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The spread of ecosystem modifying invasive plant (EMIP) species is one of the largest threats to native ecosystems in Hawaiʻi. However, differences in niche characteristics between Hawaiʻi's isolated insular environment and the wider global distribution of these species have not been carefully examined. We used species distribution modeling (SDM) methods to assess similarities and differences in niche characteristics between global and regional scales for 17 EMIPs present in Hawaiʻi. With a clearer understanding of the global context of regional plant invasion, we combined two SDM methods to better understand the potential future regional spread: (1) a nested modeling approach to integrate global and regional invasive species distribution projections; and (2) integrating all available agency and citizen science data to minimize the effect of monitoring gaps and biases. Our results show there are multiple similarities in niche characteristics across regional and global scales for most species, such as similar sets of climatic determinants of distribution, similar responses along environmental gradients, and moderate to high niche overlap between global and regional models. However, some differences were apparent and likely due to several factors including incomplete regional spread, community assembly or diversity effects. Invaders that established earlier showed a higher degree of niche overlap and similar environmental gradient responses when comparing global and regional models. This pattern, coupled with the tendency for regionally-based projections to predict narrower distributions than global projections, indicates a potential for continued spread of several invasive species across the Hawaiian landscape. Our study has broader implications for understanding the distribution and spread of invasive species in other regions, as similar analyses and models, including a novel way to characterize environmental gradient response differences across regions or scales, can likely provide valuable information for conservation and management efforts. [ABSTRACT FROM AUTHOR]

Although women can experience sexism from other women (ingroup discrimination) and men (outgroup discrimination), those who claim to experience ingroup discrimination may suffer greater social costs than those who claim outgroup sexism. In three experiments (Study 1: N = 167; Study 2: N = 119; Study 3: N = 181), participants were randomly assigned to evaluate a woman's claim of sexism that was perpetrated by a woman manager (ingroup discrimination) or man manager (outgroup discrimination). Women who claimed ingroup (vs. outgroup) discrimination (1) had their claims delegitimized more, (2) were perceived as greater complainers, but (3) were not perceived as less likeable (Studies 1–3). Claim of delegitimization (Studies 1–3) and violation of prototypes of discrimination (Study 3) mediated the effects of ingroup versus outgroup discrimination on perceptions of the employee as a complainer. These findings indicate that ingroup discrimination can be a pernicious barrier to women's advancement in the workplace as these claims are viewed less seriously than more prototypical forms of outgroup discrimination. [ABSTRACT FROM AUTHOR]

The associated uncertainties of future climate projections are one of the biggest obstacles to overcome in studies exploring the potential regional impacts of future climate shifts. In remote and climatically complex regions, the limited number of available downscaled projections may not provide an accurate representation of the underlying uncertainty in future climate or the possible range of potential scenarios. Consequently, global downscaled projections are now some of the most widely used climate datasets in the world. However, they are rarely examined for representativeness of local climate or the plausibility of their projected changes. Here we explore the utility of two such global datasets (CHELSA and WorldClim2) in providing plausible future climate scenarios for regional climate change impact studies. Our analysis was based on three steps: (1) standardizing a baseline period to compare available global downscaled projections with regional observation-based datasets and regional downscaled datasets; (2) bias correcting projections using a single observation-based baseline; and (3) having controlled differences in baselines between datasets, exploring the patterns and magnitude of projected climate shifts from these datasets to determine their plausibility as future climate scenarios, using Hawaiʻi as an example region. Focusing on mean annual temperature and precipitation, we show projected climate shifts from these commonly used global datasets not only may vary significantly from one another but may also fall well outside the range of future scenarios derived from regional downscaling efforts. As species distribution models are commonly created from these datasets, we further illustrate how a substantial portion of variability in future species distribution shifts can arise from the choice of global dataset used. Hence, projected shifts between baseline and future scenarios from these global downscaled projections warrant careful evaluation before use in climate impact studies, something rarely done in the existing literature. [ABSTRACT FROM AUTHOR]

In 2013, the U.S. Preventative Services Task Force recommended low-dose computed tomography (LDCT) for lung cancer screening (LCS) after a national trial demonstrated a 20% reduction in lung cancer mortality with LDCT. Implementation of LCS employing LDCT depends heavily on physician education regarding multiple factors, including eligibility criteria, potential benefits and harms, and shared decision-making. To date, there are no studies of educational approaches for teaching physicians about LCS. This study aims to assess the feasibility and effectiveness of implementing an interactive, group-based learning (GBL) curriculum to teach physicians about LCS. A prospective study was conducted at two nearby institutions from 2017 to 2019 comparing GBL with a lecture format as measured by total knowledge about LCS, acceptability of the educational format, and ease of implementation. We surveyed participants regarding total knowledge and format acceptance. Results were compared to determine whether GBL is an effective and feasible educational strategy for LDCT and LCS education. Residents and faculty participating in GBL demonstrated greater total knowledge compared with residents and faculty participating in the lecture format. Participants in both cohorts preferred a mix of GBL and lecture formats. All participants believed that GBL facilitates implementation of LCS better than lecture-based learning. GBL is an effective and feasible approach for educating physicians about LCS, though it is more time- and resource-intensive than a lecture approach. However, healthcare providers believe GBL will facilitate implementation of LCS more than lectures. [ABSTRACT FROM AUTHOR]

Diploid hybrid potato variety development requires the introduction of reliably transmitted self-compatibility (SC) to largely self-incompatible elite diploid germplasm. The diploid Solanum chacoense clone M6 has been widely used to introgress SC into North American potato diploid breeding programs. We determined that M6 is homozygous for six DNA Kompetitive Allele Specific PCR (KASP)™ markers spanning a 224 kb region, linked to Sli in Dutch germplasm. Self-compatible Sli alleles were identified in dihaploids of the cultivars 'Atlantic' and 'Superior' and breeding clone NY148. This finding demonstrates the potential of Sli genotyping to select S. tuberosum dihaploids that will contribute to SC. We appraised the transmission of Sli in a diploid recurrent selection population and in a diploid backcross population, each designed to introgress SC while improving agronomic traits. The frequency of the homozygous self-compatible Sli genotype at the six marker loci increased over the course of four cycles of recurrent selection. The homozygous Sli self-compatible genotype at any one of five marker loci within an 80.8 kb region on chromosome 12 (58,960,090-59,040,898 bp) perfectly predicted a SC phenotype in the recurrent selection population. The heterozygous Sli genotype was found in self-compatible and self-incompatible individuals. The discrepancy between phenotype and marker genotype can be attributed in part to the difficulty of accurately phenotyping SC. We also identified self-compatible individuals with the homozygous self-incompatible Sli genotype at all tested loci. The presence of the homozygous self-incompatible Sli haplotype in self-compatible clones 1S1 and DMRH-89 and a self-compatible individual from the S. chacoense PI 133664 further suggests that other genetic components contribute to SC. This work illustrates the ability of Sli markers to predict SC in some germplasm, but it also underscores the need to identify other genomic regions critical to SC and the role of the environment in expression of genes involved in the SC reaction. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to develop a novel approach for lung cancer screening among a diverse population that integrates the Centers for Medicare and Medicaid Services (CMS) recommended components including shared decision making (SDM), low-dose CT (LDCT), reporting of results in a standardized format, smoking cessation, and arrangement of follow-up care. Methods: Between October of 2015 and March of 2018, we enrolled patients, gathered data on demographics, delivery of SDM, reporting of LDCT results using Lung-RADS, discussion of results, and smoking cessation counseling. We measured adherence to follow-up care, cancer diagnosis, cancer treatment, and smoking cessation at 2 years after initial LDCT. Results: We enrolled 505 patients who were 57% African American, 30% Caucasian, 13% Hispanic, < 1% Asian, and 61% were active smokers. All participants participated in SDM, 88.1% used a decision aid, and 96.1% proceeded with LDCT. Of 496 completing LDCT, all received a discussion about results and follow-up recommendations. Overall, 12.9% had Lung-RADS 3 or 4, and 3.2% were diagnosed with lung cancer resulting in a false-positive rate of 10.7%. All 48 patients with positive screens but no cancer diagnosis adhered to follow-up care at 1 year, but only 35.4% adhered to recommended follow-up care at 2 years. The annual follow-up for patients with negative lung cancer screening results (Lung-RADS 1 and 2) was only 23.7% after one year and 2.8% after 2 years. All active smokers received smoking cessation counseling, but only 11% quit smoking. Conclusion: The findings show that an integrated lung cancer screening program can be safely implemented in a diverse population, but adherence to annual screening is poor. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, snakebite envenoming is a neglected disease that affects around 5.4 million people worldwide each year. In Brazil, in 2019 there were 29,000 cases of accidents, with 104 deaths. The genus Bothrops was responsible for 90% of reported envenomations, mainly the species B. jararaca. The current therapy is performed with an intravenous injection of antivenom, be it monovalent or polyvalent. However, this treatment has high manufacturing costs, may induce side effects, and it does not effectively neutralize tissue necrosis. The latter issue may lead to deformity or amputation of the affected limb. Therefore, new treatments are needed to aid or improve the efficacy of antivenoms. In this study, nine triazole compounds (AM11–AM19) were chemically synthesized, characterized using infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy analyses, and tested against some in vitro (hemolysis, coagulation, and proteolysis) and in vivo (hemorrhaging, lethal, and edema) activities of B. jararaca venom. Each compound was incubated with B. jararaca venom (incubation protocol) or injected after the venom (treatment protocol), and then, biological assays were performed. As a result, all the compounds inhibited the toxic activities of B. jararaca venom with different potencies in the incubation protocol, while the compound AM13 inhibited hemorrhaging in the treatment protocol. In addition, the compounds were devoid of toxicity, as shown through admetSAR analysis or in vitro cytotoxicity test. Thus, these compounds may be an important tool for the development of antivenom molecules to improve serum therapy for recovering patients envenomed by B. jararaca venom. [ABSTRACT FROM AUTHOR]

It is unknown if gender influences outcome of lung cancer screening with Low Dose CT (LDCT), especially with frequent and continued underrepresentation of women in clinical trials. We examined a balanced cohort of men and women with the hypothesis that there would be no difference in participation or results between men and women undergoing lung cancer screening. In an urban, academic medical center, we prospectively collected data on patients referred for lung cancer screening from October 2015 to August 2018. We studied gender, age, ethnicity, level of education and smoking history. We measured results of LDCT using Lung-RADS reporting system. 546 patients underwent LDCT between October 2015 and August 2018. 279 (51%) were female and 267 (49%) were males. Age, education status or smoking patterns did not significantly differ between females and males There was a significant difference between males and females in the distribution of LDCT results (p = 0.05). 81 females and 105 males were diagnosed with Lung-RADS 1; 99 females and 92 males with Lung-RADS 2; 15 females and 8 males with Lung-RADS 3; 19 females and 11 males with Lung-RADS 4. Overall, 10 females (3.5%) and 3 males (1.1%) were diagnosed with lung cancer (risk difference 2.4, 95% CI—0.0006–0.05, p = 0.09). Women are often underrepresented in clinical trials. Preliminary results from our lung cancer screening program demonstrate equal participation and equal benefit from the screening program. Long term data is needed to study survival benefit. [ABSTRACT FROM AUTHOR]

Background: Hypoxic-ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment despite treatment with therapeutic hypothermia. Magnetic resonance H1-spectroscopy measures concentrations of cerebral metabolites to detect derangements in aerobic metabolism.Objective: We assessed MR spectroscopy in neonates with HIE within 18-24 h of initiating therapeutic hypothermia and at 5-6 days post therapeutic hypothermia.Materials and Methods: Eleven neonates with HIE underwent MR spectroscopy of the basal ganglia and white matter. We compared metabolite concentrations during therapeutic hypothermia and post-therapeutic hypothermia and between moderate and severe HIE.Results: During therapeutic hypothermia, neonates with severe HIE had decreased basal ganglia N-acetylaspartate (NAA; 0.62±0.08 vs. 0.72±0.05; P=0.02), NAA + N-acetylaspartylglutamate (NAAG; 0.66±0.11 vs. 0.77±0.06; P=0.05), glycerophosphorylcholine + phosphatidylcholine (GPC+PCh; 0.28±0.05 vs. 0.38±0.06; P=0.02) and decreased white matter GPC+PCh (0.35±0.13 vs. 0.48±0.04; P=0.02) compared to neonates with moderate HIE. For all subjects, basal ganglia NAA decreased (-0.08±0.07; P=0.01), whereas white matter GPC+PCh increased (0.03±0.04; P=0.04) from therapeutic hypothermia MRI to post-therapeutic-hypothermia MRI. All metabolite values are expressed in mmol/L.Conclusion: Decreased NAA and GPC+PCh were associated with greater HIE severity and could distinguish neonates who might benefit most from targeted additional neuroprotective therapies. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia is the standard-of-care treatment for infants diagnosed with moderate-to-severe hypoxic-ischemic encephalopathy (HIE). MRI for assessing brain injury is usually performed after hypothermia because of logistical challenges in bringing acutely sick infants receiving hypothermia from the neonatal intensive care unit (NICU) to the MRI suite. Perhaps examining and comparing early cerebral oxygen metabolism disturbances to those after rewarming will lead to a better understanding of the mechanisms of brain injury in HIE and the effects of therapeutic hypothermia.Objective: The objectives were to assess the feasibility of performing a novel T2-relaxation under spin tagging (TRUST) MRI technique to measure venous oxygen saturation very early in the time course of treatment, 18-24 h after the initiation of therapeutic hypothermia, to provide a framework to measure neonatal cerebral oxygen metabolism noninvasively, and to compare parameters between early and post-hypothermia MRIs.Materials and Methods: Early (18-24 h after initiating hypothermia) MRIs were performed during hypothermia treatment in nine infants with HIE (six with moderate and three with severe HIE). Six infants subsequently had an MRI after hypothermia. Mean values of cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen from MRIs during hypothermia were compared between infants with moderate and severe HIE; and in those with moderate HIE, we compared cerebral oxygen metabolism parameters between MRIs performed during and after hypothermia.Results: During the initial hypothermia MRI at 23.5±5.2 h after birth, infants with severe HIE had lower oxygen extraction fraction (P=0.04) and cerebral metabolic rate of oxygen (P=0.03) and a trend toward lower cerebral blood flow (P=0.33) compared to infants with moderate HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between MRIs during and after hypothermia (although not significantly); cerebral metabolic rate of oxygen (P=0.93) was not different.Conclusion: Early MRIs were technically feasible while maintaining hypothermic goal temperatures in infants with HIE. Cerebral oxygen metabolism early during hypothermia is more disturbed in severe HIE. In infants with moderate HIE, cerebral blood flow decreased and oxygen extraction fraction increased between early and post-hypothermia scans. A comparison of cerebral oxygen metabolism parameters between early and post-hypothermia MRIs might improve our understanding of the evolution of HIE and the benefits of hypothermia. This approach could guide the use of adjunctive neuroprotective strategies in affected infants. [ABSTRACT FROM AUTHOR]

Failure to address willingness and ability to undergo lung cancer treatment before lung cancer screening could cause patients unnecessary anxiety, cost and care. We employed an enhanced shared decision making (SDM) model to address willingness and ability to undergo lung cancer screening of low dose CT (LDCT) scanning. We hypothesized that enhanced SDM was feasible and did not discourage patients from undergoing lung cancer screening. We performed a prospective study of patients referred for lung cancer screening. We measured adherence to the LCS protocol, including consent to discuss lung cancer treatment if cancer is found and direct questions to patients about willingness and ability to undergo lung cancer treatment. We measured race, gender, adherence to the consent process and questions regarding willingness and ability to undergo lung cancer treatment and subsequent uptake of LDCT. All 190 patients have a documented SDM visit addressing the risks and benefits of lung cancer screening and consented to discuss lung cancer treatment if lung cancer is diagnosed. One hundred and seventy-nine (179) of 190 (94%) answered yes to being willing and able to undergo lung cancer treatment. One hundred and eighty-seven (187) patients underwent LDCT (98.4%). Discussion about willingness and ability to undergo lung cancer treatment should be an essential component of a SDM discussion prior to LDCT. This study demonstrated that an enhanced SDM experience is feasible in a clinical setting. Furthermore, patients proceeded with LDCT following the enhanced SDM process. [ABSTRACT FROM AUTHOR]

Objective:To quantify cerebrovascular autoregulation as a function of gestational age (GA) and across the phases of the cardiac cycle.Study design:The present study is a hypothesis-generating re-analysis of previously published data. Premature infants (n=179) with a GA range of 23 to 33 weeks were monitored with umbilical artery catheters and transcranial Doppler insonation of the middle cerebral artery for 1-h sessions over the first week of life. Autoregulation was quantified by three methods, as a moving correlation coefficient between: (1) systolic arterial blood pressure (ABP) and systolic cerebral blood flow (CBF) velocity (Sx); (2) mean ABP and mean CBF velocity (Mx); and (3) diastolic ABP and diastolic CBF velocity (Dx). Comparisons of individual and cohort cerebrovascular pressure autoregulation were made across GA for each aspect of the cardiac cycle.Results:Systolic, mean and diastolic ABP increased with GA (r=0.3, 0.4 and 0.4; P<0.0001). Systolic CBF velocity was pressure-passive in infants with the lowest GA, and Sx decreased with advancing GA (r=−0.3; P<0.001), indicating increased capacity for cerebral autoregulation during systole during development. By contrast, Dx was elevated, indicating dysautoregulation, in all subjects and showed minimal change with advancing GA (r=−0.06; P=0.05). Multivariate analysis confirmed that both GA (P<0.001) and 'effective cerebral perfusion pressure' (ABP minus critical closing pressure (CrCP); P<0.01) were associated with Sx.Conclusion:Premature infants have low and usually pressure-passive diastolic CBF velocity. By contrast, the regulation of systolic CBF velocity by pressure autoregulation developed in this cohort between 23 and 33 weeks GA. Elevated effective cerebral perfusion pressure derived from the CrCP was associated with dysautoregulation. [ABSTRACT FROM AUTHOR]

Ecological and societal disruptions by modern climate change are critically determined by the time frame over which climates shift beyond historical analogues. Here we present a new index of the year when the projected mean climate of a given location moves to a state continuously outside the bounds of historical variability under alternative greenhouse gas emissions scenarios. Using 1860 to 2005 as the historical period, this index has a global mean of 2069 (±18 years s.d.) for near-surface air temperature under an emissions stabilization scenario and 2047 (±14 years s.d.) under a 'business-as-usual' scenario. Unprecedented climates will occur earliest in the tropics and among low-income countries, highlighting the vulnerability of global biodiversity and the limited governmental capacity to respond to the impacts of climate change. Our findings shed light on the urgency of mitigating greenhouse gas emissions if climates potentially harmful to biodiversity and society are to be prevented. [ABSTRACT FROM AUTHOR]

Objective:To evaluate cerebral hemodynamics during dopamine treatment in hypotensive (mean arterial blood pressure (MABP)2 was performed in hypotensive ELBW infants on the first day of life, beginning with an ∼15-min baseline reading and continued during advancing dopamine infusion until MABP was optimized. Physiological variables and CBFv reactivity were compared before and after MABP was optimized.Result:Fifteen hypotensive ELBW infants (625±174 g; 24 (23 to 24.8) weeks) were studied. Mean CBFv increased from 10.9±3.7 to 15.7±5.7 cm s−1 (P=0.001) simultaneously as MABP increased from 22.3±2.8 to 35.2±9.7 mm Hg (P<0.001). Mean CBFv reactivity (95% confidence interval (CI)) was 3.9 (1.6 to 6.2) %mm Hg−1. Nine infants died and/or developed severe intraventricular hemorrhage (IVH).Conclusion:Mean CBFv increased pressure-passively as MABP was optimized by dopamine treatment in very sick hypotensive ELBW infants on the first day of life. [ABSTRACT FROM AUTHOR]

Objective:To compare the effects of open tracheal suctioning (OS) plus intermittent mandatory ventilation (IMV) vs closed tracheal suctioning (CS) plus volume guarantee ventilation (VG) on changes in mean cerebral blood-flow velocity (CBFv) of ventilated very low birth weight (VLBW) infants.Study Design:A total of 75 normotensive, ventilated VLBW infants (with normal cranial ultrasounds) had monitoring of mean CBFv, PCO2 and mean arterial blood pressure (MABP) before, during and after 220 tracheal suctioning sessions during the first week of life. Multiple linear regression analysis was used to determine the factor(s) influencing the magnitude of relative changes from baseline in mean CBFv after suctioning.Result:In all, 49 VLBW infants receiving IMV had monitoring during 124 OS sessions between July 2002 and May 2005; 26 VLBW infants receiving VG had monitoring during 96 CS sessions between January 2006 and July 2007. The average magnitude of relative changes in mean CBFv was significantly less with CS+VG, and was associated with the magnitude of relative changes in PCO2 and suctioning-ventilator group.Conclusion:The average magnitude of relative changes in mean CBFv was reduced in VLBW infants with CS+VG vs OS+IMV. [ABSTRACT FROM AUTHOR]

This cross-temporal meta-analysis examined 6,120 American college students’ scores on the Belief in a Just World Scale (BJW; Rubin and Peplau, J Soc Issues 31(3):65–90, ) across the last three and a half decades. Drawing on models of belief threat, we examined whether the causal relationship between perceived injustice and increases in BJW could extend from the laboratory to society by using macro-economic injustice trends to predict changes in BJW across these decades. Specifically, we hypothesized that perceptions of inequality, operationalized as rising income disparities, would result in a greater need to justify this inequality and that this would be evidenced by increased commitment to just world beliefs over time. Consistent with this prediction, BJW scores increased significantly over time and this increase was positively related to increasing income disparities in society. Income inequality remained a significant predictor of BJW scores even after controlling for additional factors of general income and political ideology. Implications of increasing just world beliefs are discussed in terms of psychological and policy outcomes. [ABSTRACT FROM AUTHOR]

This experiment drew upon theoretical perspectives on group and system justification to examine whether exposure to media coverage arguing that racism was responsible for the ineffective Hurricane Katrina disaster response affected White and Black Americans’ intergroup attitudes. Consistent with a system justification perspective, Whites exposed to video clips arguing that the hurricane Katrina disaster response was due to racism displayed greater racial ingroup attachment and ingroup love compared to Whites exposed to videos conveying that the government’s incompetence was to blame for the disaster response. In contrast, Blacks displayed strong levels of ingroup attachment and ingroup love across both video conditions. This research highlights how insights from social psychology are valuable in understanding psychological responses to social justice-related events, such as the tragic response to hurricane Katrina. [ABSTRACT FROM AUTHOR]

Objectives:Examining the effects of tracheal suctioning on cerebral hemodynamics of normotensive ventilated very low birth weight (VLBW) infants with normal cranial ultrasounds; determining the factor(s) influencing changes in mean cerebral blood flow velocity (CBFv) after suctioning.Methods:Seventy-three VLBW infants had continuous monitoring of mean arterial blood pressure (MABP), PaCO2, PaO2 and mean CBFv before, during, and after 202 suctioning sessions during the first week of life. Peak (or nadir) and relative changes of the four variables for 45 min after suctioning were calculated. Multiple linear regression was used to determine the factor(s) influencing changes in mean CBFv after suctioning.Result:Birth weight was 928±244 g; gestational age was 27.0±2.0 weeks. Mean CBFv increased to 31.0±26.4% after suctioning and remained elevated for 25 min. PaCO2 was highly associated with mean CBFv (P<0.001), whereas MABP and PaO2 were not.Conclusion:We observed prolonged increases of mean CBFv following suctioning in ventilated VLBW infants that were previously unrecognized. This is concerning since disturbances of CBF may be associated with subsequent brain injury.Journal of Perinatology (2008) 28, 34–41; doi:10.1038/sj.jp.7211848; published online 25 October 2007 [ABSTRACT FROM AUTHOR]

To examine the relationships and interactions between cardiovascular autonomic nervous system (cANS) function, adiposity, and vascular function in children of varying levels of adiposity. Participants were children (19 M, 17 F, age = 11.5 ± 0.1 years) who had cANS function assessed via heart rate variability (HRV) methods during resting conditions. Vascular function was assessed with brachial artery flow-mediated dilation (FMD) and nitroglycerin-induced dilation. Spectral power of HRV was calculated for high frequency normalized units (HFnu; measure of PSNS activity) and low frequency:high frequency ratio (LF:HF; overall sympathovagal balance). A blood sample was drawn for measurement of fasting insulin, glucose, lipids, and C-reactive protein (CRP). Results were reported as mean ± SEM. FMD peak dilation was positively related to HFnu ( r = 0.48, P = 0.01) and negatively related to LF:HF ( r = −0.51, P = 0.01) indicating that reduced parasympathetic activity and states of dysfunctional sympathovagal balance were associated with decreased vascular function. After adjustment for confounding factors (insulin, CRP, age) and fat mass, the relationships between these measures of cANS and vascular function remained moderately strong and significant. These data indicate a relationship between cANS and vascular function that is independent of fat mass, inflammation (CRP), and fasting insulin in children of varying levels of adiposity. These relationships and the mechanisms by which they exist require further study to allow for the identification of appropriate therapies for children with high levels of adiposity given the likelihood of them having concomitant cANS and vascular dysfunction. [ABSTRACT FROM AUTHOR]

Objective:To examine whether hypercapnia in very low birth weight (VLBW) infants during the first 3 days of life is associated with severe intraventricular hemorrhage (IVH).Study design:Retrospective cohort study of inborn VLBW infants between January 1999 and May 2004 with arterial access during the first 3 days of life. A multiple logistic regression analysis was used where IVH was dichotomized ((grades 0/1/2)=non-severe; (grades 3/4)=severe). Measures of hypercapnia were entered into the model to ascertain their association with severe IVH.Results:In total, 574 VLBW infants met entry criteria. Worst IVH grade was 0 in 400; 1: 54; 2: 42; 3: 47; and 4: 31 infants. The logistic regression model consisted of the following predictors of severe IVH: gestational age, gender, 1 min Apgar score (dichotomized into two groups: >3 vs 3), multifetal gestation, vasopressor use, and maximum PaCO2.Conclusion:In addition to traditional risk factors, it appears maximum PaCO2 is a dose-dependent predictor of severe IVH during the permissive hypercapnia era.Journal of Perinatology (2006) 26, 279–285. doi:10.1038/sj.jp.7211492; published online 23 March 2006 [ABSTRACT FROM AUTHOR]

The large mechanical luminosity of the jets of GRS 1915+105 should give rise to luminous emission regions, similar to those observed in radio galaxies, where the jets interact with the gas surrounding the source. However, no radio synchrotron emission of the expected morphology has been found. Here we present the results of a study suggesting that radio bremsstrahlung from the compressed and heated ISM in front of the jets should be detectable, while the synchrotron lobes may be too faint. We identify these jet impact sites with two well-known IRAS regions. This identification suggests a distance of GRS 1915+105 of 6.5± 1.6 kpc, significantly closer than the usually assumed distance of 11–12 kpc. We discuss the implications of this reduced distance estimate. The non-detection of the synchrotron radio lobes implies a significant fraction of non-radiating particles, possibly protons, in the jets. The apparent motion of small-scale jet components is not superluminal, so if superluminal motion is required for an object to be termed a microquasar, GRS 1915+105 actually does not qualify. The mass of the black hole in the system is increased to 21± 9 M ⊙, while the mechanical luminosity of the jets is reduced to 14% of the Eddington luminosity. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To determine patterns of survival for very low birth weight (VLBW, birth weight 501 to 1500?g) neonates over 23 years. STUDY DESIGN:: Data for 4873 VLBW neonates born from 1977 to 2000 were divided into five epochs. The primary outcome was survival to hospital discharge. Birth weight-specific survival rates were estimated by race and gender for each epoch. Presence of comorbidities and congenital anomalies, delivery mode, and provision of artificial ventilation were investigated to determine whether they could explain observed survival patterns. RESULTS:: From 1977 to 1995, survival increased from 50.2% to 81.0% as the proportion of VLBW neonates receiving artificial ventilation rose from 59.0% to 80.9%. Survival was unchanged between 1990 to 1995 and 1996 to 2000. Black females maintained a survival advantage over the entire study period. Survival improved for neonates with congenital anomalies over time, but had little impact on race/gender survival patterns. Survival patterns also could not be explained by comorbidity status, delivery mode, or access to artificial ventilation. CONCLUSION:: The survival advantage of VLBW black females persists and remains unexplained.Journal of Perinatology (2004) 24, 343-350. doi:10.1038/sj.jp.7211113 Published online 29 April 2004 [ABSTRACT FROM AUTHOR]

The Herpes simplex virus 1 (HSV) thymidine kinase (tk) suicide gene together with ganciclovir (GCV) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in recent clinical trials. With the aim of improving this therapeutic system, we compared the potential efficacy of adenoviral (Ad) vectors expressing enhanced tk mutants in vitro and in vivo. The previously created HSV-tk mutants dm30 and sr39, created by random sequence mutagenesis, were inserted into a standard Ad.RSV E1-E3- backbone using homologous recombination. GCV killing of Ad.HSV-tk, Ad.dm30-tk and Ad.sr39-tk was assessed in various tumor cell lines with a cell proliferation assay. Cells expressing the two TK mutants were two-to-five-fold more sensitive to GCV when compared with Ad.HSV-tk transduced cells in all cell lines tested (five human mesotheliomas, one human lung cancer, a human cervical carcinoma, a mouse fibrosarcoma, and a rat glioma line) at equal TK expression levels. Flank tumor models, including cell-mixing studies, assessed the in vivo efficacy of the engineered viruses in BALB/C and SCID mice. In all animal studies, Ad.dm30-tk and Ad.sr39-tk showed more tumor growth inhibition than Ad.HSV-tk when GCV was administered. The use of adenovirus-mediated gene transfer of both tk mutants dm30-tk and sr39-tk for cancer suicide gene therapy should provide a more effective and safer alternative to wild-type HSV-tk.Cancer Gene Therapy (2003) 10, 353-364. doi:10.1038/sj.cgt.7700589 [ABSTRACT FROM AUTHOR]

Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus showed high level production of the HSVtk transgene and was more efficacious than a non-replicating virus in vitro, after injection into flank tumors, and against established intraperitoneal tumors. However, addition of ganciclovir (GCV) therapy to cells or tumor-bearing animals treated with the replicating vector containing the HSVtk suicide gene did not result in increased cell killing. Our results indicate that addition of HSVtk to a replicating Ad virus will not likely be useful in augmenting antitumor effects. [ABSTRACT FROM AUTHOR]

One of the primary limitations of adenoviral (Ad)-mediated gene therapy is the generation of anti-Ad inflammatory responses that can induce clinical toxicity and impair gene transfer efficacy. The effects of immunosuppression on these inflammatory responses, transgene expression, and toxicity have not yet been systematically examined in humans undergoing Ad-based gene therapy trials. We therefore conducted a pilot study investigating the use of systemic corticosteroids to mitigate antivector immune responses. In a previous phase I clinical trial, we demonstrated that Ad-mediated intrapleural delivery of the herpes simplex virus thymidine kinase gene (HSVtk) to patients with mesothelioma resulted in significant, but relatively superficial, HSVtk gene transfer and marked antiAd humoral and cellular immune responses. When a similar group of patients was treated with Ad.HSVtk and a brief course of corticosteroids, decreased clinical inflammatory responses were seen, but there was no demonstrable inhibition of anti-Ad antibody production or Ad-induced peripheral blood mononuclear cell activation. Corticosteroid administration also had no apparent effect on the presence of intratumoral gene transfer. Although limited by the small numbers of patients studied, our data suggest that systemic administration of steroids in the context of Ad-based gene delivery may limit acute clinical toxicity, but may not inhibit cellular and humoral responses to Ad vectors. [ABSTRACT FROM AUTHOR]