Reduction of large vessel traffic improves water quality and alters fish habitat-use throughout a large river.

Rivers are increasingly used as superhighways for the continental-scale transportation of freight goods, but the ecological impact of large vessel traffic on river ecosystems is difficult to study. Recently, the temporary maintenance closure of lock and dam systems on the Illinois Waterway (USA) brought commercial vessel traffic to a halt along the river's length, offering a rare opportunity to study the response of the ecosystem before, during, and after an extended pause of this persistent anthropogenic disturbance. We observed improvements in main- and side-channel water quality and a redistribution of fish habitat-use during a months-long, near-complete reduction of large vessel traffic. Over 3600 water quality and 1300 fish community samples indicate that large vessel traffic reduction coincided with a 33 % reduction in turbidity as well as increased use of sampling strata near vessel navigation corridors by sound-sensitive and rheophilic fishes. Gizzard shad (Dorosoma cepedianum), the most abundant species in the system, also expanded their use of these 'impact' areas. Though inland waterway transport is an economically- and climate-friendly alternative to trucking and rail for the shipment of freight, our data suggest that intense vessel traffic may have profound physical and biological impacts across a large river. Monitoring and mitigation of ecological impacts of the ongoing expansion of inland waterway transport around the world will be critical to balancing large rivers as both useful navigation corridors and functional ecosystems.

Introduction of triggers for palliative care consultation improves utilization and satisfaction within a level four NICU.

OBJECTIVE: We sought to explore the beliefs regarding palliative care team utilization, as well as increase consultation and awareness of the palliative care team's role in the NICU. STUDY DESIGN: The study design in this Level 4 NICU included observational time series with multiple planned sequential interventions. Medical chart review was conducted to determine eligibility, and statistical process control charts were used to show performance over time. RESULTS: Prior to implementation of the triggers, 26% received consultation, which increased to 46% after implementation. There was an increase in level of understanding, knowledge of team's role, and improved utilization. The time until initial consultation decreased from ~1.5 months to 1 week. CONCLUSIONS: We observed a 20% increase in consultations. Key interventions included continual education, reminders, and clear postage of the trigger list. Written guidelines increase awareness of a palliative care team's role within a NICU, and provider satisfaction.

Teaching the Art of Difficult Family Conversations.

CONTEXT: Difficult family conversations are a challenge for even the most seasoned clinicians. Teaching the skills of successful communication between providers, family members, and patients is a vital component of medical education. However, traditional teaching methods using didactics and expert role modeling are often inadequate. OBJECTIVES: The train-the-educator workshop aimed to teach educators how to create and conduct workshops on facilitating difficult family conversations that target their own learners' needs. METHODS: This three-hour workshop included instruction on scenario writing and on the use of standardized actors as patients and family members. Workshop leaders presented examples of commonly encountered clinical scenarios where difficult information is discussed. The session used experiential teaching techniques. Outcomes were measured by qualitative discussions and a questionnaire to demonstrate communication skills learned from the sessions. RESULTS: The workshop was well received by participants who consisted of educators attending the annual meeting of the Pediatric Academic Societies in May 2016. Evaluations revealed that 92% of participants agreed or strongly agreed that the workshop achieved the learning objectives. All participants believed that the workshop increased their knowledge, competency, and skills in teaching and facilitation as an educator, with 86% of participants planning to apply the skills toward curriculum development. The major themes that participants learned centered on facilitation skills as an educator and techniques on how to communicate during challenging family meetings (86% of comments). CONCLUSION: This train-the-educator workshop addresses a critical need in both palliative care and general medicine by enhancing the educators' skills in designing and implementing a curriculum on communication skills of health care providers using experiential techniques with formative feedback. The authors hope that by outlining the implementation of this three-hour interactive format, future educators will adapt and use this workshop as it works best for their learners.

Commentary: flawed science delays smelter cleanup and worsens health.

For 6,000 years, humans have known about smelter hazards. Yet these metals threats continue. Why? This commentary provides one preliminary answer. It (1) summarizes the history of smelter pollution and (2) suggests that at least 3 problems-especially flawed smelter-polluter science-allow continuing health threats. It (3) illustrates this flawed science by using one of the most dangerous of U.S. former smelters, in DePue, Illinois. There polluters are avoiding violating the law yet trying to minimize smelter-caused health threats, thus clean-up costs, by using two questionable scientific claims. The causality-denial claim denies that smelter metals cause neurodegenerative diseases. The biomagnification-denial claim denies that food-chain biomagnification of smelter metals can put citizens at risk. The commentary shows both claims err, and (4) suggests ways to address flawed smelter science and resulting health harms.

Forgotten parent: NICU paternal emotional response.

PURPOSE: To evaluate and compare the presence of perceived paternal stress and depressive symptomatology in fathers of preterm infants over time. SUBJECTS: Fathers of NICU infants born before 30 weeks of gestation. DESIGN: Prospective convenience sample. METHODS: Consenting fathers were given 2 self-report questionnaires: Center for Epidemiologic Studies-Depression Scale (CES-D) and Parent Stressor Scale: Infant Hospitalization (PSS:IH) on 7th (time 1), 21st (time 2), and 35th (time 3) days of life. Objective measurement of illness severity was quantified by Score for Neonatal Acute Physiology. Statistical methods included generalized linear estimating equation and mixed linear modeling. MAIN OUTCOME MEASURES: Stress and depressive symptomatology in fathers of preterm infants. RESULTS: Stress scores (PSS:IH) were unchanged over time (P = .62) indicating that fathers (n = 35) remain significantly stressed. Individual subcomponents of stress (parent role alteration, infant appearance/behavior, NICU sights/sounds) also remained constant over the study period (P = .05 for each). Stress scores over time were not modified by demographic characteristics (marriage, education, insurance). Mean depressive symptomatology scores (CES-D) decreased over time (P = .04). The percentage of fathers with elevated CES-D scores (>16) decreased from a baseline 60% but did not diminish between times 2 (39%) and 3 (36%). Parent Stressor Scale: Infant Hospitalization stress scores were correlated with CES-D depressive symptomatology scores (P < .01). Socioeconomic factors influenced initial CES-D scores, but only marriage ameliorated subsequent changes in measurements. Objective measurement of infant illness (Score for Neonatal Acute Physiology) did not influence paternal CES-D or PSS:IH scores. CONCLUSION: Fathers of premature infants in a medical NICU demonstrated elevated levels of stress that persisted across time for all domains of measured stress. Paternal self-reported stress and depressive symptomatology was independent of infant illness. One third of fathers had persistently elevated CES-D scores. If these findings are representative of general NICU population, then the emotional needs of our fathers are not being fully addressed.

In vitro hepatic metabolism of cediranib, a potent vascular endothelial growth factor tyrosine kinase inhibitor: interspecies comparison and human enzymology.

The in vitro metabolism of cediranib (4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) of all three VEGF receptors in late-stage development for the treatment of colorectal cancer and recurrent glioblastoma was investigated in hepatic proteins from preclinical species and humans using radiolabeled material. In human hepatocyte cultures, oxidative and conjugative metabolic pathways were identified, with pyrrolidine N(+)-glucuronidation being the major route. The primary oxidative pathways were di-and trioxidations and pyrrolidine N-oxidation. All metabolites with the exception of the N(+)-glucuronide metabolite were observed in rat and cynomolgus monkey hepatocyte preparations. Additional metabolism studies in liver microsomes from these or other preclinical species (CD-1 mouse, Han Wistar rat, Dunkin Hartley guinea pig, Göttingen mini-pig, New Zealand White rabbit, beagle dog, and cynomolgus and rhesus monkey) indicated that the N(+)-glucuronide metabolite was not formed in these additional species. Incubations with recombinant flavin-containing monooxygenase (FMO) and UDP-glucuronosyltransferase (UGT) enzymes and inhibition studies using the nonselective cytochrome P450 (P450) chemical inhibitor 1-aminobenzotriazole in human hepatocytes indicated that FMO1 and FMO3 contributed to cediranib N-oxidation, whereas UGT1A4 had a major role in cediranib N(+)-glucuronidation. P450 enzymes had only a minor role in the metabolism of cediranib. In conclusion, species differences in the formation of the N(+)-glucuronide metabolite of cediranib were observed. All other metabolites of cediranib found in humans were also detected in rat and cynomolgus monkey. Non-P450 enzymes are predominantly involved in the metabolism of cediranib, and this suggests that clinical drug interactions involving other coadministered drugs are unlikely.

Characterisation and identification of the human N+-glucuronide metabolite of cediranib.

Cediranib (4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline; RECENTIN), a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) of all three VEGF receptors, is currently in Phase III clinical trials for the first-line treatment of colorectal cancer and the treatment of recurrent glioblastoma. During its clinical development a unique human metabolite, an N(+)-glucuronide, was identified as a major circulating metabolite and one of the major metabolites excreted into faeces. Given the possibility of four sites for the conjugation of the glucuronic acid moiety, determination of the location of the conjugation site on cediranib was warranted. A small quantity of the N(+)-glucuronide metabolite of cediranib was initially generated using recombinant human uridine glucuronosyltransferase 1A4 (UGT1A4) enzymes. The metabolite generated was characterised by HPLC-UV and mass spectrometric (HPLC-MS(n)) detection and confirmed by (1)H NMR spectroscopy. However, the exact site of conjugation could not be determined without generating more of the metabolite. Hence a subsequent biosynthetic scale-up experiment was devised to generate a sufficiently large quantity for full structural characterisation by (1)H NMR spectroscopy. The identity of the N(+)-glucuronide metabolite generated in the UGT1A4 scale-up experiment was confirmed by HPLC-MS(n) and displayed the same retention time, molecular mass and mass fragmentation data as the metabolite generated in previous human liver microsomal and hepatocyte incubations. (1)H NMR spectroscopy clearly showed the characteristic anomeric doublet at approximately 4.7 ppm, which, following irradiation during selective Rotating frame Overhauser Effect Spectroscopy (ROESY) experiments, enabled the site of glucuronidation to be confirmed on the pyrrolidine nitrogen. With the exception of the N(+)-glucuronide metabolite, all other human metabolites of cediranib were observed following incubation with hepatocytes from rat and cynomolgus monkey, the species used for toxicology testing of the drug [6]. As the N(+)-glucuronide was not detected in the preclinical species, it is suggested that its formation is more likely in human and higher primates (great apes), a finding widely supported in the literature.

Stress in fathers of surgical neonatal intensive care unit babies.

The purpose of this study was to identify and measure components of perceived stress in fathers of infants in a surgical neonatal intensive care unit (NICU). The Parent Stressor Scale: Infant Hospitalization (PSS:IH) was used to assess perceived stress in 22 fathers. Paternal stress was highest in the domains of "Parental Role Alteration" and "Infant Appearance and Behavior." "Sights and Sounds" did not appear to be associated with self-reported stress. This study demonstrates elevated levels of perceived stress among fathers of surgical NICU babies. Attention to fathers may be assisted by findings.

Ghrelin and cholecystokinin in term and preterm human breast milk.

AIM: To determine whether ghrelin and cholecystokinin (CCK) are present in significant quantities in term and preterm human breast milk, and to identify their source. METHODS: Samples were collected from 10 mothers who delivered term infants and 10 mothers who delivered preterm infants. Estimated fat content was measured. Ghrelin and CCK levels were measured in whole and skim breast milk samples using radioimmunoassays (RIA). Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using RNA from human mammary epithelial cells (hMECs) and mammary gland with primers specific to ghrelin. RESULTS: The median ghrelin level in whole breast milk was 2125 pg/ml, which is significantly higher than normal plasma levels. There was a direct correlation between whole milk ghrelin levels and estimated milk fat content (r=0.84, p<0.001). Both the mammary gland and hMECs produced ghrelin. While CCK was detected in some samples, levels were insignificant. Infant gestational age, birthweight, maternal age, and maternal pre-pregnancy body mass index did not significantly affect the results. CONCLUSION: Ghrelin, but not CCK, is present in breast milk. Since the mammary gland produces ghrelin message, and ghrelin levels in breast milk are higher than those found in plasma, we conclude that ghrelin is produced and secreted by the breast.

Short-term use of umbilical artery catheters may not be associated with increased risk for thrombosis.

OBJECTIVE: Umbilical arterial catheters (UACs) have rare but serious complications related to thrombus formation. Two specific serum markers of thrombogenesis--prothrombin fragment (F1.2) and thrombin-antithrombin (TAT)--can be assayed and correlated with abdominal ultrasound visualization of UAC thrombosis. Levels of these markers of thrombogenesis have not been studied in infants with UACs. The objective of this study was to determine F1.2 and TAT levels longitudinally and compare the levels with platelet counts and ultrasound evidence of thrombi during the first week of life in infants with UACs. METHODS: This study was conducted as a prospective, nonblinded, observational study performed between June 2001 and January 2002 at Christiana Care Hospital, a level III neonatal intensive care unit. Infants with a UAC in place in the first 24 hours of life were studied. All received equal amounts of heparin in the UAC. F1.2, TAT, platelet counts, and abdominal aorta ultrasounds were examined every other day starting within 24 hours of life. Studies were not done when the UAC was removed within the 5-day study period. Enzyme-linked immunosorbent assay for TAT and F1.2 was performed using a commercially available kit from Enzyngost. Data were analyzed with repeated measures analysis of variance evaluating TAT, F1.2, and platelet count over time. RESULTS: Thirty-three patients were investigated (mean +/- standard deviation; gestational age: 27.4 +/- 3.5 weeks; birth weight: 1139 +/- 729 g). A total of 66 measurements of TAT, F1.2, and platelet counts were obtained. Sixty-one abdominal ultrasounds were performed; only 1 study was positive for UAC thrombus. There was no significant difference between F1.2 and TAT over time during the study period. Platelet counts seemed to fall over the 5-day study period, although this decrease did not reach statistical significance. CONCLUSION: Indwelling UACs in sick infants may not carry an increased risk of thrombosis during the first 5 days of use.

Family reactions during infants' hospitalization in the neonatal intensive care unit.

The purpose of this investigation is to assess family stress, coping, perceptions of their infant, and alterations in mood that may result from the hospitalization of their critically ill newborn infant. Eligible patients were those infants hospitalized in the Special Care Nursery (SCN) at Christiana Care Health Services, who were born up to 31 weeks' gestational age. Twenty-seven families (mothers and/or fathers) completed four questionnaires at 2-week intervals during the course of their premature infants' hospitalization. Data were primarily evaluated by using analysis of variance (ANOVA)/multivariate analysis of variance (MANOVA). A score for neonatal acute physiology (SNAP) was obtained in each infant to assess the effect of the severity of neonatal illness on the questionnaire variables. Families with high stress scores on the Parental Stressor Scale had different coping strategies than those with less stress scores. A high level of maternal depressive symptomatology was associated with altered methods of coping, general stress, and perception of infant health. There was no relationship between the SNAP score on the overall level of stress families. Families who completed more than two questionnaires differed from those who only completed two or less questionnaires, although the sample size was too small to assess longitudinal changes in this study population. Level of stress and depressive symptoms are two major influences of how families cope with the current hospitalization of a premature infant. The degree of neonatal illness is not a major contributor to the parents' coping ability. Healthcare providers need to understand these dynamics when supporting families during the hospitalization of their premature infant.