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Stochastic behavior of a many-channel membrane system.

A stochastic theory of channel-gating transitions is developed for a stationary system with many channels, with applications to patch-clamp single-channel experiments. Exact probability density and distribution functions for closed times, open times, and first transit times in an N-channel system are obtained in terms of N and the solutions for a one-channel system. Once N is determined, the expressions derived here can be used to analyze data records that are crowded by many channel openings and where multilevel events are common. The three-state model is treated as a specific example. Computer simulations of three-state models indicate that the equations derived here can be used to recover useful information from crowded single-channel current records. The simulations also revealed some of the limitations to the usefulness of these equations. The probability that a channel that has not opened is in a particular closed state was examined as a function of time. This analysis led to a useful limit where the distribution of unopened channels between various closed states is constant in time. This limit simplifies the mathematical treatment of closed-time probabilities, and provides a general method for the analysis of many-channel systems when channels open infrequently.

Animals↗

The mental health care context and patient characteristics: implications for provider job satisfaction.

This research examines job satisfaction among 282 staff providing mental health care to 574 patients with serious mental illness. The mental health staff worked in 18 Department of Veterans Affairs inpatient and outpatient mental health care units at 12 Veterans Affairs Medical Centers located across the contiguous 48 states. The purpose was to identify (1) aspects of the health care context that were associated with provider job satisfaction and (2) administrative and organizational procedures/interventions that might sustain or improve provider job satisfaction. The association of provider job satisfaction with patients' functional status and symptom severity was tested in multilevel statistical models that accounted for provider and unit characteristics. Provider job satisfaction was found to be greater on smaller units and units with higher patient functioning and lower illness severity. Implications of these results are discussed.

Activities of Daily Living↗

Dancing for bone health: a 3-year longitudinal study of bone mineral accrual across puberty in female non-elite dancers and controls.

INTRODUCTION: Weight-bearing exercise during growth enhances peak bone mass. However, the window of opportunity for optimizing positive effects of exercise on peak bone mass remains to be fully defined. Ballet dancing provides a model of mechanical loading patterns required to site-specifically modulate bone. METHODS: We assessed the effects of ballet dancing on bone mineral accrual in female non-elite dancers and normally active controls for 3 years across puberty. We recruited 82 ballet dancers and 61 controls age 8-11 years at baseline. Participants were measured over 3 consecutive years; however, the overlap in ages allowed analysis of the groups across 8-14 years of age. We annually assessed bone mineral content (BMC) at the total body (TB), including upper and lower limb regions, and biannually assessed BMC at the proximal femur and lumbar spine (LS) using dual x-ray absorptiometry (DXA). We derived TB lean mass and fat mass from DXA TB scans. Anthropometry, exercise levels, and calcium intake were also measured biannually. Maturational age was determined by age at peak height velocity (PHV). A multilevel regression model was used to determine the independent effects of body size, body composition, maturation, exercise levels, and calcium intake at each measurement occasion. RESULTS: When adjusted for growth and maturation, dancers had significantly greater BMC at the TB, lower limbs, femoral neck (FN), and LS than controls. Excepting the FN region, these differences became apparent at 1 year post-PHV, or the peripubertal years, and by 2 years post-PHV the differences represented a cumulative advantage in dancers of 0.6-1.3% (p<0.05) greater BMC than controls. At the FN, dancers had 4% (p<0.05) greater BMC than controls in prepuberty and maintained this advantage throughout the pubertal years. CONCLUSIONS: Results from this novel population provide evidence for modest site-specific and maturity-specific effects of mechanical loading on bone.

Adolescent↗

Multilevel health promotion research: conceptual and analytical considerations.

Health promotion research is often conceptualized through the use of socioecological frameworks. This results in data or variables associated with multiple levels such as individual, community, and provincial. These data are nested, or clustered. In other words, multilevel health promotion research is based on the idea that community influences health, above and beyond one's individual characteristics or behaviours. These contextual effects can be analyzed rigorously using multilevel modelling (MLM), thus determining whether contextual effects are truly derived from context or are the result of residents' social profile. MLM also facilitates examination of cross-level interaction effects. The authors discuss conceptual and methodological issues related to multilevel research. While multilevel pathways to health outcomes have been suggested at the conceptual level, analytical techniques that produce only average overall effects fail to reveal the various other influences on health behaviour.

Data Interpretation, Statistical↗

Evolution of metabolisms: a new method for the comparison of metabolic pathways using genomics information.

The abundance of information provided by completely sequenced genomes defines a starting point for new insights in the multilevel organization of organisms and their evolution. At the lowest level enzymes and other protein complexes are formed by aggregating multiple polypeptides. At a higher level enzymes group conceptually into metabolic pathways as part of a dynamic information-processing system, and substrates are processed by enzymes yielding other substrates. A method based on a combination of sequence information with graph topology of the underlying pathway is presented. With this approach pathways of different organisms are related to each other by phylogenetic analysis, extending conventional phylogenetic analysis of individual enzymes. The new method is applied to pathways related to electron transfer and to the Krebs citric acid cycle. In addition to providing a more comprehensive understanding of similarities and differences between organisms, this method indicates different evolutionary rates between substrates and enzymes.

Animals↗

Comparison of cine MR imaging with Doppler echocardiography for the evaluation of aortic regurgitation.

Regurgitant blood flow is associated with localized signal loss of the blood pool within the recipient chamber on cine MR images, which may be useful for assessing regurgitant valvular disease. To evaluate the potential of this technique for determining the severity of aortic regurgitation, multilevel cine MR imaging was performed in 10 normal volunteers and in 25 patients with aortic regurgitation documented and graded for severity by Doppler echocardiography. Cine MR images were analyzed to obtain cardiac chamber volumes and to measure the extent of the signal loss associated with regurgitation. All regurgitant lesions were visualized on cine MR images as areas of diastolic signal loss extending from the aortic valve into the left ventricle. The extent of signal loss and the regurgitant volume determined from analysis of MR images correlated with the echocardiographic severity of the lesion. The total area of diastolic left ventricular signal loss was 0 cm2 in 10 normal volunteers, 24 +/- 13 (+/- SD) cm2 in eight patients with mild aortic regurgitation, 49 +/- 11 cm2 in nine patients with moderate aortic regurgitation, and 62 +/- 20 cm2 in eight patients with severe aortic regurgitation (p less than .05 for moderate and severe vs mild). Left ventricular volumes calculated from MR images correlated well with echocardiographic volumes (r = .92, SEE = 30 ml, p less than .0001). Regurgitant fraction calculated from analysis of cine MR images was 4 +/- 7% in normal volunteers and 31 +/- 8% in mild, 45 +/- 11% in moderate, and 56 +/- 9% in severe aortic regurgitation (p less than .05 for moderate and severe vs mild and normal). Thus, cine MR imaging can provide useful qualitative and quantitative data regarding cardiac dimensions and regurgitant valvular flow in patients with aortic regurgitation.

Adult↗

[Structural interpretation of a supposed symptomatic schizophrenia].

A short text spoken by a patient with a supposed symptomatic schizophrenia in lupus erythematodes is analyzed by means of a structural interpretation. While the text appears schizophrenic, it is only the confusion and intermingling of five quite distinct textual levels which create this impression. These five levels are presented in three distinctive modes of narrative. (1) Deviation and periphrase: while psychopathologically these breaks in the narrative are deviations from the main thread of argument, stylistically they are periphrasic statements, all having identical structures. They are all related emotionally as well as thematically to the central subject of the text. Their informational quality is impaired by their density and their interlocked form. (2) Narrative: the text contains three meaningful and well-arranged stories. In one case a multilevel narrative structure is employed. Each story represents a response to the initial question. (3) Metalanguage: on a metatextual level, the patient repeatedly makes reference to her linguistic peculiarities. These statements coincide with objective evaluation. Delusions and misidentification of individuals and situations used in classical psychopathological diagnosis can be given a different meaning (in the sense used by Weinrich) if interpretation has deepened the knowledge of the text. In this case, the similarity to schizophrenic texts is only superficial. A more detailed analysis illustrates the difference from schizophrenia on every level.

Adult↗

Intermittent adjuvant chemo-immunotherapy after resection of non-small cell lung cancer with multilevel mediastinal lymph node metastasis.

The prognosis of patients with multilevel mediastinal lymph node metastasis remains poor notwithstanding the progress in multimodal therapy in non-small cell lung cancer. We conducted a feasible study of intermittent adjuvant chemo-immunotherapy after surgery for patients with multilevel mediastinal lymph node metastasis of non-small cell lung cancer. Eleven patients with pathologically N2 or N3 lung cancer (10, adenocarcinomas; 1, squamous cell carcinoma) were enrolled. Five completely resected cases received systemic chemo-immunotherapy and six incompletely resected cases received local chemo-immunotherapy by an indwelling catheter in the thoracic cavity. Cisplatin-based and dose-dependent anti-cancer drugs were selected on the basis of sensitivity tests. Either adoptive immunotherapy with interleukin-2 and lymphokine-activated killer cell or combination of interferon gamma# and OK432 were administered after chemotherapy. This adjuvant therapy was performed every 2-3 months after surgery for 2 years. The 2-year survival rate for all cases were 72.7% and the 2-year disease-free survival were 36.4%. The 2-year survival rate for five completely resected cases and six incompletely resected cases was 80% and 66.7%, respectively. Combined intermittent chemo-immunotherapy after surgical resection of tumors may be a promising modality to improve the survival of patients with multilevel mediastinal lymph node metastasis in non-small cell lung cancer.

Adult↗

High-performance liquid chromatographic analysis of the semisynthetic epipodophyllotoxins teniposide and etoposide using electrochemical detection.

A high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of two structurally similar and highly active anticancer drugs, etoposide (I) and teniposide (II), and their potential metabolites (hydroxy acid, picrolactone, and aglycone). The assay utilizes electrochemical detection, which imparts specificity and sensitivity sufficient to detect greater than or equal to 20 ng/mL in plasma, urine, and CSF. The mean assay coefficients of variation were 5.1 and 8.1% for teniposide (10 micrograms/mL) and etoposide (5 micrograms/mL), respectively. The extraction efficiencies were 86% for etoposide, 70% for its hydroxy acid metabolite, 66% for teniposide, and 54% for the hydroxy acid of teniposide. The correlation coefficient of the multilevel standard curve was greater than or equal to 0.995 over the concentration range of 0.05-50 micrograms/mL for the parent drugs and metabolites extracted from plasma. This method has been used to determine the concentrations of the parent drugs and their metabolites in the plasma, urine, and CSF of patients with cancer.

Body Fluids↗

[A comparative physiological study of the generalization function in primates].

Fundamental rules of the generalization function formation and development were formulated on the basis of comparative analysis of visual discrimination, summarizing and abstraction in the representatives of various primate subfamilies. It was established that monkeys and apes (Macaca mulatta, Cebus apella, Pan troglodytes) learning to define such abstract characteristic as relative size of visual pictures of natural and geometrical objects were able to use previously remembered rules elaborated under the solving of other visual tasks. Learning processes were realized more affectively, if the pictures of natural objects were represented to the monkeys. The comparison of generalization processes in monkeys and apes revealed multilevel organisation of the processes in apes. The latter showed high level of ability to operate with abstract ideas elaborated previously in the course of the experiments.

Animals↗

[Ways of improving postoperative analgesia].

Analysis of many-year experience gained in the use of a variety of methods and means for treating the painful syndrome in victims and patients after planned and urgent surgery allowed the authors to determine the optimal approaches to postoperative analgesia. Special attention is paid to introduction of new drugs and methods of analgesia with differentiated approach to prevention and treatment of the painful syndrome. A conclusion on the necessity of pathogenetically based and strictly individual postoperative analgesia is made; such analgesia is often to be multilevel and multicomponent, with consideration for the complex origin of painful reaction (including the components of the painful syndrome) and the armory of available means.

Analgesics↗

Electromyographic changes reviewed in chronic spinal arachnoiditis.

A retrospective study was done to determine if specific electromyographic findings are present in spinal arachnoiditis. The electromyographic (emg) findings in 32 surgically and 35 myelographically diagnosed cases were examined. The cases were categorized into 3 groups. The 1st groups consisted of 37 cases with surgical or myelographic evidence believed to be highly diagnostic of multilevel chronic spinal arachnoiditis. The 2nd group was composed of 23 cases with surgical or myelographic evidence consistent with a localized problem. The 3rd group was a control group with normal or minimal changes on myelography or at surgery. Electromyographic findings were divided into 3 groups of changes: localized, nonlocalized or normal. Localized emg changes were considered to be present over 2 or less root levels in either or both anterior or posterior primary ramus distribution. Nonlocalized changes occurred over more than 2 such levels. A comparative analysis of the myelographic and surgical findings with the emg changes indicated that there was not diagnostic emg picture indicative of chronic spinal arachnoiditis.

Arachnoiditis↗

The stability of reconstruction methods after thoracolumbar total spondylectomy. An in vitro investigation.

STUDY DESIGN: After total spondylectomy, five types of spinal reconstruction techniques were compared biomechanically. OBJECTIVES: To evaluate the stability provided by five reconstruction methods after total spondylectomy. SUMMARY OF BACKGROUND DATA: Total spondylectomy presents a worst-case scenario for spinal reconstruction. However, few investigators have biomechanically investigated spinal reconstruction stability after total spondylectomy. METHODS: Eight human cadaveric spines (T11-L5) were used. After intact analysis, a total spondylectomy was performed at L2 and reconstructed using Harms titanium mesh (Depuy-Motech, Warsaw, IN) as an anterior strut. Anterior, posterior, or circumferential instrumentation techniques were then performed using the Kaneda SR and ISOLA pedicle screw systems (AcroMed Corp., Cleveland, OH) as follows: 1) anterior instrumentation at L1-L3 with multisegmental posterior instrumentation at T12-L4 (AMP), 2) anterior instrumentation at L1-L3 with short posterior instrumentation at L1-L3 (ASP), 3) anterior instrumentation at L1-L3 (A), 4) multilevel posterior instrumentation at T12-L4 (MP), and 5) short posterior instrumentation at L1-L3 (SP). Nondestructive biomechanical testing was performed under axial compression, flexion-extension, and lateral bending loading modes. RESULTS: Only circumferential instrumentation techniques (AMP, ASP) exhibited higher stiffness than the intact spine in all loading modes (P < 0.05). Short circumferential fixation provided more stability than did multilevel posterior instrumentation (P < 0.05). Multilevel posterior fixation provided more stiffness than did short posterior and anterior instrumentation alone (P < 0.05). CONCLUSIONS: Only circumferential fixation techniques provide more stability than the intact spine in all testing modes. Short circumferential instrumentation provides more stability than multilevel posterior instrumentation alone and requires fewer levels of spinal fusion.

Aged↗

The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription.

The human epidermal growth factor receptor (EGFR) proto-oncogene is shown to span 110 kb of DNA divided into 26 exons. Analysis of sequences surrounding exon 1 reveals a highly CG rich region which promotes transcription. The activity of the EGF receptor promoter can be modulated by E1A protein and receptor RNA levels increased by stimulation with phorbol ester or fetal calf serum. Promoter activity is assayed by linkage to the chloramphenicol acetyl transferase gene and transfection in three cell lines, with quantitation of plasmid DNA uptake by isolation of a Hirt supernatent from each transfection. Deletion analysis of the CG rich promoter region of the gene and construction of chimeric EGFR/SV40 promoters are used to demonstrate positive transcription elements located both within exon 1 and 5' to the start of transcription. Negative regulation of transcription by sequences within a -140 to +80 region is suggested. Cotransfection experiments suggest a requirement for the interaction of DNA binding protein Sp1 for maximal activity. Finally, derepression of a positive regulatory sequence located in exon 1 during cotransfection experiments is shown. Results are discussed in reference to the multilevel regulation of EGF receptor expression.

Amino Acid Sequence↗

Perceptual voice analysis of patients with subglottic stenosis.

OBJECTIVES: To characterize the perceptual assessment of vocal quality in subglottic stenosis (SGS) patients and to identify risk factors for dysphonia. STUDY DESIGN AND SETTING: Retrospective review, academic center. METHODS: Perceptual voice assessment using GRBAS scale (Grade, Roughness, Breathiness, Asthenia, Strain); patient characteristics determined for 31 SGS cases. RESULTS: The mean GRBAS (0 to 3 scale, 0 = normal quality) for SGS patients at their initial visit was G(1.4)R(1.2)B(0.5)A(0.5)S(1.1). For males vs females: G(2.1 vs 1.1)R(2.0 vs 0.8)B(1.0 vs 0.4)A(1.0 vs 0.3)S(1.7 vs 0.9). The Grade (P < 0.03), Breathiness (P < 0.04), and Asthenia (P < 0.02) assessments were significantly more dysphonic in patients with multilevel stenosis; vocal fold motion impairment (VFMI) also impacted overall Grade (P < 0.01). Overall Grade (P < 0.002), Roughness (P < 0.007), and Breathiness (P < 0.006) were significantly worse in patients with prior airway surgery. CONCLUSION: SGS patients demonstrate a mild to moderate change in perceptual voice characteristics with males in this series being more affected than females. Negative risk factors include multiple stenoses, VFMI, and previous airway surgery. SIGNIFICANCE: This is the first systematic report of perceptual voice assessment in subglottic stenosis. SGS patients have notable degrees of dysphonia with identifiable risk factors.

Auditory Perception↗

The unwarranted use of replicate analysis in routine coagulation studies.

The need to assure the validity of semiautomated coagulation procedures by performing replicate determinations is assessed. Prothrombin times (PT) and activated partial thromboplastin times (aPTT) were run as duplicate assays using two different photo-optical detection systems. Sixty specimens with a broad range of PT and aPTT results were studied as aliquots of 80, 100, and 140 microL of plasma. A total of 1,440 studies were performed. No statistically significant differences were found among the data for complementary groups of assays. It is concluded that replicate analyses do not enhance the precision nor the accuracy of these coagulation studies. These factors are more controlled adequately by quality assurance procedures, including frequent calibration checks, the use of internal standards, and multilevel commercial controls.

Blood Coagulation Tests↗

Updating small area population estimates in England and Wales.

"Population estimates have important implications for resource allocation within government and commerce, and are often assumed to be without error. Currently, central government provides annual population estimates for all the local and health authority districts in Britain, but estimates are needed for smaller areas, typically for electoral wards and postal sectors. Small area estimates are provided by some local authorities and commercial organizations, using different methods; the accuracy of these estimates is modelled here within a multilevel framework. Certain characteristics of the small area and of the method of estimation are included as explanatory variables. Results show that the method of estimation used is of great importance."

Developed Countries↗

[Obstructive site of the upper airway in patients with obstructive sleep apnea hypopnea syndrome: analysis of dynamic MRI].

OBJECTIVE: To investigate the obstructive site and the dynamic change of the upper airway in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) during sleep and wakefulness. METHODS: After being deprived of sleeping for 20 hours, sequential midline sagittal images of the upper airway were obtained in 21 patients during sleep and wakefulness with dynamic MRI. The obstructive state was studied according to hypopnea (< 10 s) and apnea (> or = 10 s). The length of obstruction site was measured and the dynamic characteristics of obstruction was observed. Statistical analysis was performed with paired t-test. RESULTS: The obstruction at the level of the palatopharynx in patients with hypopnea during wakefulness was similar to that in patients with apnea during sleep. The maximal length [(6.61 +/- 1.23) cm], the minimal length [(0.95 +/- 0.22) cm] and maximal length difference [(5.66 +/- 1.27) cm] related to apnea during sleep were longer than those correlated with hypopnea [(2.99 +/- 0.51) cm, (0.72 +/- 0.23) cm, (2.27 +/- 0.67) cm, respectively] in wakefulness. (P < 0.01). CONCLUSIONS: The obstruction of upper airway during sleep is dynamic and multilevel in patients with OSAHS. To a certain degree, hypopnea during wakefulness can give a clue to the obstructive state during sleep.

Adult↗