Identifying the causal mechanisms of the quiet eye.

Scientists who have examined the gaze strategies employed by athletes have determined that longer quiet eye (QE) durations (QED) are characteristic of skilled compared to less-skilled performers. However, the cognitive mechanisms of the QE and, specifically, how the QED affects performance are not yet fully understood. We review research that has examined the functional mechanism underlying QE and discuss the neural networks that may be involved. We also highlight the limitations surrounding QE measurement and its definition and propose future research directions to address these shortcomings. Investigations into the behavioural and neural mechanisms of QE will aid the understanding of the perceptual and cognitive processes underlying expert performance and the factors that change as expertise develops.

Rapid changes in corticospinal excitability during force field adaptation of human walking.

Force field adaptation of locomotor muscle activity is one way of studying the ability of the motor control networks in the brain and spinal cord to adapt in a flexible way to changes in the environment. Here, we investigate whether the corticospinal tract is involved in this adaptation. We measured changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in the tibialis anterior (TA) muscle before, during, and after subjects adapted to a force field applied to the ankle joint during treadmill walking. When the force field assisted dorsiflexion during the swing phase of the step cycle, subjects adapted by decreasing TA EMG activity. In contrast, when the force field resisted dorsiflexion, they increased TA EMG activity. After the force field was removed, normal EMG activity gradually returned over the next 5 min of walking. TA MEPs elicited in the early swing phase of the step cycle were smaller during adaptation to the assistive force field and larger during adaptation to the resistive force field. When elicited 5 min after the force field was removed, MEPs returned to their original values. The changes in TA MEPs were larger than what could be explained by changes in background TA EMG activity. These effects seemed specific to walking, as similar changes in TA MEP were not seen when seated subjects were tested during static dorsiflexion. These observations suggest that the corticospinal tract contributes to the adaptation of walking to an external force field.

Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles.

Plantar flexor series elasticity can be used to dissociate muscle-fascicle and muscle-tendon behavior and thus afferent feedback during human walking. We used electromyography (EMG) and high-speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behavior in 19 healthy volunteers as they walked across a platform. On random trials, the platform was dropped (8 cm, 0.9 g acceleration) or held at a small inclination (up to +/-3 degrees in the parasagittal plane) with respect to level ground. Dropping the platform in the mid and late phases of stance produced a depression in the soleus muscle activity with an onset latency of about 50 ms. The reduction in ground reaction force also unloaded the plantar flexor muscles. The soleus muscle fascicles shortened with a minimum delay of 14 ms. Small variations in platform inclination produced significant changes in triceps surae muscle activity; EMG increased when stepping on an inclined surface and decreased when stepping on a declined surface. This sensory modulation of the locomotor output was concomitant with changes in triceps surae muscle fascicle and gastrocnemius tendon length. Assuming that afferent activity correlates to these mechanical changes, our results indicate that within-step sensory feedback from the plantar flexor muscles automatically adjusts muscle activity to compensate for small ground irregularities. The delayed onset of muscle fascicle movement after dropping the platform indicates that at least the initial part of the soleus depression is more likely mediated by a decrease in force feedback than length-sensitive feedback, indicating that force feedback contributes to the locomotor activity in human walking.

Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes.

Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group clinical trial designed to test the hypothesis that aggressive reduction in insulin resistance early in the course of T2DM is beneficial for prolongation of glycemic control, as well as improvement in associated abnormalities and risk factors. Specifically, the trial compares treatment with metformin with two alternate approaches, one pharmacologic (combining metformin treatment with rosiglitazone) and one combining metformin with an intensive lifestyle intervention program. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10-17 yr of age, within 2 yr of diagnosis of diabetes at the time of randomization, lack evidence of autoimmunity, and have sustained C-peptide secretion. The primary outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for 6 consecutive months. Secondary outcomes include the effect of the alternative treatments on insulin secretion and resistance, body composition, nutrition, physical activity and fitness, cardiovascular risk monitoring, microvascular complications, quality of life, depression, eating pathology, and resource utilization. TODAY is the first large-scale, systematic study of treatment effectiveness for T2DM in youth. When successfully completed, this study will provide critical new information regarding the natural history of T2DM in youth, the benefits of initiating early aggressive treatment in these patients, and the efficacy of delivering an intensive and sustained lifestyle intervention to children with T2DM.

Evidence for a supraspinal contribution to the human quadriceps long-latency stretch reflex.

In sitting humans a rapid unexpected lengthening of the knee extensors elicits a stretch reflex (SR) response as recorded by the electromyogram (EMG) which comprises multiple bursts. These are termed short latency responses (SLR), medium latency responses (MLR) and long latency responses (LLR). The aim of this study was to determine if a transcortical pathway contributes to any of these bursts. Flexion perturbations (amplitude =4 degrees, velocity=150 degrees/s) were imposed on the right knee joint of sitting subjects (n=11). The effect of the perturbation on the electromyographic (EMG) response of the pre-contracted quadriceps muscle to magnetic stimulation of the contralateral motor cortex was quantified. Transcranial magnetic stimulation (TMS) was applied to elicit a compound motor evoked potential (MEP) in the target muscle rectus femoris (RF), in the vastus lateralis (VL), vastus medialis (VM) and biceps femoris (BF). The MEP and SR were elicited either in combination or separately. When applied in combination the delay between the SR and the MEP varied from 0 to 150 ms in steps of 4, 5 and 10 ms. Somatosensory evoked potentials (SEPs) were recorded from four subjects during the imposed stretch to quantify the latency of the resulting afferent volley. Onset latencies of responses in RF were 25+/-2 ms for the SR and 20+/-4 ms for the MEP. The average SEP latency was 24+/-2 ms. A transcortical pathway thus has the potential to contribute to the RF SR no earlier than 54+/-6 ms (SEP + MEP + 10 ms central processing delay) following the stretch onset. The duration of the total reflex burst was 85+/-6 ms. Significant facilitation of the MEP commenced at 78 ms, coinciding with the LLR component of the stretch response. No such facilitation was observed in the synergists VL and VM, or in the antagonist BF. Our results indicate that the LLR of the RF likely involves supraspinal pathways. More importantly, of the investigated muscles, this involvement of higher centers in the shaping of the LLR is specific to the RF muscle during the investigated task.

Trends in work-related musculoskeletal disorder reports by year, type, and industrial sector: a capture-recapture analysis.

BACKGROUND: Musculoskeletal disorders (MSD) are thought to be declining based on Bureau of Labor Statistics survey data, but there is also evidence of MSD under-reporting, raising the possibility of contrary trends. The magnitude of MSD under-reporting over time, and its industry distribution have not been adequately described. METHODS: Capture-recapture analysis of 7 years of Connecticut MSD (1995-2001), utilizing Workers' Compensation and physician reporting data was performed. RESULTS: Only 5.5%-7.9% of MSD cases appear to be reported to Workers Compensation annually. The capture-recapture estimated average annual rate for upper-extremity MSD was 133.1 per 10,000 employed persons, far above BLS rates. By industry, Manufacturing, State Government, and the Finance/Insurance/Real Estate sectors all had significantly higher MSD rates than Wholesale/Retail Trade. CONCLUSIONS: Upper-extremity MSD appears to be significantly under-reported, and rates are not decreasing over time. Capture-recapture methods provide an improved surveillance method for monitoring temporal trends in injury rates.

Compost odor control using high carbon wood ash.

A pilot study on the feasibility of using high carbon wood ash to control composting odor emissions was conducted at a green material composting facility. The study's treatments consisted of adding 0%, 12.5%, and 25% high carbon wood ash by volume to green-material compost feedstock in three separate windrows. The wood ash has properties similar to activated carbon with an active surface area of 105 square metres per gram on a dry weight basis. The odorant emission data suggest that the higher percentage wood ash treatment results in the most effective control of most compost odors and that wood ash provides effective treatment of volatile fatty acids and some aldehydes and ketones. The 25% wood ash treatment resulted in more effective treatment of odors for a longer time period than the 12.5% treatment. Acetaldehyde had the highest concentration in the control (14,000 times its odor threshold concentration), was reduced by high carbon ash by over 97% but remained 386 times its reported odor threshold concentration after 14 days. Ethyl mecaptan and ammonia were produced in the process and were also over their reported human detection limits.

Constant vigilance: mothers' work parenting young children with type 1 diabetes.

Little is known about the experiences of mothers raising young children with type 1 diabetes. The purpose of this study was to describe the day-to-day experiences of mothers (N = 28) raising young children under 4 years of age with type 1 diabetes. Descriptive, naturalistic inquiry principles were used to interview subjects, as well as to manage and analyze the data. The mothers reported using the management behavior of constant vigilance. Their concerns about hypoglycemia and providing competent care reflected the interplay between their fears and profound sense of responsibility for managing the disease. Mothers reported having to learn the management behaviors and to occasionally adjust the day-to-day management when either severe hypoglycemia or developmental milestones occurred. Although mothers initially had feelings of incompetence with the care they provided, with time, they became very skilled. There were also reports of limited access to babysitting, child care, or respite services. The intensity of their constant vigilance associated with their concerns, responsibility, and lack of supports resulted in some mothers having physical and/or emotional problems. The findings of the study highlight the importance of identifying family and/or community resources that may provide mothers with support that could reduce some of the tremendous stress and burden of responsibility experienced after diagnosis of diabetes.

Thermoconditional modulation of the pleiotropic sensitivity phenotype by the Saccharomyces cerevisiae PRP19 mutant allele pso4-1.

The conditionally-lethal pso4-1 mutant allele of the spliceosomal-associated PRP19 gene allowed us to study this gene's influence on pre-mRNA processing, DNA repair and sporulation. Phenotypes related to intron-containing genes were correlated to temperature. Splicing reporter systems and RT-PCR showed splicing efficiency in pso4-1 to be inversely correlated to growth temperature. A single amino acid substitution, replacing leucine with serine, was identified within the N-terminal region of the pso4-1 allele and was shown to affect the interacting properties of Pso4-1p. Amongst 24 interacting clones isolated in a two-hybrid screening, seven could be identified as parts of the RAD2, RLF2 and DBR1 genes. RAD2 encodes an endonuclease indispensable for nucleotide excision repair (NER), RLF2 encodes the major subunit of the chromatin assembly factor I, whose deletion results in sensitivity to UVC radiation, while DBR1 encodes the lariat RNA splicing debranching enzyme, which degrades intron lariat structures during splicing. Characterization of mutagen-sensitive phenotypes of rad2Delta, rlf2Delta and pso4-1 single and double mutant strains showed enhanced sensitivity for the rad2Delta pso4-1 and rlf2Delta pso4-1 double mutants, suggesting a functional interference of these proteins in DNA repair processes in Saccharomyces cerevisiae.

Mutant pso8-1 of Saccharomyces cerevisiae, sensitive to photoactivated psoralens, UV radiation, and chemical mutagens, contains a rad6 missense mutant allele.

A novel mutant isolate of Saccharomyces cerevisiae, sensitive to photoactivated mono- and bi-functional psoralens, to UV at 254 nm (UVC), and to nitrosoguanidine, was found to complement the photoactivated psoralen-sensitivity phenotype conferred by the pso1- pso7 mutations and was therefore named pso8-1. A constructed pso8-1 rad4-4 double mutant was super-sensitive to UVC, thus indicating a synergistic interaction of the two mutant alleles. Molecular cloning via complementation of the pso8 mutant's sensitivity phenotype and genetic studies revealed that pso8 is allelic to RAD6. While a pso8-1 mutant had low mutagen-induced mutability, homoallelic diploids showed nearly wild-type sporulation. Sequence analysis of the mutant allele showed pso8-1 to contain a novel, hitherto undescribed T-->C transition in nucleotide position 191, leading to a substitution by leucine of a highly conserved proline at position 64, Rad6-[P64L], which may have severe consequences for the tertiary structure (and hence binding to Rad18p) of the mutant protein.

Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans.

1. The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. 2. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h(-1) with the left ankle attached to a portable stretching device. The soleus stretch reflex was elicited by applying small amplitude (approximately 8 deg) dorsiflexion perturbations 200 ms after heel contact. 3. Short and medium latency responses were observed with latencies of 55 +/- 5 and 78 +/- 6 ms, respectively. The short latency response was velocity sensitive (P < 0.001), while the medium latency response was not (P = 0.725). 4. Nerve cooling increased the delay of the medium latency component to a greater extent than that of the short latency component (P < 0.005). 5. Ischaemia strongly decreased the short latency component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). 6. Two hours after the ingestion of tizanidine, an alpha(2)-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P = 0.007), whereas the short latency component was unchanged (P = 0.653). 7. An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. 8. Our results support the hypothesis that, during walking the medium latency component of the stretch reflex resulting from an unexpected perturbation is contributed to by group II muscle afferents.

Reinforcement of occupational history taking: a success story.

BACKGROUND: This article describes the results of a retrospective study of 3 classes of medical students who participated in a targeted occupational and environmental health curriculum at the University of Connecticut School of Medicine. PURPOSE: We wanted to determine if targeted focused curricular interventions which integrated occupational and environmental health principles into routine history taking would result in increased scores on the number of questions posed during the Clinical Skills Assessment Program in the 4th year. METHODS: We analyzed Clinical Skills Assessment Program questions for 3 graduating medical school classes from 1997 to 1999. RESULTS: It appears that intense, focused training may increase the occupational and environmental questions which students ask. By revisiting the components of the history during the 3rd year, the final assessment of 4th-year students substantially and significantly increased. CONCLUSIONS: Those who wish to stem the decline in history-taking skills as students enter their clinical years should consider reinforcing these skills using structured programs and practice in areas of the history that are traditionally neglected but recognized as essential in gathering comprehensive data on patients.

Clinical and psychosocial factors associated with achievement of treatment goals in adolescents with diabetes mellitus.

PURPOSE: To examine the following questions with regard to the initiation of a new intensive management program for adolescents with Type 1 diabetes mellitus: (a) What clinical and psychosocial factors are associated with achievement of metabolic control treatment goals after 1 year? and (b) What baseline clinical and psychosocial factors are associated with improvement in the quality of life after 12 months? METHODS: Eighty-one subjects (of 83 who began; aged 14.3 +/- 2.0 years at entry; 48 females, 33 males; 95% white; diabetes duration 8.9 +/- 3.9 years) with Type 1 diabetes completed 12 months of follow-up in a study of intensified treatment of diabetes. Assessments at baseline and at 12 months used the Diabetes Quality of Life for Youth scale, the Self-efficacy for Diabetes Scale, the Children's Depression Inventory, the Issues in Coping with Diabetes Scale, and the Diabetes Family Behavior Scale. Data were analyzed using multiple and logistic regression. RESULTS: From a baseline of >9%, HbA1c levels decreased to a mean of 7.8 +/- 0.7%, with 30% of the subjects achieving our treatment goal of

Soleus stretch reflex during cycling.

The modulation and strength of the human soleus short latency stretch reflex was investigated by mechanically perturbing the ankle during an unconstrained pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A torque pulse was applied to the crank at various positions during the crank cycle, producing ankle dorsiflexion perturbations of similar trajectory. The stretch reflex was greatest during the power phase of the crank cycle and was decreased to the level of background EMG during recovery. Matched perturbations were induced under static conditions at the same crank angle and background soleus EMG as recorded during the power phase of active pedaling. The magnitude of the stretch reflex was not statistically different from that during the static condition throughout the power phase of the movement. The results of this study indicate that the stretch reflex is not depressed during active cycling as has been shown with the H-reflex. This lack of depression may reflect a decreased susceptibility of the stretch reflex to inhibition, possibly originating from presynaptic mechanisms.

How do Australian doctors with different pre-medical school backgrounds perform as interns?

AIM: To assess whether there is any advantage to be gained with respect to performance in the first year of postgraduate medical training (internship) by selecting medical school candidates with different educational backgrounds. Specifically, we were interested in comparing the performance ratings of interns who entered medical school with secondary (directly from high school) or tertiary (at least one year of a university degree) level educational backgrounds. FOCUS: We compared the performance ratings of interns according to the subjects or degree undertaken at a secondary or tertiary level, respectively. The effects of age and gender were also examined to determine their influence on performance ratings. METHOD: All graduates (N=235) from the University of Newcastle Medical School, Australia who commenced their intern year in the state of New South Wales from 1993 to 1996 inclusive were eligible for the study. The outcome measure was a score derived from a valid and reliable clinical supervisor rating scale. Independent variables were level of previous educational experience (secondary or tertiary entry), and subjects studied by secondary level entrants (predominantly science or equal proportions of humanities and science) and degree undertaken by tertiary level entrants (arts or science or allied health or nursing). RESULTS: The records of 173 (73% of eligible sample) were included in the analyses. There were no significant differences between the mean ratings of interns with respect to previous educational background, subjects studied at secondary school or degree undertaken. Age and gender did not significantly affect performance ratings.

CPMG sequences with enhanced sensitivity to chemical exchange.

Improved relaxation-compensated Carr-Purcell-Meiboom-Gill pulse sequences are reported for studying chemical exchange of backbone 15N nuclei. In contrast to the original methods [J. P. Loria, M. Rance, and A. G. Palmer, J. Am. Chem. Soc. 121, 2331-2332 (1999)], phenomenological relaxation rate constants obtained using the new sequences do not contain contributions from 1H-1H dipole-dipole interactions. Consequently, detection and quantification of chemical exchange processes are facilitated because the relaxation rate constant in the limit of fast pulsing can be obtained independently from conventional 15N spin relaxation measurements. The advantages of the experiments are demonstrated using basic pancreatic trypsin inhibitor.

Culturing the throat to protect the heart: Dr. Milton Markowitz and the prevention of rheumatic fever.

The purpose of this article is to briefly review how the understanding of rheumatic fever has evolved over the last 50 years. Particular emphasis is given to the identification of the Group A streptococcus as the causative agent of rheumatic fever and the use of antibiotics to treat and prevent rheumatic fever. Throughout his 50-year career, Dr. Milton Markowitz, former chairman of the department of pediatrics at the University of Connecticut School of Medicine, has been involved in these advances as an international expert on rheumatic fever prevention. Using archival materials, including some of the earliest literature descriptions of rheumatic fever, as well as an extended interview with Dr. Markowitz, the authors present a unique personal perspective both on the history of rheumatic fever and the context within which the scientific advances that have led to contemporary treatment and prevention strategies have evolved.

Interventions for children with diabetes and their families.

The purpose of this review is to examine the research literature on interventions for children with type 1 diabetes and their families, with a specific focus on three types of intervention (educational and psychosocial/behavioral interventions that focus on individuals with diabetes and family interventions for families, usually parents, of individuals with diabetes). The aim of the review is to determine what interventions produce what outcomes in what populations of children and families. The review includes articles that met the following criteria: (a) empirical study reporting the impact of an intervention on such outcomes as knowledge, behavior, self-care, and metabolic control; (b) children with type 1 diabetes and/or their families as primary subjects; (c) publication between 1980 and January 1, 1999; and (d) publication in English. A total of 41 published papers were included. On the basis of this review, conclusions are as follows: (a) Educational interventions are useful in improving diabetes knowledge but not consistently helpful in improving metabolic control; (b) psychosocial interventions, especially coping skills training and peer support, assist primarily adolescents to improve adjustment and sometimes metabolic control; and (c) family interventions may be helpful in reducing parent-child conflict about diabetes management and care.