Mixed control for perception and action: timing and error correction in rhythmic ball-bouncing.

The task of bouncing a ball on a racket was adopted as a model system for investigating the behavioral dynamics of rhythmic movement, specifically how perceptual information modulates the dynamics of action. Two experiments, with sixteen participants each, were carried out to definitively answer the following questions: How are passive stability and active stabilization combined to produce stable behavior? What informational quantities are used to actively regulate the two main components of the action-the timing of racket oscillation and the correction of errors in bounce height? We used a virtual ball-bouncing setup to simultaneously perturb gravity (g) and ball launch velocity (v b) at impact. In Experiment 1, we tested the control of racket timing by varying the ball's upward half-period t up while holding its peak height h p constant. Conversely, in Experiment 2, we tested error correction by varying h p while holding t up constant. Participants adopted a mixed control mode in which information in the ball's trajectory is used to actively stabilize behavior on a cycle-by-cycle basis, in order to keep the system within or near the passively stable region. The results reveal how these adjustments are visually controlled: the period of racket oscillation is modulated by the half-period of the ball's upward flight, and the change in racket velocity from the previous impact (via a change in racket amplitude) is governed by the error to the target.

A multi-analyte serum test for the detection of non-small cell lung cancer.

BACKGROUND: In this study, we appraised a wide assortment of biomarkers previously shown to have diagnostic or prognostic value for non-small cell lung cancer (NSCLC) with the intent of establishing a multi-analyte serum test capable of identifying patients with lung cancer. METHODS: Circulating levels of 47 biomarkers were evaluated against patient cohorts consisting of 90 NSCLC and 43 non-cancer controls using commercial immunoassays. Multivariate statistical methods were used on all biomarkers achieving statistical relevance to define an optimised panel of diagnostic biomarkers for NSCLC. The resulting biomarkers were fashioned into a classification algorithm and validated against serum from a second patient cohort. RESULTS: A total of 14 analytes achieved statistical relevance upon evaluation. Multivariate statistical methods then identified a panel of six biomarkers (tumour necrosis factor-α, CYFRA 21-1, interleukin-1ra, matrix metalloproteinase-2, monocyte chemotactic protein-1 and sE-selectin) as being the most efficacious for diagnosing early stage NSCLC. When tested against a second patient cohort, the panel successfully classified 75 of 88 patients. CONCLUSIONS: Here, we report the development of a serum algorithm with high specificity for classifying patients with NSCLC against cohorts of various 'high-risk' individuals. A high rate of false positives was observed within the cohort in which patients had non-neoplastic lung nodules, possibly as a consequence of the inflammatory nature of these conditions.

Coupling of posture and gait: mode locking and parametric excitation.

We investigate the temporal coordination of human gait and posture and infer the nature of their coupling. Participants viewed a sinusoidally oscillating visual display which induced medial-lateral postural sway during treadmill walking, while display frequency was varied (0.075-1.025 Hz). First, postural responses exhibited the usual low-pass characteristic but with an additional resonance peak near the preferred stride frequency, although shifted downward by 0.12 Hz; this provides evidence of a coupling from gait to posture. Second, the step cycle adapted to mode lock with the visual driver and postural sway, as well as displaying instances of intermittency (slipping in and out of phase) and quasiperiodicity (phase wandering); this provides evidence of a coupling from posture to gait. We observed a spectrum of integer mode locks, including a large 1:1 trapping region about the stride frequency and superharmonic entrainment (stride frequency > driver frequency) at lower driver frequencies. A coupled-oscillator model that incorporates a novel parametric coupling from posture to the gait "stiffness" term reproduces these features of the data, including the resonance peak shift. Biological coordination patterns may thus emerge naturally as properties of a system of appropriately coupled oscillators.

Optic flow is used to control human walking.

How is human locomotion visually controlled? Fifty years ago, it was proposed that we steer to a goal using optic flow, the pattern of motion at the eye that specifies the direction of locomotion. However, we might also simply walk in the perceived direction of a goal. These two hypotheses normally predict the same behavior, but we tested them in an immersive virtual environment by displacing the optic flow from the direction of walking, violating the laws of optics. We found that people walked in the visual direction of a lone target, but increasingly relied on optic flow as it was added to the display. The visual control law for steering toward a goal is a linear combination of these two variables weighted by the magnitude of flow, thereby allowing humans to have robust locomotor control under varying environmental conditions.

Epithelial tumors of the lung.

Our knowledge and understanding of bronchopulmonary tract tumors have grown considerably; modern pathology enables the phenotyping of many tumors with increasingly improving techniques and tools and, arguably, improving criteria. By the same token, at least some of the new data may not be readily grafted onto traditional classification schemes. Some traditional designations will be dropped and replaced. And, although it has been overenthusiastically argued that molecular classifications may be attained, that ideal might not be truly an improvement. For classifications to be useful, they should be relatively simple, easily reproducible, and clinically significant. Still, modern marker pathology has revealed new vistas for the evaluation, diagnosis, and therapy of at least some tumors. These developments merit optimism but also caution from clinicians and pathologists.

Perception of heading during rotation: sufficiency of dense motion parallax and reference objects.

How do observers perceive the path of self-motion during rotation? Previous research suggests that extra-retinal information about eye movements is necessary at high rotation rates (2-5 degrees /s), but those experiments used sparse random-dot displays. With dense texture-mapped displays, we find the path can be perceived from retinal flow alone at high simulated rotation rates if (a) dense motion parallax and (b) at least one reference object are available. We propose that the visual system determines instantaneous heading from the first-order motion parallax field, and recovers the path of self-motion by updating heading over time with respect to reference objects in the scene.

Palliation of dysphagia.

This article discusses the diagnosis and interventional options apart from surgical resection for carcinoma of the esophagus. Other topics discussed are methods of inserting plastic and self-expanding metal stents in conjunction with their complications, and neodymium:yttrium-aluminum-garnet photodynamic therapy, cryoablation, and BICAP (bipolar cautery probe) options. Clinical scenarios illustrate the pros and cons of these approaches.

Malignancies involving the pericardium.

Malignancies rarely arise from the pericardium. Mesothelioma, the most common of these, is usually unresectable and almost always incurable. Malignancies may secondarily involve the pericardium by direct extension. Carcinoma of the lung and malignant thymoma with limited direct invasion of the pericardium both can undergo complete and potentially curative resections, but adjuvant therapy is usually indicated. More frequently, malignancies involve the pericardium by a process of retrograde lymphangitic spread or hematogenous dissemination. These patients present with a symptomatic pericardial effusion and occasionally pericardial tamponade. Subxiphoid pericardiostomy and drainage is a safe procedure that provides effective and durable symptomatic relief in these terminally ill patients. More aggressive open procedures should be reserved for loculated or recurrent pericardial effusions.

Cytokine biosynthesis by tumor-infiltrating T lymphocytes from human non-small-cell lung carcinoma.

PURPOSE: The purpose of this work was to assess the capacity of tumor-infiltrating leukocytes (TIL) from human non-small-cell lung carcinoma (NSCLC) specimens to synthesize type-1 and type-2 cytokines. METHODS: TIL were isolated from tumors following digestion with collagenase/DNase and further enriched by ficoll-hypaque gradient centrifugation. Membrane phenotypes and intracellular cytokine protein expression of TIL were assessed by flow cytometry. RESULTS: The majority of TIL expressed the CD3 antigen with a CD4:CD8 ratio of approximately 2:1. Other leukocytes such as macrophages (CD14), B lymphocytes (CD20), and natural killer (NK) cells (CD56) were also found to infiltrate the tumors, but in significantly lower numbers. Owing to the limited recovery of non-CD3(+) leukocytes, our analysis of cytokine biosynthesis has focused on T lymphocytes. In the absence of activation, a small percentage of CD3(+) TIL synthesized cytokines ( <4%). Following activation with anti-CD3+interleukin-2 (IL-2), CD3(+) TIL synthesized predominantly a type-1 cytokine profile; however, the type-2 cytokines, IL-6 and IL-10, were also detected in a small percentage of infiltrating cells. Following activation with phorbol 12-myristate 13-acetate + ionomycin, CD3(+) TIL also expressed more type-1 than type-2 cytokines and in significantly greater numbers of cells. The CD3(+)CD8(+) component of the TIL synthesized only type-1 cytokines, whereas the CD3(+)CD4(+) component synthesized both type-1 and type-2 cytokines. CONCLUSION: These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize type-1 cytokines.

The role of central and peripheral vision in postural control during walking.

Three hypotheses have been proposed for the roles of central and peripheral vision in the perception and control of self-motion: (1) peripheral dominance, (2) retinal invariance, and (3) differential sensitivity to radial flow. We investigated postural responses to optic flow patterns presented at different retinal eccentricities during walking in two experiments. Oscillating displays of radial flow (0 degree driver direction), lamellar flow (90 degrees), and intermediate flow (30 degrees, 45 degrees) patterns were presented at retinal eccentricities of 0 degree, 30 degrees, 45 degrees, 60 degrees, or 90 degrees to participants walking on a treadmill, while compensatory body sway was measured. In general, postural responses were directionally specific, of comparable amplitude, and strongly coupled to the display for all flow patterns at all retinal eccentricities. One intermediate flow pattern (45 degrees) yielded a bias in sway direction that was consistent with triangulation errors in locating the focus of expansion from visible flow vectors. The results demonstrate functionally specific postural responses of both central and peripheral vision, contrary to the peripheral dominance and differential sensitivity hypotheses, but consistent with retinal invariance. This finding emphasizes the importance of optic flow structure for postural control regardless of the retinal locus of stimulation.

Pericardial effusion: subxiphoid pericardiostomy versus percutaneous catheter drainage.

BACKGROUND: Optimal management of cardiac tamponade resulting from pericardial effusion remains controversial. METHODS: Cardiac tamponade in 117 patients was treated with either subxiphoid pericardiostomy (n = 94) or percutaneous catheter drainage (n = 23). Percutaneous catheter drainage was used for patients with hemodynamic instability that precluded subxiphoid pericardiostomy. Effusions were malignant in 75 (64%) of 117 patients and benign in 42 (36%) of 117. RESULTS: Subxiphoid pericardiostomy had no operative deaths and a complication rate of 1.1% (1 of 94). In contrast, percutaneous drainage had significantly (p < 0.05) higher mortality and complication rates of 4% (1 of 23) and 17% (4 of 23), respectively. Patients with an underlying malignancy had a median survival of 2.2 months, with a 1-year actuarial survival rate of 13.8%. In comparison, patients with benign disease had a median survival of 42.8 months and a 1-, 2-, and 4-year actuarial survival rate of 79%, 73%, and 49%, respectively (p < 0.05). Effusions recurred in 1 (1.1%) of 94 patients after subxiphoid pericardiostomy compared with 7 (30.4%) of 23 patients with percutaneous drainage (p < 0.0001). CONCLUSIONS: Benign and malignant pericardial tamponade can be safely and effectively managed with subxiphoid pericardiostomy. Percutaneous catheter drainage should be reserved for patients with hemodynamic instability.

Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.

Lung volume reduction surgery: an analysis of hospital costs.

OBJECTIVE: Lung volume reduction surgery (LVRS) represents a potential breakthrough in the management of advanced emphysema, although questions remain about clinical and economic implications of widespread application of LVRS. In this report, we describe hospital costs, excluding physicians' fees, for LVRS. DESIGN: Hospital charges were obtained from billing records and converted to costs by applying multiple cost-to-charge ratios. SETTING: A large, urban academic medical center. PATIENTS: Fifty-two consecutive patients who received bilateral LVRS through a median sternotomy between April 1995 and August 1996. RESULTS: Median hospital stay was 10 days (mean= 14.8+/-12.8 days; range=3 to 48 days), including 2 days (mean=6+/-9.2 days; range=1 to 35 days) in the ICU. One hospital death occurred. Hospital costs per case ranged from $11,712 to $121,829, with mean costs of $30,976 and median costs of $19,771. Costs were related significantly to duration of ICU stay and length of hospitalization. Patients who accrued the highest costs were significantly older than the remainder of the sample (69.3 years vs 62.4 years). CONCLUSIONS: Hospital costs of LVRS vary significantly but are related directly to hospital stay. Identification of factors associated with prolonged stays can be used in assessing benefits and risks of LVRS against utilization of health-care dollars.

The dynamics of gait transitions: effects of grade and load.

Diedrich and Warren (1995a) proposed that gait transitions behave like bifurcations between attractors, with the relative phase of the leg segments as an order parameter and stride frequency and stride length as control parameters. In the present experiments, the authors tested the prediction that manipulation of the attractor layout, either through the addition of load to the ankles or through an increase in the grade of the treadmill, induces corresponding changes in the walk-run transition. As predicted, the load manipulation shifted the most stable walk and the transition to lower stride frequencies. In contrast, the grade manipulation shifted the most stable walk and the transition to shorter stride lengths. Other features of the dynamic theory were also replicated, including enhanced fluctuations of phase and systematic changes in stride length and frequency at the transition. Overall, in these experiments a shift of the attractors in control parameter space yielded a corresponding shift of the transition.

Immunolocalization of integrins in the normal lung and in pulmonary carcinomas.

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.