Registry and survey of circadian rhythm sleep-wake disorder patients.

Objective: Circadian Sleep Disorders Network has created a registry of circadian rhythm sleep-wake disorder (CRSWD) patients, and a survey of their experiences. The purpose of the registry is to provide volunteers willing to participate in research; the purpose of the survey is to fill some of the knowledge gaps on these disorders, including information on subjective patient experience and the efficacy and durability of treatments.Researchers are invited to contact Circadian Sleep Disorders Network for permission to use the registry to find potential research participants, and to further analyze the survey data. Patients: Over 1627 patients have participated; 1298 have completed the entire survey. Here we present results based on the 479 clinically diagnosed CRSWD patients. Methods: The survey covers a variety of topics relating to CRSWDs, including diagnosis, comorbidities, treatments, and work/educational accommodations. Conclusions: Results of this survey diverged from much of the literature. More than half the participants reported tiredness even when sleeping on their preferred schedule. While depression may cause sleep problems, our data suggests that sleep/circadian problems often precede depression.There were more people suffering from sighted non-24-hour sleep-wake rhythm disorder than some of the literature would lead us to expect.Current treatments did not appear to be helpful to a large percentage of our participants. Most of them did not find light therapy helpful and nearly all participants who tried phase-delay chronotherapy reported at best only short-term improvement. A sizable proportion of people who tried phase-delay chronotherapy subsequently developed non-24-hour sleep-wake rhythm disorder.

Alpha oscillations and stimulus-evoked activity dissociate metacognitive reports of attention, visibility, and confidence in a rapid visual detection task.

Variability in the detection and discrimination of weak visual stimuli has been linked to oscillatory neural activity. In particular, the amplitude of activity in the alpha-band (8-12 Hz) has been shown to impact the objective likelihood of stimulus detection, as well as measures of subjective visibility, attention, and decision confidence. Here we investigate how preparatory alpha in a cued pretarget interval influences performance and phenomenology, by recording simultaneous subjective measures of attention and confidence (experiment 1) or attention and visibility (experiment 2) on a trial-by-trial basis in a visual detection task. Across both experiments, alpha amplitude was negatively and linearly correlated with the intensity of subjective attention. In contrast with this linear relationship, we observed a quadratic relationship between the strength of alpha oscillations and subjective ratings of confidence and visibility. We find that this same quadratic relationship links alpha amplitude with the strength of stimulus-evoked responses. Visibility and confidence judgments also corresponded with the strength of evoked responses, but confidence, uniquely, incorporated information about attentional state. As such, our findings reveal distinct psychological and neural correlates of metacognitive judgments of attentional state, stimulus visibility, and decision confidence when these judgments are preceded by a cued target interval.

Antibiotic-Loaded Polymersomes for Clearance of Intracellular Burkholderia thailandensis.

Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.

Time contracts and temporal precision declines when the mind wanders.

Our perception of time varies considerably from moment to moment, but how this variability relates to endogenous fluctuations in attentional states has been neglected. Here, we tested the hypothesis that perceptual decoupling during spontaneous mind wandering episodes distorts interval timing. In two studies with different visual subsecond interval timing paradigms, participants judged their attentional state on a trial-by-trial basis. Mind wandering states were characterized by underestimation of temporal intervals and a decline in temporal discrimination. Further analyses suggested that temporal contraction during mind wandering, but not the decline in temporal discrimination, could be attributed in part to attentional lapses. By contrast, we did not find any robust evidence that metacognition pertaining to interval timing was altered during mind wandering states. These results highlight the role of transient fluctuations in attentional states in intraindividual variability in time perception and have implications for the perceptual consequences, behavioral markers, and costs and benefits, of mind wandering. (PsycINFO Database Record

Attentional sampling of multiple wagon wheels.

Attending to a periodic motion stimulus can induce illusory reversals of the direction of motion. This continuous wagon wheel illusion (c-WWI) has been taken to reflect discrete sampling of motion information by visual attention. An alternative view is that it is caused by adaptation. Here, we attempt to discriminate between these two interpretations by asking participants to attend to multiple periodic motion stimuli: The discrete attentional sampling account, but not the adaptation account, predicts a decrease of c-WWI temporal-frequency tuning with set size (with a single periodic motion stimulus the c-WWI is tuned to a temporal frequency of 10 Hz). We presented one to four rotating gratings that occasionally reversed direction while participants counted reversals. We considered reversal overestimations as manifestations of the c-WWI and determined the temporal-frequency tuning of the illusion for each set size. Optimal temporal frequency decreased with increasing set size. This outcome favors the discrete attentional sampling interpretation of the c-WWI, with a sampling rate for each individual stimulus dependent on the number of stimuli attended.

Perceptual echoes at 10 Hz in the human brain.

The occipital alpha rhythm (∼10 Hz) is the most prominent electrophysiological activity in the awake human brain, yet its functional role and relation to visual perception are little understood. Transient stimuli normally elicit a short series of positive and negative deflections lasting between 300 and 500 ms: the visual-evoked potential (VEP). Alpha oscillations, on the other hand, are generally suppressed by transient visual input; they only augment in response to periodic ("steady-state") inputs around 10 Hz. Here, we applied reverse-correlation techniques to the visual presentation of random, nonperiodic dynamic stimulation sequences and found that the brain response to each stimulus transient was not merely a short-lived VEP but also included a strong ∼10 Hz oscillation that lasted for more than 1 s. In other words, the alpha rhythm implements an "echo" or reverberation of the input sequence. These echoes are correlated in magnitude and frequency with the observer's occipital alpha rhythm, are enhanced by visual attention, and can be rendered perceptually apparent in the form of ∼10 Hz flicker. These findings suggest a role for the alpha rhythm in the maintenance of sensory representations over time.

Trial-by-Trial Variations in Subjective Attentional State are Reflected in Ongoing Prestimulus EEG Alpha Oscillations.

Parieto-occipital electroencephalogram (EEG) alpha power and subjective reports of attentional state are both associated with visual attention and awareness, but little is currently known about the relationship between these two measures. Here, we bring together these two literatures to explore the relationship between alpha activity and participants' introspective judgments of attentional state as each varied from trial-to-trial during performance of a visual detection task. We collected participants' subjective ratings of perceptual decision confidence and attentional state on continuous scales on each trial of a rapid serial visual presentation detection task while recording EEG. We found that confidence and attentional state ratings were largely uncorrelated with each other, but both were strongly associated with task performance and post-stimulus decision-related EEG activity. Crucially, attentional state ratings were also negatively associated with prestimulus EEG alpha power. Attesting to the robustness of this association, we were able to classify attentional state ratings via prestimulus alpha power on a single-trial basis. Moreover, when we repeated these analyses after smoothing the time series of attentional state ratings and alpha power with increasingly large sliding windows, both the correlations and classification performance improved considerably, with the peaks occurring at a sliding window size of approximately 7 min worth of trials. Our results therefore suggest that slow fluctuations in attentional state in the order of minutes are reflected in spontaneous alpha power. Since these subjective attentional state ratings were associated with objective measures of both behavior and neural activity, we suggest that they provide a simple and effective estimate of task engagement that could prove useful in operational settings that require human operators to maintain a sustained focus of visual attention.

Visual perceptual load induces inattentional deafness.

In this article, we establish a new phenomenon of "inattentional deafness" and highlight the level of load on visual attention as a critical determinant of this phenomenon. In three experiments, we modified an inattentional blindness paradigm to assess inattentional deafness. Participants made either a low- or high-load visual discrimination concerning a cross shape (respectively, a discrimination of line color or of line length with a subtle length difference). A brief pure tone was presented simultaneously with the visual task display on a final trial. Failures to notice the presence of this tone (i.e., inattentional deafness) reached a rate of 79% in the high-visual-load condition, significantly more than in the low-load condition. These findings establish the phenomenon of inattentional deafness under visual load, thereby extending the load theory of attention (e.g., Lavie, Journal of Experimental Psychology. Human Perception and Performance, 25, 596-616, 1995) to address the cross-modal effects of visual perceptual load.

Load induced blindness.

Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005, for a review). Here we varied the level of perceptual load in a letter-search task and assessed its effect on the conscious perception of a search-irrelevant shape stimulus appearing in the periphery, using a direct measure of awareness (present/absent reports). Detection sensitivity (d') was consistently reduced with high, compared to low, perceptual load but was unaffected by the level of working memory load. Because alternative accounts in terms of expectation, memory, response bias, and goal-neglect due to the more strenuous high load task were ruled out, these experiments clearly demonstrate that high perceptual load determines conscious perception, impairing the ability to merely detect the presence of a stimulus--a phenomenon of load induced blindness.

Biomechanical characteristics of allogeneic cortical bone pins designed for fracture fixation.

The biomechanical characteristics of 1.2 mm diameter allogeneic cortical bone pins harvested from the canine tibia were evaluated and compared to 1.1 mm diameter stainless steel pins and 1.3 mm diameter polydioxanone (PDS) pins using impact testing and four-point bending. The biomechanical performance of allogeneic cortical bone pins using impact testing was uniform with no significant differences between sites, side, and gender. In four-point bending, cortical bone pins harvested from the left tibia (204.8 +/- 77.4 N/mm) were significantly stiffer than the right tibia (123.7 +/- 54.4 N/mm, P = 0.0001). The site of bone pin harvest also had a significant effect on stiffness, but this was dependent on interactions with gender and side. Site C in male dogs had the highest mean stiffness in the left tibia (224.4 +/- 40.4 N/mm), but lowest stiffness in the right tibia (84.9 +/- 24.2 N/mm). Site A in female dogs had the highest mean stiffness in the left tibia (344.9 +/- 117.4 N/mm), but lowest stiffness in the right tibia (60.8 +/- 3.7 N/mm). The raw and adjusted bending properties of 1.2 mm cortical bone pins were significantly better than 1.3 mm PDS pins, but significantly worse than 1.1 mm stainless steel pins (P < 0.0001). In conclusion, cortical bone pins may be suitable as an implant for fracture fixation based on initial biomechanical comparison to stainless steel and PDS pins used in clinical practice.

Synthesis and properties of melt-processable hyaluronan esters.

A series of melt-processable hyaluronan (HA) esters were synthesized for potential biomedical applications (e.g., hot molding with thermoplastic ultra high molecular weight polyethylene for total joint replacements or molding tissue engineering scaffold). A silylated complex of HA with cetyltrimethylammonium cations (silyl HA-CTA) was used as the starting material. The reactions were performed with acid chlorides as the acylation agents in xylenes or no solvent other than the acid chloride. The disappearance of all characteristic FT-IR vibration bands associated with the -OSi(CH3)3 groups and the appearance of the strong ester carbonyl peak at 1753 cm-1 demonstrated the success of esterification. Thermoplasticity was achieved when the length of aliphatic chains in the HA esters was equal to or greater than 10 carbon atoms. It was found that the longer the ester chain, the lower the melting point; thus, to meet various needs different melting temperatures can be obtained by adjusting the acid chloride chain length.

Assessing the dog as a model for human total hip replacement. Analysis of 38 canine cemented femoral components retrieved at post-mortem.

Post-mortem retrieval of canine, cemented femoral components was analysed to assess the performance of these implants in the dog as a model for human total hip replacement (THR). Mechanical testing and radiological analysis were performed to determine the stability of the implant and the quality of the cement. Thirty-eight implants from 29 dogs were retrieved after time intervals ranging from 0.67 to 11.67 years. The incidence of aseptic loosening was 63.2%, much higher than in human patients (6% in post-mortem studies). Failure of the femoral implants began with debonding at the cement-metal interface, similar to that in implants in man. The incidence of aseptic loosening was much lower in bilateral than in unilateral implants. Significant differences were observed for three different designs of implant. While the dog remains the animal model of choice for THR, results from this study provide insight into interspecies differences in the performance of implants. For example, the performance of THR in dogs should be compared with that in young rather than in elderly human patients.

A comparison of canine and human UHMWPE acetabular component wear.

The objective of this study is to compare the wear patterns and wear rates of ultra high molecular weight polyethylene in acetabular components used in human and canine total hip arthroplasty. This comparison may help elucidate both the appropriateness of the dog as an orthopaedic model for humans as well as the clinical performance of canine total hip arthroplasties. Twenty-nine postmortem retrieved and three revision retrieved canine acetabular components were analyzed. The volumetric wear rates in the canine postmortem retrievals of 6.9 mm3/year for modular (BioMedtrix) implants and 8.3 mm3/yr for monolithic (Richards) implants were considerably lower than those of 35.0 mm3/yr measured in human postmortem retrievals, reported using a similar measurement technique. The canine revision retrieval volumetric wear rate of 34.8 mm3/yr was significantly higher than postmortem rates, yet considerably lower than the reported retrieval rates of 62.0 mm3/yr seen in humans. These results may have negative implications for the use of the dog as an orthopaedic model for humans in total hip arthroplasty studies.

The effect of immobilization on rotator cuff healing using modified Mason-Allen stitches: a biomechanical study in sheep.

Long-term biomechanical integrity of the surgical site is crucial to the outcome of rotator cuff repair. Usually after rotator-cuff surgery, the arm is immobilized for 6-12 weeks to minimize disruption at the healing site. Unfortunately, currently there is very little clinical data on the effects of immobilization after rotator cuff surgery. This study analyzed the effect of immobilization on rotator cuff healing by comparing the healing strength of the tendon in a bone trough using a sheep model. In sixteen (16) female adult sheep, the right infraspinatus tendons were reattached into a bone trough using a modified Mason-Allen suture pattern. After surgery, each sheep was randomly assigned into either an immobilized or non-immobilized treatment group. The immobilized group was fitted with a softball taped under the foot to restrict limb movement for 6 weeks. The non-immobilized treatment group was allowed to fully bear weight on the treated shoulder. At 26 weeks, the animals were sacrificed and the surgical shoulders were harvested and stored in a -30 degrees C freezer. Biomechanical testing was performed using a MTS 809 Axial/Torsional Servohydraulic System. Special cryo-grips were used to test the infraspinatus tendon-bone interface in anatomical alignment. All samples were preloaded with 10 +/- 5 N, and then force was measured during a crosshead displacement of 500 mm/min until failure. Force and displacement were acquired at 100 Hz and used to calculate load-to-failure and stiffness of the bone-tendon interface. The load-to-failure (N) and stiffness (N/cm) were determined for both treatment groups. For the non-immobilized group, the loads to failure and stiffness means were 2571.95 +/- 329.9 N and 2319.09 +/- 457.72 N/cm. The immobilized group means were 2954.42 +/- 473.52 N (load-to-failure) and 2579.13 +/- 383.51 N/cm (stiffness). A two-tailed two-samples unequal variance student t-test with significance set at 0.05, found no significant difference between the treatment groups for load-to-failure (p = 0.2174) and stiffness (p = 0.8286).

The effect of IPN surface modification on the mechanical properties of UHMWPE.

This paper investigates the effect of IPN surface treatment on the mechanical properties of ultra high molecular weight polyethylene (UHMWPE). Traditional UHMWPE was modified by introducing poly-L-lysine (PLL) into their surface and forming a semi-interpenetrating network (IPN). Tensile, creep and fatigue tests were performed on these IPN and the control specimens. The tensile and creep results show that the IPN modification did plasticize the UHMWPE in that it decreased modulus and strength, increased ductility, and degraded creep resistance. However, these property changes are not so large as to be unacceptable. In the fatigue tests, there were no failures of control nor IPN samples up to 10 million cycles.

A gravity-independent constant force resistive exercise unit.

This study designed, developed and tested a novel, practical, gravity-independent exercise machine, the Constant Force Resistance Exercise Unit (CFREU). A CFREU prototype was designed and built according to National Aeronautic and Space Administration (NASA) hardware and physiological requirements, and was evaluated for potential exercise countermeasure viability. Life cycle data exhibit lower life than required by NASA guidelines; however, current CFREU re-designs are addressing this issue. Electromyography (EMG) data indicate that the CFREU used on the ground and in microgravity during exercise is capable of providing forces on the muscles that are similar to a standard free-weight machine used in gravity. Given the results of this study, the CFREU has proven to be a viable potential resistive exercise countermeasure to the deconditioning of the musculoskeletal system in microgravity.

Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia.

A significant portion of gastric cancers exhibit defective DNA mismatch repair, manifested as microsatellite instability (MSI). High-frequency MSI (MSI-H) is associated with hypermethylation of the human mut-L homologue 1 (hMLH1) mismatch repair gene promoter and diminished hMLH1 expression in advanced gastric cancers. However, the relationship between MSI and hMLH1 hypermethylation has not been studied in early gastric neoplasms. We therefore investigated hMLH1 hypermethylation, hMLH1 expression and MSI in a group of early gastric cancers and gastric adenomas. Sixty-four early gastric neoplasms were evaluated, comprising 28 adenomas, 18 mucosal carcinomas, and 18 carcinomas with superficial submucosal invasion but clear margins. MSI was evaluated using multiplex fluorescent PCR to amplify loci D2S123, D5S346, D17S250, BAT 25 and BAT 26. Methylation-specific PCR was performed to determine the methylation status of hMLH1. In two hypermethylated MSI-H cancers, hMLH1 protein expression was also evaluated by immunohistochemistry. Six of sixty-four early gastric lesions were MSI-H, comprising 1 adenoma, 4 mucosal carcinomas, and 1 carcinoma with superficial submucosal invasion. Two lesions (one adenoma and one mucosal carcinoma) demonstrated low-frequency MSI (MSI-L). The remaining 56 neoplasms were MSI-stable (MSI-S). Six of six MSI-H, one of two MSI-L, and none of thirty MSI-S lesions showed hMLH1 hypermethylation (P<0.001). Diminished hMLH1 protein expression was demonstrated by immunohistochemistry in two of two MSI-H hypermethylated lesions. hMLH1 promoter hypermethylation is significantly associated with MSI and diminished hMLH1 expression in early gastric neoplasms. MSI and hypermethylation-associated inactivation of hMLH1 are more prevalent in early gastric cancers than in gastric adenomas. Thus, hypermethylation-associated inactivation of the hMLH1 gene can occur early in gastric carcinogenesis.

The role of subchondral bone in joint disease: a review.

Subchondral bone plays a role in the pathogenesis of osteochondral damage and osteoarthritis in horses and humans. Osteochondral fragmentation and fracture, subchondral bone necrosis and osteoarthritis are common diseases in athletic horses, and subchondral bone is now thought to play an integral role in the pathogenesis of these diseases. There have been numerous research efforts focused on articular cartilage damage and its pathogenesis, yet comparatively little effort focused on subchondral bone pathology or the coordinated disease states of the osteochondral tissues. The purpose of this report is to review the current understanding of osteochondral disease in all species and its application to equine research and practice. It can be concluded from this review that our current understanding of osteochondral disease is based on clinical and pathological sources; and that the lack of information about joint tissue adaptation and disease has hampered objective studies of osteochondral tissues.

Induction of polyclonal immunoglobulin synthesis.

This unit is designed to examine the effects of T cells or lymphokines on B cell differentiation in situations where the antigen specificity of the B cells is not of interest. In these cases, antibody production induced by polyclonal stimuli (e.g., mitogens, antibodies, Epstein-Barr virus (EBV), or lymphokines) can be measured instead of antigen-specific immunoglobulin production. Because B cells in the circulation and tissues are pleomorphic (containing subpopulations of cells that may be resting, cells that may have had prior antigenic exposure, and cells that may have undergone prior isotype commitment), the antibody responses of these subpopulations to various growth and differentiation factors differ. Therefore, the choice of which lymphocyte subpopulation to culture and which activation signal to use is determined by the particular experimental question.

Owner assessment of the outcome of total hip arthroplasty in dogs.

OBJECTIVE: To evaluate owners' perceptions of the outcomes of dogs that have undergone total hip arthroplasty (THA). DESIGN: Survey. SAMPLE POPULATION: Owners of 145 dogs that had undergone THA. PROCEDURE: Surveys were mailed to owners of 353 dogs that underwent THA between 1982 and 1996. Owners were asked to answer multiple-choice questions and provide written comments. RESULTS: The response rate was 41%. For owners who responded to the survey, time from surgery to completion of the questionnaire ranged from 6 months to 11 years. Overall, 122 respondents (84.1%) rated results of THA in their dog as excellent or good. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that owners are generally satisfied with the results of THA in their dogs.