Genetic patterns and changes in availability of suitable habitat support a colonisation history of a North American perennial plant.

Climatic fluctuations during the Pleistocene influenced the geographical distribution of plant species across the southern region of California. Following an integrative approach, we combined genetic data analysis with Environmental Niche Models (ENMs) to assess the historical range expansion of Yucca schidigera, a long-lived desert perennial native of the Baja California Peninsula. We genotyped 240 individuals with seven nuclear microsatellite to investigate genetic diversity distribution across 13 populations. Indeed, we used Environmental Niche Models to examine the changes on the distribution of suitable climatic conditions for this species during the LIG (~120 ka), LGM (~22 ka) and Mid Holocene (~6 ka). We detected high genetic diversity across Y. schidigera populations (AR = 9.94 ± 0.38 SE; Hexp = 0.791 ± 0.011 SE) with genetic variation decreasing significantly with latitude (allelic richness: R 2 = 0.38, P = 0.023; expected heterocigosity: R2 = 0.32, P = 0.042). We observed low, but significant genetic differentiation (FST = 0.0678; P < 0.001) which was consistent with the parapatric distribution of the three genetic groupings detected by the Bayesian clustering algorithm. The ENMs suggest that suitable habitat for this species increased since the LGM. Our results support a range expansion of Y. schidigera across northwestern Baja California during the late Quaternary. Genetic data suggest that colonization of the current distribution followed a southward directionality as suitable climatic conditions became widely available in this region. High genetic variation across our sample suggests large historic effective population sizes for this section of the geographical range.

Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

BACKGROUND: The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. METHOD: In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. RESULT: Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. CONCLUSION: These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment.

Results from a Ukrainian-US collaborative study: prevalence and predictors of respiratory symptoms among Ukrainian coal miners.

BACKGROUND: Underground coal mining is an expanding industry in Ukraine, yet little is known about the burden of respiratory disease among Ukrainian miners. METHODS: A Fogarty International Center-supported collaboration between researchers at the University of Illinois and the Institute of Occupational Health in Kyiv, Ukraine formed to improve capacity for conducting and monitoring medical surveillance among Ukrainian coal miners. A cross-sectional survey among a random sample of working and former miners was conducted; demographic, work, and health information were collected using a standardized questionnaire. Weighted prevalence rates were calculated and predictors of respiratory symptoms explored. RESULTS: Improvements in infrastructure, including spirometry and chest radiography testing, transformed medical surveillance among these miners. Results from the health study included that the prevalence of respiratory symptoms was higher among former compared to current miners (shortness of breath 35.6% vs. 5.1%; chronic bronchitis 18.1% vs. 13.9%, respectively). A statistically significant exposure-response relationship was observed between years mining and respiratory symptoms in former miners and between years mining at the coal face and respiratory symptoms among current miners. Evidence of downward bias from the healthy worker survivor effect was observed. CONCLUSIONS: This successful international collaboration built a sustainable infrastructure for conducting workplace medical surveillance and research. The resulting study was the first in the western literature to report on respiratory symptoms in this population; likely underestimation of disease rates due to selection and measurement biases was demonstrated. Efforts should continue to build this collaboration and to characterize and reduce respiratory illness among Ukrainian coal miners.

Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma.

BACKGROUND AND PURPOSE: IL-13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. Here we describe the preclinical in vitro and in vivo characterization of CAT-354, an IL-13-neutralizing IgG4 monoclonal antibody (mAb), currently in clinical development. EXPERIMENTAL APPROACH: In vitro the potency, specificity and species selectivity of CAT-354 was assayed in TF-1 cells, human umbilical vein endothelial cells and HDLM-2 cells. The ability of CAT-354 to modulate disease-relevant mechanisms was tested in human cells measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin generation by normal lung fibroblasts, CD23 upregulation in peripheral blood mononuclear cells and IgE production by B cells. In vivo CAT-354 was tested on human IL-13-induced air pouch inflammation in mice, ovalbumin-sensitization and challenge in IL-13 humanized mice and antigen challenge in cynomolgus monkeys. KEY RESULTS: CAT-354 has a 165 pM affinity for human IL-13 and functionally neutralized human, human variant associated with asthma and atopy (R130Q) and cynomolgus monkey, but not mouse, IL-13. CAT-354 did not neutralize human IL-4. In vitro CAT-354 functionally inhibited IL-13-induced eotaxin production, an analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE production. In vivo in humanized mouse and cynomolgus monkey antigen challenge models CAT-354 inhibited airways hyperresponsiveness and bronchoalveolar lavage eosinophilia. CONCLUSIONS AND IMPLICATIONS: CAT-354 is a potent and selective IL-13-neutralizing IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate to severe uncontrolled asthma.

Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation.

The significance of detection of herpes viruses in respiratory secretions of critically ill patients is controversial. The study aim was to determine the prevalence of herpes virus DNA in respiratory secretions in patients on artificial ventilation. Respiratory secretions taken thrice weekly from 174 patients in a tertiary center intensive therapy unit (ITU) were tested for herpes simplex virus (HSV) by nested PCR. Samples from 61 patients in ITU for 4 days or more were also tested for Epstein Barr Virus (EBV) and cytomegalovirus (CMV) using real-time PCR. HSV positivity increased with ITU stay with 18.6% admission samples positive, 32.5% day 2-5 samples, and 65.9% day 6-39 samples. Being HSV positive on admission did not influence mortality (9/27, 33.3% vs. 38/118, 32.2%) however, subsequently, mortality of those negative but becoming positive was higher than in those remaining negative (10/35, 29% vs. 5/24 21%). At least one sample was EBV positive in 61% and CMV positive in 19% of patients tested. Of 63 patients tested for all three viruses, 4 were positive for three viruses, 23 patients for two viruses, 24 for one virus and 12 were negative for all the above viruses. Detection of HSV, EBV and CMV is common in ITU patients. Becoming HSV positive while in ITU may increase mortality.

Impact of currently used or potentially useful insecticides for canola agroecosystems on Bombus impatiens (Hymenoptera: Apidae), Megachile rotundata (Hymentoptera: Megachilidae), and Osmia lignaria (Hymenoptera: Megachilidae).

Pest management practices may be contributing to a decline in wild bee populations in or near canola (Brassica napus L.) agroecosystems. The objective of this study was to investigate the direct contact toxicity of five technical grade insecticides--imidacloprid, clothianidin, deltamethrin, spinosad, and novaluron--currently used, or with potential for use in canola integrated pest management on bees that may forage in canola: common eastern bumble bees [Bombus impatiens (Cresson); hereafter bumble bees], alfalfa leafcutting bees [Megachile rotundata (F.)], and Osmia lignaria Cresson. Clothianidin and to a lesser extent imidacloprid were highly toxic to all three species, deltamethrin and spinosad were intermediate in toxicity, and novaluron was nontoxic. Bumble bees were generally more tolerant to the direct contact applications > O. lignaria > leafcutting bees. However, differences in relative toxicities between the three species were not consistent, e.g., whereas clothianidin was only 4.9 and 1.3x more toxic, deltamethrin was 53 and 68x more toxic to leafcutting bees than to bumble bees and O. lignaria, respectively. Laboratory assessment of direct contact toxicity, although useful, is only one measure of potential impact, and mortality under field conditions may differ greatly depending on management practices. Research conducted using only honey bees as the indicator species may not adequately reflect the risk posed by insecticides to wild bees because of their unique biology and differential susceptibility. Research programs focused on determining nontarget impact on pollinators should be expanded to include not only the honey bee but also wild bee species representative of the agricultural system under investigation.

Progression of atherosclerosis in the Apo E-/- model: 12-month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet.

This study was performed to gain information about the influence of two cardiovascular risk factors, cigarette mainstream smoke (MS) and high-cholesterol/fat diet, on the progression of atherosclerosis in apolipoprotein E-deficient (Apo E-/-) mice. Eight to 12-week-old mice were whole-body exposed for up to 12 months (6h/day, 5 days/week) to diluted cigarette mainstream smoke at total particulate matter (TPM) concentrations of 100 or 200mg/m(3), or to filtered fresh air (sham) in combination with a normal chow diet or a high-cholesterol/fat diet. Cholesterol in the aortic arch was elevated in the high-cholesterol/fat diet groups exposed to 200 mg TPM/m(3) compared to sham at all time points. In the brachiocephalic artery (BA), absolute plaque size and fraction area of plaques was elevated over the 12-month time course in mice exposed to 200 mg TPM/m(3) compared to sham (both diets). Exposure to 100 and 200 mg TPM/m(3) altered the number of elastin-rich layers in the BA in mice fed a high-cholesterol/fat diet, indicating changes in plaque morphology at 6 and 9 months. This study shows for the first time the influence of two different risk factors, MS and high-cholesterol/fat diet, both alone and in combination over a period of 12 months, on the progression of atherosclerosis in Apo E-/- mice. Data suggest that long-term exposure to cigarette mainstream smoke accelerates the development of atherosclerosis in Apo E-/- mice, particularly in combination with a high-cholesterol/fat diet.

Eye injury in migrant farm workers and suggested hazard controls.

The eyes are a common site of injury in agricultural operations. Identification of the cause of injury is important to inform preventive interventions. The objective of this study was to describe the hazards and mechanisms of acute traumatic injury to the eyes of agricultural workers who are hired in farming operations on a seasonal basis. A review of the literature was performed to summarize the mechanisms of eye injuries in agriculture. Field observations and informal interviews were performed to verify the literature and to determine whether there are eye hazards for farm workers that have not been reported in the literature. Additional mechanisms of injury were elicited, and suggested methods of injury prevention are presented here.

Aspergillus surveillance project at a large tertiary-care hospital.

A one-year surveillance project was conducted at a large tertiary hospital, which had extensive indoor renovation and extensive demolition/building at several nearby sites. This study collected viable fungi samples in the hospital every six days and analysed 74 duct dust samples for Aspergillus fumigatus mycelial asp f1 protein. Mean total fungi were 257.8 cfu/m3 outdoors, 53.2 cfu/m3 in all indoor samples and 83.5 cfu/m3 in the bone marrow transplant patient rooms. Mean total aspergillus was 6.8 cfu/m3 outdoors, 12.1 cfu/m3 in all indoor samples and 7.3 cfu/m3 in the bone marrow transplant patient rooms. The five most prevalent Aspergillus species collected inside the hospital (mean cfu/m3) were Aspergillus niger 7.57 cfu/m3, Aspergillus candidus 1.72 cfu/m3, Aspergillus flavus 0.97 cfu/m3, A. fumigatus 0.88 cfu/m3 and Aspergillus glaucus 0.45 cfu/m3. In rooms undergoing duct cleaning, mean A. fumigatus concentrations were 11.0 cfu/m3. Forty-eight of 74 (65%) duct dust samples had measurable levels of asp f1 protein, with a mean level of 0.41 ppm and maximum level of 1.94 ppm. Three major incidents involved increased hospital aspergillus concentrations. A. niger levels reached 680 cfu/m3 in an organ transplant room after a water leak from a ceiling pipe. Total aspergillus concentrations rose to 77 cfu/m3 in a bone marrow transplant patient room after improper sealing and water infiltration of the unit's dedicated high-efficiency particulate air filter system. Total aspergillus levels of 160 cfu/m3 were recorded in a renovation area during wood cutting. The higher concentrations of aspergillus seen inside the hospital compared with outdoors and the various moisture/HEPA filter/renovation incidents suggest that numerous small to moderate sources of aspergillus exist in the hospital.

Fatal falls in the US construction industry, 1990 to 1999.

The Occupational Safety and Health Administration's (OSHA's) Integrated Management Information System (IMIS) database allows for the detailed analysis of risk factors surrounding fatal occupational events. This study used IMIS data to (1) perform a risk factor analysis of fatal construction falls, and (2) assess the impact of the February 1995 29 CFR Part 1926 Subpart M OSHA fall protection regulations for construction by calculating trends in fatal fall rates. In addition, IMIS data on fatal construction falls were compared with data from other occupational fatality surveillance systems. For falls in construction, the study identified several demographic factors that may indicate increased risk. A statistically significant downward trend in fatal falls was evident in all construction and within several construction categories during the decade. Although the study failed to show a statistically significant intervention effect from the new OSHA regulations, it may have lacked the power to do so.

Characterization of publication rotogravure press emission rates and compositions.

Emission compositions and rates were determined during production for a publication rotogravure press room at a large rotogravure printing company. The press room housed a single 4-color, 8-print-stand press, with an 84" paper web. Average press speed was 1800 feet per minute. Data were collected over a 2-day period and included measurements of ventilation, room area concentrations, duct exhaust compositions, amount and composition of inks used, and worker exposures. These data were used with mass balance models that were appropriate for the workspace. Toluene comprised more than 90 percent of the inks and solvents and accounted for more than 90 percent of the press emissions. Average toluene emissions during press operation and press off conditions were 222 kg/hr and 8-38 kg/hr, respectively. The uncontrolled toluene emission on the basis of printed paper throughput was 3 g/m2. Of the total toluene released, 90 percent was captured by the local exhaust ventilation. The measured control efficiency was much lower than the average efficiency of 97 percent for the month of the test reported by the plant. A mass balance model evaluation demonstrated that only the lower efficiency was consistent with measured room concentrations. Using the measured emission rates and actual monthly press on and press off conditions, the difference in efficiency for the plant (10 rotogravure presses) extrapolates to the additional release to the workspace and ambient environment of over 700 tons/yr of toluene.

Indoor air quality in a middle school, Part I: Use of CO2 as a tracer for effective ventilation.

The overall objective of the study was to evaluate the indoor air quality at a middle school with an emphasis on characterizing baseline conditions. The focus of this article is on the relationship between occupancy and measured concentrations of carbon dioxide, and an evaluation of the use of carbon dioxide as a tracer for ventilation in the school. The school was characterized as having no health complaints, good maintenance schedules, no carpeting within the classrooms or hallways, and no significant remodeling, and its officials had agreed to allow the sampling to take place during school hours. Monitoring followed the guidelines recommended in the "Preliminary Draft: Conceptual Standardized EPA Protocol For Characterizing Indoor Air Quality in School Buildings." Four indoor locations including the cafeteria, a science classroom, an art classroom, and the lobby outside the main office, and one outdoor location were sampled for various environmental comfort and pollutant parameters for one week in February 1997. A consistent relationship between hourly occupancy and corresponding carbon dioxide concentrations was seen. Carbon dioxide concentrations in the cafeteria, art room, and lobby were within specified American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) guidelines for comfort (< 1000 ppm). The science room had the highest concentrations (frequently exceeding 1000 ppm) due to high occupancy and non-functioning unit ventilators. Measured ventilation rates were within specified ASHRAE guidelines for the art room, cafeteria, and lobby. The science room, which relied on natural ventilation only, was not able to meet the ASHRAE guideline on one of the three days studied. The use of a completely mixed space, one compartment mass balance model with estimated CO2 generation rates and measured CO2 concentrations is shown to be a useful method for evaluating ventilation. Modeled effective ventilation, air changes per hour, and mixing factors reflected measured carbon dioxide concentrations and measured ventilation in each room. Mechanical ventilation afforded better mixing than natural ventilation. This study demonstrates the usefulness of collecting indoor CO2 and occupancy data when carrying out indoor air quality evaluations in schools.

Indoor air quality in a middle school, Part II: Development of emission factors for particulate matter and bioaerosols.

A middle school (grades 6 to 8) in a residential section of Springfield, Illinois, with no known air quality problems, was selected for a baseline indoor air quality survey. The study was designed to measure and evaluate air quality at the middle school with the objective of providing a benchmark for comparisons with measurements in schools with potential air quality problems. The focus of this article is on the development of emission factors for particulate matter and bioaerosols. The school was characterized as having no health complaints and good maintenance schedules. Four indoor locations including the cafeteria, a science classroom, an art classroom, the lobby outside the main office, and one outdoor location were sampled for various environmental comfort and pollutant parameters for one week in February 1997. Integrated samples (eight-hour sampling time) for respirable and total particulate matter, and short-term measurements (two-minute samples, three times per day) for bioaerosols were collected on three consecutive days at each of the sampling sites. Continuous measurements of carbon dioxide were logged at all locations for five days. Continuous measurements of respirable particulate matter were also collected in the lobby area. A linear relationship between occupancy and corresponding carbon dioxide and particle concentrations was seen. A completely mixed space, one compartment mass balance model with estimated CO2 generation rates and actual CO2 and particulate matter concentrations was used to model ventilation and pollutant emission rates. Emission factors for occupancy were represented by the slope of emission rate versus occupancy scatter plots. The following particle and bioaerosol emission factors were derived from the indoor measurements: total particles: 1.28 mg/hr/person-hr; respirable particles: 0.154 g/hr/person-hr; total fungi: 167 CFU/hr/person-min; thermophilic fungi: 35.8 CFU/hr/person-min; mesophilic fungi: 119 CFU/hr/person-min; total bacteria: 227 CFU/hr/person-min; gram-negative bacteria: 69.5 CFU/hr/person-min; gram-positive bacteria: 191 CFU/hr/person-min; Aspergillus: 17.0 CFU/hr/person-min; Penicillium: 161 CFU/hr/person-min; and yeasts: 16.4 CFU/hr/person-min.

An analytical, numerical, and experimental comparison of the fluid velocity in the vicinity of an open tank with one and two lateral exhaust slot hoods and a uniform crossdraft.

The objective of this research was to compare mathematical models of the fluid velocity in the vicinity of an open tank with lateral slot exhaust. Two approaches were explored: a numerical solution assuming turbulent flow and an analytical solution assuming potential flow. A numerical simulation of the flow field in and around an open surface tank was performed using the commercial software FLUENT. An analytical solution was obtained using two-dimensional potential fluid flow determined using the Schwarz-Christoffel transformation and complex potential theory. The numerical and analytical solutions were compared with numerical solutions and experimental measurements published by others. The numerical solution using FLUENT and the two numerical solutions published by others appear to reflect experimental conditions with equal accuracy. In some regions, the FLUENT solution appears better while in other regions the other two solutions appear better. Differences in geometry and boundary conditions could explain these differences. Greater differences were observed between the FLUENT and CFX-F3D solutions than between the EOL-2D and CFX-F3D solutions. This was unexpected since the geometry, boundary conditions, and turbulence model were more similar in the former case than in the latter. The potential flow solution, while simpler and less computationally intensive than the numerical solutions, resulted in estimates of experimental velocity that were equally as good as those of the numerical solutions. The simplicity and conservative estimates of this model make it useful for estimating exhaust hood flow fields.

Vocational outcome following spinal cord injury.

STUDY DESIGN: Non-experimental (ex post facto) survey research design involving the use of a fixed alternative format questionnaire. OBJECTIVES: To investigate variables influencing vocational outcome, to identify barriers to gaining and sustaining employment and to identify the effects of variables on the type of work engaged in following spinal cord injury. The two sets of independent variables considered were, individual and injury-related factors (age at onset of injury, time since injury, extent/level of injury, highest educational qualification achieved pre-injury, and pre-injury occupation) and circumstantial factors (means of transport, access difficulties, perceived workplace discrimination, financial disincentives to work and perceived level of skill). SETTING: The Princess Alexandra Hospital Spinal Injuries Unit, Queensland, Australia. METHODS: Data on the variables and the vocational outcomes of having ever worked or studied post-injury, current employment status and post-injury occupation were obtained from survey responses. Demographical and medical data were gathered from medical records. RESULTS: Forward stepwise logistic regression revealed that having ever worked or studied post-injury was associated with all individual and injury-related factors except pre-injury occupation, and two circumstantial factors, namely means of transport and access difficulties. Current employment was associated with all circumstantial factors as well as age at injury and pre-injury occupation. Standard multiple regression analyses revealed that post-injury occupation was correlated with all individual and injury-related factors as well as means of transport and perceived workplace discrimination. CONCLUSIONS: Tailored rehabilitation programs for individuals with characteristics associated with less successful vocational outcomes may facilitate their employment status after injury.

CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.

Induction of apoptosis by death receptors such as Fas or tumour necrosis factor (TNF) R1 leads to distinct changes in cell morphology, activation of the caspase protease cascade, and the degradation of nuclear chromatin by activated nucleases. Here, we describe the purification and cDNA cloning of a novel 40 kDa endonuclease from Jurkat cells that is activated by caspases. This protein, designated caspase-activated nuclease (CPAN), is sufficient to degrade naked DNA and to induce apoptotic morphology and DNA fragmentation in naive nuclei. CPAN is highly homologous to a recently described mouse nuclease, CAD [1], and may represent the human homologue. Our data on the human cDNA as well as additional data on the mouse homologue suggest that a 30 amino-acid portion of the recently published mouse sequence [1] is incorrect. We show that the activity of human CPAN is regulated by DFF45 [2], an inhibitor necessary for CPAN expression and stabilization in an inactive state in living cells. Proteolytic cleavage of DFF45 by caspases in vitro leads to dissociation of DFF45 fragments from CPAN and activation of CPAN as an endonuclease. CPAN is a tightly regulated endonuclease with unique characteristics that might represent a distinctive family of endonucleases.

Lead exposure in ironworkers.

In adults, lead toxicity is most commonly caused by occupation in a lead industry. Whereas lead toxicity has been described in workers who are involved in bridge rehabilitation, as of this date there has been no systematic evaluation published regarding the conditions responsible for lead toxicity in ironworkers. This is a report of a study designed to identify risk factors for elevated blood-lead levels in ironworkers. One hundred fifty members of a 2,400-member local ironworkers union volunteered to have their blood drawn for lead and zinc protoporphyrin analysis and to complete a questionnaire regarding demographics, health, and occupation. The relationships between these variables and blood-lead level were analyzed using student's t-test, chi-square, and logistic regression. Current work on a lead job, rivet busting as the predominant job task, and cigarette smoking were all found to be significantly associated with elevated blood-lead level. Whereas cigarette smoking and current work with lead have been previously identified as risk factors for toxicity, interventions to prevent lead toxicity in ironworkers should also focus on work practices during rivet busting.