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The purpose of this study was to explore female farmers' perspectives on barriers to engaging with resources for physical and mental healthcare faced by agriculture producers in the state of Georgia. In-depth interviews were conducted with female farm owners and managers ( n = 16) across the state. Interviews were recorded and transcribed, and researchers coded interviews separately before thematic analysis was used to identify common themes. Three primary themes were identified: (i) formal healthcare challenges, (ii) stigma, and (iii) cultural norms. Formal healthcare challenges included time constraints, healthcare costs, and a lack of cultural competence from healthcare providers. Both community and self-stigma were identified as barriers to engaging with mental health resources. Cultural norms that acted as a barrier to care included the prioritization of farm operations, self-reliance, pride, and the minimization of health concerns. Interviewees identified gender differences in the impact of stigma and cultural norms, reporting that these sociocultural barriers were more prominent among older, male producers. Central to many of these barriers is the concept of 'farm identity', where farmers' commitment to their operations consistently trumped concerns about physical or mental health. Future efforts to improve health outcomes among farmers should utilize the concept of farm identity as a guide for tailoring interventions and improving cultural competence among rural healthcare providers.

Background: Parents exposed to psychosocial adversities often experience challenges which, combined with the needs of a new-born infant, can be difficult to manage and increase the risk of poor outcomes for both parents and infants. Psychosocial adversity can disrupt the development of parental-foetal attachment to the baby during pregnancy, which can have a negative effect on parental care and quality of interaction during the postnatal period. This intervention is based on the proposition that enhanced parental capacity to mentalise and emotionally connect to unborn children during pregnancy, and better understanding about how to manage distressing infant behaviour (i.e., persistent crying and sleep problems) will: (i) promote the development of secure parent-infant attachment; (ii) improve antenatal bonding and postnatal parenting; and, (ii) reduce parental distress., Method: This protocol is for a pilot randomised control trial evaluating a new intervention, which makes use of innovative technologies to support parents experiencing moderate psychosocial adversity (Australian New Zealand Clinical Trials Registry: ACTRN12622000287730). The New Technology for New Parents (NTNP) intervention provides support using antenatal ultrasound scans and 'virtual home visits' during the perinatal period. Quantitative outcomes include mentalising capacity, parental-foetal/infant attachment, and parental competence., Conclusion: To the best of our knowledge, no study has evaluated the combined effectiveness of two novel technologies (3D/4D ultrasound scans and virtual home visits) to support parents across the antenatal and postnatal periods. This protocol, which includes the rationale for this innovative intervention, addresses a gap in services for parents experiencing moderate psychosocial adversity.

Nanoparticle (NP) size and proximity are two physical descriptors applicable to practically all NP-supported catalysts. However, with conventional catalyst design, independent variation of these descriptors to investigate their individual effects on thermocatalysis remains challenging. Using a raspberry-colloid-templating approach, we synthesized a well-defined catalyst series comprising Pd 12 Au 88 alloy NPs of three distinct sizes and at two different interparticle distances. We show that NP size and interparticle distance independently control activity and selectivity, respectively, in the hydrogenation of benzaldehyde to benzyl alcohol and toluene. Surface-sensitive spectroscopic analysis indicates that the surfaces of smaller NPs expose a greater fraction of reactive Pd dimers, compared to inactive Pd single atoms, thereby increasing intrinsic catalytic activity. Computational simulations reveal how a larger interparticle distance improves catalytic selectivity by diminishing the local benzyl alcohol concentration profile between NPs, thus suppressing its readsorption and consequently, undesired formation of toluene. Accordingly, benzyl alcohol yield is maximized using catalysts with smaller NPs separated by larger interparticle distances, overcoming activity-selectivity trade-offs. This work exemplifies the high suitability of the modular raspberry-colloid-templating method as a model catalyst platform to isolate individual descriptors and establish clear structure-property relationships, thereby bridging the materials gap between surface science and technical catalysts.

This study introduces a novel iterative Bragg peak removal with automatic intensity correction (IBR-AIC) methodology for X-ray absorption spectroscopy (XAS), specifically addressing the challenge of Bragg peak interference in the analysis of crystalline materials. The approach integrates experimental adjustments and sophisticated post-processing, including an iterative algorithm for robust calculation of the scaling factor of the absorption coefficients and efficient elimination of the Bragg peaks, a common obstacle in accurately interpreting XAS data, particularly in crystalline samples. The method was thoroughly evaluated on dilute catalysts and thin films, with fluorescence mode and large-angle rotation. The results underscore the technique's effectiveness, adaptability and substantial potential in improving the precision of XAS data analysis. While demonstrating significant promise, the method does have limitations related to signal-to-noise ratio sensitivity and the necessity for meticulous angle selection during experimentation. Overall, IBR-AIC represents a significant advancement in XAS, offering a pragmatic solution to Bragg peak contamination challenges, thereby expanding the applications of XAS in understanding complex materials under diverse experimental conditions., (open access.)

Objectives: The purposes of this study were to explore behavioral and mental health outcomes among a sample of farmers living in the United States and to compare differences between male and female farmers., Methods: An online cross-sectional survey was distributed within the farming community by researchers, farming consultants, and community partners. χ 2 and analysis or variance analyses were used to explore relationships between variables of interest., Results: Female survey respondents reported significantly higher perceived stress and significantly lower resilience than their male counterparts. A significant interaction effect was observed between gender and farm roles on alcohol consumption patterns, with female farm owners and managers reporting binge drinking behavior most frequently., Conclusions: This study identified distinct differences between respondents in terms of stress, resilience, and alcohol consumption patterns, based on both gender and occupational roles., Competing Interests: Proctor, Hopkins, and Reece have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

A detailed knowledge of reaction kinetics is key to the development of new more efficient heterogeneous catalytic processes. However, the ability to resolve site dependent kinetics has been largely limited to surface science experiments on model systems. Herein, we can bypass the pressure, materials, and temperature gaps, resolving and quantifying two distinct pathways for CO oxidation over SiO 2 -supported 2 nm Pt nanoparticles using transient pressure pulse experiments. We find that the pathway distribution directly correlates with the distribution of well-coordinated (e.g., terrace) and under-coordinated (e.g., edge, vertex) CO adsorption sites on the 2 nm Pt nanoparticles as measured by in situ DRIFTS. We conclude that well-coordinated sites follow classic Langmuir-Hinshelwood kinetics, but under-coordinated sites follow non-standard kinetics with CO oxidation being barrierless but conversely also slow. This fundamental method of kinetic site deconvolution is broadly applicable to other catalytic systems, affording bridging of the complexity gap in heterogeneous catalysis., (© 2024. The Author(s).)

(R,S)-methadone ((R,S)-MTD) is a µ-opioid receptor (MOR) agonist comprised of (R)-MTD and (S)-MTD enantiomers. (S)-MTD is being developed as an antidepressant and is considered an N-methyl-D-aspartate receptor (NMDAR) antagonist. We compared the pharmacology of (R)-MTD and (S)-MTD and found they bind to MORs, but not NMDARs, and induce full analgesia. Unlike (R)-MTD, (S)-MTD was a weak reinforcer that failed to affect extracellular dopamine or induce locomotor stimulation. Furthermore, (S)-MTD antagonized motor and dopamine releasing effects of (R)-MTD. (S)-MTD acted as a partial agonist at MOR, with complete loss of efficacy at the MOR-galanin Gal 1 receptor (Gal 1 R) heteromer, a key mediator of the dopaminergic effects of opioids. In sum, we report novel and unique pharmacodynamic properties of (S)-MTD that are relevant to its potential mechanism of action and therapeutic use. One-sentence summary: (S)-MTD, like (R)-MTD, binds to and activates MORs in vitro, but (S)-MTD antagonizes the MOR-Gal 1 R heteromer, decreasing its abuse liability., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Subanesthetic ketamine is increasingly used for the treatment of varied psychiatric conditions, both on- and off-label. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine's mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of subanesthetic ketamine may be opioid dependent. Using pharmacological functional ultrasound imaging in rats, we found that blocking opioid receptors suppressed neurophysiologic changes evoked by ketamine, but not by a more selective NMDAR antagonist, in limbic regions implicated in the pathophysiology of depression and in reward processing. Importantly, this opioid-dependent response was strongly sex-dependent, as it was not evident in female subjects and was fully reversed by surgical removal of the male gonads. We observed similar sex-dependent effects of opioid blockade affecting ketamine-evoked postsynaptic density and behavioral sensitization, as well as in opioid blockade-induced changes in opioid receptor density. Together, these results underscore the potential for ketamine to induce its affective responses via opioid signaling, and indicate that this opioid dependence may be strongly influenced by subject sex. These factors should be more directly assessed in future clinical trials., (© 2024. The Author(s).)

Background: (S)-ketamine is an NMDA receptor antagonist, but it also binds to and activates mu opioid receptors (MORs) and kappa opioid receptors in vitro. However, the extent to which these receptors contribute to (S)-ketamine's in vivo pharmacology is unknown., Methods: We investigated the extent to which (S)-ketamine interacts with opioid receptors in rats by combining in vitro and in vivo pharmacological approaches, in vivo molecular and functional imaging, and behavioral procedures relevant to human abuse liability., Results: We found that the preferential opioid receptor antagonist naltrexone decreased (S)-ketamine self-administration and (S)-ketamine-induced activation of the nucleus accumbens, a key brain reward region. A single reinforcing dose of (S)-ketamine occupied brain MORs in vivo, and repeated doses decreased MOR density and activity and decreased heroin reinforcement without producing changes in NMDA receptor or kappa opioid receptor density., Conclusions: These results suggest that (S)-ketamine's abuse liability in humans is mediated in part by brain MORs., (Published by Elsevier Inc.)

Herein, we present a design for a transient flow reactor system with high detection sensitivity and minimal dead volume, such that it is capable of sub-second switching of the gas stream flowing through a catalytic bed. We demonstrate the reactor's capabilities for step transient, pulse, and stream oscillation experiments using the model system of CO oxidation over Pd catalysts, and we find that we are able to precisely model step transients for CO oxidation using a pseudo-homogenous-packed bed reactor model. The design principles leading to minimal gas hold-up time and increased sensitivity that are described in this paper can be implemented into existing flow reactor designs with minimal cost, providing a readily accessible alternative to the existing transient instrumentation., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: 6-O-(2-[ 18 F]Fluoroethyl)-6-O-desmethyl-diprenorphine ([ 18 F]FE-DPN) is regarded as a non-selective opioid receptor radiotracer., Procedure: Here, we report the first characterization of [ 18 F]FE-DPN synthesized from the novel precursor, 6-O-(2-tosyloxyethoxy)-6-O-desmethyl-3-O-trityl-diprenorphine (TE-TDDPN), using a one-pot, two-step nucleophilic radiosynthesis to image opioid receptors in rats and mice using positron emission tomography., Results: We also show that [ 18 F]FE-DPN and [ 3 H]DPN exhibit negligible brain uptake in mu opioid receptor (MOR) knockout mice., Conclusions: Taken together with prior findings, our results suggest that [ 18 F]FE-DPN and [ 3 H]DPN preferentially bind to MOR in rodents in vivo., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Privately protected areas (PPAs) are internationally considered to be important policy implementation instruments to augment and strengthen protected area networks. However, there has been limited reflection on the performance of PPAs over time. This paper aims to identify key risks to the performance of PPAs as policy implementation instruments through the application of Theory of Change (ToC). Identifying and understanding these risks are important to allow for the evaluation and monitoring of PPA performance. The ToC method was applied to a specific PPA policy instrument namely, private nature reserves (PNRs) in the South African context. The research results produced 29 key assumptions translated into 29 key risks. These risk are critically discussed against existing South African and international literature. To test and refine the risks further it is recommended that they be applied to PPA case studies in different contexts., (Copyright © 2022. Published by Elsevier Ltd.)

Myocardial strain offers new insights into ventricular performance, There are software packages from several different companies used to ascertain this, and little data is available in patients with single right ventricle (sRV) physiology. We aimed to compare the analysis of two strain software applications using a cohort of patients with sRV for both inter-vendor and inter-observer variability. Echocardiograms from 85 patients with sRV (122 separate studies) were prospectively evaluated. All had Glenn and/or Fontan palliation. Longitudinal 4-chamber (4LS), inflow/outflow (IO), circumferential, and radial strain were assessed using Velocity Vector Imaging (VVI, Seimens, Munich) and Automated Functional Imaging (AFI, General Electric, Boston) software. In a subset of 45 patients (61 separate studies), strain measurements were obtained by two sonographers so a paired "inter-observer" analysis could be performed. A moderate correlation between measurements made by the two systems was observed. Circumferential strain assessment had the highest R value (0.77) with all others having R values < 0.6. Both software packages showed modest inter-observer reproducibility for longitudinal and circumferential strain. VVI intraclass correlation coefficients (ICC) for 4LS and average circumferential strain (ACS) were 0.6 and 0.58, compared to 0.68 and 0.59 for AFI. Other than radial strain and VVI IO inferior strain, mean strain differences between AFI and VVI were ≤ 1%. Inter-observer variability is modest, however, mean differences are minimal suggesting reasonable clinical reliability. Inter-vendor variability is greater and not as clinically reliable. In patients with sRV, serial assessments with strain should be performed using the same software., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The CT of PET CT provides diagnostic information, anatomic localisation and attenuation correction (AC). When only AC is required, very lose dose CT is desirable. CT iterative reconstruction (IR) improves image quality with lower exposures however there is little data on very low dose IR CT for AC of PET. This work assesses the impact of CT exposure and reconstruction algorithm on PET voxel values., Method: An anthropomorphic torso phantom was filled with physiologically typical [18]F concentrations in heart, liver and background compartments. A 17-mm-diameter right lung "tumour" filled with [18]F was included (surrounding lung contained no 18[F]). PET was acquired followed by 24 CT acquisitions with varying CT exposures (15-50 mAs, 80-120 kVp, pitch 0.671 or 0.828). Each CT was reconstructed twice using filtered back projection (FBP) or IR and these used for AC of PET. The reference PET reconstruction (RR) used CT acquired at 50 mAs, 120 kVp, pitch 0.828, IR, all others were test PET reconstructions (TR). Regions of interest (ROIs) were drawn in the liver, soft tissue and over "tumour" on each TR and compared with the RR. Voxel values in each TR were compared to the RR using a paired t test and by calculating which and what proportion of voxels in each TR differed by a quantitatively significant difference (QSD) from the RR., Results: TRs reconstructed using lower dose CTs underestimated mean and maximum ROI activity relative to the RR; greater with IR than FBP. Once CT dose index (CTDI) increased to 1 mGy, differences were less than QSD. On voxel analysis, all TRs were significantly different to the RR (p < 0.0001). TRs reconstructed at the lowest CT exposure with IR had 6% of voxels that differed by greater than QSD. Differences were reduced with increasing CTDI and FBP reconstruction. Voxels which exceeded the QSD were spatially localised to regions of high activity, interfaces between different attenuation and areas of CT beam hardening., Conclusions: Very low dose CT exposures are feasible for accurate PET AC. Scanner- and reconstruction-specific validation should be employed prior very low dose CT AC for PET.

Superconducting radio frequency niobium cavities are the building blocks of modern accelerators for scientific applications. Lower surface resistance, higher fields, and high operating temperatures advance the reach of the future accelerators for scientific discovery as well as potentially enabling cost-effective industrial solutions. We describe the design and performance of an Nb 3 Sn coating system that converts the inner surface of niobium cavities to an Nb 3 Sn film. The niobium surface, heated by radiation from the niobium retort, is exposed to Sn and SnCl 2 vapor during the heat cycle, which results in about 2 μm Nb 3 Sn film on the niobium surface. Film composition and structure as well as radio frequency properties with 1-cell R&D cavities and 5-cell practical accelerator cavities are presented.

Controlling the selectivity of catalytic reactions is a critical aspect of improving energy efficiency in the chemical industry; thus, predictive models are of key importance. Herein the performance of a heterogeneous, nanoporous Au catalyst is predicted for the complex catalytic self-coupling of the series of C 2 -C 4 alkyl alcohols, based solely on the known kinetics of the elementary steps of the catalytic cycle for methanol coupling, using scaling methods augmented by density functional theory. Notably, a sharp decrease in selectivity for ester formation with increasing molecular weight to favor the aldehyde due to van der Waals interactions of reaction intermediates with the surface was predicted and subsequently verified quantitatively by experiment. Further, the agreement between theory and experiment clearly demonstrates the efficacy of this approach for building a predictive model of catalytic behavior for a homologous set of reactants using a small set of experimental information., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Purpose: The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example., Methods: Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples., Results: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample., Conclusions: The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting., (© 2020 European Academy of Neurology.)

Introduction: In the clinic, the assessment of patients with multiple sclerosis (MS) is typically qualitative and non-standardized., Objectives: To describe the MS Performance Test (MSPT), an iPad Air ® 2 (Apple, Cupertino, CA, USA)-based neurological assessment platform allowing patients to input relevant information without the aid of a medical technician, creating a longitudinal, clinically meaningful, digital medical record. To report results from human factor (HF) and usability studies, and the initial large-scale implementation in a practice setting., Methods: The HF study examined use-error patterns in small groups of MS patients and healthy controls (n = 14), the usability study assessed the effectiveness of patient interaction with the tool by patients with a range of MS disability (n = 60) in a clinical setting, and the implementation study deployed the MSPT across a diverse population of patients (n = 1000) in a large MS center for routine clinical care., Results: MSPT assessments were completed by all users in the HF study; minor changes to design were recommended. In the usability study, 73% of patients with MS completed the MSPT, with an average administration time of 32 min; 85% described their experience with the tool as satisfactory. In the initial implementation for routine care, 84% of patients with MS completed the MSPT, with an average administration time of 28 min., Conclusion: Patients with MS with varying disability levels completed the MSPT with minimal or no supervision, resulting in comprehensive, efficient, standardized, quantitative, clinically meaningful data collection as part of routine medical care, thus allowing for large-scale, real-world evidence generation., Funding: Biogen., Trial Registration: NCT02664324.

Our study aims at understanding multigenerational communication among grandmothers, mothers, and daughters experiencing reproductive health transitions from menarche to menopause. Thirty women, 10 triads of grandmothers, mothers, and daughters, participated in narrative interviews to recount their menarche and menopause experiences. Analysis was read using a multilayered approach to interpret discourse positioned from self, reflexive others, and those stories informed by societal meanings. Four dialectical themes informed by generational discursive shifts in talk included (1) covert versus overt talk, (2) recollection of versus indifference to menarche, (3) bound to versus freedom from menstruation, and (4) controlling versus managing bodily changes. The theoretical significance of this piece indicates a slight, transformative change in how messages about menarche and menstruation are communicated or passed down from one generation to the next.

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.)

Grb7 is a non-catalytic protein, the overexpression of which has been associated with the proliferative and migratory potentials of cancer cells. Virtual screening strategies involving a shape-based similarity search, molecular docking, and 2D-similarity searches complemented by experimental binding studies (Thermofluor and isothermal titration calorimetry) resulted in the identification of nine novel phenylbenzamide-based antagonists of the Grb7 SH2 domain. Moderate binding affinities were observed, ranging from K(d)=32.3 μM for lead phenylbenzamide NSC 104999 (1) to K(d)=1.1 μM for a structurally related compound, NSC 57148 (2). Deconvolution of the affinity data into its components revealed differences in lead binding, from being entropy based (lead 1) to enthalpically driven (NSC 100874 (3), NSC 55158 (4), and compound 2). Finally, the lead compound 1 was found to decrease the growth of MDA-MB-468 breast cancer cells, with an IC(50) value of 39.9 μM. It is expected that these structures will serve as novel leads in the development of Grb7-based anticancer therapeutics., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

A radio frequency (RF) surface impedance characterization (SIC) system that uses a novel sapphire-loaded niobium cavity operating at 7.5 GHz has been developed as a tool to measure the RF surface impedance of flat superconducting material samples. The SIC system can presently make direct calorimetric RF surface impedance measurements on the central 0.8 cm(2) area of 5 cm diameter disk samples from 2 to 20 K exposed to RF magnetic fields up to 14 mT. To illustrate system utility, we present first measurement results for a bulk niobium sample.

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.)