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Objective To assess the burden of invasive infection following surgery (surgery-associated infections [SAI]) among infants born extremely premature. Study design This was an observational, prospective study of infants born at gestational age 22-28 weeks hospitalized for >3 days, between April 1, 2011, to March 31, 2015, in academic centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. SAI was defined by culture-confirmed bacteremia, fungemia, or meningitis ≤14 days following a surgical procedure. Results Of 6573 infants, 1154 (18%) who underwent surgery were of lower gestational age (mean [SD]: 25.5 [1.6] vs 26.2 [1.6], P Conclusions Surgical procedures were associated with bacteremia, fungemia, or meningitis in 7% of infants. The epidemiology of invasive postoperative infections as described in this report may inform the selection of empiric antimicrobial therapy and postoperative preventive care.

To determine if preterm infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP) with short bowel syndrome (SBS) have worse neurodevelopmental and growth outcomes than those with sNEC/SIP without SBS, and those with no necrotizing enterocolitis, SIP, or SBS.We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26 weeks of gestation in the National Institute of Child Health and Human Development Neonatal Research Network centers from January 1, 2008, to December 31, 2016. Survivors were assessed at 18-26 months corrected age by standardized neurologic examination and Bayley Scales of Infant and Toddler Development, Third Edition. The primary outcome was moderate-severe neurodevelopmental impairment. Growth was assessed using World Health Organization z-score standards. Adjusted relative risks were estimated using modified Poisson regression models.Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26 months corrected age. Moderate-severe neurodevelopmental impairment was present in 77% of children with SBS compared with 62% with sNEC/SIP without SBS (adjusted relative risk, 1.22; 95% CI, 1.02-1.45; P = .03) and 44% with no necrotizing enterocolitis, SIP, or SBS (adjusted relative risk, 1.60; 95% CI, 1.37-1.88; P .001). Children with SBS had lowcognitive, language, and motor scores than children with sNEC/SIP without SBS. At follow-up, length and head circumference z-scores remained more than 1 SD below the mean for children with SBS.Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26 months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions.

Cytokines mediate the host immune response to infectious micro-organisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6, and IL-10) and inflammatory cytokines (Interferon-γ [INF-γ], tumor necrosis factor-β [TNF-β], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the five sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (p=0.01), and higher levels of the regulatory cytokines, IL-6 (p=0.01) and IL-10 (p0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population.

The cocktail party effect in analytical chemistry refers to the ability to measure a complex mixture of analytes and to resolve the signals from a single analyte. We describe a new approach that we have coined mathematical chromatography, where data from complex spectra are resolved into pure-analyte information by so-called three-way modeling. Three-way analysis requires the addition of an extra dimension to the signals being acquired. Here, as an example, mathematical chromatography is applied to a series of diffusion-edited 2D NMR spectra of mixtures of glucose, maltose and maltotriose to demonstrate that it is possible to identify and to resolve individual components in highly overlapping 2D NMR spectra.

Cellobiohydrolases are the dominant components of the commercially relevant Trichoderma reesei cellulase system. Although natural cellulases can totally hydrolyze crystalline cellulose to soluble sugars, the current enzyme loadings and long digestion times required render these enzymes less than cost effective for biomass conversion processes. It is clear that cellobiohydrolases must be improved via protein engineering to reduce processing costs. To better understand cellobiohydrolase function, new simulations have been conducted using CHARMM of cellobiohydrolase I (CBH I) from T. reesei interacting with a model segment (cellodextrin) of a cellulose microfibril in which one chain from the substrate has been placed into the active site tunnel mimicking the hypothesized configuration prior to final substrate docking (i.e., the +1 and +2 sites are unoccupied), which is also the structure following a catalytic bond scission. No tendency was found for the protein to dissociate from or translate along the substrate surface during this initial simulation, nor to align with the direction of the cellulose chains. However, a tendency for the decrystallized cellodextrin to partially re-anneal into the cellulose surface hints that the arbitrary starting configuration selected was not ideal.

Background and Objectives This prospective, observational study compared disease progression and death in HIV-1 patients treated with stavudine vs. zidovudine in the Collaborations in HIV Outcomes Research/U.S. (CHORUS) cohort. Methods Patients with a first occurrence of CD4 count n =3301) were grouped as: no nucleoside reverse transcriptase inhibitor (NRTI) use; other NRTI without stavudine or zidovudine; stavudine with no zidovudine, with or without other NRTIs; and zidovudine with no stavudine, with or without other NRTIs. The risk for death or disease progression was evaluated in unadjusted analyses and using a Cox proportional hazards model, adjusting for: study site, age, gender, race, route of HIV infection, previous AIDS-defining conditions, number of previous antiretroviral regiments, CD4 count, HIV-1 RNA, and treatment variables. Sensitivity analyses were conducted to determine the sensitivity of the results to major modeling assumptions. A landmark analysis was conducted to determine the absolute difference in time to event. Results During a median follow-up of 2.4 years, there were 57 deaths and 348 AIDS-defining conditions in 405 patients. Stavudine treatment compared with zidovudine resulted in a greater percentage of patients with AIDS-defining events (14.5 vs. 10.9%; P =.013), and an increased risk of disease progression (HR=1.30; 95% CI: 1.01,1.7; P =.04). This result was not sensitive to modeling assumptions. Landmark analysis demonstrated an absolute difference in time to 95% event-free survival of 2.7 months for those with a CD4⩽200 cells/μL and 11 months for those 6 months after model entry. Conclusions In unadjusted and adjusted analyses of 3301 HIV-1 infected patients, stavudine containing combination therapy was associated with an increased risk of disease progression or death compared to therapy containing zidovudine. Most of the difference was attributable to new cases of wasting.

Infection is a serious complication among very low birth weight (VLBW) preterm infants hospitalized in neonatal intensive care units. This article reviews studies from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network including infection data from observational studies and randomized controlled trials. Blood culture-proven early-onset sepsis (or = 72 hours) was found in less than 2% of VLBW infants, but was associated with substantial morbidity and mortality. A change in pathogens causing early-onset sepsis among Network patients has been observed over the past decade, with a significant reduction in early-onset group B streptococcal infections, but also a significant increase in early-onset Escherichia coli infections. This change is particularly worrisome, because of the high death rate associated with gram-negative infections, including E coli. Late-onset (72 hours) sepsis developed in almost a quarter of infants. The vast majority of infections were caused by gram-positive agents, especially coagulase-negative staphylococci. The risk of late-onset sepsis was inversely related to birth weight and gestational age. Infants with late-onset sepsis were at increased risk for a number of neonatal morbidities, for prolonged hospitalization, and for death. The percentage of deaths attributed to infection increased with increasing postnatal age. The increasing survival of extremely immature infants has resulted in a cohort of infants at prolonged risk for acquired infection. Successful strategies to reduce infections among VLBW infants would improve survival, reduce neonatal morbidity, and reduce the high medical and social costs of VLBW infant care.

To determine the rates of Enterobacter sakazakii (ES) infections among very low birth weight infants, culture data from the National Institute of Child Health and Human Development Neonatal Research Network were reviewed. Only one case of ES sepsis was identified among 10660 neonates. These data suggest that outside of the epidemic situation, ES is very rare in very low birth weight infants.

The objective of this experiment was to investigate the effect of rearing density on pecking behaviour and plumage during rearing and throughout the laying period in aviaries. Chicks were reared on sand at high (H; 13 m −2 ) or low (L; 6.5 m −2 ) density, in four rearing pens of 390 chicks and eight pens of 195 chicks, respectively, each pen measuring 30 m 2 . Proportions of chicks per pen performing various types of pecking behaviour were recorded by scan sampling during 16 observation bouts in each rearing pen at 6 weeks of age and during 24 observation bouts at 12 weeks. Individual body weights and plumage condition were recorded. Later, these pullets were housed at 17 hens m −2 in Tiered Wire Floor (TWF; 3 H and 3 L pens of 275 hens) and Laco-Voletage (2 H and 2 L pens of 275 hens) aviaries. At 35 weeks, two samples of eight hens from each aviary pen were observed for pecking behaviour in a test pen. Throughout the laying period, additional records were collected on pecking behaviour, body weight, plumage condition, egg production, and mortality. The L birds had better plumage condition at 6 weeks of age and throughout the laying period. These birds also ground pecked more frequently than H birds during rearing and the laying period. At 12 weeks, L birds feather pecked less than H birds, but no relationship was found between rearing density and feather-pecking behaviour during the laying period. Although TWF hens feather pecked more frequently than Voletage hens, there was no interaction between rearing density and type of aviary for the various pecking behaviours.

Isocaloric substitution of sucrose for starch results in hyperinsulinemia and deterioration of glucose tolerance, suggesting a loss of insulin sensitivity. In this study we have quantitated the insulin resistance which develops with sucrose feeding, and evaluated the ability of dietary fiber, or an increase in skeletal muscle activity, to inhibit, or even prevent, the detrimental effect of sucrose feeding on in vivo insulin action. Thus, 6-wk-old rats were fed one of the following regimens for three weeks: a 64% cornstarch diet (C), a 32% cornstarch + 32% sucrose diet (S), the (S) diet containing added wheat bran fiber (S/F), and the (S) diet given to rats running spontaneously in exercise wheel cages (S/ET). Insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels approximately 70 microU/ml attained during the continuous infusion of epinephrine (0.08 micrograms/kg/min), propranolol (1.7 micrograms/kg/min), glucose (8 mg/kg/min), and insulin (2.5 mU/kg/min) to each experimental group. The results show that rats fed the S diet had a significant increase (p less than 0.01) in mean (+/- SEM) SSPG concentration compared with rats fed the C diet (255 +/- 14 versus 165 +/- 3 mg/dl). SSPG concentrations, although lower (p less than 0.05) in rats fed S/F (205 +/- 8 mg/dl), were still higher (p less than 0.05) than the C levels (165 +/- 3 mg/dl). However, S/ET completely inhibited the increase in SSPG concentration seen in rats fed S and the values were actually lower (p less than 0.05) than in rats fed C (100 +/- 10 versus 165 +/- 3 mg/dl). In conclusion 1) sucrose feeding results in a loss of insulin sensitivity in normal rats; 2) addition of fiber attenuates, but does not completely prevent, the loss of insulin sensitivity associated with feeding sucrose; 3) exercise training prevents the loss of insulin sensitivity seen in sucrose-fed rats, and actually improves glucose uptake beyond that seen in the control group. These results document the profound effect of environmental factors on in vivo insulin action.

Using resonance fluorescence the kinetics of NH (X p3 Σ − ) was studied in the pulsed vacuum UV photolysis of mixtures of NH 3 and NO. The rate constant of the reaction NH + NO was determined to be (4.7 ± 1.2) × 10 p−11 cm p3 molecule p−1 s p−1 .