Smoothing tool design and performance during subaperture glass polishing.

During subaperture tool grinding and polishing, overlaps of the tool influence function can result in undesirable mid-spatial frequency (MSF) errors in the form of surface ripples, which are often corrected using a smoothing polishing step. In this study, flat multi-layer smoothing polishing tools are designed and tested to simultaneously (1) reduce or remove MSF errors, (2) minimize surface figure degradation, and (3) maximize the material removal rate. A time-dependent convergence model in which spatial material removal varies with a workpiece-tool height mismatch, combined with a finite element mechanical analysis to determine the interface contact pressure distribution, was developed to evaluate various smoothing tool designs as a function of tool material properties, thicknesses, pad textures, and displacements. An improvement in smoothing tool performance is achieved when the gap pressure constant, h¯ (which describes the inverse rate at which the pressure drops with a workpiece-tool height mismatch), is minimized for smaller spatial scale length surface features (namely, MSF errors) and maximized for large spatial scale length features (i.e., surface figure). Five specific smoothing tool designs were experimentally evaluated. A two-layer smoothing tool using a thin, grooved IC1000 polyurethane pad (with a high elastic modulus, E p a d =360M P a), thicker blue foam (with an intermediate modulus, E f o a m =5.3M P a) underlayer, and an optimized displacement (d t=1m m) provided the best overall performance (namely, high MSF error convergence, minimal surface figure degradation, and high material removal rate).

Understanding and reducing mid-spatial frequency ripples during hemispherical sub-aperture tool glass polishing.

During sub-aperture tool polishing of glass optics, mid-spatial surface ripples are generated because of material removal non-uniformities during tool linear translation (resulting in feed ripples) and tool pathway step overlaps (resulting in pitch ripples). A variety of tool influence function (TIF) spots, trenches, and patches were created to understand and minimize such ripples on fused silica workpieces after polishing with cerium oxide slurry using a rotating hemispherical pad-foam tool. The feed ripple amplitude can be decreased by reducing the non-uniformities in the pad texture and/or by minimizing a derived feed ripple metric (rf=Vmax0.5Vf/Rt) via adjustments in processing parameters. Pitch ripples can be minimized by reducing relative step distance to spot radius ratio (xs/at) and by achieving a flat bottom trench shape cross section or by reducing the material removal per pass. Using the combined methods, an overall ripple error of ∼1.2nm rms has been achieved.

Effect of workpiece curvature on the tool influence function during hemispherical sub-aperture tool glass polishing.

The influence of workpiece curvature on the tool influence function spot during polishing of fused silica glass with cerium oxide slurry, while using a rotating hemispherical pad-foam tool for a wide variety of process conditions (tool displacement, inclination angle, and rotation rate), has been investigated. (Workpiece curvature ranged from 500 mm radius concave to 43 mm radius convex.) The TIF spot decreases in diameter and increases in the peak removal rate on more convex workpieces. In contrast, the TIF spot increases both in diameter and peak removal rate on more concave workpieces. For the range of workpiece curvatures investigated, both the spot size and the peak removal rate changed significantly, as much as 2 times. An elastic sphere-sphere contact mechanics model, which utilizes both a modified displacement (that leads to a change in the applied load) as well as a mismatch factor (that influences the pressure distribution shape), has been developed. The model was validated using both offline load-displacement measurements and finite-element analysis simulations. The model quantitatively describes the measured change in the relative contact diameter and relative pressure distribution, as well as semiquantitively describes the change in the relative volumetric removal rate on a large variety of TIF spots. The change in the volumetric removal rate for convex workpieces is a result of the balance between a decreasing spot size (reducing removal) and an increasing peak pressure (increasing removal), which usually results in relatively small changes in volumetric removal. In the case of concave workpieces, the volumetric removal rate change is also governed by a similar balance, but the spot size increase contribution dominates, resulting in a significant increase in volumetric removal rate. Understanding these trends can enable methods to add greater determinism during the fabrication of freeform optics by adjusting polishing parameters (such as dwell time) while the tool translates along a workpiece surface with different local curvatures.

Mechanisms influencing and prediction of tool influence function spots during hemispherical sub-aperture tool polishing on fused silica.

Sub-aperture tool polishing of precision optics requires a detailed understanding of the local material removal [tool influence function (TIF)] at the contact spot between the workpiece and tool to achieve high removal determinism and hence precision of the optic relative to the desired/design surface figure. In this study, the mechanisms influencing and the quantitative prediction of the removal rate and shape of TIF spots during polishing of fused silica glass with cerium oxide slurry using a rotating hemispherical pad-foam tool for a wide variety of process conditions (including tool properties, kinematics, and applied displacements) are investigated. The TIF volumetric removal rate can be estimated utilizing the average relative velocity and contact area using a simple analytical model. In addition, stability of the volumetric removal rate for fixed process conditions is shown to be greatly dependent on the pad preparation and amount of tool use (affecting both pad topography and slurry buildup), whose general behavior shows an increase in removal rate followed by stabilization with polishing time. The determination of the TIF removal shape is more complex. An extended version of the Preston removal model is developed to explain a comprehensive set of measured TIF removal shapes to within ∼22%. This model incorporates a number of phenomena impacting the TIF removal shape including: (a) temporal and spatial dependent relative velocity between the workpiece and tool; (b) an elastic mechanics based, as well as hydrodynamic, pressure distribution; (c) a spatially dependent friction coefficient possibly caused by both reduced slurry replenishment in low velocity regions and pad slurry islands (100 µm scale) and porosity (millimeter scale); and (d) a shear-based removal mechanism on the periphery of the contact spot.

CD8- dendritic cell activation status plays an integral role in influencing Th2 response development.

Whether dendritic cells (DC) play a passive or active role in Th2 response induction is poorly understood. In this study, we show that CD8- DC pulsed with Th2-polarizing Ag (soluble egg Ag (SEA)) from Schistosoma mansoni potently stimulate Th2 responses in vivo and in vitro while failing to undergo a conventional maturation process. Thus, in contrast to DC pulsed with the Th1 response inducing Ag Propionebacterium acnes, SEA-exposed DC exhibit a phenotype that is most similar to that of immature DC, failing to up-regulate expression of CD40, CD54, CD80, CD86, or OX40L; producing no detectable IL-4, IL-10, or IL-12; and displaying only a minor increase in MHC class II expression. Importantly, in vitro derived DC exposed to SEA were phenotypically similar to CD8- DC isolated from active S. mansoni infection. By discriminating between different types of pathogen and responding appropriately, CD8- DC play a major role in the decision process to mount either a Th1 or Th2 response.

The exacerbating effect of infectious bronchitis virus infection on the infectious bursal disease virus-induced suppression of opsonization by Escherichia coil antibody in chickens.

Chickens infected with infectious bronchitis virus (IBV) and infectious bursal disease virus (IBDV) commonly develop secondary infection of the respiratory tract with Escherichia coli, resulting in significant economic losses. To understand the host factors that may contribute to the E. coli infection, we investigated macrophage-mediated E. coli phagocytosis, intracellular bacterial killing, and development of opsonizing antibody in previously uninfected chickens and in those infected with IBV, IBDV, and IBDV plus IBV. Macrophages from the peripheral blood and the respiratory tracts of chickens infected with IBV or IBDV plus IBV efficiently performed in vitro phagocytosis of E. coli in the presence of positive-control serum (i.e., E. coli antiserum produced in normal chickens). Those macrophages also had adequate bactericidal activity, indicating that IBV and IBDV infections had not affected their phagocytic activity or bactericidal function. The phagocytic activity of macrophages remained unaffected (P < 0.05) when the positive-control serum was replaced with E. coli antiserum produced in chickens infected with IBV alone. However, when E. coli antisera raised in IBDV-infected and, especially, that produced in IBDV plus IBV-infected chickens were supplemented, the percentage of phagocytosis and number of bacteria ingested per phagocyte were significantly (P < 0.05) less. These results indicate that although IBDV alone has the potential to markedly reduce opsonizing ability of antibody, this effect is significantly (P < 0.05) exacerbated by IBV infection.

IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis.

Liver enlargement and hepatocyte proliferation, normal responses in wild-type (WT) mice infected with the parasitic helminth Schistosoma mansoni, were found to be severely impaired in infected IL-4(-/-) mice. Compared with WT mice, increased levels of O(2)(-), NO, and the more highly reactive ONOO(-) were detected in the liver and produced by lesional cells isolated from liver granulomas of infected IL-4(-/-) mice. Concurrently, antioxidant defenses in the liver, specifically catalase levels, diminished dramatically during the course of infection in these animals. This contrasted to the situation in infected WT mice, where catalase levels remained as high as those in normal mice. Actual levels of reactive oxygen and nitrogen intermediates in the livers of infected IL-4(-/-) animals are thus likely to be considerably higher than those in the livers of infected WT mice. To determine whether these changes contributed to the development of the more severe disease that characterizes infection in the IL-4(-/-) animals, we treated infected IL-4(-/-) mice with uric acid, a potent scavenger of ONOO(-). This resulted in significantly increased hepatocyte proliferation, decreased morbidity, and prolonged survival. Taken together, these data indicate that IL-4 is playing a protective role during schistosomiasis by controlling the tight regulation of the generation of reactive oxygen and nitrogen intermediates in the liver.

Contemporary cardiac rehabilitation: patient characteristics and temporal trends over the past decade.

BACKGROUND: Recent and dramatic therapeutic advances, aggressive care of the elderly, and a heightened awareness of secondary prevention have had a significant, albeit incompletely described, impact on cardiac rehabilitation (CR) programs. The authors did a retrospective analysis on 1,848 patients from their phase II CR program that were treated over the past decade. The authors sought to identify and analyze how advances in cardiovascular care might be related to temporal changes in demographics, medical comorbidities, coronary artery disease risk factors, and cardiovascular history among individuals with cardiac disease who have completed the phase II CR program over a 10-year period. METHODS: Cardiac rehabilitation records were reviewed from 1986 to 1996 at Akron City Hospital. The data were compiled prospectively by nurses and exercise physiologists and were subsequently analyzed. The charts reviewed were from 1,848 patients who completed outpatient phase II CR. RESULTS: The program began in 1986 with 53 patients completing CR and evolved to 309 in 1996. There has been an increase in the number of elderly patients referred to and completing the program. The number of participants older than 65 years of age increased from 28.3% in 1986 to 52.1% in 1996. Cardiac rehabilitation participants reflect the known demographics of patients with clinical coronary artery disease. Men outnumber women and, on average, the female participants are older than the male participants. There has been a statistically significant increase in medical comorbidities over the course of the study. Although the absolute number of patients entering CR after coronary artery bypass graft survey has remained fairly constant, there has been a dramatic increase in the absolute number of patients entering CR after percutaneous tansluminal coronary angioplasty (with the latter recently comprising a majority of CR participants). CONCLUSION: There is a significant trend in the attendance and completion of CR programs by older individuals, which suggests a greater awareness of patients and their physicians. The growth of the program is fueled by high-risk patients with more comorbidities who potentially are the group of patients able to obtain the greatest absolute benefit from CR.

Systemic and local antibody responses to infectious bronchitis virus in chickens inoculated with infectious bursal disease virus and control chickens.

Serum and local (respiratory) antibody responses to infectious bronchitis virus (IBV) were studied in 5-wk-old white leghorn-type control chickens and chickens inoculated with infectious bursal disease virus (IBDV) at 1 day of age. Of the chickens inoculated with IBV alone, 93% had detectable levels of IBV antibodies in the sera and 87% had detectable antibodies in the respiratory lavage fluids. Compared to this group, only 73% and 65% of IBDV-IBV inoculated chickens had serum and respiratory antibodies, respectively. In chickens inoculated with IBV alone, the IBV antibodies were evenly associated with immunoglobulin classes IgM, IgG, and IgA, whereas the IBDV-IBV inoculated chickens mainly produced IgM-associated antibodies with low to negligible levels of IgA- and IgG-associated antibodies. These results suggest that the lack of adequate IgA- and IgG-associated antibody production in IBDV-infected chickens may account for their increased susceptibility to IBV infection.

Two types of growth hormone rhythm in boys with constitutional short stature.

The relationship between temporal and quantitative changes in pulsatile growth hormone (GH) secretion and growth of constitutionally short children (CSS) was studied in 19 prepubertal boys and 4 with early adrenarche aged 7.8 to 14 years. Continuous plasma GH monitoring was performed at 30 minutes intervals during 24 hours. The data were analysed by single and serial best fit (BFT) cosinor analysis for rhythm parameters and the Pulsar peak detection program for determining pulsatile properties. The pulsatile patterns were expressed in mean GH concentration, area under the curve, mean pulse area and maximal pulse height but not in the number of pulses. Thirteen out of 23 patterns exhibited significant 24-h compatible rhythms. The studied cohort was divided into two groups, those who exhibited the 24-h circadian rhythm (CIR) and those who lacked it (NCIR). Ultradian 2.5-4 h rhythms were observed in all patients. The NCIR children were significantly shorter than the CIR group (p = 0.017). The CIR boys secreted a significantly higher (p = 0.01) amount of GH during the 24-h span, most of which was during sleep. Our data indicate that the magnitude of pulses rather than their number is responsible for the quantitative differences observed between the two groups of boys with CSS. It is suggested that a lack of 24-h rhythmicity and the associated reduced nocturnal pulsatility play a role in the manifestation of short stature.

Use of a cervical brush for Papanicolaou smear collection. A meta-analysis.

Inadequacy of Papanicolaou smear specimens, specifically lack of endocervical cells, has been cited as a major reason why between 0.5% and 44% of cases of dysplasia are not detected by conventional screening tools. Of several sampling instruments devised and tested in an attempt to increase endocervical cell retrieval, one of the most promising in the last decade has been a cervical brush. Studies comparing the cervical brush to more conventional devices such as the spatula and cotton swab were examined in this review. A meta-analysis of these studies indicated a significant mean risk difference or increase in endocervical cell retrieval of 0.22 when the cervical brush was used either alone or in combination with a spatula compared to a spatula alone or with a cotton swab. Subpopulations such as pregnant or postmenopausal women, women with cervical stenosis, or women with a history of cervical surgery also showed significant mean increases in endocervical cell retrieval with the cervical brush. The evidence for whether use of a cervical brush actually increases detection of cervical dysplasia is less clear, although there appears to be a trend in that direction.

A monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for identification of infectious bronchitis virus serotypes.

An antigen-capture enzyme-linked immunosorbent assay (C-ELISA) was developed for detection and identification of infectious bronchitis virus (IBV) serotypes Arkansas, Connecticut, and Massachusetts using monoclonal antibodies (MAbs) specific to the S1 glycoprotein of the respective serotype. The assay (designed as a double-antibody sandwich assay) gave the best results when the S1-specific MAb, antigen, and chicken serum were of the same serotype. However, when a group-specific (M glycoprotein-specific) MAb was used for antigen capture, a distinctive pattern of cross-reactivity was observed between the antigens and heterologous chicken sera, suggesting a complex distribution of epitopes on the IBV M glycoproteins. Treatment of antigen with NP40 enhanced the ELISA signal only when the M glycoprotein-specific MAb was used for antigen capture. Although C-ELISA was inconsistent in detecting IBV in chicken tissue homogenates, it was highly effective in detecting the virus in allantoic fluid after the homogenates were given one chicken embryo passage.

Mortality in Israeli Jewish patients with type 1 (insulin-dependent) diabetes mellitus diagnosed prior to 18 years of age: a population based study.

A total of 614 Jewish patients under the age of 18 with Type 1 (insulin-dependent) diabetes mellitus, diagnosed in Israel during the period 1 January 1965 to 31 December 1979, were identified by exhaustive screening of all possible sources. Mortality experience of this cohort was updated to 31 March 1988 through the Central Population Registry and 14 deaths were identified. The ascertainment rate for diagnosed cases as well as for deaths is estimated at about 95%. There was a significantly higher (p less than 0.001) by 3.2-fold excess mortality relative to the age and sex-adjusted mortality as expected the general Jewish population in Israel. This excess was due to three cause-of-death categories: diabetic ketoacidosis (n = 3; p less than 0.001), cardiovascular diseases (n = 3; p less than 0.001) and infections (n = 2; p = 0.03). The rate of malignancies (n = 2), external causes (n = 3) and other general causes (n = 1) did not differ significantly from that expected. During the first 15 years of the disease cumulative mortality resembled that of the general population, with a subsequent steep increase so that by 20 years disease duration, the rate was four-fold higher than expected. This mortality pattern was similar irrespective of age at onset, sex and ethnic group (Ashkenazi vs non-Ashkenazi Jews). A factor contributing to the lack of increase in mortality rate in the first 15 years of Type 1 diabetes may be the comprehensive multidisciplinary treatment approach employed for most juvenile diabetic patients in Israel leading to early referral and an overall better metabolic control.

Greater efficiency of human growth hormone therapy in children below five years of age with growth hormone deficiency. A 5-year follow-up study.

The effect of human growth hormone (hGH) therapy was studied in 39 prepubertal children with growth hormone deficiency (24 with isolated growth hormone deficiency; 15 with multiple pituitary hormone deficiencies) who had been treated for 2-5 years. They were divided into two groups according to age at the initiation of therapy: group A (n = 21), 0.7-4.8 years (mean chronological age, 2.9 +/- 1.4 years, and bone age, 1.2 +/- 0.9 years); group B (n = 18), 5.2-9.9 years (mean chronological age, 7.4 +/- 1.3 years, and bone age, 4.0 +/- 1.5 years). hGH was given at an initial dose of 2-4 IU 3 times/week, raised to 4-6 IU 3 times/week when growth velocity slowed. In the first year, the mean height SDS gain was 1.7 for group A and 0.8 for group B, and in the second year, 1.1 and 0.1, respectively. Subsequently this remained consistent. Bone age advancement was significantly slower in the younger group (3.8 vs. 5.8 years during 5 years) although this group had a greater catch-up response to therapy. It is concluded that hGH therapy is significantly more effective in achieving normalization of height when treatment is initiated at an early age.

Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity.

The response of plasma hGH to an iv bolus injection of GRH1-44 (1 microgram/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 +/- 0.05 standard deviation score (SDS). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 +/- 2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 +/- 1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.