Impact of Voluntary Muscle Activation on Stretch Reflex Excitability in Individuals With Hemiparetic Stroke.

Objective: To characterize how, following a stretch-induced attenuation, volitional muscle activation impacts stretch reflex activity in individuals with stroke. Methods: A robotic device rotated the paretic elbow of individuals with hemiparetic stroke from 70° to 150°, and then back to 70° elbow flexion at an angular speed of 120°/s. This stretching sequence was repeated 20 times. Subsequently, participants volitionally activated their elbow musculature or rested. Finally, the stretching sequence was repeated another 20 times. The flexors' stretch reflex activity was quantified as the net torque measured at 135°. Results: Data from 15 participants indicated that the stretching sequence attenuated the flexion torque (p < 0.001) and resting sustained the attenuation (p = 1.000). Contrastingly, based on data from 14 participants, voluntary muscle activation increased the flexion torque (p < 0.001) to an initial pre-stretch torque magnitude (p = 1.000). Conclusions: Stretch reflex attenuation induced by repeated fast stretches may be nullified when individuals post-stroke volitionally activate their muscles. In contrast, resting may enable a sustained reflex attenuation if the individual remains relaxed. Significance: Stretching is commonly implemented to reduce hyperactive stretch reflexes following a stroke. These findings suggest that stretch reflex accommodation arising from repeated fast stretching may be reversed once an individual volitionally moves their paretic arm.

Array Microcell Method (AMCM) for Serial Electroanalysis.

We describe a method for electrochemical measurement and synthesis based on the combination of a mobile micropipette and a microelectrode array, which we term the array microcell method (AMCM). AMCM has the ability to address single electrodes within a microelectrode array (MEA) and provides a simple, low-cost format to enable versatile electrochemical measurements. In AMCM, a droplet at the tip of a movable micropipette (inner diameter of 50 µm) functions as an electrochemical cell, in which the electrode area is defined by a microelectrode of the array. We also report carbon MEAs that are well suited for AMCM and are fabricated from pyrolyzed photoresist films (PPFs). PPF-MEAs with nominal electrode diameters of 5.5 µm are characterized by AMCM, standard macroscale electrochemical methods, and finite element modeling. The versatility of AMCM is demonstrated by measurement of single Pt microparticles and by electrodeposition of shapecontrolled Pt nanoparticles.

Experimentally Modifiable Parameters and Their Relation to the Tonic Vibration Reflex in Chronic Hemiparetic Stroke.

The tonic vibration reflex (TVR), a reflexive muscle contraction resulting from muscle or tendon vibration, is a useful tool in assessing spinal motoneuron excitability, particularly in hyperexcitable conditions, such as in chronic hemiparetic stroke. The influence of experimental parameters, for example the type of vibratory stimulus and limb configuration, and their interactions on the TVR response in chronic stroke is unknown, yet this knowledge is crucial for designing experiments with reliable TVR responses. Therefore, we conducted a screening experiment of six potential driving factors affecting the TVR response, with a D-optimal split plot fractional design matrix consisting of thirty-two combinations for each of the four participants with chronic hemiparetic stroke. Our results suggest that pre-vibration muscle activation level, vibration frequency, and stimulus application force, are all significant contributors to the TVR response in chronic hemiparetic stroke, along with an interaction between elbow flexion angle and muscle activity level. This investigation highlights the sensitivity of the TVR response in chronic hemiparetic stroke and motivates future designed experiments in understanding this reflex as it relates to motoneuron excitability.

Clinical tests to determine femoral version category in people with chronic hip joint pain and asymptomatic controls.

STUDY DESIGN: Controlled laboratory cross-sectional. OBJECTIVES: To investigate the relationship between femoral version (FV), measured by MRI (FVMRI), Craig's test and hip rotation range of motion (ROM). To determine rotation ROM values associated with FVMRI categories: excessive anteversion, normal version and retroversion. BACKGROUND: Abnormal FV values are associated with hip disorders, such as osteoarthritis, structural instability, acetabular labral tears and femoroacetabular impingement. Clinical assessment of FV may allow clinician to identify the effect of bony abnormalities on hip rotation ROM to guide clinical decisions. METHODS: Thirty-eight participants with chronic hip joint pain (CHJP) and 38 matched controls participated. MRI was used to determine FVMRI. A digital inclinometer was used to assess Craig's test, hip internal rotation (IR) and external rotation (ER) with hip flexed to 90° (90°), and hip IR/ER with hip in neutral flexion/extension (0°). ROM differences (ROMdif) were determined by subtracting ER from IR. Pearson correlation coefficients were used to assess the relationship between FVMRI and clinical variables. One-way analysis of variance (ANOVA) was used to compare rotation ROM among FVMRI categories. RESULTS: There were no differences between CHJP and control groups in demographics, FVMRI, Craig's test or ROM. ROMdif0° showed the highest correlation (r = 0.63) with FVMRI, then IR90° (r = 0.61) and Craig's test (r = 0.61). Differences were noted among FVMRI categories for rotation ROM except hip ER90°. CONCLUSION: Hip rotation ROM and Craig's test may be used for screening when imaging is not indicated. A 20° difference between hip IR and ER ROM would be suggestive of abnormal FV.

Limb position drift results from misalignment of proprioceptive and visual maps.

Previous work (Brown et al., 2003a,b) has shown that limb position drifts when individuals make repetitive movements in the absence of visual feedback. The purpose of this study was to examine whether limb position drift might reflect a misalignment in visual and proprioceptive maps by examining the nature of information used to specify new movements from a drifted limb position. In a virtual reality (VR) environment, participants made continuous movements with their dominant right hand between two targets positioned 15cm apart, paced by a 0.625-Hz metronome. After 5 cycles, cursor feedback of the hand was removed for the next 44 cycles, which induced an average drift in hand position of roughly 5cm. On the 50th cycle, participants were required to move to one of 6 new targets from the drifted hand position. Kinematic analysis indicated that movement direction was unambiguously determined by the visual input marked by the original start position, or the last-seen hand position. Forward dynamics analysis revealed that current limb configuration was used to inform joint torques to produce this parallel direction. For new movement specification, accurate proprioceptive information about the drifted limb position was used, even though it was apparently not available for detecting drift in the first place. Movement distance varied directly with the extent of limb drift, although the differentiation of visual and proprioceptive control of distance could not be analyzed, as our control conditions were not significantly different for this measure. We suggest that movement drift, in the absence of visual feedback during cyclic repetitive movements, reflects a misalignment between largely accurate visual and proprioceptive maps, rather than a weighted fusion of the two modalities.

Lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays). To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key learnings and recommendations related to future EDSP evaluations emanated from the collective sessions.

Dose-response approaches for nuclear receptor-mediated modes of action for liver carcinogenicity: Results of a workshop.

A public workshop, organized by a Steering Committee of scientists from government, industry, universities and research organizations, was held at the National Institute of Environmental Health Sciences (NIEHS) in September, 2010. The workshop explored the dose-response implications of toxicant modes of action (MOA) mediated by nuclear receptors. The dominant paradigm in human health risk assessment has been linear extrapolation without a threshold for cancer, and estimation of sub-threshold doses for non-cancer and (in appropriate cases) cancer endpoints. However, recent publications question the application of dose-response modeling approaches with a threshold. The growing body of molecular toxicology information and computational toxicology tools has allowed for exploration of the presence or absence of sub-threshold doses for a number of receptor-mediated MOAs. The workshop explored the development of dose-response approaches for nuclear receptor-mediated liver cancer, within a MOA Human Relevance Framework (HRF). Case studies addressed activation of the AHR, the CAR and the PPARα. This article describes the workshop process, key issues discussed and conclusions. The value of an interactive workshop approach to apply current MOA/HRF frameworks was demonstrated. The results may help direct research on the MOA and dose-response of receptor-based toxicity, since there are commonalities for many receptors in the basic pathways involved for late steps in the MOA, and similar data gaps in early steps. Three additional papers in this series describe the results and conclusions for each case-study receptor regarding its MOA, relevance of the MOA to humans and the resulting dose-response implications.

Bony abnormalities of the hip joint: a new comprehensive, reliable and radiation-free measurement method using magnetic resonance imaging.

OBJECTIVES: To develop comprehensive and reliable radiation-free methods to quantify femoral and acetabular morphology using MRI. METHODS: 32 hips (16 subjects, 6 with intra-articular hip disorder (IAHD); 10 controls) were included. A 1.5T magnetic resonance system was used to obtain 3D fat suppressed gradient echo images at the pelvis and distal femora. After acquisition, pelvic images were post-processed to correct for coronal, axial and sagittal rotation. Measurements performed included acetabular version (AV), femoral version (FV), lateral center edge angle (LCEA), femoral neck angle (FNA) and alpha angle (AA) at 3, 2, 1 and 12 o'clock. Two experienced raters, a musculoskeletal radiologist and an orthopaedic physical therapist, and a novice rater, a research assistant, completed reliability testing. Raters measured all hips twice with minimum 2 weeks between sessions. Intraclass Correlation Coefficients were used to determine rater reliability; standard error of measurements was reported to estimate the reasonable limits of the expected error in the different raters' scores. RESULTS: Interrater reliability was good to excellent for all raters for AV, FV, FNA, and LCEA (ICCs: 0.82-0.98); good to excellent between experienced raters (ICCs: 0.78-0.86) and poor to good between novice and experienced raters (ICCs: 0.23-0.78) for AA. Intrarater reliability was good to excellent for all raters for AV, FV and FNA (ICCs: 0.93-0.99); for one experienced and novice rater for LCEA (ICCs: 0.84-0.89); moderate to excellent for the experienced raters for AA (ICCs: 0.72-0.89). Intrarater reliability was poor for the second experienced rater for LCEA (ICC: 0.56), due to a single measurement error and for the novice rater for AA (ICCs: 0.17-0.38). CONCLUSION: We described MRI methods to comprehensively assess femoral and acetabular morphology. Measurements such as AV, FV and FNA and the LCEA can be made reliably by both experienced and novice raters, however the AA measurement was reliable only among experienced raters.

Peer consultation on relationship between PAC profile and toxicity of petroleum substances.

An expert peer consultation panel reviewed a report by the PAC Analysis Task Group, which hypothesized that systemic, developmental, and reproductive toxicity observed in repeated-dose dermal toxicity studies was related to polycyclic aromatic compound (PAC) content. Peer consultations seek to solicit scientific and technical input from experts on the scientific basis and merits of the subject report. This peer consultation panel included nine scientists with expertise in petroleum chemistry, biostatistics, toxicology, risk assessment, structure activity, and reproductive and developmental toxicology. The panel evaluated the technical quality of the PAC report and provided recommendations for improving the statistical and biological approaches. The PAC report authors revised their methods and documentation, which are published elsewhere in this supplement. A review of the post peer consultation manuscripts confirmed that many of the key suggestions from expert panel members were considered and incorporated. In cases where the PAC report authors did not fully incorporate panel suggestions from the peer consultation, they have provided an explanation and support for their decision. This peer consultation demonstrates the value of formal engagement of peers in development of new scientific methods and approaches.

Solid-pseudopapillary tumour of the pancreas as a rare cause of gastric outlet obstruction: a case report.

The presence of a large bulky pancreatic tumour in a young female should raise suspicions of the diagnosis of solid-pseduopapillary tumour of the pancreas.This rare tumour has the characteristics of a low-grade malignancy with indolent behaviour. Most patients present with vague non-specific abdominal pain resulting in delayed diagnosis. The light microscopic features show solid areas alternating with pseudopapillary formations. Metastases are frequently amenable to resection.Favourable prognosis with long-term survival has been shown even in patients with metastatic disease. Herein we present the case of a 21 year-old female patient of Afro-Caribbean extract who presented with gastric outlet obstruction from a large pancreatic tumour.

Engaging expert peers in the development of risk assessments.

The participation of external technical experts in the development of risk assessment documents and methodologies has expanded and evolved in recent years. Many government agencies and authoritative organizations have experts peer review important works to evaluate the scientific and technical defensibility and judge the strength of the assumptions and conclusions (OMB, 2004; IPCS, 2005; IARC, 2006; Health Canada, 2007; U.S. EPA, 2006). Expert advice has been solicited in other forms of peer involvement, including peer consultation in, for example, the U.S. EPA's Voluntary Children's Chemical Evaluation Program (VCCEP). This article discusses how the principles and practices of peer review can be extended to other types of peer involvement activities (i.e., peer input and peer consultation) to develop high-quality risk assessment work products. A comprehensive process for incorporating peer input, peer consultation, and peer review into risk assessment science is outlined. Four key principles for peer involvement-independence, inclusion of appropriate experts, transparency, and a robust scientific process-are discussed. Recent examples of peer involvement in the development of Health Canada's Priority Substances and Domestic Substance List (DSL) programs under the Canadian Environmental Protection Act (CEPA) serve to highlight the concepts.

VCCEP pilot: progress on evaluating children's risks and data needs.

The Voluntary Children's Chemical Evaluation Program (VCCEP) is designed to provide information to the public on children's potential health risks associated with chemical exposures. The key question of the VCCEP is whether the potential hazards, exposures, and risks to children have been adequately characterized, and, if not, what additional data are necessary. To answer this question, manufacturers or importers of 23 chemicals were asked by the U. S. Environmental Protection Agency (U.S. EPA) to sponsor their chemicals in the first tier of a pilot program. These chemicals were selected for evaluation because they have been found as contaminants in human tissue or fluids (adipose tissue, blood, breath, breast milk, or urine); food and water children may eat and drink; or air children may breathe (including residential or school air). Under the VCCEP framework, sponsoring companies agree to prepare Tier 1 hazard, exposure, and risk assessments on the individual chemicals, and identify the need for additional data. These assessment documents are submitted to the U.S. EPA and subsequently undergo review by experts in an independent peer consultation meeting that is open to the public. Following this peer consultation process, the U.S. EPA reviews each submission and makes a data-needs determination, which may include requesting further data collection or generation by the sponsor. Sponsoring companies then decide whether to volunteer for the next tier and collect or generate the requested data. The purpose of this article is to describe the VCCEP process and to review and present the key findings from the first set of chemicals that have been fully or partially evaluated under the pilot program (vinylidene chloride, decabromodiphenyl ether, pentabromodiphenyl ether, octabromodiphenyl ether, acetone, methyl ethyl ketone, decane, undecane, and dodecane). Specifically, we provide a brief summary of the sponsors' submissions, the peer consultation panels' discussions, and the U.S. EPA's data-needs decisions. Although we do not attempt to conduct independent analyses of the underlying data, we do identify a number of common themes that have emerged during implementation of the pilot program and discuss several key issues that could become important in the future. The information presented here should be useful for various parties interested in the progress of the VCCEP and the results of the initial (Tier 1) children's assessments.

Weighing health benefit and health risk information when consuming sport-caught fish.

Fish consumers may incur benefits and risks from eating fish. Health advisories issued by states, tribes, and other entities typically include advice about how to limit fish consumption or change other behaviors (e.g., fish cleaning or cooking) to reduce health risks from exposure to contaminants. Eating fish, however, may provide health benefits. Risk communicators and fish consumers have suggested the importance of including risk comparison information, as well as health risk-benefit comparisons in health advisory communications. To improve understanding about how anglers fishing in waters affected by health advisories may respond to such risk-risk or risk-benefit information, we surveyed Lake Ontario (NY, USA) anglers. We interviewed by telephone 4,750 anglers, 2,593 of which had fished Lake Ontario in the past 12 months and were sent a detailed mail questionnaire (1,245 responded). We posed questions varying the magnitude of health risks and health benefits to be gained by fish consumption, and varied the population affected by these risks and benefits (anglers, children, women of childbearing age, and unborn children). Respondents were influenced by health benefit and health risk information. When risks were high, most respondents would eat less fish regardless of the benefit level. When risks were low, the magnitude of change in fish consumption was related to level of benefit. Responses differed depending on the question wording order, that is, whether "risks" were posed before "benefits." For a given risk-benefit level, respondents would give different advice to women of childbearing age versus children, with more conservative advice (eat less fish) provided to women of childbearing age. Respondents appeared to be influenced more strongly by risk-risk comparisons (e.g., risks from other foods vs. risks from fish) than by risk-benefit comparisons (e.g., risks from fish vs. benefits from fish). Risk analysts and risk communicators should improve efforts to include risk-risk and risk-benefit comparisons in communication efforts, and to clarify to whom the health risks and benefits from fish consumption may accrue.

Review of procedures for protecting human subjects in recent clinical studies of pesticides.

Arguments have been made for and against the regulatory use of data from human subjects on both scientific and ethical grounds. One argument against the use of data from human clinical studies involving pesticides asserts that such data are obtained from studies that do not follow the Common Rule (40 CFR 26), which provides procedures for protecting human subjects in studies funded by federal agencies, including the U.S. Environmental Protection Agency (U.S. EPA). Although privately conducted studies using human subjects are not legally subject to or required to comply with the Common Rule, the protections of the Declaration of Helsinki and the International Conference on Harmonisation (ICH) Good Clinical Practice are commonly followed. We sought to answer the question of whether recent human clinical studies with insecticides performed according to Good Clinical Practice provided volunteers with the same protections as the Common Rule. All three sets of guidance have in common the intent to protect volunteer human subjects by providing standards for the conduct of studies in which they participate. This analysis compares the elements of the Common Rule with comparable elements from the Declaration of Helsinki and Good Clinical Practice to evaluate similarities and differences in procedural requirements. It then evaluates the documentation from 15 recent human studies of twelve insecticides conducted at four clinical laboratories in order to determine whether the conduct of those studies is consistent with the protections of the Common Rule. There were some cases for which we could not verify compliance with certain Common Rule elements; however, based on our evaluation it is apparent that the studies we reviewed were conducted in a manner substantially consistent with the fundamental protections of the Common Rule-voluntary participation, informed consent, and review by an ethical committee or institutional review board.

Human health risk assessment: selected Internet and world wide web resources.

The world wide web (WWW) has become a valuable source of 24 hour-a-day access to information needed by human health risk assessors. Various web sites and other Internet resources provide information needed for human hazard identification, dose-response evaluation, exposure assessment, risk characterization, and risk management. Information on risk communication is also available. Substantial collections of information on multiple aspects of risk assessment are found in sites sponsored by RiskWorld, the (US) EPA's National Center for Environmental Assessment (NCEA), the (US) National Library of Medicine's TOXNET, the (US) Agency for Toxic Substances and Disease Registry (ATSDR), and the International Programme on Chemical Safety (IPCS). Also valuable are various web sites providing information on the physical and chemical properties of chemicals, the environmental fate and transport of chemicals, government regulations, and guidance and training for performing risk assessments. Several professional societies and other organizations have web sites addressing risk assessment issues and information, and there are Internet mailing lists for online help and for sharing information and perspectives. We classify selected web sites according to user needs and provide the reader with a collection of selected sites that can serve as entry points to risk assessment-related web resources.