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The impact of venous thromboembolism in Japanese colorectal cancer patients has not been elucidated. This prespecified subanalysis of the Cancer-VTE Registry aimed to report venous thromboembolism and event data after 1 year of follow-up in 2477 patients with colorectal cancer and investigate risk factors of venous thromboembolism. Of 2477 patients, 158 (6.4%) had venous thromboembolism in venous thromboembolism screening at enrollment. Asymptomatic distal deep-vein thrombosis accounted for 123/158 (77.8%) of venous thromboembolism cases. During the follow-up period, symptomatic, incidental events requiring treatment and composite venous thromboembolism incidences were 0.3%, 0.8%, and 1.0%, respectively. The incidence of bleeding events, cerebral infarction/transient ischemic attack/systemic embolic event, and all-cause death were 1.0%, 0.3%, and 4.8%, respectively. These results were consistent with the main study results. In multivariable analysis, venous thromboembolism at baseline was a risk factor of composite venous thromboembolism during the follow-up period. Japanese patients with colorectal cancer and advancing cancer stage before treatment had more frequent venous thromboembolism complications at baseline, higher incidence of venous thromboembolism events during cancer treatment, and higher mortality.

High biomass yields have been documented for Tripidium spp. (Erianthus spp., Saccharum spp.), but targeted breeding for bioenergy applications has been limited. Advanced, interspecific hybrids between Tripidium ravennae and T. arundinaceum were planted in replicated field plots in 2016. Comparative feedstock evaluations examined biomass yields, cytogenetics, plant fertility, and compositional analyses relative to Miscanthus × giganteus. Dry biomass yields varied as a function of year and accession and increased each year ranging from 3.4 to 10.6, 8.6 to 37.3, and 23.7 to 60.6 Mg/ha for Tripidium hybrids compared to 2.3, 16.2 and 27.9 Mg/ha for M. × giganteus in 2016, 2017, and 2018, respectively. Cytology and cytometry confirmed that Tripidium hybrids were tetraploid with 2n = 4x = 40 (2C genome size = 5.06 pg) and intermediate between T. ravennae with 2n = 2x = 20 (2C genome size = 2.55 pg) and T. arundinaceum with 2n = 6x = 60 (2C genome size = 7.61 pg). Plant fertility characteristics varied considerably with some accessions producing no viable seeds or fewer than that observed for M. × giganteus. Accessions varied significantly for flowering culm number and height and dates of peak anthesis ranging from 14 September to 2 October. Variations in yield and compositional analyses contributed to variations in theoretical ethanol yields ranging from 10,181 to 27,546 L/ha for Tripidium accessions compared to 13,095 L/ha for M. × giganteus. Relative feed value (RFV) indices for winter‐harvested Tripidium accessions varied from 52.8 to 60.0 compared to M. × giganteus with 45.4. RFV for summer‐harvested Tripidium accessions varied from 71.6 to 80.5 compared to M. × giganteus with 61.0. These initial findings for Tripidium hybrids, including high biomass yields, cold hardiness, and desirable traits for multiple markets (e.g., forage, bioenergy, bioproducts), are promising and warrant further development of Tripidium as a temperate bioenergy feedstock.

Current research on bioenergy crops shows that perennial grasses can yield substantial amounts of dry biomass with relatively low inputs of water and fertilizer. In order to minimize competition with food production, it has been suggested that bioenergy crops could be directed to land areas less suitable for commodity crops, commonly referred to as “marginal” lands. These are land units with inherent limitations to vegetative growth and production, which may be due to several factors (soil physical and chemical properties, climatic conditions, etc.). However the term “marginal” is an adjective with imprecise meaning, and objective criteria for determining “marginal” lands for siting bioenergy crops are necessary. Here we propose that such criteria may be based on soil survey classifications and realistic yield estimates, and we show an example of its use to justify site selection for bioenergy crops in different regions of North Carolina.

Implementing telecare requires experience and knowledge from different disciplines and sectors; business, technology and care. The uptake of telecare has been slow, which is assumed to be caused by difficulties in co-operation within telecare partnerships. This article presents a new approach to improve understanding of telecare partnerships. The approach builds on theories of trust and partnership working and is informed by rational choice theory. Within this article the approach is applied to recent experiences from a telecare project in Norway, to demonstrate how different ways of interpreting the complex social interactions in telecare partnerships yield new insight and understanding. Examples from the Norwegian project illustrate how different understandings of actions and choices affected trust and caused either improved or deteriorated co-operation in the partnership. The partners that were able to develop trust through a common evaluation of the problems co-operated better. However, when partners lacked or had insufficient knowledge, either of each other or of the situation, this led to disparate understandings that threatened trust and affected further co-operation. The new approach presented here is helpful in analyzing and understanding the actions of different partners within a telecare partnership and identifying why things worked well or went wrong. The approach may have wider relevance for other partnerships.

Aim The aim of this study was to evaluate the association between oligohydramnios and other perinatal factors in preterm small-for-gestational-age (SGA) infants who had cerebral palsy at 18 months of age or who had died before this age. Methods This retrospective study included 320 infants with birthweights

Objectives This study aimed to assess the perinatal outcome in monochorionic diamniotic (MD) twin pregnancies complicated by amniotic fluid discordance (AFD) adjoining twin–twin transfusion syndrome (TTTS). Methods An observational study of 84 consecutive MD twin pregnancies complicated by AFD that resembled TTTS was conducted. AFD adjoining TTTS was defined by a maximal vertical pocket of amniotic fluid ≤3 cm in one twin and ≥7 cm in the other excluding TTTS. The study population was divided into two groups, group 1 and group 2, according to positive and absent or reversed end-diastolic flow (AREDF) in the umbilical artery, respectively. Results Fifteen of the 35 (42.9%) group 1 cases and 30 of the 49 (61.2%) group 2 cases progressed to TTTS. The overall survival and intact survival rate in constant AFD that never progressed to TTTS in group 1 was 100% (40/40) and 90% (36/40), respectively. The overall survival and intact survival rate of constant AFD in group 2 with selective intrauterine growth restriction (sIUGR) was 54.2% (13/24) and 41.7% (10/24), respectively, and for those without sIUGR was 64.3% (9/14) and 57.1% (8/14), respectively. Conclusions Constant AFD with AREDF in the umbilical artery represents an extremely high risk for adverse outcomes regardless of the presence of sIUGR. © 2015 John Wiley & Sons, Ltd.

Collective victimhood, which results from the experience of being targeted as members of a group, has powerful effects on individuals and groups. The focus of this Special Issue is on how people respond to collective victimhood and how these responses shape intergroup relations. We introduce the Special Issue with an overview of emerging social psychological research on collective victimhood. To date, this research has focused mostly on destructive versus positive consequences of collective victimhood for relations with an adversary group, and examined victim groups' needs, victim beliefs, and underlying social identity and categorization processes. We identify several neglected factors in this literature, some of which are addressed by the empirical contributions in the current issue. The Special Issue offers novel perspectives on collective victimhood, presenting findings based on a diverse range of methods with mostly community samples that have direct and vicarious experiences of collective harm in different countries.

Aim The aim of this study was to elucidate the risk of poor pregnancy outcomes in women with adenomyosis by comparing their outcomes to those of women without uterine abnormalities. Material and Methods The subjects were 36 women diagnosed with adenomyosis before pregnancy who were managed at a tertiary care center between January 2002 and December 2012. Our hospital database was retrospectively reviewed to identify pregnancy outcomes associated with adenomyosis. The control group consisted of 144 women without uterine abnormalities who gave birth during the same period and whose age at delivery was adjusted by applying propensity scores. Pregnancy outcomes were compared between the adenomyosis and control groups. The main outcomes were gestational age at delivery, preterm delivery, preterm premature rupture of membranes, fetal malpresentation, cesarean delivery, small-for-gestational age, 5-min Apgar score

Although there are many reports on the resistance of Kawasaki disease (KD) to initial intravenous immunoglobulin (IVIg) therapy, risk factors for coronary artery lesions in such cases remain to be established. The objective of this study was to explore when additional therapies should be administered and to identify factors helpful for selecting a therapeutic option. Based on their written clinical records, we performed a retrospective review of KD patients who did not respond to initial IVIg therapy and who therefore then underwent plasma exchange (PE) therapy. This was a case-control study to compare the presence or absence of acute coronary lesions in patients treated by PE for IVIg-unresponsive KD at Yokohama City University Hospital or at Yokohama City University Medical Center. Fifteen of 44 patients had acute coronary artery lesions (CAL) correlating with high levels of white blood cells (WBC) (P = 0.045), D-dimer (P = 0.008), and fibrin/fibrinogen degradation products (P = 0.009) and lower levels of fibrinogen (P = 0.013) prior to PE therapy. There was a strong correlation between pre-PE levels of albumin and D-dimer (Pearson's correlation coefficient of 0.610). Multivariate analyses revealed that the odds ratio for CAL when D-dimer was ≥ 4.5 μg/mL was 25.06 (95% CI, 2.56-244.91, P = 0.006). D-dimer elevation and albumin decline in IVIg-unresponsive KD patients could be risk factors for acute CAL, suggesting the possibility that angitis has spread throughout the arterial system, as far as the coronary artery.

The Kv2.1 delayed rectifier potassium channel exhibits high-level expression in both principal and inhibitory neurons throughout the central nervous system, including prominent expression in hippocampal neurons. Studies of in vitro preparations suggest that Kv2.1 is a key yet conditional regulator of intrinsic neuronal excitability, mediated by changes in Kv2.1 expression, localization and function via activity-dependent regulation of Kv2.1 phosphorylation. Here we identify neurological and behavioral deficits in mutant (Kv2.1(-/-) ) mice lacking this channel. Kv2.1(-/-) mice have grossly normal characteristics. No impairment in vision or motor coordination was apparent, although Kv2.1(-/-) mice exhibit reduced body weight. The anatomic structure and expression of related Kv channels in the brains of Kv2.1(-/-) mice appear unchanged. Delayed rectifier potassium current is diminished in hippocampal neurons cultured from Kv2.1(-/-) animals. Field recordings from hippocampal slices of Kv2.1(-/-) mice reveal hyperexcitability in response to the convulsant bicuculline, and epileptiform activity in response to stimulation. In Kv2.1(-/-) mice, long-term potentiation at the Schaffer collateral - CA1 synapse is decreased. Kv2.1(-/-) mice are strikingly hyperactive, and exhibit defects in spatial learning, failing to improve performance in a Morris Water Maze task. Kv2.1(-/-) mice are hypersensitive to the effects of the convulsants flurothyl and pilocarpine, consistent with a role for Kv2.1 as a conditional suppressor of neuronal activity. Although not prone to spontaneous seizures, Kv2.1(-/-) mice exhibit accelerated seizure progression. Together, these findings suggest homeostatic suppression of elevated neuronal activity by Kv2.1 plays a central role in regulating neuronal network function.

Most human physiologic set points like body temperature are tightly regulated and show little variation between healthy individuals. Red blood cell (RBC) characteristics such as hematocrit and mean cell volume are stable within individuals but can vary by 20% from one healthy person to the next. The mechanisms for the majority of this inter-individual variation are unknown and do not appear to involve common genetic variation. Here, we show that environmental conditions present during development, namely in utero iron availability, can exert long-term influence on a set point related to the RBC life cycle. In a controlled study of rhesus monkeys and a retrospective study of humans, we use a mathematical model of in vivo RBC population dynamics to show that in utero iron deficiency is associated with a lowered threshold for RBC clearance and turnover. This in utero effect is plastic, persisting at least 2 years after birth and after the cessation of iron deficiency. Our study reports a rare instance of developmental plasticity in the human hematologic system and also shows how mathematical modeling can be used to identify cellular mechanisms involved in the adaptive control of homeostatic set points.

Sources of variability in hemoglobin concentration in blood were examined in over 600 rhesus infants at the California National Primate Research Center who had complete blood counts (CBCs) conducted at three-to-four months of age. These infants were born and raised in outdoor social housing. Hemoglobin values ranged from 8.5 to 15.3 µg/dL with a mean and standard deviation of 12.2 ± 0.8 µg/dL. As expected, hemoglobin was strongly associated with the number of red blood cells (RBCs). Plasma protein concentration, an indicator of blood volume, was not a predictor. Associations with infant age, weight and sex, infant serum cortisol, dam’s reproductive history, and birth year, month and location were evaluated in regression analyses. Cage of origin, maternal age at delivery and infant weight were associated with hemoglobin concentrations. Unexpectedly, serum cortisol, determined at the same time as CBC samples were taken, was the strongest predictor of hemoglobin concentration. The basis, as well as the functional significance, of the variation in infant hemoglobin and its association with serum cortisol in this population of rhesus fed a nutritionally optimized diet and housed under standard conditions is relevant to the development of both nonhuman and human primate infants.

Aim Interleukin (IL)-28B gene polymorphism is closely linked with treatment response to peginterferon plus ribavirin combination therapy for hepatitis C virus genotype 1. However, few studies have reported its effects on therapy for genotype 2. We aimed to examine the effects of IL-28B gene polymorphism on treatment response in hepatitis C virus genotype 2 patients. Methods In a retrospective study of 101 patients infected with either genotype 2a (n = 65) or 2b (n = 36) and treated with peginterferon plus ribavirin, we investigated predictive factors for a sustained virological response (SVR), including genetic variations near the IL-28B gene (rs8099917, rs11881222 and rs8103142) and clinical variables such as age, sex, body mass index, stage of fibrosis and drug adherence. Results Ultra-rapid virological response, rapid virological response (RVR), end-of-treatment response, SVR and relapse rates were 22.2%, 61.4%, 95.0%, 87.1% and 7.9%, respectively. In univariate analysis, RVR and IL-28B single nucleotide polymorphisms (SNP) (rs8099917, rs11881222 and rs8103142) were significantly associated with SVR. In subgroup analysis, IL-28B SNP were significantly associated with SVR in genotype 2a patients but not in genotype 2b patients. In multiple logistic regression analysis, RVR and IL-28B SNP (rs8099917) were independently associated with SVR. Furthermore, IL-28B SNP was significantly associated with relapse but RVR was not. Conclusion In genotype 2 patients treated with peginterferon plus ribavirin combination therapy, IL-28B gene polymorphism was a significant independent predictor of SVR as well as RVR. IL-28B major allele may favor reduced relapse rates in patients with genotype 2 chronic hepatitis C.

Social and emotional behaviors are known to be sensitive to both developmental iron deficiency (ID) and monoamine oxidase A (MAOA) gene polymorphisms. In this study, male rhesus monkey infants deprived of dietary iron in utero were compared with iron sufficient (IS) controls (n = 10/group). Half of each group had low MAOA activity genotypes and half had high MAOA activity genotypes. A series of social response tests were conducted at 3-14 months of age. MAOA genotype influenced attention to a video of aggressive behavior, emotional expression (fear, grimace and sniff) in the social intruder test, social actions (displacement, grooming) in the social dyad test, and aggressive responses to a threatening picture. Interactions between MAOA and prenatal ID were seen in response to the aggressive video, in temperament ratings, in affiliative behavior in the social dyad test, in cortisol response in the social buffering test and in response to a social intruder and to pictures with social and nonsocial themes. In general, the effects of ID were dependent on MAOA genotype in terms of both direction and size of the effect. Nutrition/genotype interactions may shed new light on behavioral consequences of nutritional deprivation during brain development.

ACADEMIC EMERGENCY MEDICINE 2012; 19:85–91 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: The 24-hour physician coverage of the emergency department (ED) requires shift work, which can result in desynchronosis and cognitive decline. We measured changes in cognition and sleep disturbance in attending emergency physicians (EPs) before and after day and overnight shifts. Methods: Thirteen EPs were tested before and after day and overnight shifts using the Paced Auditory Serial Addition Test (PASAT), the University of Southern California Repeatable Episodic Memory Test (REMT), the Trail Making Test (TMT), and the Stroop Color-Word Test. Sleep quality and fatigue were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Chalder Fatigue Questionnaire (CFQ). Saliva samples were collected from each physician immediately before and after day shifts and night shifts for neurohormonal assays. Results: Significantly fewer words were recalled on the REMT after both day (−2.4, 95% confidence interval [CI] = −4.4 to −0.4) and overnight shifts (−4.6, 95% CI = −6.4 to −2.8). There was a significant postshift increase in words recalled from the last third of the REMT list after overnight shifts (6.6, 95% CI = 2.8 to 10.4). Sleep quality was worse in EPs (mean PSQI = 4.8, SD ± 2.5) compared to the normal population, with 31% of subjects reporting poor sleep quality. Postshift fatigue was correlated with the perceived difficulty of the shift. Salivary cortisol and melatonin demonstrated diurnal variation consistent with normal circadian rhythms. Morning cortisol peak was decreased or delayed in samples from physicians after a night shift. Conclusions: These data indicate that short-term memory appears to decline after day and overnight shifts and confirms the high incidence of disturbed sleep in this population.

Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development are not yet widely studied in human populations. This review presents research on the consequences for offspring of BPA exposure during pregnancy. Extensive work in laboratory rodents has evaluated survival and growth of the conceptus, interference with embryonic programs of development, morphological sex differentiation, sex differentiation of the brain and behavior, immune responsiveness, and mechanism of action. Sensitive measures include RAR, aryl hydrocarbon receptor, and Hox A10 gene expression, anogenital distance, sex differentiation of affective and exploratory behavior, and immune hyperresponsiveness. Many BPA effects are reported at low doses (10-50 µg/kg d range) by the oral route of administration. At high doses (>500,000 µg/kg d) fetal viability is compromised. Much of the work has centered around the implications of the estrogenic actions of this agent. Some work related to thyroid mechanism of action has also been explored. BPA research has actively integrated current knowledge of developmental biology, concepts of endocrine disruption, and toxicological research to provide a basis for human health risk assessment.

Kell (ECE-3), a highly polymorphic blood group glycoprotein, displays more than 30 antigens that produce allo-antibodies and, on red blood cells (RBCs), is complexed through a single disulfide bond with the integral membrane protein, XK. XK is a putative membrane transporter whose absence results in a late onset form of neuromuscular abnormalities known as the McLeod syndrome. Although Kell glycoprotein is known to be an endothelin-3-converting enzyme, the full extent of its physiological function is unknown. To study the functions of Kell glycoprotein, we undertook targeted disruption of the murine Kel gene by homologous recombination. RBCs from Kel(–/–) mice lacked Kell glycoprotein, Kell/XK complex, and endothelin-3-converting enzyme activity and had reduced levels of XK. XK mRNA levels in spleen, brain, and testis were unchanged. In Kel(–/–) mice RBC Gardos channel activity was increased and the normal enhancement by endothelin-3 was blunted. Analysis of the microvessels of tumors produced from LL2 cells indicated that the central portion of tumors from wild-type mice were populated with many mature blood vessels, but that vessels in tumors from Kel(–/–) mice were fewer and smaller. The absence of Kell glycoprotein mildly affected some motor activities identified by foot splay on the drop tests. The targeted disruption of Kel in mouse enabled us to identify phenotypes that would not be easily detected in humans lacking Kell glycoprotein. In this regard, the Kell knockout mouse provides a good animal model for the study of normal and/or pathophysiological functions of Kell glycoprotein. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.

Proteins of the Homer1 immediate early gene family have been associated with synaptogenesis and synaptic plasticity suggesting broad behavioral consequences of loss of function. This study examined the behavior of male Homer1 knockout (KO) mice compared with wild-type (WT) and heterozygous mice using a battery of 10 behavioral tests probing sensory, motor, social, emotional and learning/memory functions. KO mice showed mild somatic growth retardation, poor motor coordination, enhanced sensory reactivity and learning deficits. Heterozygous mice showed increased aggression in social interactions with conspecifics. The distribution of mGluR5 and N-methyl-D-aspartate receptors (NMDA) receptors appeared to be unaltered in the hippocampus (HIP) of Homer1 KO mice. The results indicate an extensive range of disrupted behaviors that should contribute to the understanding of the Homer1 gene in brain development and behavior.

Restraint has been used as a procedure to study the effects of stress on gestation outcome in rodents. The effects of restraint could potentially be used as a model for the impact of general stress produced by high doses of toxicants and other interventions. In mice, restraint in the peri-implantation period leads to implantation failure, and restraint at appropriate times in organogenesis produces cleft palate, supernumerary ribs, and resorption. In rats, there is some evidence for an association with restraint for implantation failure, but not for the morphological anomalies. Restraint in late gestation alters adult sexual behavior of male rat offspring, but consequences for their fertility are not known. Intrauterine growth retardation is not commonly associated with gestational restraint. In the few studies where they have been directly compared, different restraint procedures produced graded, qualitatively different, or no effects. Adrenocortical hormones have been implicated as mediating the effect of restraint on cleft palate, but not on supernumerary ribs, implantation failure, or sexual differentiation. Given the variety of restraint procedures and the varying species-dependent consequences, it is not possible to infer a generalizable pattern of developmental effects due to gestational stress from the restraint literature. As an alternative approach, contemporary methods in gene expression and developmental biology could profitably be applied to understanding different patterns of stress-mediated effects of toxicant exposures on intrauterine development.

Objectives: Despite the existence of various clinical prediction rules, no data exist defining what frequency of death or serious nonfatal outcomes comprises a realistic “low-risk” group for clinicians. This exploratory study sought to identify emergency physicians’ (EPs) definition of low-risk acute decompensated heart failure (ADHF) emergency department (ED) patients. Methods: Surveys were mailed to full-time physicians (n = 88) in a multihospital EP group in southwestern Pennsylvania between December 2004 and February 2005. Participation was voluntary, and each EP was asked to define low risk (low risk of all-cause 30-day death and low risk of either hospital death or other serious medical complications) and choose a risk threshold at which they might consider outpatient management for those with ADHF. A range of choices was offered (

In order to describe the timing and extent of accelerated pubertal weight gain in female rhesus, we examined a large colony data base consisting of over 10,000 weight records for animals between 1.5 and 3.0 years of age (menarche occurs at about 2.6 years). Average colony weights were determined by week of age from information on age at weighing. Cross-sectional analyses with linear regression demonstrated an acceleration in weight increase from 196 to 231 weeks (28-33 months) when colony weights increased 381 g/12 weeks as opposed to an average of 193 and 203 g, respectively, during the preceding and succeeding age intervals of the same length. Longitudinal analyses (n = 428) indicated that maximum individual growth velocity averaged 499 +/- 18 g/12 weeks and occurred at 119 +/- 5.6 weeks (29.7 +/- 0.2 months) of age. Nonlinear modeling with the Gompertz function indicated that decelerating growth rates seen at earlier ages were not characteristic of the period of accelerated pubertal growth.

We investigated whether opiate analgesics as commonly administered to women during labor would affect later response to maternal separation in infant guinea pigs. Meperidine hydrochloride (10–15 mg/kg i.m.) was administered to late-pregnant guinea pigs 5 min prior to labor induction with oxytocin. On Day 11 or 12 postnatal, pup distress vocalizations, locomotor activity, and plasma cortisol were measured under one of two conditions: alone (alone in a novel environment for 30 min) or mother (with the dam in the novel environment). Female pups exposed to intrapartum meperidine emitted fewer vocalizations than controls in the alone condition. Plasma cortisol was higher in meperidine females in the alone condition than in controls at the end of the separation period, but the difference was not significant. There was no drug effect on vocalizations or cortisol in males. Neither test condition nor drug affected activity level. The data suggest that intrapartum opiates may alter separation-induced distress in female guinea pig infants. © 1995 John Wiley & Sons, Inc.