Continuous-wave laser damage and conditioning of particle contaminated optics.

This paper describes the physical processes that occur when high-power continuous-wave laser light interacts with absorbing particles on a low-absorption optical surface. When a particulate-contaminated surface is illuminated by high-power continuous-wave laser light, a short burst of light is emitted from the surface, and the particles rapidly heat over a period of milliseconds to thousands of degrees Celsius, migrating over and evaporating from the surface. The surviving particles tend to coalesce into larger ones and leave a relatively flat residue on the surface. The total volume of the material on the surface has decreased dramatically. The optical surface itself heats substantially during illumination, but the surface temperature can decrease as the material is evaporated. Optical surfaces that survive this process without catastrophic damage are found to be more resistant to laser damage than surfaces that have not undergone the process. The surface temperature of the conditioned surfaces under illumination is lower than that of unconditioned surfaces. These conditioning effects on particles occurred within the first 30 s of laser exposure, with subsequent laser shots not affecting particle distributions. High-speed photography showed the actual removal and agglomeration of individual particles to occur within about 0.7 ms. Elemental changes were measured using time-of-flight secondary ion mass spectroscopy, with conditioned residuals being higher in hydrocarbon content than pristine particles. The tests in this study were conducted on high-reflectivity distributed Bragg reflector coated optics with carbon microparticles in the size range of 20-50 µm, gold particles of size 250 nm, and silica 1 µm in size.

Surgeons versus radiologists: do we care what they think?

BACKGROUNDS: Acute surgical care nowadays usually involves access to urgent imaging. There is a paucity of data on how often the images or radiologist reports of these images are used by the surgical team. We aimed to identify the rates and timeliness of radiology images and report viewing for acute surgical admissions in an Australian tertiary university teaching hospital. METHODS: We utilized a data set comprising radiological studies completed at our institute during a one-month period. Investigations were classified by modality and whether images or reports were available 'in-hours' or 'after-hours'. The time taken from imaging to reports available for viewing by the surgical team was calculated using timestamps derived from electronic hospital systems. Spearman's rho test was used to assess correlation between the Study Ascribable Time and time to view an image or report. RESULTS: Of 40 042 investigations, 1156 (3%) satisfied study criteria. Both images and reports were viewed in 82% (n = 950/1156) of cases. CT scans had the shortest median time for image (14 min, IQR 4-47 min) and report (25 min, IQR 8-68 min) viewing. CT (95%, n = 410/430) and MRI (95%, n = 38/40) scans had the highest proportion of both images and reports viewed, regardless of whether the scan was completed 'in-hours' or 'after-hours'. X-ray reports were viewed least often (73%). CONCLUSION: This study demonstrates a high level of viewing of acute surgical radiological imaging and reports by surgical teams. The 'simpler' the study the less likely the radiology report will be viewed.

Perioperative considerations for patients exposed to hallucinogens.

Hallucinogen exposure in patients in the perioperative period presents challenges for anesthesiologists and other anesthesia providers. Acute and chronic exposure to these substances can cause physiological impacts that can affect the function of anesthetic and analgesic medications used during perioperative care. The objective of this narrative review is to educate readers on the wide array of hallucinogens and psychedelics that may influence the perioperative management of patients exposed to these substances. A narrative review of the literature surrounding hallucinogens and psychedelics was completed. Hallucinogens and psychedelics are quite varied in their mechanisms of action and therefore present a variety of perioperative implications and perioperative considerations. Many of these substances increase serotonin levels or act directly at serotonergic receptors. However, there are other relevant actions that may include varied mechanisms from N-methyl-D-aspartate receptor antagonism to stimulation of muscarinic receptors. With hallucinogen exposure rates on the rise, understanding the effects of hallucinogens is important for optimizing management and reducing risks perioperatively for patients with acute or chronic exposure.

Association of autotaxin and lysophosphatidic acid receptor 3 with aggressiveness of human breast carcinoma.

In vitro and in vivo experimental studies have demonstrated the role of lysophosphatidic acid (LPA) signaling in tumor proliferation, invasiveness, and metastasis. Among LPA receptors, the overexpression of LPA receptor 3 (LPAR3) in transgenic mice has resulted in the highest rate of breast cancer metastasis. Our goal is to evaluate the LPA-producing enzyme autotaxin and LPAR3 as potential therapeutic targets in breast cancer patients. The expression of autotaxin and LPAR3 was examined by immunohistochemical analysis of 87 invasive human breast carcinomas. Carcinomas were more frequently positive for autotaxin and LPAR3 (24.4 and 43 %, respectively) compared to adjacent normal breast tissue (6.1 and 2.9 %, respectively). Increased stromal autotaxin expression was found in 16.3 % of the tumors. LPAR3 overexpression was associated with less differentiated tumors, human epidermal growth factor receptor 2 expression, and absence of progesterone receptors. The luminal type A carcinomas showed the lowest frequency of autotaxin and LPAR3 expression. Strong desmoplastic stromal reaction was more frequent among the carcinomas with autotaxin-positive tumor cells or autotaxin-positive stroma. Patients with carcinomas overexpressing LPAR3 in epithelial cells or autotaxin in stromal cells were more likely to have larger tumors, nodal involvement, and higher stage disease. Autotaxin overexpression in tumor cells also correlated with tumor size and clinical stage. Our data indicate that the increased expression of LPAR3 and autotaxin in human breast cancer is associated with tumor aggressiveness. They also suggest that LPA mediates tumor metastatic ability and peritumoral desmoplastic reaction through autocrine-paracrine mechanisms. A substantial portion of breast cancer patients might benefit from autotoxin/LPA receptor-targeted therapies.

A uniform fish consumption advisory protocol for the Ohio River.

ORSANCO and the six Ohio River main stem states have been working to align states' fish consumption advisories (FCAs) to enhance the value of advice issued to the public. To achieve this goal, ORSANCO worked closely with a panel consisting of state and USEPA representatives. The result of this effort is the Ohio River Fish Consumption Advisory Protocol (ORFCAP). The ORFCAP represents a single set of variables agreed upon by the panel that allows for a standardized protocol to create advisory thresholds to which states can defer to issue consumption advice for the Ohio River. The ORFCAP identifies ORSANCO as a clearinghouse for data which will be distributed to the panel for decision making. Other components include identifying primary contaminants of concern (PCBs and mercury) and dividing the river into four reporting units. The protocol was developed to issue FCAs for the protection of sensitive populations using five advisory groupings for PCBs and four for mercury. Specific variables used in the calculation of advisory thresholds such as health protection values, cooking reductions, average meal sizes, etc., were selected by the panel. Lastly, the protocol calls for FCA decisions to be based on analysis of the most recent 10 years of data for each species in each reporting unit to determine size class needs and advisory groupings. Upon pending implementation of the protocol by the main stem states, these decisions will be made annually through a series of discussions involving ORSANCO, the panel, and other appropriate state personnel.

Translational repression during chronic hypoxia is dependent on glucose levels.

Translation is often repressed in cell lines that are exposed to hypoxic conditions (0.5% - 1.5% O2) but this repression requires prolonged exposure (> 16 h). We report here that prolonged exposure to hypoxia results in the depletion of glucose from the media and that the loss of glucose correlates with the shut down in translation. Furthermore, we show that the addition of glucose or reoxygenation restores translation in hypoxic PC3 cells. This indicates that both glucose depletion and hypoxia are required for translational repression. We also show that eIF2alpha phosphorylation is reversed by glucose addition. Moreover, we present data that strongly indicate that eIF2alpha phosphorylation as well as the translational inhibition that occurs when cells are grown under conditions of glucose depletion and hypoxia is pancreatic eIF2alpha kinase (PERK) independent. We believe this is the first report to show that glucose depletion is required for translational repression under hypoxic conditions and that this explains why prolonged exposure to hypoxia is required for this inhibition. Since the physiological conditions that lead to tumor hypoxia would also likely lead to reduced glucose levels, understanding the interplay of glucose and hypoxia in regulating tumor metabolism will provide important information on the growth and development of solid tumors.

Sampling effort needed to estimate condition and species richness in the Ohio river, USA.

The level of sampling effort required to characterize fish assemblage condition in a river for the purposes of bioassessment may be estimated via different approaches. However, the goal with any approach is to determine the minimum level of effort necessary to reach some specific level of confidence in the assessment. In the Ohio River, condition is estimated and reported primarily at the level of pools defined by lock and dam structures. The goal of this study was to determine the minimum level of sampling effort required to adequately characterize pools in the Ohio River for the purpose of bioassessment. We followed two approaches to estimating required sampling effort using fish assemblage data from a long-term intensive survey across a number of Ohio River pools. First, we estimated the number of samples beyond which variation in the multimetric Ohio River Fish Index (ORFIn) leveled off. Then, we determined the number of samples necessary to collect approximately 90% of the fish species observed across all samples collected within the pool. For both approaches, approximately 15 samples were adequate to reduce variation in IBI scores to acceptable levels and to capture 90% of observed species in a pool. The results of this evaluation provide a basis not only for the Ohio River Valley Water Sanitation Commission (ORSANCO) but also states and other basin commissions to develop sampling designs for bioassessment that ensure adequate sampling of all assessment units.

Physical Origin of Early Failure for Contaminated Optics.

Laser-Induced optical breakdown often occurs unexpectedly at optical intensities far lower than those predicted by ultra-short pulse laser experiments, and is usually attributed to contamination. To determine the physical mechanism, optical coatings were contaminated with carbon and steel microparticles and stressed using a 17 kW continuous-wave laser. Breakdown occurred at intensity levels many orders of magnitude lower than expected in clean, pristine materials. Damage thresholds were found to strongly follow the bandgap energy of the film. A thermal model incorporating the particle absorption, interface heat transfer, and free carrier absorption was developed, and it explains the observed data, indicating that surface contamination heated by the laser thermally generates free carriers in the films. The observed bandgap dependence is in direct contrast to the behavior observed for clean samples under continuous wave and long-pulse illumination, and, unexpectedly, has similarities to ultra-short pulse breakdown for clean samples, albeit with a substantially different physical mechanism.

BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women.

OBJECTIVE: The timing and duration of menopause is important when evaluating the risk for cardiovascular disease in postmenopausal women, likely related in part to nitric oxide (NO) bioavailability. The flow-mediated dilation (FMD) test is a noninvasive assessment of NO bioavailability in humans, and tetrahydrobiopterin (BH4) is essential for NO synthesis. A high-fat meal (HFM) has been used to increase lipemia and reduce NO bioavailability. Thus, this study sought to determine if menopausal transition has any impact on the postprandial endothelial function response to a HFM, and evaluate the effect of BH4 on postprandial endothelial function in postmenopausal women and men. METHODS: Utilizing a randomized, double-blind, placebo-controlled design, sex-steroid hormones and FMD were determined in 30 older adults (10 postmenopausal women aged below 3 y [W < 3], 10 postmenopausal women aged above 10 y [W > 10], and 10 men) at baseline and 4 hours after the ingestion of a HFM alone or a HFM with BH4 (HFM + BH4; 5 mg/kg). RESULTS: Data are presented as mean ±â€ŠSEM. Independent of treatment, postprandial testosterone was significantly (P < 0.05) decreased in men (-64 ±â€Š11 ng/dL), whereas no changes were observed in W < 3 or W > 10 group. In addition, concentrations of progesterone were higher (P = 0.019) and the testosterone/estradiol ratio was lower (P = 0.026) in all groups after the ingestion of HFM + BH4 compared with the ingestion of HFM alone. Overall, an increase in FMD was observed after the ingestion of HFM + BH4 (Δ1.9% ±â€Š0.6%), whereas no change in FMD was observed after the ingestion of HFM alone (Δ-0.7% ±â€Š0.6%). CONCLUSIONS: Co-ingestion of BH4 with a HFM not only alters the sex-steroid hormone ratio, it improves postprandial FMD after a HFM regardless of postmenopause status or sex.

Bone-metastatic potential of human prostate cancer cells correlates with Akt/PKB activation by alpha platelet-derived growth factor receptor.

Prostate adenocarcinoma metastasizes to the skeleton more frequently than any other organ. An underlying cause of this phenomenon may be the ability of bone-produced factors to specifically select disseminated prostate cancer cells that are susceptible to their trophic effects. Platelet-derived growth factor (PDGF), a potent mitogen for both normal and tumor cells, is produced in several tissues including bone, where it is synthesized by both osteoblasts and osteoclasts. Here, we show that PDGF causes a significantly stronger activation of the Akt/PKB survival pathway in bone-metastatic prostate cancer cells compared to nonmetastatic cells. Normal prostate epithelial cells and DU-145 prostate cells, originally derived from a brain metastasis, are not responsive to PDGF. In contrast, epidermal growth factor stimulates Akt to the same extent in all prostate cells tested. This difference in PDGF responsiveness depends on the higher expression of alpha-PDGFR in bone-metastatic compared to nonmetastatic prostate cells and the lack of alpha-PDGFR expression in normal and metastatic prostate cells derived from tissues other than bone. Thus, alpha-PDGFR expression might identify prostate cancer cells with the highest propensity to metastasize to the skeleton.

A case study of smoke detector assembly work method intervention and evaluation.

The study aimed to evaluate a work method intervention in a smoke detector assembly line. High hand gripping forces and extreme wrist postures were found in the smoke detector assembly line at UTC Fire & Security Company in Maine. A fixture was introduced to replace the old assembly method. Electromyography (EMG) and electrogoniometry were used to measure the workers' hand gripping force and wrist motions with both the old and new assembly methods. Results show both hand gripping forces and wrist postures improved significantly with the new method.

Challenges of developing and validating immunogenicity assays to support comparability studies for biosimilar drug development.

Imminent patent expiry for a number of biological products currently on the market (many of which are blockbusters) has created an increasing opportunity for the development of biosimilars in the biotechnology industry. The key for successful biosimilar development is to demonstrate biosimilarity to the originator drug. In addition to demonstrating the similarity of physical and chemical properties between biosimilar and originator compounds, regulatory agencies require that immunogenicity be evaluated in comparative studies between biosimilar and originator drugs. Immunogenicity assays are generally non-quantitative (qualitative) and proving similarity/comparability based on qualitative assays can be very challenging. This review will discuss the challenges of developing and validating immunogenicity assays to support preclinical and clinical comparative studies for biosimilar drug development as well as the challenges in association with the interpretation of the data.

Evaluation of sorbent amendments for in situ remediation of metal-contaminated sediments.

The present study evaluated sorbent amendments for in situ remediation of sediments contaminated with two divalent metals. A literature review screening was performed to identify low-cost natural mineral-based metal sorbents and high-performance commercial sorbents that were carried forward into laboratory experiments. Aqueous phase metal sorptivity of the selected sorbents was evaluated because dissolved metals in sediment porewater constitute an important route of exposure to benthic organisms. Based on pH-edge sorption test results, natural sorbents were eliminated due to inferior performance. The potential as in situ sediment amendment was explored by comparing the sorption properties of the engineered amendments in freshwater and saltwater (10 PPT salinity estuarine water) matrices. Self-assembled monolayers on mesoporous supports with thiols (Thiol-SAMMS) and a titanosilicate mineral (ATS) demonstrated the highest sorption capacity for cadmium (Cd) and lead (Pb), respectively. Sequential extraction tests conducted after mixing engineered sorbents with contaminated sediment demonstrated transfer of metal contaminants from a weakly bound state to a more strongly bound state. Biouptake of Cd in a freshwater oligochaete was reduced by 98% after 5-d contact of sediment with 4% Thiol-SAMMS and sorbed Cd was not bioavailable. While treatment with ATS reduced the small easily extractable portion of Pb in the sediment, the change in biouptake of Pb was not significant because most of the native lead was strongly bound. The selected sorbents added to sediments at a dose of 5% were mostly nontoxic to a range of sensitive freshwater and estuarine benthic organisms. Metal sorbent amendments in conjunction with activated carbon have the potential to simultaneously reduce metal and hydrophobic contaminant bioavailability in sediments.

Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain.

The insulin-like growth factor type 1 (IGF-I) plays an important role in neuronal physiology. Reduced IGF-I levels are observed during aging and this decrease may be important to age-related changes in the brain. We studied the effects of IGF-I on total protein oxidation in brain tissues and in cell cultures. Our results indicate that in frontal cortex the level of oxidized proteins is significantly reduced in transgenic mice designed to overproduce IGF-I compared with wild-type animals. The frontal cortex of IGF-I-overproducing mice exhibited high chymotrypsin-like activity of the 20S and 26S proteasomes. The proteasome can also be activated in response to IGF-I in cell cultures. Kinetic studies revealed peak activation of the proteasome within 15 min following IGF-I stimulation. The effects of IGF-I on proteasome were not observed in R(-) cells lacking the IGF-I receptor. Experiments using specific kinase inhibitors suggested that activation of proteasome by IGF-I involves phosphatidyl inositol 3-kinase and mammalian target of rapamycin signaling. IGF-I also attenuated the increase in protein carbonyl content induced by proteasome inhibition. Thus, appropriate levels of IGF-I may be important for the elimination of oxidized proteins in the brain in a process mediated by activation of the proteasome.

Identification of mRNAs that continue to associate with polysomes during hypoxia.

Tumors must adapt to the hypoxic environment in order to grow beyond a benign microscopic mass. In addition to transcriptional activation mediated by HIF-1alpha, hypoxia has also been reported to inhibit translation. The degree of translational inhibition is dependent on the duration as well as the severity of the hypoxic insult. Anoxia (<0.02% O(2)) seems to have a more rapid and dramatic effect on translation as compared to hypoxia. We show here that prolonged hypoxia dramatically and reversibly inhibits translation in PC-3 cells. We also found that mTOR is inactivated and eIF-2alpha is phosphorylated during hypoxic treatment but only the eIF-2alpha phosphorylation correlates with the translational repression. We further used polysome analysis and microarray technology to analyze the impact of this translational repression on gene expression. We found that 33 mRNAs were refractory to this translational repression and that there was no correlation between mRNA induction and the ability to recruit ribosomes during hypoxia. We also found that ribosomal protein encoding mRNAs are more sensitive to this translational repression as compared to the majority of mRNAs. Although other reports have analyzed the effect of translation inhibition on gene expression under anoxic conditions, we believe that this is the first report in hypoxic cells. Our results show that the translational repression that occurs during hypoxia does impact gene expression in the highly transformed prostate cancer cell line, PC-3.