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PubMed1995

In vitro fertilisation and gamete intrafallopian transfer: an integrative analysis of research, 1987-1992.

OBJECTIVE: To provide a statistically integrated analysis and review of all published outcome studies of in vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) occurring in English language journals between 1987 and 1992; to provide information regarding outcome of assisted reproduction not otherwise available from national registers; and to assess correspondence of these outcomes with outcome data presented in the national registers of the Fertility Societies of Australia and the United States. DESIGN: Computer literature review and manual search of major infertility journals to identify all papers reporting clinical pregnancy rates for IVF and GIFT. A secondary analysis of three factors, including 1. treatment (IVF vs GIFT), 2. stimulation protocol [combinations using clomiphene citrate (CC), combinations using gonadotrophin agonists (GnRHa), and combinations using neither clomiphene citrate nor gonadotrophin agonists, (designated by the symbols and acronyms approximately CC approximately GnRHa throughout this article)], and 3. cause of infertility, assessed their impact upon three clinical pregnancy rates: 1. cycles commenced, 2. cycles reaching retrieval and 3. cycles reaching oocyte/embryo transfer, via a series of one-way analyses of variance with either planned contrasts or post hoc comparisons. SUBJECTS: The unit of observation was the published study. Data were obtained from 31 journals and 216 papers, containing 509 samples and 39,754 per cycles commenced. Data from the national registers of the Fertility Societies of Australia and the United States were used for comparison of literature-based outcomes, where appropriate. RESULTS: The concordance between the outcomes reported in the national registers of Australia and the United States and the amalgamated literature-based data was such that cautious confidence was placed in the results of the subsequent analyses of the literature-based data which provided information not otherwise available. GIFT resulted in significantly more clinical pregnancies than IVF for each stage of the treatment cycle. Differences in pregnancy rates between IVF and GIFT were 8.6% more pregnancies for GIFT for cycles commenced, 14.2% for cycles reaching retrieval, and 7.5% for cycles reaching oocyte or embryo transfer. Stimulation protocols using gonadotrophin agonists (GnRHa) resulted in more clinical pregnancies than protocols using clomiphene citrate for each stage of the treatment cycle: from commencement (10.22%), to retrieval (8.36%), and to transfer (9.36%). Interaction effects indicated that GIFT-GnRHa combinations were superior to IVF-clomiphene citrate combinations for all rates. For cycles reaching retrieval and transfer, GIFT-GnRHa resulted in significantly more clinical pregnancies than IVF-GnRHa. GIFT-clomiphene citrate was better than IVF-clomiphene citrate and IVF-GnRHa was better than IVF-clomiphene citrate. Women with endometriosis (Stages I or II) achieved higher rates of clinical pregnancy than participants with other causes of infertility. CONCLUSIONS: Significantly higher pregnancy rates for GIFT and GnRHa were demonstrated in this study. It was argued that since the differences in clinical pregnancy rates were smaller between IVF and GIFT when a GnRHa protocol was employed, the apparent superiority of GIFT may in fact be due, at least in part, to GnRHa. This question needs further prospective investigation. Women with endometriosis (Stage I or II) achieved higher pregnancy rates than those with other causes of infertility. Overall, this study provides confirmation that well-held clinical conclusions have a true basis in the published literature and that the published literature reflects population data reported in national registers. Further prospective research is needed to clarify the unique probabilities of a live birth for individual couples.

Chorionic Gonadotropin↗
PubMed1998

Instrumentation for the remote monitoring of physiological and behavioral variables.

Few commercial products are available for investigators who wish to monitor multiple physiological and behavioral variables in unrestrained subjects. When telemetry is not practical, e.g., in studies of at-sea diving physiology, one of the only options is to design and build a custom data-logging instrument. This paper describes how a data logger was developed for the successful long-term monitoring of dive depth, swim speed, heart rate, water temperature, and multiple body temperatures from free-ranging northern elephant seals. The task was facilitated by using a commercially available single-board computer designed specifically for portable multichannel data acquisition and, where possible, off-the-shelf sensors/transducers available with integrated signal-conditioning circuits. A smaller data logger for monitoring the electrocardiogram, body temperature, and dive behavior of double-crested cormorants is also described to illustrate the flexibility and simplicity of this approach. Although it is customized for diving animals, with incorporation of the appropriate sensors the basic design should be applicable to studies of comparative, environmental, or exercise physiology involving most medium-to-large animals, including humans.

Animals↗
PubMed1981

Comparisons of confidence intervals for attributable risk.

Confidence intervals for the attributable risk in various epidemiologic study designs are obtained, via a transformation, from the confidence interval for the natural logarithm of the product of the probability of being exposed to the risk factor, and the risk ratio minus one. When the estimated attributable risk is between .21 and .79, the width of the logarithmic transformation (LT)-based interval is less than that for a maximum likelihood (ML)-based interval. This simple sufficient condition applies to all three well-known epidemiologic study designs. Computer simulation results further demonstrate the superiority of the LT-based interval to the ML-based one when the sufficient condition is satisfied.

Epidemiologic Methods↗
PubMed2006

Synthetic biology--putting engineering into biology.

Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis-synthetic biology's system fabrication process-supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

Animals↗
PubMed2002

Influence of a bite-plane according to Jeanmonod, on bruxism activity during sleep.

One way to look at nocturnal oral parafunction such as bruxism, is using polysomnography. Although in recent years several studies have been carried out, it is almost impossible to compare the respective results because of the lack of standardization in the methodology used. The nocturnal muscular activity of m. Masseter and m. Temporalis Anterior has been registered in 21 patients suffering from bruxism, prior and after treatment with a bite-plane made according to Jeanmonod. A group of five persons without any dental or muscular parafunction has been included as a control. A computer program based on the biomechanical principles of muscle contraction has been developed and was used to analyse the raw electromyography (EMG) signal. The data shows a significant decrease (P = 0.008) in nocturnal parafunctional muscle activity with the bite-plane in situ. The present study shows that by analysing the raw signal obtained via EMG using a specially designed computer program, it becomes possible to isolate the occurrence of parafunctional events in the EMG signal and to study the influence of a given therapy on this EMG signal.

Adolescent↗
PubMed1994

Structure-property relations and crack resistance at the bovine dentin-enamel junction.

The present report is a study of the fracture behavior of the dentin-enamel complex, involving enamel, dentin, and the dentin-enamel junction (DEJ), that combines experimental design, computational finite element analysis, and fractography. Seven chevron-notched short-bar bovine DEJ specimens were utilized in this study. The general plane of the DEJ was approximately perpendicular to the fracture plane. All specimens were stored at 37 degrees C and 100% relative humidity for 24 h prior to being tested. A fracture test set-up was designed for application of tensile load on the DEJ specimens to initiate a crack at the vertex of the chevron in the enamel, across the DEJ zone and into the bulk dentin. During fracture testing, a water chamber was used to avoid dehydration of the specimen. The results showed that the lower boundary value of the fracture toughness of the DEJ perpendicular to its own plane was 3.38 +/- 0.40 MN/m1.5 and 988.42 +/- 231.39 J/m2, in terms of KIC and GKC, respectively. In addition, there was an extensive plastic deformation (83 +/- 12%) collateral to the fracture process at the DEJ zone. The fractography revealed that the deviation of the crak path involved an area which was approximately 50-100 microns deep. The parallel-oriented coarse collagen bundles with diameters of 1-5 microns at the DEJ zone may play a significant role in resisting the enamel crack. This reflects the fact, that in the intact tooth, the multiple full thickness cracks commonly found in enamel do not typically cause total failure of the tooth by crack extension into the dentin.

Animals↗
PubMed2005

Simulated folding in polypeptides of diversified molecular tacticity: implications for protein folding and de novo design.

Stereochemistry could be a powerful variable for conformational tune up of polypeptides for de novo design. It may be also useful probe of possible role of interamide energetics in selection and stabilization of conformation. The homopolypeptides Ac-Xxx30-NHMe, with Xxx = Ala, Val, and Leu, of diversified stereochemical structure are generated by simulated racemization with a modified GROMOS-96 force field. The polypeptides, and other systematic stereochemical variants, are folded by simulated annealing with another modified GROMOS-96 force field under the dielectric constant values 1, 4, and 10. The resultant 15,000 molecular folds of isotactic (poly-L-chiral), syndiotactic (alternating L,D-chiral), and heterotactic (random-L,D-chiral) stereochemical structure, belonging to three polypeptide series, achieved under three different folding conditions, are assessed statistically for structure-to-energy-to-conformation relationship. The results suggest that interamide electrostatics could be a major factor in secondary-structure selection in polypeptides while main-chain stereochemistry could dictate molecular packing and therefore the relative magnitude of hydrogen-bond and Lennard-Jones (LJ) contributions in conformational energy. A method for computational design of heterotactic molecular folds in polypeptide structure has been developed, and the first road map for a chiral tune up of polypeptide structure based on stereochemical engineering has been laid down. Broad implications for protein structure, folding, and de novo design are briefly discussed.

Amino Acid Motifs↗
PubMed1989

Comparison of automated and manual shielding block fabrication.

This work reports the results of a study comparing computer controlled and manual shielding block cutting. The general problems inherent in automated block cutting have been identified and minimized. A system whose accuracy is sufficient for clinical applications has been developed. The relative accuracy of our automated system versus experienced technician controlled cutting was investigated. In general, it is found that automated cutting is somewhat faster and more accurate than manual cutting for very large fields, but that the reverse is true for most smaller fields. The relative cost effectiveness of automated cutting is dependent on the percentage of computer designed blocks which are generated in the clinical setting. At the present time, the traditional manual method is still favored.

Humans↗
PubMed2005

Correlated evolutionary pressure at interacting transcription factors and DNA response elements can guide the rational engineering of DNA binding specificity.

Understanding the molecular mechanisms of the specific interaction between transcription factor proteins and DNA is key to comprehend the regulation of gene expression and to develop technologies to engineer transcription factors. Thus far, although there have been several attempts to elucidate protein-DNA interaction through amino acid-base recognition codes, sequence based profiles, or physical models of interaction, the greatest successes in engineering DNA binding specificity remain experimental. Here we present the first systematic evidence of correlated evolutionary pressure at interacting amino acid residues and DNA base-pairs in transcription factors, and show that it can be used to rationally engineer DNA binding specificity. The correlation is between the relative evolutionary importance of protein residues and DNA bases, measured, respectively, in terms of the Evolutionary Trace (ET) rank and information entropy. The evolutionarily most important residues interact with the most conserved base-pairs within the response element while residues of least importance interact with the most variable base-pairs. The correlation averages 0.74 over 12 unrelated families of transcriptional regulators, including nuclear hormone receptors, basic helix-loop-helix, ETS- and homeo-domain family. To test the predictive power of this correlation, we targeted a mutational swap of top-ranked ET residues in a transcription factor, LRH-1. This redirects LRH-1 binding as predicted and showed that, in this case, evolutionary importance and binding specificity are coupled sufficiently strongly for the Evolutionary Trace to guide the computational design of DNA binding specificity. This establishes the existence of evolutionary importance correlation at protein-DNA interfaces, and demonstrates that it is a useful principle for the rational engineering of binding specificity.

Animals↗
PubMed2026

Creating bottom-up RNA transfer vehicles from synthetic protein assemblies.

Evolution guides biological systems to populate ecological niches, with viruses among the most successful examples of this principle. Viruses evolved over billions of years to efficiently transfer genetic information. Although viruses are highly diverse, most have converged towards remarkable similarity in the size and shape of their capsids1,2. By contrast, generative models for protein design enable the creation of protein architectures that are absent from nature3-5. Here we investigate whether protein assemblies designed by artificial intelligence can be functionalized to construct nucleic acid transport vehicles that are independent of evolutionary trajectories. By combining natural protein domains with synthetic protein assemblies, we create more than 100 bottom-up RNA transfer vehicles with unique sizes and shapes. These vehicles surpass the RNA transfer efficiency of widely used delivery vehicles by several orders of magnitude. In addition, we demonstrate that their tropism can be programmed by incorporation of computationally designed peptide binders and use them to deliver therapeutically relevant cargo RNAs into a wide range of cellular models. We show the in vivo biodistribution of one of these vehicles in a mouse at near-single-cell resolution, confirm its safety, and use it to perform a gene-editing treatment strategy for Duchenne muscular dystrophy in patient-derived cells and a pig. Our work demonstrates how proteins created by generative artificial intelligence can be harnessed for the rational engineering of RNA transport systems with the desired properties by overcoming the limitations of natural protein diversity.

Journal Article↗
PubMed2000

Application of genetic programming for the differential diagnosis of acid-base and anion gap disorders.

Differential diagnostics of very complex disorders in the acid-base status and in the accompanying electrolyte balance belongs to the most difficult diagnostic procedures in clinical practice. The goal of our study was to create computer genetic programs, able to aid the diagnostics of acid-base disorders, taking into account a set of laboratory gasometric and electrolyte measurements. Seven (7) single acid-base disorders, eleven (11) double acid-base disorders and six (6) triple complicated disorders with accompanying anion gap alterations were approached by our study. A set of simulated laboratory measurements was prepared, providing 250 results for the evaluation of the fitness function of the designed computer genetic programs, plus some additional results for testing.

Acid-Base Equilibrium↗
PubMed2006

Three dimensional electrode array for cell lysis via electroporation.

Microfabricated devices for cell lysis have demonstrated many advantages over conventional approaches. Among various design of microdevices that employ electroporation for cytolysis, most utilize Ag/AgCl wires or 2D planar electrodes. Although, simple in fabrication the electric field generated by 2D electrodes decays exponentially, resulting in rather non-uniform forcing on the cell membrane. This paper investigates the effect of electric field generated by 3D cylindrical electrodes to perform cell lysis via electroporation in a microfluidic platform, and compared with that by 2D design. Computational results of the electric field for both 2D and 3D electrode geometries showed that the 3D configuration demonstrated a significantly higher effective volume ratio-volume which electric field is sufficient for cell lysis to that of net throughflow volume. Hence, the efficacy of performing cell lysis is substantially greater for cells passing through 3D than 2D electrodes. Experimentally, simultaneous multi-pores were observed on leukocytes lysed with 3D electrodes, which is indicative of enhanced uniformity of the electric field generated by 3D design. Additionally, a single row of 3D electrode demonstrated a substantially higher lysing percentage (30%) than that of 2D (8%) under that same flow condition. This work should aid in the design of electrodes in performing cell lysis via electroporation.

Cell Culture Techniques↗
PubMed1987

Guidelines for maintenance treatment of childhood asthma: development of a score card system by multivariate cluster analysis.

Multivariate cluster analysis of data on 128 asthmatic children resulted in the identification of 8 major discriminating variables. Stepwise divisions by this computer programme resulted in the formation of 6 grades of severity. There was significant correlation between higher grades of severity and early onset of the disease (P less than 0.02). There was also significant correlation between higher grades of severity and greater use of interval medications (P less than 0.002). However, 27.3% were receiving inadequate interval medications in respect of their grade of severity. Assignation of a 5-point scale to each of the 8 major discriminating variables resulted in the generation of computer-designated scores commensurate with each grade of severity. This was coupled to current recommendations for stepwise maintenance medications appropriate for each grade. This Score Card system for maintenance management of childhood asthma may prove useful in busy clinical settings.

Adolescent↗
PubMed2002

Image preprocessing for improving computational efficiency in implementation of restoration and superresolution algorithms.

Computational complexity is a major impediment to the real-time implementation of image restoration and superresolution algorithms in many applications. Although powerful restoration algorithms have been developed within the past few years utilizing sophisticated mathematical machinery (based on statistical optimization and convex set theory), these algorithms are typically iterative in nature and require a sufficient number of iterations to be executed to achieve the desired resolution improvement that may be needed to meaningfully perform postprocessing image exploitation tasks in practice. Additionally, recent technological breakthroughs have facilitated novel sensor designs (focal plane arrays, for instance) that make it possible to capture megapixel imagery data at video frame rates. A major challenge in the processing of these large-format images is to complete the execution of the image processing steps within the frame capture times and to keep up with the output rate of the sensor so that all data captured by the sensor can be efficiently utilized. Consequently, development of novel methods that facilitate real-time implementation of image restoration and superresolution algorithms is of significant practical interest and is the primary focus of this study. The key to designing computationally efficient processing schemes lies in strategically introducing appropriate preprocessing steps together with the superresolution iterations to tailor optimized overall processing sequences for imagery data of specific formats. For substantiating this assertion, three distinct methods for tailoring a preprocessing filter and integrating it with the superresolution processing steps are outlined. These methods consist of a region-of-interest extraction scheme, a background-detail separation procedure, and a scene-derived information extraction step for implementing a set-theoretic restoration of the image that is less demanding in computation compared with the superresolution iterations. A quantitative evaluation of the performance of these algorithms for restoring and superresolving various imagery data captured by diffraction-limited sensing operations are also presented.

Journal Article↗
PubMed2003

Comparison of endocrine tests with respect to their predictive value on the outcome of ovarian hyperstimulation in IVF treatment: results of a prospective randomized study.

BACKGROUND: This study was designed to compare endocrine tests [clomiphene citrate challenge test (CCT), exogenous FSH ovarian reserve test (EFORT) and basal FSH, basal estradiol (E(2)) and basal inhibin B as an integral part of all CCT and EFORT], with respect to their ability to estimate the stimulable cohort of follicles in the ovaries (ovarian capacity) and to analyse which test or combination of tests would give the best prediction of ovarian capacity. METHODS: A total of 110 regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized by a computer-designed 4-block system study into two groups. Fifty-six patients underwent a CCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard. RESULTS: Univariate linear regression analysis showed that the best correlation with the number of follicles after ovarian hyperstimulation (Y) is found by the inhibin B increment (InhB incr.) in the EFORT (Y = 3.957 + 0.081 x InhB incr. (95% CI 0.061-0.101); r = 0.751; P < 0.001). Multiple linear regression analysis showed a significant contributing value of the variables basal FSH, E(2) increment of the EFORT and inhibin B increment to the basic model with the variable age. The best prediction of ovarian capacity (Y) was seen when E(2) increment and inhibin B increment were used simultaneously in a stepforward multiple regression prediction model [Y = 2.659 + 0.052 x InhB incr. (0.026-0.078) + 0.027 x E(2) incr. (95% CI 0.012-0.054); r = 0.796; P < 0.001]. The CCT could not be used in a prediction model. CONCLUSIONS: The EFORT is the endocrine test which gives the best prediction of ovarian capacity.

Adolescent↗
PubMed2004

Intercycle variability of ovarian reserve tests: results of a prospective randomized study.

BACKGROUND: This study was designed to assess prospectively the intercycle variability (ICV) of basal FSH (bFSH), clomiphene citrate challenge test (CCCT) (analysis of the CCCT was performed by the parameter: sum bFSH + sFSH) and exogenous FSH ovarian reserve test (EFORT) (analysis of the EFORT included the following parameters: estradiol (E(2)) increment and inhibin B increment 24 h after administration of FSH), and secondarily to assess the influence of the variability of these ovarian reserve tests. METHODS: Eighty-five regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized, by a computer-designed four-blocks system into two groups. Forty-three patients underwent a CCCT, and 42 patients underwent an EFORT. Each test was performed 1-4 times in subsequent cycles, one test per cycle. During the first three cycles, patients were treated with intrauterine insemination (IUI). Follicle number and oocyte yield during IVF ovarian stimulation in the fourth cycle were taken as measures for ovarian reserve. RESULTS: The per cycle variance of bFSH ranged from 1.8 to 4.4 (maximum to minimum ratio of 2.44, P < 0.0001), while that of CCCT ranged from 21.3 to 70.6 (3.31, P < 0.0001). No significant change in per cycle variance was found for the E(2) increment (1.25, P > 0.2) and inhibin B increment (1.31, P > 0.2), which were the EFORT parameters. A large ICV of CCCT and bFSH test results was strongly associated with lower ovarian reserve. CONCLUSIONS: Our study shows that the ICV of the inhibin B increment and the E(2) increment in the EFORT is stable in consecutive cycles, which indicates that this reproducible test is a more reliable tool for determination of ovarian reserve than bFSH and CCCT. Women with limited ovarian reserve show a strong ICV of bFSH and FSH response to clomiphene citrate.

Adult↗