Performance of a gradient-based shift estimator in a spatially sparse data environment: tracking the sub-pixel motion of fluorescent particles.

Through a series of numerical simulations, we investigate the suitability of a relatively new gradient-based particle-tracking algorithm for efficiently quantifying sub-pixel shifts of fluorescently labelled cells or particles from a sequence of video microscopy images. The algorithm excels at estimating sub-0.5 pixel per frame shifts in both data-dense (e.g. laser speckle imaging) and data-sparse (e.g. fluorescence imaging) applications. No upsampling (i.e. interpolation) is required to achieve the sub-pixel shift resolution, and thus the approach avoids the complexity and potential errors associated with the interpolation process. An efficient MATLAB sub-routine is provided for implementing the algorithm.

Mechanical properties of coagulated albumin and failure mechanisms of liver repaired with the use of an argon-beam coagulator with albumin.

Hemostasis in the traumatized liver has been achieved by thermally denaturing topically applied albumin. In this article, the mechanical properties of liver and denatured albumin (solder) were measured, and the failure methods of liver repaired with albumin were identified. The ultimate tensile strength and Young's modulus were measured for healthy liver (N = 20) and thermally damaged liver (N = 20). The ultimate tensile strength and Young's modulus were measured for three concentrations of coagulated albumin (25, 38, and 53%) in a single layer and for two layers of denatured 38% albumin. Failure under tension of argon-beam coagulator soldered liver on the parenchymal surface (N = 30) with 38% albumin in two layers had a 70% occurrence for tearing at a mean stress of 39 kPa and a 23% occurrence for shearing at a mean stress of 7 kPa. Liver repaired on the interior surface (N = 11) failed in tension by tearing (64%) at a mean stress of 34 kPa and by shearing (36%) at a mean stress of 6 kPa. Argon-beam coagulator soldering with 38% albumin took 6 s/cm(2) for two layers of solder and gave the best balance of usability, strength, and matching of mechanical properties with those of the liver.

Processing algorithms for tracking speckle shifts in optical elastography of biological tissues.

Parametric and nonparametric data processing schemes for analyzing translating laser speckle data used to investigate the mechanical behavior of biological tissues are examined. Cross-correlation, minimum mean square estimator, maximum likelihood, and maximum entropy approaches are discussed and compared on speckle data derived from cortical bone samples undergoing dynamic loading. While it was not the purpose of this paper to demonstrate that one processing technique is superior to another, maximum likelihood and maximum entropy approaches are shown to be particularly useful when the observed speckle motion is small.

High resolution imaged laser speckle strain gauge for vascular applications.

An imaged laser speckle strain gauge that yields strain rates directly is described for vascular applications. The strain gauge does not rely upon cross correlations between a reference image and subsequent strain-modulated images as most current speckle interferometric methods do. Instead, it relies upon a two-dimensional frequency transform of "stacked speckle histories" which are time series of one-dimensional views of the speckle patterns arranged into a spatio-temporal array such that space is along the abscissa and time is along the ordinate. The tilt of the stacked speckle histories is related to the time rate of speckle pattern shift. The strain gauge is sensitive only to in-plane strains. Strain rates of 30.1 +/- 3.2 and 24.83 +/- 2.1 mu epsilon/s were evaluated in vitro on a fresh human tibial artery and rat inferior vena cava, respectively. The total strains measured were 21.6 and 19.86 mu epsilon, respectively. This is at least one order of magnitude more sensitive than other current soft-tissue strain measurement techniques.

Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome.

Renal-Coloboma syndrome, an autosomal dominant disorder characterized by colobomatous eye defects, vesicoureteral reflux, and abnormal kidneys, results from mutations in PAX2. The purpose of this study was to identify mutations in PAX2 and understand the associated patient phenotypes. We report a severely affected girl and a mildly affected mother and daughter, all of whom have PAX2 homoguanine tract (7 G) missense mutations. The mother and daughter have optic nerve colobomas and the daughter has vesicoureteral reflux. The severely affected girl developed renal failure and has bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari 1 malformation. We examined genomic DNA from these individuals by SSCP and sequencing. The mother and daughter had a novel mutation: a contraction in a string of 7 G's to 6 G's in one allele of PAX2, leading to a premature stop codon two amino acids downstream. The severely affected girl had an expansion to 8 G's, leading to a premature stop codon 27 amino acids downstream. The 8 G expansion has been found in other patients without brain anomalies and has occurred spontaneously in a mouse model, PAX2(1Neu). We expand the known phenotype associated with mutations in PAX2 to include brain malformations. The homoguanine tract in PAX2 is a hot spot for spontaneous expansion or contraction mutations and demonstrates the importance of homonucleotide tract mutations in human malformation syndromes.

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation.

Micromechanical behavior of cortical bone as inferred from laser speckle data.

We investigated the micromechanical behavior of porcine femoral cortical bone using a novel, nondestructive, noncontacting, laser-based strain measurement technique. The technique is based upon the well-known concept of tracking translating laser speckle with a linear array CCD camera, but employs a unique data-processing scheme based upon a two-dimensional frequency transform of the data. The method proved to be successful in evaluating strain rates in the bone samples. Measured strain rates ranged between 4.61 and 23.84 micro epsilon/s. Total strains recorded were between 3.7 and 19.1 micro epsilon. Estimated Young's moduli averaged 9.01 +/- 3.93 GPa, which, considering the extremely slow strain rates, is an acceptable value for porcine cortical bone. General advantages of the technique include high sensitivity, insensitivity to zero-mean noise sources, compact design, and the fact that it is truly noncontact. A brief discussion of possible error sources within the method is also given.

Acoustically modulated speckle imaging of biological tissues.

A video laser speckle imaging technique yields images with contrast based on the mechanical properties of a tissue. Fluctuations of laser speckle patterns induced by acoustically driving the tissue at various frequencies in the 0-30-Hz range encode the mechanical strain of the tissue. At each acoustic frequency and within the camera acquisition time, each camera pixel integrates a temporally fluctuating speckle intensity whose variance encodes the mechanical strain in response to the acoustic modulation. The magnitude and the frequency dependence of this strain provide mechanical information about the tissue and are the contrast mechanism for images.

Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23.

Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are mostly benign, slow-growing tumors of the head and neck region, inherited from carrier fathers in an autosomal dominant fashion subject to genomic imprinting. Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We ascertained a total of 11 North American PGL families and confirmed maternal imprinting (inactivation). In three of six families, linkage analysis provided evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the critical region to an approximately 4.5-Mb interval flanked by markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly different between fathers and children (Wilcoxon rank-sum test, P < .002). Affected children had an earlier age at onset of symptoms in 39 of 57 father-child pairs (chi2 = 7.74, P < .006). However, a more conservative comparison of the number of pairs in which a child had > or = 5 years earlier age at onset (n = 33) vis-a-vis that of complementary pairs (n = 24) revealed no significant difference (chi2 = 1.42, P > .2). Whether these data represent genetic anticipation or ascertainment bias can be addressed only by analysis of a larger number of father-child pairs.

Noncontact microstrain measurements in orthodontic wires.

A technique is presented that allows for highly sensitive and highly accurate measurements of microstrain in biomaterials. It is particularly useful for measuring strains in materials where the use of conventional extensometers or strain gauges is impracticable, such as reinforcement fibers and orthodontic wires and in hostile environments. The technique is based on the well known technique of observing translating laser speckle with a linear-array charge-coupled device (CCD) camera. However, it employs a relatively new data processing algorithm involving a two-dimensional frequency transform of the data. Advantages of the technique include: insensitivity to slow surface microstructure changes, insensitivity to zero-mean noise processes, compact design, modest resolution requirements, and the fact that it is truly noncontact. Strain rate measurements were made on an 0.028-gauge round stainless steel orthodontic wire as an example of this technique. The Young's modulus of the wire based on the speckle technique was 2.04 x 10(11) Nm(-2), which is very close to the textbook value.

The development of personal dosimeters for use in the visible and ultraviolet wavelengths regions. The Salisbury Eye Evaluation Team.

We have designed, developed, and field evaluated a two-part personal dosimeter for estimating ocular exposure to visible and ultraviolet radiation. The detector head id compact enough to be mounted on the bow of eyeglass frames, and the recorder is small enough to be carried in a shirt pocket. The detector head consists of a silicon photodiode with filter (Schott glass GG400) and diffuser for visible light measurements and a polysulphone film badge for ultraviolet-B (UVB, 290-320 nm) measurements. The measurements correspond well to those obtained using ambient monitors and should be useful for studies of ocular UVB exposure.

Dubowitz syndrome: long-term follow-up of an original patient.

Dubowitz syndrome is an autosomal recessive disorder of growth retardation, characteristic face, mild mental retardation, and eczema originally described by Dubowitz [1965]. Little information is available on natural history and adulthood in this disorder. We report on a 30-year-old woman who was one of the first patients to be diagnosed with the condition [Grosse et al., 1971, Z Kinderheilkd 110:175-187]. Microcephaly, short stature, leg length discrepancy, hyperextensible joints, spina bifida occulta, and absence of anterior cruciate ligaments were present. Her facial appearance had been modified by several plastic surgery procedures. Eczema resolved with age, with occasional flareups. Asthma, headaches, and seizures were additional medical findings. Speech delays, an unusually soft, high-pitched voice, submucous cleft palate, and velopharyngeal insufficiency were noted in childhood. Mild mental retardation was present. At age 30 years she is living independently in her own apartment and working full-time in a nearby sheltered workshop.

Scale effects on the stresses and safety factors in the wing bones of birds and bats.

The effects of scale on the estimated stresses and safety factors in the humeri of several bird and bat species were investigated. This was accomplished by estimating the lift distribution across the wings at two extremes of flight, gliding flight and the downstroke in hovering, finding the center of lift on the wings at these two extremes and calculating the applied bending and twisting moments. This information, along with measurements of mechanically important morphological variables, allowed for estimates of bending and shearing stresses in the humeri for both gliding flight and on the downstroke in hovering. The stresses in flapping flight other than hovering should fall somewhere between these two values. It was found that the stresses in the humeri are not scale-dependent and that the bending stresses are slightly lower than those found in the limbs of terrestrial animals, while the shearing stresses are larger than those in terrestrial limbs. The breaking stress of bird and bat wing bone was also investigated. Both materials were found to have a lower breaking stress than that of typical long bone material. The ratio between the breaking stress of the material and the estimated stresses was defined as the safety factor. Bird humeri have safety factors that are generally greater than those of bat humeri. This is because bat bone has a lower breaking stress than does bird bone, although the estimated stresses in the wings are similar. The mean safety factor against failure due to bending in gliding flight was 6.63 for birds and 3.99 for bats. In hovering, the mean safety factors against failure due to bending were 2.22 for birds and 1.41 for bats. The safety factors against failure due to shearing stresses were estimated to be seven times greater than those against failure due to pure bending stresses.

Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community-based program for etiologic investigation of intrauterine deaths.

Although stillbirth is a common event, few programs have previously been established for the comprehensive etiologic investigation of intrauterine death. Fewer still have been prospective, unbiased in ascertainment, and consistent in protocol utilization. The Wisconsin Stillbirth Service Program was established in 1983 as a unique model for the investigation of the causes of stillbirth. This community-based, University-supported model for health care delivery is here described. Through it more than a thousand infants have been etiologically investigated. We demonstrate that a community-based program of stillbirth assessment can succeed, that compliance with recommended protocols is high and that a specific primary cause of fetal death can be demonstrated in about 40% of referrals. A majority of the established causes of intrauterine death are fetal etiologies. Furthermore, it appears that there are no substantial referral biases. Lack of such biases, together with the prospective, protocol driven nature of the program provides a unique population upon which to base estimates of the frequency of various etiologic diagnoses and classes and categories of cause.

Transform method of processing for speckle strain-rate measurements.

We have developed a highly sensitive method for measuring thermal expansion, mechanical strain, and creep rates. We use the well-known technique of observing laser speckle with a pair of linear array cameras, but we employ a data-processing approach based on a two-dimensional transform of the speckle histories from each camera. This technique can effect large gauge sizes, which are important in the assessment of the spatial statistics of creep. Further, the algorithm provides simultaneous global estimates of the strain rates at both small- and large-scale sizes. This feature may be of value in the investigation of materials with different short- and long-range orders. General advantages of our technique are compact design, modest resolution requirements, insensitivity to slow surface microstructure changes (as seen with oxidation), and insensitivity to zero-mean-noise processes such as turbulence and vibration. Herein we detail the theory of our technique and the results of a number of experiments. Thesetests are intended to demonstrate the performance advantages and limitations of the transform method of processing speckle strain-rate data.

Further evidence that arthrogryposis multiplex congenita in the human sometimes is caused by an intrauterine vascular accident.

A 7 1/2-year-old girl with arthrogryposis multiplex congenita of the amyoplasia type in association with intestinal atresias, gastroschisis, Möbius anomaly, and hypoplasia of the pectoral, biceps, and deltoid muscles is described. Several combinations of these birth defects have been previously described. There is considerable evidence that gastroschisis, intestinal atresia, Poland sequence, and Möbius anomaly each has a vascular pathogenesis. Based on the associations seen in this child and past reports of more limited, similar cooccurrences, we suggest that arthrogryposis multiplex congenita may sometimes be caused by an intrauterine vascular catastrophe.

Chromosomal deletion 4p15.32----p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region.

Treacher Collins syndrome is an autosomal dominant condition of bilateral craniofacial abnormalities of structures derived from the first and second branchial arches. A patient with severe manifestations of Treacher Collins syndrome and a de novo chromosomal deletion in region 4p15.32----p14 was identified. Anonymous DNA sequences of loci D4S18, D4S19, D4S20, D4S22, and D4S23 were mapped to the deleted region. DNA probes previously mapped to loci on chromosome 4p (D4S10, D4S15, D4S16, D4S26, D4S35, D4S95, D4S144, RAF1P1, QDPR, and HOX7) were not deleted in this patient. Linkage analysis between the D4S18, D4S23, and QDPR loci and Treacher Collins syndrome in eight families excluded the Treacher Collins syndrome locus from the region of the deletion.

Neonatal death in cousins with trisomy 10q and monosomy 4p due to a familial translocation.

Two cousins with trisomy for a part of the long arm of chromosome 10 and monosomy for the distal portion of the short arm of chromosome 4 are reported. These infants had severe, neonatally lethal multiple malformations. Certain of these malformations--including severe lower limb reductions, marked ophthalmologic anomalies and certain craniofacial features--are inconsistent with either a simple additive effect of the two component chromosomal anomalies, or chromosomal "epistasis" that would result in observing the phenotypic effect of only one of the chromosomal aberrations. Rather a synergistic effect of these two karyotypic anomalies has resulted in unique phenotypic features.