Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Variability in antifungal utilization among neonatal, pediatric, and adult inpatients in academic medical centers throughout the United States of America

Abstract Background Identification of factors associated with antifungal utilization in neonatal, pediatric, and adult patient groups is needed to guide antifungal stewardship initiatives in academic medical centers. Methods For this hospital-level analysis, we analyzed antifungal use in hospitals across the United States of America, excluding centers only providing care for hematology/oncology patients. Analysis of variance was used to compare antifungal use between patient groups. Three multivariable linear regression models were used to determine independent factors associated with antifungal use in the neonatal, pediatric, and adult patient groups. Results For the neonatal, pediatric, and adult patient groups, 54, 44, and 60 hospitals were included, respectively. Total antifungal use was significantly lower in the neonatal patient group (14 days of therapy (DOT)/1000 patient days (PDs) versus 76 in pediatrics and 74 in adults, p < 0.05). There were no significant associations identified with total antifungal DOT/1000 PDs in the neonatal patient group (model R2 = 0.11). In the pediatric patient group (model R2 = 0.55), admission to immunosuppressed service lines and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 1.95 and 0.41, both p < 0.05). In the adult patient group (model R2 = 0.79), admission to immunosuppressed service lines, total invasive fungal infections, and total broad-spectrum antibiotic use were positively associated with total antifungal use (coefficients of 5.08, 5.17, and 0.137, all p < 0.05). Conclusions Variability in antifungal use in the neonatal group could not be explained well, whereas factors were associated with antifungal use in the adult and pediatric patient groups. These data can help guide antifungal stewardship initiatives

Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants \u3c 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older. Summary Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population

The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs

<p>Brett MT, Ahopelto SK, Brown HK, Brynestad BE, Butcher TW, Coba EE, Curtis CA, Dara JT, Doeden KB, Evans KR, Fan L, Finley JD, Garguilo NJ, Gebreeyesus SM, Goodman MK, Gray KW, Grinnell C, Gross KL, Hite BRE, Jones AJ, Kenyon PT, Klock AM, Koshy RE, Lawler AM, Lu M, Martinkosky L, Miller-Schulze JR, Nguyen QTN, Runde ER, Stultz JM, Wang S, White FP, Wilson CH, Wong AS, Wu SY, Wurden PG, Young TR, Arhonditsis GB. 2016. The modeled and observed response of Lake Spokane hypolimnetic dissolved oxygen concentrations to phosphorus inputs. Lake Reserv Manage. 32:246–258.</p> <p>Lake Spokane, a reservoir in eastern Washington State, was previously hypereutrophic due to phosphorus discharges from the City of Spokane wastewater treatment plant (WWTP). This reservoir subsequently recovered to a meso-oligotrophic state after implementation of advanced phosphorus removal. The present study tested whether the mechanistic Lake Spokane water quality (WQ) model realistically represents the sensitivity of this reservoir's hypolimnetic oxygen concentrations to phosphorus inputs. We compared the observed relationship between the mean summer input total phosphorus concentration (TP_IN) and the minimum volume weighted hypolimnetic dissolved oxygen concentration (DO_MIN) to model values for conditions ranging from hypereutrophic to oligotrophic. Prior to advanced phosphorus removal, TP_IN and DO_MIN averaged 86 ± 37 (SD) µg/L and 1.4 ± 1.3 mg/L, respectively. Currently (2010–2014), these values average 14 ± 3 µg/L and 6.5 ± 0.8 mg/L, respectively. By contrast, the model's DO_MIN response for similar TP_IN concentrations was much less pronounced, with hypereutrophic and contemporary DO_MIN averaging 3.8 ± 0.4 and 4.7 ± 0.04 mg/L, respectively. The model also has a structural DO deficit (saturated DO − DO_MIN) of 5.3 mg/L that was evident when all TP inputs to the reservoir were set to zero. Similarly, when all WWTP effluent sources were set to TP_EFF = 0 µg/L, the reservoir epilimnetic TP concentrations were ≈8 µg/L higher than the Spokane River inputs. The water quality model indicates that even if effluent phosphorus concentrations are reduced to zero, the dissolved oxygen goals for Lake Spokane cannot be met.</p