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Effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy.

OBJECTIVE: To evaluate the effects of ablation diameter on long-term refractive stability and corneal transparency after photorefractive keratectomy (PRK). DESIGN: Long-term, prospective, follow-up study. PARTICIPANTS: One hundred twenty-three eyes treated between 1990 and 1993 at one institution as part of a number of ethical committee-approved clinical studies underwent long-term follow-up at 10 to 12 years after PRK. INTERVENTION: Photorefractive keratectomy was performed using the Summit Technology UV 200 and OmniMed Excimer lasers with either 4.0-mm (n = 36), 5.0-mm (n = 47), or 6.0-mm (n = 40) optical zones and either -3.0-diopters (D) or -6.0-D myopic spherical corrections, based on the original Munnerlyn algorithms. MAIN OUTCOME MEASURES: Refractive stability, refractive predictability, best spectacle-corrected visual acuity, and corneal haze. RESULTS: Refractive outcome at 1 and 10 to 12 years of follow-up was better with 6.0-mm treatments, especially for -6.0-D corrections (P>0.001). The early hyperopic shift was significantly reduced with 6.0-mm zones, with less regression between 1 and 6 months, compared with 5.0- and 4.00-mm PRK, especially for -6.0-D corrections (P<0.001). The postoperative refraction remained stable between 1 and 10 to 12 years in all groups. Objective measurements of haze were less with 6.0-mm compared with 4.0- and 5.0-mm treatments (P<0.001). Night vision problems were significantly less with 6.0-mm PRK (P<0.01). There was no evidence of progressive hyperopic shift, corneal ectasia, or late onset of corneal haze in any of the eyes during the follow-up period. CONCLUSIONS: Refractive stability was maintained between 1 year and 10 to 12 years after PRK with 4.0-, 5.0-, and 6.0-mm optical zones. A significant linear trend was observed in terms of refractive predictability, early hyperopic shift, regression, corneal transparency, and night haloes with better outcomes in PRK with a larger ablation zone. None of the eyes had sight-threatening complications such as ectasia or late-onset corneal haze during the follow-up.

Cornea↗

The recovery of dipolar relaxation times from fluorescence decays as a tool to probe local dynamics in single tryptophan proteins.

The dipolar relaxation process induced by the excitation of the single tryptophan residue of four proteins (staphylococcal nuclease, ribonuclease-T1, phosphofructokinase, and superoxide dismutase) has been studied by dynamic fluorescence measurements. A new algorithm taking into account the relaxation effect has been applied to the fluorescence decay function obtained by phase-shift and demodulation data. This approach only requires that fluorescence be collected through the whole emission spectrum, avoiding the time-consuming determination of the data at different emission wavelengths, as usual with time-resolved emission spectroscopy. The results nicely match those reported in the literature for staphylococcal nuclease and ribonuclease-T1, demonstrating the validity of the model. Furthermore, this new methodology provides an alternative explanation for the complex decay of phosphofructokinase and human superoxide dismutase suggesting the presence of a relaxation process even in proteins that lack a lifetime-dependent spectral shift. These findings may have important implications on the analysis of small-scale protein dynamics, since dielectric relaxation directly probes a local structural change around the excited state of tryptophan.

Algorithms↗

Accurate direct spectrophotometric bilirubin measurement combined with blood gas analysis.

BACKGROUND: A new total bilirubin (B(T)) method, based on multiple wavelength absorbance measurements, and an algorithm to calculate concentration, were evaluated for accuracy in specimens containing variable amounts of unconjugated bilirubin (B(U)), conjugated bilirubin (B(C)) and delta (protein-bound) bilirubin (B(D)). METHODS: Quantitation of B(U), B(C), and B(T) (with calculation of B(D)) using a Vitros 250 analyzer served as the comparison method. RESULTS: Analysis of neonatal specimens using a preliminary algorithm yielded good overall agreement with the Vitros B(T) method, but there was considerable variation in the agreement for individual specimens. When specimens from adults selected to yield a range of B(C) and B(D) levels were analyzed, the preliminary algorithm underestimated B(T). Refinement of the method in the form of a finalized algorithm resulted in elimination of the negative bias seen with specimens with high B(D) and B(C) levels, and better agreement for individual neonatal specimens. CONCLUSIONS: This new method overcomes the limitations observed in earlier spectrophotometric methods, and provides accurate results in specimens containing a range of bilirubin forms.

Adult↗

Spontaneous daily variability of atrial sensitivity. A study with an implanted DDD pacemaker.

BACKGROUND: Spontaneous variations in the chronic stimulation threshold were widely investigated in the last few years and formed the basis of the safety margin concept of stimulation energy. The dynamic variability of sensitivity, particularly in the atrium, is less studied and, in the literature, contrasting data are present about the actual entity of these variations. A 2:1 safety margin is still recommended by many authors, although some papers reported that this value was inadequate to guarantee a correct sensing function. AIM OF THE STUDY: We evaluated daily variability of atrial sensitivity (AS) in patients implanted with the Cosmos 3 DDD cardiac pacemaker, with a special algorithm that continuously measures the minimum-maximum sensitivity values in atrium or in the ventricle during a 12-h sampling period. MATERIALS AND METHODS: 34 patients, 20 males and 14 females, with a mean age of 72+/-5 years, were implanted with a Cosmos 3 DDD pacemaker (PM). The indication to implant a PM was sick sinus syndrome in 21 patients and a high degree of AV block in 13 patients. Atrial bipolar leads were always employed. At 1, 2, 3 and 6 months after the implant, we analyzed the minimum-maximum values of atrial sensitivity for the last 12-h. This analysis was performed in the late afternoon. RESULTS: The mean AS varied more than threefold, from a mean minimum of 0.68 to a mean maximum value of 2.19 mV at 1 month, from 0.68 to 2.21 mV at 2 months, from 0.69 to 2.19 mV at 3 months and from 0.67 to 2.17 mV at 6 months, without significant differences among the four follow-up controls. In seven patients, there was a fourfold variation, while the variation was fivefold in five patients. CONCLUSION: In conclusion, from our data, we can confirm that atrial sensitivity may vary widely during the day and, consequently, we recommend that a 3:1 safety margin should be programmed and the recommended 2:1 ratio should be abandoned. Moreover, at implant, particular attention should be paid to obtaining the best atrial signal amplitude, at least threefold higher than the highest sensitivity value available in the implanted PM. To achieve this goal and to obviate to the oversensing phenomena, bipolar leads are preferable to unipolar leads.

Aged↗

Feasibility of multidimensional substance abuse treatment matching: automating the ASAM Patient Placement Criteria. American Society of Addiction Medicine.

UNLABELLED: The Patient Placement Criteria published by the American Society of Addiction Medicine (ASAM Criteria) established a non-proprietary standard for matching substance use disorder patients to treatment settings. METHODS: Data from 593 substance dependent adults who were assessed using the first computerized implementation of the ASAM Criteria were analyzed to determine whether the level of care assignments showed significant differences on a variety of clinical measures. RESULTS: The algorithm showed acceptable discrimination between each of three ASAM Levels of Care across numerous clinical subscales. CONCLUSIONS: It is feasible to implement complex, multidimensional criteria for substance abuse treatment that may improve reliability and facilitate validity studies.

Adolescent↗

Geometrical rectification for images from a mobile large container inspection system.

The mobile large container inspection system (MLCIS) is a more flexible X-ray radiographic system than conventional fixed systems. Ideally, the X-ray detectors should be arranged along an arc with the source at the center. However, detectors of the MLCIS are arranged in an L-shaped frame and result in a factual image which is distorted compared with the ideal image. We propose a geometrical rectification algorithm to convert the factual image to the ideal image. We choose the dimension ratios of identical objects shown on the factual and processed images with our algorithm as a measure, and the results is desirable.

Journal Article↗

Quantum-enhanced positioning and clock synchronization.

A wide variety of positioning and ranging procedures are based on repeatedly sending electromagnetic pulses through space and measuring their time of arrival. The accuracy of such procedures is classically limited by the available power and bandwidth. Quantum entanglement and squeezing have been exploited in the context of interferometry, frequency measurements, lithography and algorithms. Here we report that quantum entanglement and squeezing can also be employed to overcome the classical limits in procedures such as positioning systems, clock synchronization and ranging. Our use of frequency-entangled pulses to construct quantum versions of these protocols results in enhanced accuracy compared with their classical analogues. We describe in detail the problem of establishing a position with respect to a fixed array of reference points.

Journal Article↗

Experimental one-way quantum computing.

Standard quantum computation is based on sequences of unitary quantum logic gates that process qubits. The one-way quantum computer proposed by Raussendorf and Briegel is entirely different. It has changed our understanding of the requirements for quantum computation and more generally how we think about quantum physics. This new model requires qubits to be initialized in a highly entangled cluster state. From this point, the quantum computation proceeds by a sequence of single-qubit measurements with classical feedforward of their outcomes. Because of the essential role of measurement, a one-way quantum computer is irreversible. In the one-way quantum computer, the order and choices of measurements determine the algorithm computed. We have experimentally realized four-qubit cluster states encoded into the polarization state of four photons. We characterize the quantum state fully by implementing experimental four-qubit quantum state tomography. Using this cluster state, we demonstrate the feasibility of one-way quantum computing through a universal set of one- and two-qubit operations. Finally, our implementation of Grover's search algorithm demonstrates that one-way quantum computation is ideally suited for such tasks.

Journal Article↗

Autologous transplantation in elderly patients with multiple myeloma: are we asking the right questions?

Multiple myeloma is a disease of the elderly. Survival outcomes remain unacceptably low in older adults with multiple myeloma. To date, no obvious difference in tumor biology has been elucidated to explain the survival disparity between older and younger patients. Multiple factors including comorbidity, performance status, decreased physiologic reserve and potentially undertreatment contribute to poor outcomes in elderly patients with multiple myeloma. High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly being used to treat elderly patients with multiple myeloma in an effort to improve survival outcomes. Recent case comparison studies, and preliminary transplant registry data suggest that selected older patients can be treated with high-dose chemotherapy effectively with similar toxicity and survival benefits compared to younger patients. Traditional upper age limits for autologous transplantation are being challenged along with the definition of 'elderly' itself. Ultimately, the role of high-dose chemotherapy with stem cell rescue in the upfront treatment of older adults with multiple myeloma can only be established by prospective randomized trials. In the process of designing studies to investigate the use of ASCT in older patients, multiple issues unique to the elderly population will need to be considered. First, it will be critical to develop and validate patient selection algorithms that incorporate measures of comorbidity, cognitive function, physiologic reserve and psychosocial function to identify patients most likely to tolerate and benefit from ASCT. Second, preparative and conditioning regimens will need to be further tailored to maximize the benefit to risk ratio. Finally, outcome measures in clinical trials should include disability and quality of life measures, which may be equally important in making treatment decisions for older patients. The future application and study of autologous transplantation in older patients with multiple myeloma provides a unique opportunity to challenge ageism and serve as a model for development of tailored assessments and interventions in this population.

Adult↗

Evaluation of global analysis algorithms for single frequency fluorescence lifetime imaging microscopy data.

Global analysis of fluorescence lifetime image microscopy (FLIM) data can be used to obtain an accurate fit of multi-exponential fluorescence decays. In particular, it can be used to fit a bi-exponential decay to single frequency FLIM data, which is not possible with conventional fitting techniques. Bi-exponential fluorescence decay models can be used to analyse quantitatively single frequency FLIM data from samples that exhibit fluorescence resonance energy transfer (FRET). Global analysis algorithms simultaneously fit multiple measurements acquired under different experimental conditions to achieve higher accuracy. To demonstrate that bi-exponential models can indeed be fitted to single frequency data, we derive an analytical solution for the special case of two measurements and use this solution to illustrate the properties of global analysis algorithms. We also derive a novel global analysis algorithm that is optimized for single frequency FLIM data, and demonstrate that it is superior to earlier algorithms in terms of computational requirements.

Journal Article↗

[Computer-assisted surgery of the paranasal sinuses with an opto-electronic stereotaxic system].

BACKGROUND: A basic problem common to all systems for computer-assisted surgery (CAS) is the exact registration and referencing, that is, the transfer of preoperative image data to the intraoperative pathology. A system for computer-assisted ENT surgery should provide high precision as well as noninvasive registration and referencing. We present a system designed for such use in paranasal sinus surgery that is based on optical digitizing with several custom-made self-localizing surgical instruments. METHODS AND RESULTS: The system tracks the correct alignment of the head during CT data acquisition and continuously throughout surgery. A transformation matrix and a plane equation of the CT scan are used to match points of the object space to the image space detecting fiducial markers on the CT scans by an automatic algorithm. For position measurements a special reference frame and surgical instruments were developed and equipped with infrared light-emitting diodes that could be detected in real time. Measurements for repositioning of the reference system in a model and during real operations demonstrated a mean error ranging from 0.69 to 1.01 mm and from 0.76 to 1.67 mm respectively. Clinical experience with the application of the system for 15 patients who underwent surgery for different paranasal sinus pathologies is reported. CONCLUSIONS: Results suggest that the non-invasive reference system and the locatable surgical tools may be effective, accurate and useful for computer-assisted identification of intranasal structures. Such systems may contribute to further improvement of minimal invasive intranasal sinus surgery.

Equipment Design↗

Thermoacoustic tomography with correction for acoustic speed variations.

Thermoacoustic tomography (TAT) is a technique that measures microwave-induced thermoacoustic waves at the boundary of biological tissue and generates images of internal microwave absorption distributions from the measurements. Existing reconstruction algorithms for TAT are based on the assumption that the acoustic properties in the tissue are homogeneous. Biological tissue, however, has heterogeneous acoustic properties, which lead to distortion and blurring of small buried objects in the reconstructed images. In this paper we develop a correction method based on ultrasonic transmission tomography (UTT) to improve the image quality of TAT. Numerical simulations and phantom experiments verify the effectiveness of this correction method.

Acoustics↗

Discovering simple regions in biological sequences associated with scoring schemes.

Let A denote an alphabet consisting of n types of letters. Given a sequence S of length L with v(i) letters of type i on A, to describe the compositional properties and combinatorial structure of S, we propose a new complexity function of S, called the reciprocal complexity of S, as C(S) = (i=1) product operator (n) (L/nv(i))(vi) Based on this complexity measure, an efficient algorithm is developed for classifying and analyzing simple segments of protein and nucleotide sequence databases associated with scoring schemes. The running time of the algorithm is nearly proportional to the sequence length. The program DSR corresponding to the algorithm was written in C++, associated with two parameters (window length and cutoff value) and a scoring matrix. Some examples regarding protein sequences illustrate how the method can be used to find regions. The first application of DSR is the masking of simple sequences for searching databases. Queries masked by DSR returned a manageable set of hits below the E-value cutoff score, which contained all true positive homologues. The second application is to study simple regions detected by the DSR program corresponding to known structural features of proteins. An extensive computational analysis has been made of protein sequences with known, physicochemically defined nonglobular segments. For the SWISS-PROT amino acid sequence database (Release 40.2 of 02-Nov-2001), we determine that the best parameters and the best BLOSUM matrix are, respectively, for automatic segmentation of amino acid sequences into nonglobular and globular regions by the DSR program: Window length k = 35, cutoff value b = 0.46, and the BLOSUM 62.5 matrix. The average "agreement accuracy (sensitivity)" of DSR segmentation for the SWISS-PROT database is 97.3%.

Aggrecans↗

Genetic network inference: from co-expression clustering to reverse engineering.

MOTIVATION: Advances in molecular biological, analytical and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-cluster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e. who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting and bioengineering.

Animals↗

Predicting genetic regulatory response using classification.

MOTIVATION: Studying gene regulatory mechanisms in simple model organisms through analysis of high-throughput genomic data has emerged as a central problem in computational biology. Most approaches in the literature have focused either on finding a few strong regulatory patterns or on learning descriptive models from training data. However, these approaches are not yet adequate for making accurate predictions about which genes will be up- or down-regulated in new or held-out experiments. By introducing a predictive methodology for this problem, we can use powerful tools from machine learning and assess the statistical significance of our predictions. RESULTS: We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences ('motifs') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment ('parents'). Thus, our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurements to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S.cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. We also show how to extract significant regulators, motifs and motif-regulator pairs from the learned models for various stress responses. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks. AVAILABILITY: The MLJava package is available upon request to the authors. Supplementary: Additional results are available from http://www.cs.columbia.edu/compbio/geneclass

Binding Sites↗

Unbiased pattern detection in microarray data series.

MOTIVATION: Following the advent of microarray technology in recent years, the challenge for biologists is to identify genes of interest from the thousands of genetic expression levels measured in each microarray experiment. In many cases the aim is to identify pattern in the data series generated by successive microarray measurements. RESULTS: Here we introduce a new method of detecting pattern in microarray data series which is independent of the nature of this pattern. Our approach provides a measure of the algorithmic compressibility of each data series. A series which is significantly compressible is much more likely to result from simple underlying mechanisms than series which are incompressible. Accordingly, the gene associated with a compressible series is more likely to be biologically significant. We test our method on microarray time series of yeast cell cycle and show that it blindly selects genes exhibiting the expected cyclic behaviour as well as detecting other forms of pattern. Our results successfully predict two independent non-microarray experimental studies.

Algorithms↗

Short stature and cardiovascular disease among men and women from two southeastern New England communities.

BACKGROUND: Short stature has been associated with an increased risk of coronary heart disease (CHD), although the reason for the association remains unclear. Data on the relation between stature and stroke is more limited. We examined the association between stature and CHD as well as between stature and stroke in men and women from two communities in southeastern New England. METHODS: Coronary heart disease and stroke events were abstracted from medical records between January 1980 and December 1991. An epidemiological diagnostic algorithm developed to measure CHD was used in the present analysis. Unadjusted relative risks (RR) and RR adjusted for age, smoking status, obesity, high-density lipoprotein (HDL) cholesterol <0.91 mmol/l, total cholesterol >6.21 mmol/l, hypertension, diabetes, education, and being foreign born were computed by gender-specific height categories separately for men (n = 2826) and women (n = 3741). RESULTS: A graded inverse association between stature and risk of CHD was observed among men which persisted after adjustment for confounders. Men >69.75 inches had an 83% lower risk of CHD compared with men < or = 65 inches. In addition, the tallest men had a 67% decreased risk of stroke compared with the shortest men. No significant relation between stature and CHD or stroke was observed among women. CONCLUSIONS: These data support the hypothesis that stature is inversely related to both risk of CHD and stroke at least among men. Factors which might explain this association remain to be determined.

Adolescent↗

A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers.

UNLABELLED: We determined whether two different devices for measuring near-infrared spectroscopy (NIRS)---the INVOS 4100 and the NIRO 300---produce similar cerebral oxygenation data during the CO(2) challenge test. Nineteen patients anesthetized with sevoflurane, 67% nitrous oxide in oxygen, and fentanyl were studied. A series of measurements of regional cerebral oxygen saturation (rSO(2)), measured by the INVOS 4100, and tissue oxygen index (TOI), measured by the NIRO 300, were performed in the following conditions: 1) normocapnia (PaCO(2), 35--45 mm Hg); 2) hypocapnia (PaCO(2), 25--35 mm Hg); 3) normocapnia; and 4) hypercapnia (PaCO(2), 45--55 mm Hg). Hemodynamic variables, including arterial blood gases and cerebral blood flow velocity, were measured at the same time with transcranial Doppler. The values and percentage changes of rSO(2) and TOI were compared by using regression analysis and Bland and Altman analysis. The rSO(2) showed a significant positive correlation with TOI (r = 0.58, P < 0.01). The percentage change of rSO(2) also showed a significant positive correlation with the percentage change of TOI during the CO(2) challenge (r = 0.85, P < 0.01). Bland and Altman analysis revealed a bias of -0.5% with 2 SD of 15.6% when comparing the rSO(2) value with the TOI value, and it showed a bias of -3.4% with 2 SD of 15.2% when comparing the percentage change of rSO(2) with the percentage change of TOI, indicating unacceptable disagreement of these data. These results indicate that cerebral oxygen saturation and its relative change during the CO(2) challenge may vary depending on the type of NIRS used. Because the measurement technique and algorithm were different in each device, we should carefully consider the clinical application of the values produced by NIRS. IMPLICATIONS: Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive clinical method for assessing cerebral oxygenation. The acceptable reliability and validity of NIRS values have not been established despite their widespread use. The INVOS 4100 and the NIRO 300 can display cerebral oxygen saturation as regional cerebral oxygen saturation and tissue oxygenation index, but they produce differing results.

Adult↗