolarity = 302 mosmol/l) during 60 minutes, or nothing at all. In group “Fluid”, fluid load increased from -0.2 ± 1.0 l extracellular volume at baseline to its maximum of 1.0 ± 0.9 l in minute 70, and remained continuously elevated throughout minute 300. In group “Zero”, fluid load decreased from 0.5 ± 1.1 l at baseline to its minimum of -1.1 ± 1.1 l in minute 300. In group “Fluid”, intracellular volume decreased from 26.8 ± 3.9 l at baseline to its minimum of 26.0 ± 3.9 l in minute 70, and remained continuously decreased throughout minute 300. In group “Zero”, intracellular volume increased from 26.5 ± 3.8 l at baseline to its maximum of 27.1 ± 3.9 l in minute 120, and decreased thereafter. In group “Fluid” compared to “Zero”, systolic blood pressure was significantly higher, from minute 50-90. In conclusion, intravenous fluid therapy caused a clinically meaningful, sustained increase in fluid load, and a decrease in intracellular volume. These data raise interest in studying fluid administration by the gastrointestinal route, perhaps even when managing critical illness.

Concepts: Blood pressure, Intravenous therapy, Human body, Critical point, Maxima and minima, Hebrew numerals, 1, Identity element

0

The aim of this study was to identify pharmaceutical issues encountered during regulatory review in European Procedures. A database of issues from Day 70 assessment reports of 150 EU procedures was compiled; most procedures were for generics (108). Frequencies of common deficiencies have been calculated and summarized for use of all stakeholders. Out of the 150 procedures reviewed, covering 309 products, a total of 4,796 concerns were identified. Of these concerns, 167 were Potential Serious Risks to Public Health, 67 were raised on drug substance and 100 on the drug product. The distribution of total concerns was as follows: 2,168 concerns on drug substance and 2,584 on drug product. Most concerns raised were on control of drug substance and drug product (834 & 626for 3.2.S.4 and 3.2.P.5 respectively), followed by concerns on the manufacturing (482 & 564 for 3.2.S.2 and 3.2.P.3 respectively) and stability 147 & 398 for 3.2.S.7 and 3.2.P.8 respectively). In conclusion, the frequencies and trends of identified deficiencies together with their impact were discussed from a regulatory point of view. The main findings indicate that applicants would benefit from following published guidelines so that delays in the registration of medicines could be avoided.

Concepts: Pharmacology, Medicine, European Union, Drug, Harshad number, Review, Pharmaceutical drug, Hebrew numerals

0

By using dehydroabietyltrimethyl ammonium bromine (DTAB), a novel rosin-derived quaternary ammonium salt, as template and peroxotitanium acid as precursor, ordered lamellar supermicroporous titania has been synthesized via a hydrothermal process. The template agent:titanium source molar ratio in the synthesis system and the hydrothermal temperature have great impact on the microstructure characteristics of the samples. The increase of DTAB:TiO2 molar ratio from 0.04:1 to 0.10:1 is favorable to the increase of regularity of pore structures, but has no significant effects on the crystalline structures. The increase of the hydrothermal temperature from 343 to 393 K can induce an increase in crystallinity of the samples. However, the exorbitant hydrothermal temperature will reduce the regularity of pore structures. When the mole ratio of DTAB:TiO2 is 0.10:1 and the hydrothermal temperature is 373 K, the as-synthesized sample possesses pore structure with the highest level of long-range order, as well as pore wall with semicrystallized anatase phase. The pore size and the pore wall thickness are about 2.0 nm and 1.0 nm, respectively.

Concepts: Ammonia, Quaternary ammonium cation, Ammonium, Salt, Hebrew numerals

0

Antiretroviral postexposure prophylaxis (PEP) may be underutilized in sexual assault cases in Kenya. This study evaluated the characteristics of survivors of sexual violence attending the Gender-Based Violence Recovery Center (GBVRC) at the Kenyatta National Hospital and reviewed the uptake, adherence, and outcomes of those initiated on PEP. In a retrospective cohort, data from charts of the assaulted seen at the GBVRC from 2009 to 2012 were abstracted. Data were collected describing sociodemographic characteristics, nature of sexual assault, HIV serostatus, and aspects of the PEP care cascade. Characteristics of participants who received PEP were compared with those who did not receive PEP. We enrolled 385 assaulted persons; 331 (86%) were female; the median age of the assaulted persons was 21 (interquartile range 14-28) years; and 61 (15.8%) were children aged 10 years and younger. Of 379 assaults with descriptions, 330 (85.7%) were vaginal assaults and 40 (10.3%) were penile-anal assaults. Most perpetrators were unknown to the assaulted 220 of 384 (57.3%). All assaulted persons were offered HIV testing and 359 (93%) accepted testing; 346 (96.4%) of 359 assaulted persons tested HIV negative. In total, 207 (53.8%) of 385 sexual assault survivors initiated PEP. Only 70 (34%) completed 28 days of PEP, and only 21 (10.1%) returned for repeat HIV test at 3 months. In conclusion, PEP was only initiated in 54% of sexual assault cases. The care cascade showed that late presentation and poor adherence were the greatest gaps in PEP provision. Earlier presentation for PEP should be promoted among sexual assault in areas of high HIV prevalence.

Concepts: HIV, HIV/AIDS, Domestic violence, Violence, Rape, Hebrew numerals, 300, 360