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The objective of this study was to investigate the prevalence and predictors of suicide ideation among primary, middle and high school students. We used multilevel modelling to investigate suicide ideation among 12,733 Chinese children and adolescents aged 9-18 years from wide range of areas across China. Approximately, 32.09% of children and adolescents reported suicide ideation, with females were more likely to report suicide ideation than males (38.09% vs. 29.95%). Our results showed that the risk factors in primary school students were different from middle and high school student groups, whereas significant risk factors for middle and high school students were similar. The city's standard of living as indicated by the Engel coefficient and the city's divorce rate were positively associated with the prevalence of suicide ideation; in contrast, the school's pupil-to-teacher ratio was negatively correlated with elevated suicide ideation. Significant risk factors for suicide ideation included study anxiety, self-accusation tendency, impulsive tendency, terror tendency and physical symptoms. These results have important implications for the prevention of suicide, suggesting that both contextual (city-level) and compositional (individual-level) factors could be important targets for prevention and intervention for children and adolescents at risk of suicide ideation., (© 2016 International Union of Psychological Science.)

A highly modular synthesis of designed catalysts with controlled bimetallic nanoparticle size and composition and a well-defined structural hierarchy is demonstrated. Exemplary catalysts-bimetallic dilute Ag-in-Au nanoparticles partially embedded in a porous SiO 2 matrix (SiO 2 -Ag x Au y )-were synthesized by the decoration of polymeric colloids with the bimetallic nanoparticles followed by assembly into a colloidal crystal backfilled with the matrix precursor and subsequent removal of the polymeric template. This work reports that these new catalyst architectures are significantly better than nanoporous dilute AgAu alloy catalysts (nanoporous Ag 3 Au 97 ) while retaining a clear predictive relationship between their surface reactivity with that of single-crystal Au surfaces. This paves the way for broadening the range of new catalyst architectures required for translating the designed principles developed under controlled conditions to designed catalysts under operating conditions for highly selective coupling of alcohols to form esters. Excellent catalytic performance of the porous SiO 2 -Ag x Au y structure for selective oxidation of both methanol and ethanol to produce esters with high conversion efficiency, selectivity, and stability was demonstrated, illustrating the ability to translate design principles developed for support-free materials to the colloid-templated structures. The synthetic methodology reported is customizable for the design of a wide range of robust catalytic systems inspired by design principles derived from model studies. Fine control over the composition, morphology, size, distribution, and availability of the supported nanoparticles was demonstrated., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cognitive dysfunction is common in multiple sclerosis (MS) patients and has important consequences for daily activities, yet, unlike motor function, is not routinely assessed in the clinic setting. We developed the Processing Speed Test (PST), a self-administered iPad ® -based tool to measure MS-related deficits in processing speed., Objective: To determine whether the PST is valid for screening cognitive dysfunction by comparing it to the paper-and-pencil Symbol Digit Modalities Test (SDMT)., Methods: We assessed PST test-retest reliability, sensitivity of PST and SDMT in discriminating MS patients from healthy controls (HC), convergent validity between PST and SDMT, correlations between T2 lesion load and PST and SDMT, and PST performance with and without technician present during administration., Results: PST had excellent test-retest reliability, was highly correlated with SDMT, was slightly more sensitive than SDMT in discriminating MS from HC groups, and correlated better with cerebral T2 lesion load than did SDMT. Finally, PST performance was no different with or without a technician in the testing environment., Conclusion: PST has advantages over SDMT because of its efficient administration, scoring, and potential for medical record or research database integration. PST is a practical tool for routine screening of processing speed deficits in the MS clinic.

Hydrogen peroxide synthesis from hydrogen and oxygen in the gas phase is postulated to be a key reaction step in the gas phase epoxidation of propene using gold-titanium silicate catalysts. During this process H 2 O 2 is consumed in a secondary step to oxidise an organic molecule so is typically not observed as a reaction product. We demonstrate that using AuPd nanoparticles, which are known to have high H 2 O 2 synthesis rates in the liquid phase, it is possible to not only oxidise organic molecules in the gas phase but to detect H 2 O 2 for the first time as a reaction product in both a fixed bed reactor and a pulsed Temporal Analysis of Products (TAP) reactor without stabilisers present in the gas feed. This observation opens up possibility of synthesising H 2 O 2 directly using a gas phase reaction.

Forty-five women participated in a variant of the social orienting paradigm employed in "Maternal Touch Predicts Attentional Bias Towards Faces in Young Children" (Reece, in press) [1]. On a given trial, they saw a mathematical equation and indicated whether this equation was true or false. Equations were superimposed on face or house distractors. A female experimenter sat next to the participant. In separate blocks, she either rested her hand on the participants arm or refrained from touching. Performance was poorer on trials with face than house distractors. However, experimenter touch failed to modulate this effect. Here we present raw and analyzed data of this companion experiment.

Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington's disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington's disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Mild to moderate traumatic brain injury (TBI) due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes). Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI) study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female) who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females) with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females) and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females) without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate). Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results could not be attributed to caudate atrophy or the presence of PTSD symptoms. Our results point to a specific vulnerability of the caudate to blast injury. Changes in activation during the Sternberg Item Recognition Task, and potentially other tasks that recruit the caudate, may serve as biomarkers for blast TBI.

Addressing the health care needs of a 21st-century nation that is experiencing increased diversity and disparity will require new models of educating future providers. The cultural competence and confidence model was the guiding framework in a study evaluating the influence of cultural educational offerings on the transcultural self-efficacy (TSE) perceptions in baccalaureate nursing students. The Transcultural Self-Efficacy Tool was used to measure perceived TSE in a pretest (N = 260), posttest (N = 236) study over an academic year. Significant changes were demonstrated in overall self-efficacy and on the cognitive, practical, and affective subscales. A classification and regression tree analysis identified social orientation as the demographic variable most predictive of the TSE level. This study supports previous research where positive changes were found in students' TSE based on the inclusion of cultural interventions in the nursing curriculum., (© The Author(s) 2014.)

Casual social touch influences emotional perceptions, attitudes, and behaviours of interaction partners. We asked whether these influences extend to third-party observers. To this end, we developed the Social Touch Picture Set comprising line drawings of dyadic interactions, half of which entailed publicly acceptable casual touch and half of which served as no-touch controls. In Experiment 1, participants provided basic image norms by rating how frequently they observed a displayed touch gesture in everyday life and how comfortable they were observing it. Results implied that some touch gestures were observed more frequently and with greater comfort than others (e.g., handshake vs. hug). All gestures, however, obtained rating scores suitable for inclusion in Experiments 2 and 3. In Experiment 2, participants rated perceived valence, arousal, and likeability of randomly presented touch and no-touch images without being explicitly informed about touch. Image characters seemed more positive, aroused, and likeable when they touched as compared to when they did not touch. Image characters seemed more negative and aroused, but were equally likeable, when they received touch as compared to when there was no physical contact. In Experiment 3, participants passively viewed touch and no-touch images while their eye movements were recorded. Differential gazing at touch as compared to no-touch images emerged within the first 500 ms following image exposure and was largely restricted to the characters' upper body. Gazing at the touching body parts (e.g., hands) was minimal and largely unaffected by touch, suggesting that touch processing occurred outside the focus of visual attention. Together, these findings establish touch as an important visual cue and provide novel insights into how this cue modulates socio-emotional processing in third-party observers., (© 2014 The British Psychological Society.)

Varying degrees of order have been found experimentally for a series of covalent triazine-based frameworks (CTFs) when synthesised under different reaction conditions. Here, we use molecular modelling to discuss the potential origins of this structural order by analysis of the node and strut building blocks. We use a combination of small model structures based on DFT optimised monomer units and more extended simulations using automated structure growth and molecular dynamics to discuss the influence of the strut structure on the local crystallinity of these materials.

Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient's home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

Purpose: New femtosecond laser platforms may reduce ocular surface interference and LASIK-associated dry eye. This study investigated tear protein profiles in subjects who underwent LASIK using two femtosecond lasers to assess differences in protein expression., Methods: This was a randomized interventional clinical trial involving 22 patients who underwent femtosecond laser refractive surgery with a contralateral paired eye design. Corneal flaps of 22 subjects were created by either Visumax or Intralase laser. Tear samples were collected preoperatively, and at 1 week and 3 months postoperatively using Schirmer's strips. Tear protein ratios were calculated relative to preoperative protein levels at baseline. The main outcome measures were the levels of a panel of dry eye protein markers analyzed using isobaric tagging for relative and absolute quantitation (iTRAQ) mass spectrometry., Results: A total of 824 unique proteins were quantifiable. Tear protein ratios were differentially regulated between the eyes treated with different lasers. The secretoglobulins Lipophilin A (1.80-fold) and Lipophilin C (1.77) were significantly upregulated (P < 0.05) at 1 week postoperatively in Visumax but not in Intralase-treated eyes. At 1 week, orosomucoid1 was upregulated (1.78) in Intralase but not Visumax-treated eyes. In the same eyes, lysozyme, cathepsin B, and lipo-oxygenase were downregulated at 0.44-, 0.64-, and 0.64-folds, respectively. Transglutaminase-2 was downregulated in both groups of eyes., Conclusions: Different laser platforms induce distinct biological responses in the cornea and ocular surface, which manifests as different levels of tear proteins. This study has implications for surgical technology and modulation of wound healing responses. (ClinicalTrials.gov number, NCT01252654.)., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To describe the subjective experience of patients and surgeons during laser in situ keratomileusis (LASIK) using the Intralase 60 kHz or the Visumax 500 kHz femtosecond laser., Setting: Singapore National Eye Centre, Singapore., Design: Prospective randomized clinical study., Methods: In myopic patients, LASIK was performed with the corneal flap created using the 60 kHz laser in 1 eye and the 500 kHz laser in the contralateral eye. Postoperatively, patients completed a standardized validated questionnaire about their subjective intraoperative experiences (eg, light perception, pain, fear). Surgeons reported their intraoperative experiences and preferences., Results: Loss of light perception occurred in 50.0% of 60 kHz laser cases and 0% of 500 kHz laser cases during docking and in 63.0% and 0% of cases, respectively, during laser flap creation (P < .0001). The mean pain score with the 60 kHz laser was significantly higher during docking (P < .0001) but not during laser flap cutting (P = .006). Subconjunctival hemorrhage occurred in 67.4% of eyes with the 60 kHz laser and in 2.2% of eyes with the 500 kHz laser (P < .0001). The 500 kHz laser was preferred by 78.3% of patients, while 21.7% preferred the 60 kHz laser (P < .0001). The surgeons preferred the 60 kHz laser in 50.0% of cases and the 500 kHz laser in 8.7% (P < .0001); 41.3% had no preference., Conclusions: Patients preferred surgery with the 500 kHz laser with no loss of light perception, less pain, less fear, and less subconjunctival hemorrhage. Surgeons preferred the 60 kHz laser., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Grb7 is an adapter protein, aberrantly co-overexpressed with HER2 and identified as an independent prognostic marker in breast cancer. It has been established that Grb7 exacerbates the cellular growth and migratory behaviour of HER2+ve breast cancer cells. Less is known about Grb7's role in the context of HER2-ve cells. Here we directly compare the effect of stable Grb7 knockdown in oestrogen sensitive (T47D), HER2+ve (SKBR3) and triple-negative (MDA-MB-468 and MDA-MB-231) breast cancer cell lines on anchorage dependent and independent cell growth, wound healing and chemotaxis. All cell lines showed reduced ability to migrate upon Grb7 knockdown, despite their greatly varied endogenous levels of Grb7. Decreased cell proliferation was not observed in any of the cell lines upon Grb7 knockdown; however, decreased ability to form colonies was observed for all but the oestrogen sensitive cell line, depending upon the stringency of the growth conditions. The data reveal that Grb7 plays an important role in breast cancer progression, beyond the context of HER2+ve cell types.

Military personnel involved in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) commonly experience blast-induced mild to moderate traumatic brain injury (TBI). In this study, we used task-activated functional MRI (fMRI) to determine if blast-related TBI has a differential impact on brain activation in comparison with TBI caused primarily by mechanical forces in civilian settings. Four groups participated: (1) blast-related military TBI (milTBI; n=21); (2) military controls (milCON; n=22); (3) non-blast civilian TBI (civTBI; n=21); and (4) civilian controls (civCON; n=23) with orthopedic injuries. Mild to moderate TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI. Brain activation was evaluated with 2 (mil, civ)×2 (TBI, CON) analyses of variance, corrected for multiple comparisons. During correct inhibitions, fMRI activation was lower in the TBI than CON subjects in regions commonly associated with inhibitory control and the default mode network. In contrast, inhibitory failures showed significant interaction effects in the bilateral inferior temporal, left superior temporal, caudate, and cerebellar regions. Specifically, the milTBI group demonstrated more activation than the milCON group when failing to inhibit; in contrast, the civTBI group exhibited less activation than the civCON group. Covariance analyses controlling for the effects of education and self-reported psychological symptoms did not alter the brain activation findings. These results indicate that the chronic effects of TBI are associated with abnormal brain activation during successful response inhibition. During failed inhibition, the pattern of activation distinguished military from civilian TBI, suggesting that blast-related TBI has a unique effect on brain function that can be distinguished from TBI resulting from mechanical forces associated with sports or motor vehicle accidents. The implications of these findings for diagnosis and treatment of TBI are discussed.

Purpose: To compare the efficacy, predictability, and refractive outcomes of laser in situ keratomileusis (LASIK) using 2 femtosecond platforms for flap creation., Setting: Multisurgeon single center., Design: Clinical trial., Methods: Bilateral femtosecond LASIK was performed using the Wavelight Allegretto Eye-Q 400 Hz excimer laser system. The Visumax femtosecond platform (Group 1) was used to create the LASIK flap in 1 eye, while the Intralase femtosecond platform (Group 2) was used to create the LASIK flap in the contralateral eye. The preoperative, 1-month, and 3-month postoperative visual acuities, refraction, and contrast sensitivity in the 2 groups were compared., Results: The study enrolled 45 patients. Three months after femtosecond LASIK, 79.5% of eyes in Group 1 and 82.1% in Group 2 achieved an uncorrected distance visual acuity of 20/20 (P=.808). The mean efficacy index was 0.97 in Group 1 and 0.98 in Group 2 at 3 months (P=.735); 89.7% of eyes in Group 1 and 84.6% of eyes in Group 2 were within ± 0.50 diopter of emmetropia at 3 months (P=.498). No eye in either group lost more than 2 lines of corrected distance visual acuity. The mean safety index at 3 months was 1.11 in Group 1 and 1.10 in Group 2 (P=.570)., Conclusion: The results of LASIK with both femtosecond lasers were similar, and both platforms produced efficacious and predictable LASIK outcomes., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers., Methods: In a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer's test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively., Results: There were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P > 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P < 0.05), 1 month (P < 0 .001), and 3 months (P < 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of -6.00 diopters (D) to -11.25 D as compared with eyes that had a relatively lower level of myopia of less than -6.00 D (P < 0.001). TBUT and Schirmer's test values were significantly diminished at 1 week postoperatively (P < 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P < 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer's test values, or corneal staining (P > 0.05)., Conclusion: This study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications.

Two calorimeters, with stainless steel and Cu as the thermal path material for high precision and high power versions, respectively, have been designed and commissioned for the 7.5 GHz surface impedance characterization system at Jefferson Lab to provide low temperature control and measurement for CW power up to 22 W on a 5 cm diameter disk sample which is thermally isolated from the radiofrequency (RF) portion of the system. A power compensation method has been developed to measure the RF induced power on the sample. Simulation and experimental results show that with these two calorimeters, the whole thermal range of interest for superconducting radiofrequency materials has been covered. The power measurement error in the interested power range is within 1.2% and 2.7% for the high precision and high power versions, respectively. Temperature distributions on the sample surface for both versions have been simulated and the accuracy of sample temperature measurements have been analyzed. Both versions have the ability to accept bulk superconductors and thin film superconducting samples with a variety of substrate materials such as Al, Al(2)O(3), Cu, MgO, Nb, and Si.

Purpose: To evaluate the between-observer (interobserver) and between-instrument (intraobserver) variability in flap thickness measurements after laser in situ keratomileusis (LASIK) using spectral-domain and time-domain anterior segment optical coherence tomography (AS-OCT)., Setting: Singapore National Eye Centre., Design: Evaluation of diagnostic test or technology., Methods: Two independent masked observers measured flap thickness 1 month after LASIK using spectral-domain (RTVue) or time-domain (Visante) AS-OCT. The measurements were taken at central (0.0 mm), -1.5 mm, and +1.5 mm locations. Measurements were repeated to assess between-instrument variability., Results: There was no statistically significant difference in mean flap thickness between the 2 observers at -1.5 mm, 0.0 mm, and +1.5 mm on spectral-domain AS-OCT and at -1.5 mm and +1.5 mm on time-domain AS-OCT (P < .01). There was a statistically significant difference between the 2 observers in the central (0.0 mm) values on time-domain AS-OCT (P=.0008). There was stronger interobserver correlation for spectral-domain AS-OCT at -1.5 mm (r = 0.82), 0.0 mm (r = 0.88), and +1.5 mm (r = 0.88) than for time-domain AS-OCT (r = 0.73, r = 0.62, and r = 0.79, respectively). There was no statistically significant difference in between-instrument measurements. There was stronger between-instrument correlation with spectral-domain AS-OCT than with time-domain AS-OCT at all locations. The mean standard deviation (measure of instrument repeatability) for spectral-domain AS-OCT was 4.19 μm., Conclusion: Spectral-domain AS-OCT had closer agreement in between-observer and between-instrument measurements than time-domain AS-OCT and provided more consistent measurements of post-LASIK flap thickness., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Grb7 is an adapter protein found to be overexpressed in several breast and other cancer cell types along with ErbB2. Grb7 is normally an interaction partner with focal adhesion kinase and in cancer cells also aberrantly interacts with ErbB2. It is thus implicated in the migratory and proliferative potential of cancer cells. Previous studies have shown that the phage display-derived cyclic nonphosphorylated inhibitor peptide, G7-18NATE, when linked to Penetratin, is able to interfere with the interaction of Grb7 with its upstream binding partners and to impact on both cell migration and proliferation. Here we report the synthesis of a biotinylated G7-18NATE covalently attached to just the last seven residues of Penetratin (G7-18NATE-P-Biotin). We demonstrate that this construct is taken up efficiently into MDA-MB-468 breast cancer cells and colocalizes with Grb7 in the cytoplasm. We also used isothermal titration calorimetry to determine the binding affinity of G7-18NATE-P-Biotin to the Grb7-SH2 domain, and showed that it binds with micromolar affinity (K(d) = 14.4 microM), similar to the affinity of G7-18NATE (K(d) = 35.4 microM). Together this shows that this shorter G7-18NATE-P-Biotin construct is suitable for further studies of the antiproliferative and antimigratory potential of this inhibitor.

Growth factor receptor bound protein 7 (Grb7) is an adapter protein that functions as a downstream effector of growth factor mediated signal transduction. Over-expression of Grb7 has been implicated in a variety of cancers such as breast, blood, pancreatic, esophageal, and gastric carcinomas. Inhibition of Grb7 has been shown to reduce the migratory and proliferative potential of these cancers, making it an attractive therapeutic target. Starting with a known peptide antagonist, the present work reports the application of a succession of computational ligand design tools comprising a ligand shape based similarity search, molecular docking and a 2D-similarity search to identify small molecular antagonists of the Grb7-SH2 domain from the NCI chemical database. Binding to the Grb7-SH2 domain was then experimentally tested using melting point shift assays and isothermal titration calorimetry. Overall, a total of 11 benzopyrazine based small molecular antagonists were identified with affinity for the Grb7-SH2 domain. Representative compounds tested using ITC were revealed to possess moderate binding affinity in the low micromolar range. Finally, the lead compound (NSC642056) was found to reduce the growth of a Grb7-expressing breast cancer cell line with an IC(50) of 86μM. It is expected that the identified antagonists will be useful additions to further explore the function of Grb7 and for the development of inhibitors with therapeutic potential., (Copyright © 2010. Published by Elsevier Ltd.)

After the significant population decline of several pelagic fish species in the Northern Sacramento-San Joaquin (SSJ) Estuary (CA, USA) in 2002, a study was performed to monitor water column toxicity using the amphipod Hyalella azteca. From January 1, 2006 to December 31, 2007, water samples were collected biweekly from 15 to 16 sites located in large delta channels and main-stem rivers, selected based on prevalent distribution patterns of fish species of concern. Ten-day laboratory tests with H. azteca survival and relative growth as toxicity endpoints were conducted. The enzyme inhibitor piperonyl butoxide ([PBO], 25 µg/L) was added to synergize or antagonize pyrethroid or organophosphate (OP) insecticide toxicity, respectively. Significant amphipod mortality was observed in 5.6% of ambient samples. Addition of PBO significantly changed survival or growth in 1.1% and 10.1% of ambient samples, respectively. Sites in the Lower Sacramento River had the largest number of acutely toxic samples, high occurrence of PBO effects on amphipod growth (along with sites in the South Delta), and the highest total ammonia/ammonium concentrations (0.28 ± 0.15 mg/L). Ammonia/ammonium, or contaminants occurring in mixture with these, likely contributed to the observed toxicity. Pyrethroid insecticides were detected at potentially toxic concentrations. Overall, results of this study identified specific areas and contaminants of concern and showed that water in the Northern SSJ Estuary was at times acutely toxic to sensitive invertebrates., (Environ. Toxicol. Chem. 2010;29:2190-2199. © 2010 SETAC.)

Purpose: To compare pterygium excision conjunctival autograft surgery using Tisseel fibrin glue versus Vicryl sutures., Method: Prospective randomized clinical trial. Fifty patients were randomized into either sutured graft or glued graft groups. Twenty-five received standard conjunctival autograft sutured with Vicryl and 25 received surgery with the autograft placed with Tisseel fibrin glue. Outcome measures include surgical time, patient discomfort, pathology, complications and recurrence rates at 3, 6 and 12 months. Patients were followed up at days 1, 7, 14, 30, 90, 180 and 365., Results: The mean surgical time for the glue group was significantly shorter at 12 min compared with the suture group at 26 min (P < 0.001). Postoperative pain was significantly less at day 1 (P < 0.001) and day 2 (P < 0.05) but was not significantly different following these visits. Complications in the glue group included one patient with an absent graft at week 1 that required revision of the graft. At 3 months there were no recurrences in the glue group and two recurrences in the suture group. The 6- and 12-month recurrence rate was unchanged and not significantly different between the glue and suture groups (both 0/24 and 2/23, respectively)., Conclusion: Both glued and sutured conjunctival autografting procedures are safe and effective methods for pterygium surgery. The glued autograft recurrence rate at 12 months was similar to that of sutured grafts. Conjunctival autograft with fibrin glue in pterygium surgery decreased surgical time and resulted in less postoperative pain in the first 48 hours but had a higher complication rate.

Combination therapies aim to overcome the limitations of individual drugs by selecting diverse targets of action to enhance effectiveness synergistically. This article reviews the principles of combination therapy and its applications for benign prostatic hyperplasia and overactive bladder. It then examines pathophysiological, pharmacological, and clinical evidence for currently available drug and device combinations for erectile dysfunction that has not responded to first-line, single-agent therapy.

We determined whether apolipoprotein E epsilon4 (ApoE4) or catechol-O-methyltransferase (COMT) genotypes were associated with dementia, hallucinations, Alzheimer's disease pathological findings (AP), or cortical Lewy bodies (CLBs) in autopsy-confirmed cases of Parkinson's disease (PD). Outcomes were obtained from medical records. Pathology reports identified AP and CLBs. Brain tissue was genotyped. A total of 47 subjects (33 men, 14 women) had PD onset at 62.4 +/- 8.7 years of age and died at 77.8 +/- 5.6 years of age. Demented and hallucinating patients did not differ in age at onset (AO) of PD or age at death, or the proportion ApoE4+, AP+, or CLB+ compared to nondemented patients or non-hallucinating patients. ApoE4 and COMT (low metabolizer [LH], intermediate metabolizer [HL], or high metabolizer [HH]) did not influence AO, death, or dementia- or hallucination-free survival, based on age or duration of treatment. All seven subjects with AP were demented and had hallucinations. CLBs were associated with dementia but not hallucinations. In Cox regression models adjusting for AO and duration of treatment, increased risk of dementia was associated with male sex but not significantly with ApoE4; inclusion of AP in the model did not affect the results; COMT was not a risk factor for dementia. Psychosis risk was not associated with ApoE4, COMT, or sex. The observation that males have increased dementia risk and the trend for ApoE4 requires confirmation in larger prospective autopsy studies., (Copyright 2005 Movement Disorder Society)

Purpose: To identify which organisms cause bacterial keratitis in a local community and to determine how patients with suspected bacterial keratitis should be initially treated., Methods: The results of all corneal scrapes performed in the ophthalmology department of Christchurch Hospital between 1997 and 2001 were reviewed. All samples were collected at the 'bedside' by a technician from the microbiology department and were processed immediately., Results: Eighty-seven corneal scrapes were performed on 78 patients. There was a positive Gram stain in 43.7% (38/87) of scrapes. There was a positive culture in 58.6% (51/87) of scrapes. The commonest Gram-positive organisms were coagulase negative Staphylococci (19.4%) and Corynebacterium spp. (16.1%). The commonest Gram-negative organisms were Moraxella spp. (19.4%) and Pseudomonas aeruginosa (3.2%). Every Gram-positive organism was sensitive to chloramphenicol and every Gram-negative organism was sensitive to ciprofloxacin. In contrast, 89% of Gram-negative organisms were sensitive to chloramphenicol and 88% of Gram-positive organisms were sensitive to ciprofloxacin., Conclusion: The results are very different to those reported by other centres. Most notably, a much higher incidence of infection by Corynebacterium spp. and Moraxella spp. and a lower incidence of Pseudomonas aeruginosa was found. In this centre it appears appropriate to initially treat patients with Gram-positive organisms with chloramphenicol and patients with Gram-negative organisms with ciprofloxacin. Patients with a negative Gram stain should be treated with alternating chloramphenicol and ciprofloxacin while awaiting culture results.

The effect of traumatic spinal cord injury (SCI) on the expression of tumor necrosis factor (TNFalpha) and its mRNA was examined. Quantitative reverse transcription polymerase chain reaction assay showed TNFalpha mRNA level increased > 20-fold at the lesion site by 1 h after the injury compared to that in uninjured controls. The TNFalpha mRNA level was still significantly higher than in the controls 72 h after the injury. TNFalpha mRNA in the samples collected immediately caudal to the lesion site was also increased. Levels of TNFalpha protein, determined by a cytotoxic bioassay, were also significantly increased at the lesion site. The TNFalpha protein level was maximal 1 and 8 h after the injury and still significantly higher than in the controls 24 h post-injury. The present results demonstrate that TNFalpha is rapidly induced in the spinal cord after the injury, and it may play a significant role in secondary events in SCI.

During Drosophila metamorphosis, the 'early-late' genes constitute a unique class regulated by the steroid hormone 20-hydroxyecdysone. Their induction is comprised of both a primary and a secondary response to ecdysone. Previous work has suggested that the epidermal expression of the dopa decarboxylase gene (Ddc) is likely that of a typical early-late gene. Accumulation of the Ddc transcript is rapidly initiated in the absence of protein synthesis, which implies that the ecdysone receptor plays a direct role in induction. However, full Ddc expression requires the participation of one of the transcription factors encoded by the Broad-Complex. In this paper, we characterize an ecdysone response element (EcRE) that contributes to the primary response. Using gel mobility shift assays and transgenic assays, we identified a single functional EcRE, located at position -97 to -83 bp relative to the transcription initiation site. This is the first report of an EcRE associated with an early-late gene in Drosophila. Competition experiments indicated that the affinity of the Ddc EcRE for the ecdysone receptor complex was at least four-fold less than that of the canonical EcRE of the hsp27 gene. Using in vitro mutagenesis, we determined that the reduced affinity of the EcRE resided at two positions where the nucleotides differed from those found in the canonical sequence. The ecdysone receptor, acting through this EcRE, releases Ddc from a silencing mechanism, whose cis-acting domain we have mapped to the 5'-upstream region between -2067 and -1427 bp. Deletion of this repressive element resulted in precocious expression of Ddc in both epidermis and imaginal discs. Thus, epidermal Ddc induction at pupariation is under the control of an extended genomic region that contains both positive and negative regulatory elements., (Copyright 2002 Elsevier Science Ireland Ltd.)

Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250,1000,1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.

Fungi comprise a large monophyletic group of uni- and multicellular eukaryotic organisms in which many species are of economic or medical importance. Fungal genomes are variable in size (13-42 Mb), and multicellular species support true spatial and temporal cell-type-specific regulation of gene expression. In a 38.8-kb Aspergillus nidulans contiguous genomic DNA region, a transposable element and 12 potential genes were identified, 7 similar to genes in other organisms. This observation is consistent with the prediction that multicellular ascomycetous fungi harbor 8000-9000 genes in a 36-Mb average genome. Thus, the genomic DNA sequence of filamentous fungi will provide substantial amounts of genetic and functional information that is not available in yeast, for the human and other metazoan minimal gene complement.

In the context of global climate change, an understanding of the long-term effects of increasing concentrations of atmospheric trace gases (carbon dioxide, CO(2), ozone, O(3), oxides of nitrogen, NO(x) etc.) on both cultivated and native vegetation is of utmost importance. Over the years, under field conditions, various trace gas-vegetation exposure methodologies with differing advantages and disadvantages have been used. Because of these variable criteria, with elevated O(3) or CO(2) levels, at the present time the approach of free-air experimental-release of the gas into study plots is attracting much attention. However, in the case of CO(2), this approach (using 15 m diameter study plot with a single circular array of vent pipes) has proven to be cost prohibitive (about 59000-98000 dollars/year/replicate) due to the consumption of significant quantities of the gas to perform the experiment (CO(2) level elevated to 400 ppm above the ambient). Therefore, in this paper, we present a new approach consisting of a dual, concentric exposure array of vertical risers or vent pipes. The purpose of the outer array (17 m diameter) is to vent ambient air outward and toward the incoming wind, thus providing an air curtain to reduce the velocity of that incoming wind to simulate the mode or the most frequently occurring wind speed at the study site. The inner array (15 m diameter) vents the required elevated levels of trace gases (CO(2), O(3), etc.) into the study plot. This dual array system is designed to provide spatial homogeneity (shown through diffusion modeling) of the desired trace-gas levels within the study plot and to also reduce its consumption. As an example, while in the single-array free-air CO(2)-release system the consumption of CO(2) to elevate its ambient concentration by 400 ppm is calculated to be about 980 tons/year/replicate, it is estimated that in the dual array system it would be approximately 590 tons/year/replicate. Thus, the dual array system may provide substantial cost savings (24000-39000 dollars/year/replicate) in the CO(2) consumption (60-100 dollars/ton of CO(2)) alone. Similarly, benefits in the requirements of other trace gases (O(3), NO(x), etc.) are expected, in future multivariate studies on global climate change.

BALB/cByJ (J) mice have short-chain acyl-CoA dehydrogenase (SCAD) deficiency and an organic aciduria similar to that of human SCAD deficiency. [9,10(n)-3H]- and [15,16(n)-3H]palmitate oxidations in J mouse fibroblasts were 96 and 35% of control, respectively, consistent with an isolated SCAD defect. Acyl-CoA dehydrogenase activities were assayed in muscle and fibroblast mitochondria from BALB/cBy controls (Y) and SCAD-deficient J mice. Medium-chain acyl-CoA dehydrogenase (MCAD) activities were comparable in both J and Y mice from all tissues. In the presence of MCAD antiserum, SCAD activities in J mice were undetectable in both tissues. Apparent Km and Vmax values in liver mitochondria suggested a somewhat increased affinity of MCAD for butyryl-CoA in J mice, as compared with MCAD from other species. Immunoblot studies using mitochondria revealed identical apparent SCAD molecular weight in liver, muscle, and fibroblasts from Y mice and no detectable SCAD antigen in J mice; MCAD antigen was detected in comparable amounts from both Y and J mice. Radiolabeling and immunoprecipitation studies in J mouse fibroblasts revealed no SCAD synthesis, but normal MCAD synthesis. These data argue against the existence of tissue-specific SCAD isoforms in the mouse and confirm that this mouse strain is a model for the human organic aciduria resulting from this beta-oxidation defect.

Quantitative imaging of bremsstrahlung from pure beta emitters is proposed as a means for in vivo management of antibody therapy. The method involves the use of high-energy collimation, an empirically selected broad photon energy window to enhance detector sensitivity, and a Wiener restoration filter to compensate for system blur. The measured and filtered data were obtained for an idealized scattering medium and isolated spherical sources. An effective linear attenuation coefficient of about 0.13 cm-1 was determined from the raw image data of 32P. A coefficient of 0.14 cm-1 was determined after the images were restored using the Wiener filter. The measured attenuation was not significantly dependent on the size of the region of interest or the size of the source. Its variation was within the experimental error of measurement (+/- 5%). The measured sensitivity (6 x 10(-6) cps/Bq) was sufficient for imaging therapy doses of 32P or 90Y.

Sixteen untrained males, age 46 +/- 11 yr (mean +/- SD), were studied to determine the effects of 20 wk of strength training on lipoprotein-lipid profiles and post-heparin lipase activities. All subjects had abnormal lipoprotein-lipid profiles and at least two other risk factors for coronary heart disease (CHD). To control for day-to-day variations in blood lipoprotein levels, baseline values were established by taking at least two blood samples on separate days from the training and control groups. The training program resulted in a 50% increase in upper body strength (P less than 0.001) and a 37% increase in lower body strength (P less than 0.001) as measured by the one repetition maximum test (1-RM). No changes in the 1-RM test were observed in the control group. There were no significant changes in VO2max (34.5 +/- 6.4 vs 36.2 +/- 7.4 ml.kg-1.min-1 or percent fat (25.4 +/- 4.2 vs 24.9 +/- 4.1%) with training. There were also no significant changes in plasma concentrations of triglyceride (193 +/- 96 vs 171 +/- 101 mg.dl-1), total cholesterol (231 +/- 22 vs 210 +/- 22 mg.dl-1), and HDL-C (35 +/- 6 vs 36 +/- 8 mg.dl-1), or LDL-C (139 +/- 16 vs 139 +/- 21 mg.dl-1). Furthermore, the activities of post-heparin lipoprotein lipase (9 +/- 4 vs 13 +/- 5 moles.ml-1.h-1) and hepatic lipase (35 +/- 10 vs 35 +/- 9 moles.ml-1.h-1) did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of severe multiple acyl-CoA dehydrogenation disorder is described. This is the second such case reported to have had an elevated maternal serum alpha-fetoprotein and normal amniotic alpha-fetoprotein. The child's 3-day extrauterine life was characterized by intractable acidosis, respiratory distress, and ventricular fibrillation. The characteristic biochemical, morphologic, and microscopic findings of this condition are reviewed. A subsequent pregnancy was evaluated using chorionic villus sampling and analysis of cultured trophoblasts. The trophoblasts were biochemically normal, and a normal child was subsequently delivered. Since the manifestations of this disorder developed in utero, prenatal diagnosis and therapy offer the only hope for a more prolonged survival.

Phleborheography is a well-established technique for the noninvasive diagnosis of deep venous thrombosis of the lower extremity. For ten years we have used phleborheography in the diagnosis of axillary and subclavian venous thrombosis. We developed modifications in technique and interpretation that are necessary for accurate application of phleborheography to the upper extremity. When compared with venography, the sensitivity and specificity of this technique approached 90%. Therefore, phleborheography appears to be a useful screening examination for deep venous thrombosis of the upper extremity.

Thiazolidine formed from trace quantities of formaldehyde in an aqueous solution containing cysteamine at pH 8 was extracted with chloroform and subsequently analyzed by a gas chromatograph equipped with a fused silica capillary column and a thermionic nitrogen-phosphorus specific detector. Recoveries of formaldehyde from the aqueous solutions at levels lower than 1 ppm were slightly over 100%. Quantitative analysis of formaldehyde in commercial brewed and instant coffees showed 3.4-4.5 ppm in the brewed and 10-16.3 ppm in the instant coffee.