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Objective: The glucose and dehydroascorbic acid (DHA) transporter GLUT1 contains a phosphorylation site, S490, for ataxia telangiectasia mutated (ATM). The objective of this study was to determine whether ATM and GLUT1-S490 regulate GLUT1., Research Design and Methods: L6 myoblasts and mouse skeletal muscles were used to study the effects of ATM inhibition, ATM activation, and S490 mutation on GLUT1 localization, trafficking, and transport activity., Results: In myoblasts, inhibition of ATM significantly diminished cell surface GLUT1, glucose and DHA transport, GLUT1 externalization, and association of GLUT1 with Gα-interacting protein-interacting protein, C-terminus (GIPC1), which has been implicated in recycling of endosomal proteins. In contrast, ATM activation by doxorubicin (DXR) increased DHA transport, cell surface GLUT1, and the GLUT1/GIPC1 association. S490A mutation decreased glucose and DHA transport, cell surface GLUT1, and interaction of GLUT1 with GIPC1, while S490D mutation increased transport, cell surface GLUT1, and the GLUT1/GIPC1 interaction. ATM dysfunction or ATM inhibition reduced DHA transport in extensor digitorum longus (EDL) muscles and decreased glucose transport in EDL and soleus. In contrast, DXR increased DHA transport in EDL., Conclusions: These results provide evidence that ATM and GLUT1-S490 promote cell surface GLUT1 and GLUT1-mediated transport in skeletal muscle associated with upregulation of the GLUT1/GIPC1 interaction.

This study investigated the role of autonomy satisfaction in the development of suicidal ideation by integrating two theoretical models of suicide-related behaviors. The first hypothesized a direct effect of autonomy on suicidal ideation. The second hypothesized an indirect effect of autonomy on suicidal ideation via perceived burdensomeness and thwarted belongingness. This was a cross-sectional study of 449 college students, who were predominantly female (73.1%) and Hispanic (70.6%), with a mean age of 20.40 years (SD = 4.38, range 18-50 years). Participants were recruited from a psychology participant pool and completed self-report survey measures for course credit. The model of indirect effects provided the best fit to the data; relatedness, autonomy, and competence were significantly associated with higher thwarted belongingness and perceived burdensomeness, which, in turn, were significantly associated with higher suicidal ideation. Future studies should test this model longitudinally and consider autonomy as a possible avenue for the prevention of suicide-related behaviors.

Objective: The aim of this study was to examine low hedonic responsivity, a facet of hedonic capacity, as a potential explanatory variable in the relationship between attention deficit/hyperactivity disorder (ADHD) symptoms and depressive symptoms., Method: One hundred ninety-eight undergraduate students (mean age = 21.3, standard deviation = 4.6; 59.6% women) from a large, public university completed self-report measures for this cross-sectional study., Results: Results indicated that ADHD symptoms were significantly associated with depressive symptoms, and that low hedonic responsivity partially accounted for this association. This effect was statistically significant for total ADHD symptoms and inattentive symptoms, but not for hyperactive-impulsive symptoms., Conclusions: Findings are consistent with the possibility that impaired hedonic responsiveness may be a common endophenotype for depression and the inattentive symptoms of ADHD. Implications for future research and clinical work are discussed., (© 2012 Wiley Periodicals, Inc.)

A theoretical model in which perceived burdensomeness and thwarted belongingness were hypothesized to account for the association between sexual orientation and suicidal ideation among college students was tested. Among 198 college students (mean age 21.28 years), gay, lesbian, and bisexual students (n = 50) reported significantly higher levels of perceived burdensomeness and suicidal ideation than heterosexual students. The relationship between sexual orientation and suicidal ideation was partially accounted for by perceived burdensomeness, but not thwarted belongingness. This indirect effect was stronger at higher levels of perceived or anticipated rejection due to one's sexual orientation. Implications for intervention and prevention science are discussed., (© 2012 The American Association of Suicidology.)

This chapter presents an overview of computational modeling as a tool for multilevel cancer care and intervention research. Model-based analyses have been conducted at various "beneath the skin" or biological scales as well as at various "above the skin" or socioecological levels of cancer care delivery. We review the basic elements of computational modeling and illustrate its applications in four cancer control intervention areas: tobacco use, colorectal cancer screening, cervical cancer screening, and racial disparities in access to breast cancer care. Most of these models have examined cancer processes and outcomes at only one or two levels. We suggest ways these models can be expanded to consider interactions involving three or more levels. Looking forward, a number of methodological, structural, and communication barriers must be overcome to create useful computational models of multilevel cancer interventions and population health.

Factors distinguishing adolescents who experienced a precipitating event in the week preceding a suicidal crisis from those who did not were examined. Among 130 suicidal inpatients (mean age = 15.01 years), those who experienced a precipitating event reported significantly lower depressive symptom scores, better perceived problem solving, less suicidal intent, and a lower rate of prior suicide attempts than those without a precipitating event. Levels of trait impulsivity, suicidal ideation, and current attempt status did not differentiate groups. Findings provide preliminary evidence consistent with at least two possible pathways to a suicidal crisis. Clinical implications and future directions are discussed., (© 2012 The American Association of Suicidology.)

This experimental study examined the effect of communication about type of screening follow-up (in-person follow-up vs. no in-person follow-up) on adolescents' responses to a self-report suicide risk screen. Participants were 245 adolescents (131 girls, 114 boys; ages 13-17; 80% White, 21.6% Black, 9.8% American Indian, 2.9% Asian) seeking medical emergency services. They were randomized to a screening follow-up condition. Screening measures assessed primary risk factors for suicidal behavior, including suicidal thoughts, depressive symptoms, alcohol use, and aggressive/delinquent behavior. There was no main effect of follow-up condition on adolescents' screening scores; however, significant interactions between follow-up condition and public assistance status were evident. Adolescents whose families received public assistance were less likely to report aggressive-delinquent behavior if assigned to in-person follow-up. Adolescents whose families did not receive public assistance reported significantly higher levels of suicidal ideation if assigned to in-person follow-up. Findings suggest that response biases impact some adolescents' responses to suicide risk screenings. Because national policy strongly recommends suicide risk screening in emergency settings, and because screening scores are used to make critical decisions regarding risk management and treatment recommendations, findings indicate the importance of improving the reliability and validity of suicide risk screening for adolescents.

This paper reviews empirical evidence of the association between suicide-related behaviors and anxiety among children and adolescents. It begins with a review of suicide-related behaviors and anxiety, discusses methodological issues related to measurement, and reviews empirical findings published since the last review of this topic in 1988. Evidence is summarized on four criteria necessary to establish anxiety as a causal risk factor for suicide-related behaviors among children and adolescents. There is consistent evidence for a significant association between anxiety and suicide-related behaviors (Criterion 1). Evidence that the influence of anxiety on suicide-related behaviors is not due to a third variable (Criterion 2) is mixed and hindered by methodological limitations. The literature is also unclear as to whether anxiety temporally precedes suicide-related behaviors (Criterion 3). Finally, this review found no evidence to support or refute anxiety's stability independent of and across instances of suicide-related behaviors (Criterion 4). Theoretical and clinical implications of these findings and directions for future research are discussed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The coping strategies used by adolescents to deal with stress may have implications for the development of depression and suicidal ideation. This study examined coping categories and specific coping behaviors used by adolescents to assess the relation of coping to depression and suicidal ideation. In hierarchical regression models, the specific coping behaviors of behavioral disengagement and self-blame were predictive of higher levels of depression; depression and using emotional support were predictive of suicidal ideation. Results suggest that specific behaviors within the broad coping categories of emotion-focused coping (e.g., self-blame) and avoidant coping (e.g., behavioral disengagement) account for these categories' associations with depression and suicidal ideation. Specific problem-focused coping strategies did not independently predict lower levels of depression or suicidal ideation. It may be beneficial for interventions to focus on eliminating maladaptive coping behaviors in addition to introducing or enhancing positive coping behaviors., (Copyright © 2010 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

We demonstrate that although auditory sampling is a useful tool, this method alone will not provide a truly accurate indication of population size, density and distribution of gibbons in an area. If auditory sampling alone is employed, we show that data collection must take place over a sufficient period to account for variation in calling patterns across seasons. The population of Hylobates albibarbis in the Sabangau catchment, Central Kalimantan, Indonesia, was surveyed from July to December 2005 using methods established previously. In addition, auditory sampling was complemented by detailed behavioural data on six habituated groups within the study area. Here we compare results from this study to those of a 1-month study conducted in 2004. The total population of the Sabangau catchment is estimated to be about in the tens of thousands, though numbers, distribution and density for the different forest subtypes vary considerably. We propose that future density surveys of gibbons must include data from all forest subtypes where gibbons are found and that extrapolating from one forest subtype is likely to yield inaccurate density and population estimates. We also propose that auditory census be carried out by using at least three listening posts (LP) in order to increase the area sampled and the chances of hearing groups. Our results suggest that the Sabangau catchment contains one of the largest remaining contiguous populations of Bornean agile gibbon.

Purpose: The purpose of this study was to assess the corneal response, as measured by corneal oxygen uptake, of keratoconic corneas to SoftPerm and SynergEyes hybrid contact lenses at the central cornea, 2.0 and 4.5 mm temporal to the central cornea, and 1 mm temporal to the limbus., Methods: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the right eyes of 14 subjects and the left eye of 1 subject, all with keratoconus. Measurements were made at the central cornea, 2.0 and 4.5 mm temporal to the central cornea, and 1 mm temporal to the limbus. They were made for the open eye condition, as well as following 300 s of SoftPerm and SynergEyes hybrid contact lens wear. A one-way analysis of variance (ANOVA) was used to determine the effect of measurement location on oxygen uptake rates under uncovered eye conditions. To determine the difference among oxygen uptake rates relative to those of the uncovered eye at each measurement location for each hybrid lens, a two-way repeated measures ANOVA was used. Multiple comparisons with Tukey-Kramer adjustment were used post hoc to determine which locations were significantly different., Results: For the uncovered keratoconic cornea, there was no significant difference among the oxygen uptake rates associated with the three corneal locations; however, the oxygen uptake rates measured 1 mm temporal to the limbus were significantly higher than those measured at the three corneal locations. Comparison of oxygen uptake rates measured with the SoftPerm and SynergEyes lenses relative to those of the uncovered eye at each location revealed significantly higher rates at the peripheral cornea than at the central cornea. At all locations, the relative oxygen uptake rates obtained with the SynergEyes lenses were lower than those obtained with the SoftPerm lenses., Conclusions: The SynergEyes lens allows significantly more oxygen to reach the cornea during wear than the SoftPerm lens at the central cornea, as well as 2.0 mm and 4.5 mm temporal to the central cornea.

Purpose: The purpose of this study was to determine the effects of static (without blinking) and dynamic (with blinking once every 5 seconds) wear of piggyback contact lens systems on corneal oxygen uptake., Methods: Corneal oxygen uptake rates were measured on the right eyes of 11 human subjects by using a polarographic electrode. Measurements were made for the normal open eye and after 5 minutes of wear of 4 rigid lens materials (Dk/t 0-82.5), 4 soft lens materials (Dk/t 13-122), and 16 combinations of rigid and soft lens materials. The piggyback systems were worn under both static and dynamic conditions. Repeated-measures analysis of variance was used to compare oxygen uptake rates associated with the wear of the rigid lens components, soft lens components, piggyback systems, and static versus dynamic wearing conditions. Spearman correlation coefficients and regression analyses were used to examine relationships between corneal oxygen uptake rates., Results: Measurable differences were found among oxygen uptake rates associated with the rigid lens components, soft lens components, and piggyback systems. Blinking resulted in no reduction in corneal oxygen uptake with the piggyback systems. Corneal oxygen uptake associated with the wear of the piggyback systems could not be predicted from those associated with the rigid and soft lens components of the systems., Conclusions: Piggyback combinations of rigid and soft lens components with the highest transmissibilities resulted in the least increase in corneal oxygen uptake beyond that of the normal open eye.

Purpose: The effects of sequencing of test conditions, in this case contact lens thicknesses, on the measurement of the oxygen shortfall of human corneas were studied., Methods: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the central, unanesthetized right corneas of 14 human subjects. Measurements were made under the following conditions: (1) the normal open eye; (2) after 5 min of static (without blinking) wear of each of seven rigid gas permeable lenses of seven center thicknesses (0.18, 0.12, 0.16, 0.20, 0.24, 0.28, and 0.32 mm); (3) after 5 min of static wear of a polymethylmethacrylate (PMMA) contact lens. Lens thicknesses were randomly assigned numbers, which were sequenced in seven cycles. Two subjects were assigned to each sequencing cycle, and each subject participated in two identical sessions., Results: The interaction of order x thickness was determined to be insignificant (F=0.99; p=0.5101). The effect of lens order was also insignificant (F=0.76; p=0.6239), indicating that the order of lens placement did not affect the measured corneal oxygen shortfall. Not surprisingly, the analysis indicated a significant effect of lens thickness on corneal oxygen shortfall (F=3.94; p=0.0032)., Conclusions: The sequencing of lenses of various thicknesses on the cornea does not affect the measurement of corneal oxygen shortfall.

Factors that influence the polarographic measurement of the oxygen uptake of the cornea are reviewed. These factors include the technique, electrode assembly, oxygen reservoir, membrane material and thickness, oxygen tension of the corneal environment, duration of exposure to environmental conditions and time to application of the probe all influencing measured oxygen uptake rates. Subject factors include lid position, palpebral aperture size, blinking, corneal thickness, and corneal integrity. Contact lens wear influences corneal oxygen uptake, with lens material and design parameters influencing rates obtained both under static (without blinking) and dynamic (with blinking) conditions. Measurement of corneal oxygen uptake rates remains an excellent method to quantify the oxygen supply in contact lens systems that include the contact lens, the tears, and the cornea, in which oxygen flux is influenced by the thickness and diffusion characteristics of each component.

Purpose: The purpose of this study is to determine the effects of rigid gas-permeable contact lens thickness, base curve radius, and material permeability on corneal hypoxic stress., Methods: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the right eye of 10 human subjects for the normal open eye (air) and after 5 minutes of static wear of rigid contact lenses of four cornea-to-contact lens base curve fitting relationships: 0.2 mm steeper-than-K (STK), 0.1 mm STK, on K, and 0.1 mm flatter-than-K (FTK). There were also four materials (polymethylmethacrylate [Dk=0], lotifocon B [OP-2, Dk=15.9], lotifocon A [OP-3, Dk=30], lotifocon C [OP-6; Dk=60]) and three center thicknesses (0.14, 0.28, and 0.53 mm for the OP-6 lenses and 0.14 mm for all other materials) with all other parameters being constant. Each subject participated in two identical sessions. A repeated-measures analysis of variance was performed to compare the mean response across lens materials/thicknesses and the four curvature values., Results: Significant differences were found only for lens material/thickness (p<0.0001). Although OP-2 and OP-6 (0.53 mm) were manufactured to have the same Dk/t, post hoc comparisons showed that the oxygen uptake rate with OP-6 (0.53 mm) was significantly lower. The same is also true for OP-3 and OP-6 (0.28 mm), with OP-6 (0.28 mm) having a significantly lower oxygen uptake rate., Conclusions: In contrast to past studies with PMMA, cornea-to-contact lens base curve fitting relationship, with the lens materials and designs studied here, did not affect corneal hypoxic stress, and thick, high Dk lenses resulted in less change in corneal response than did thin, lower Dk lenses of the same Dk/t. This is attributed to the lens reservoir effect that has been previously described.

A method is described for recording interference images from the full thickness of the precorneal tear film (PCTF). Simultaneous images are recorded by two video cameras. One camera responds to broadband spectral illumination and records interference from the superficial lipid layer of the tear film. The other camera uses narrowband illumination and records interference from both the lipid layer and the full thickness of the PCTF. Thus the full-thickness interference fringes are derived from the difference between, or ratio of, narrowband broadband images. This method has the potential for evaluating the role of both tear film flow and evaporation in tear film thinning and breakup. It therefore may be applied to the analysis of dry eye disease.

Electron crystallography determines the structure of membrane embedded proteins in the two-dimensionally crystallized state by cryo-transmission electron microscopy imaging and computer structure reconstruction. Milestones on the path to the structure are high-level expression, purification of functional protein, reconstitution into two-dimensional lipid membrane crystals, high-resolution imaging, and structure determination by computer image processing. Here we review the current state of these methods. We also created an Internet information exchange platform for electron crystallography, where guidelines for imaging and data processing method are maintained. The server (http://2dx.org) provides the electron crystallography community with a central information exchange platform, which is structured in blog and Wiki form, allowing visitors to add comments or discussions. It currently offers a detailed step-by-step introduction to image processing with the MRC software program. The server is also a repository for the 2dx software package, a user-friendly image processing system for 2D membrane protein crystals.

The routine use of surgical drains in total hip arthroplasty remains controversial. They have not been shown to decrease the rate of wound infection significantly and can provide a retrograde route for it. Their use does not reduce the size or incidence of post-operative wound haematomas. This prospective, randomised study was designed to evaluate the role of drains in routine total hip arthroplasty. We investigated 552 patients (577 hips) undergoing unilateral or bilateral total hip arthroplasty who had been randomised to either having a drain for 24 hours or not having a drain. All patients followed standardised pre-, intra-, and post-operative regimes and were independently assessed using the Harris hip score before operation and at six, 18 and 36 months follow-up. The rate of superficial and deep infection was 2.9% and 0.4%, respectively, in the drained group and 4.8% and 0.7%, respectively in the undrained group. One patient in the undrained group had a haematoma which did not require drainage or transfusion. The rate of transfusion after operation in the drained group was significantly higher than for undrained procedures (p < 0.042). The use of a drain did not influence the post-operative levels of haemoglobin, the revision rates, Harris hip scores, the length of hospital stay or the incidence of thromboembolism. We conclude that drains provide no clear advantage at total hip arthroplasty, represent an additional cost, and expose patients to a higher risk of transfusion.

Block copolymer poly(styrene-b-dimethylsiloxane) fibers with submicrometer diameters in the range 150-400 nm were produced by electrospinning from solution in tetrahydrofuran and dimethylformamide. Contact angle measurements indicate that the nonwoven fibrous mats are superhydrophobic, with a contact angle of 163 degrees and contact angle hysteresis of 15 degrees . The superhydrophobicity is attributed to the combined effects of surface enrichment in siloxane as revealed by X-ray photoelectron spectroscopy and surface roughness of the electrospun mat itself. Additionally, the fibers are shown by transmission electron microscopy to exhibit microphase-separated internal structures. Calorimetric studies confirm the strong segregation between the polystyrene and poly(dimethylsiloxane) blocks.

Purpose: The human corneal oxygen uptake responses associated with the static (nonblinking) and dynamic (blinking) wear of five rigid gas-permeable materials with high oxygen permeabilities were determined for three different center thicknesses and compared with the responses for the normal open eye and severe hypoxic stress (static wear of polymethylmethacrylate)., Methods: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode during two sessions with each of 10 human subjects. Measurements were made on the right eye for the normal open eye (air) and after 5 minutes of static and dynamic wear of polymethylmethacrylate and five rigid gas-permeable contact lens materials: Fluoroperm 92 (paflufocon A, Dk = 92), Fluoroperm 151 (paflufocon D, Dk = 151), 1992 Menicon SF-P (melafocon A, Dk = 102), 1995 Menicon SF-P (melafocon A, Dk = 159), and Menicon Z (tisilfocon A, Dk = 163-250). Lenses were manufactured in three different center thicknesses (0.12, 0.16, and 0.20 mm), with all other parameters remaining constant. Repeated-measures analysis of variance was used and included lens material (five levels), blinking condition (two levels), and lens thickness (three levels) as within-subject effects., Results: Significant differences were found in corneal oxygen responses to lens material (p < 0.001) and lens thickness (p < 0.001), with lenses of lower oxygen permeability and thicker lenses being associated with higher oxygen uptake. No statistically significant differences were noted between static or dynamic wear of the lens materials (p = 0.59)., Conclusions: For those very high Dk rigid lens materials studied here, moderate changes in lens thickness or material permeability may result in modest differences in corneal hypoxic relief, whereas blinking results in no significant improvement to corneal oxygenation.

Measurements of the thickness of the pre-corneal tear film, pre-lens tear film, post-lens tear film, and the lipid layer on the surface of the tear film are summarized. Spatial and temporal variations in tear film thickness are described. Theoretical predictions of tear film thickness are discussed. Mechanisms involved in the upward drift of the tear film after a blink, and in the formation of dry spots, are considered.

The self-associating structures at the solid-liquid interface of three nonionic trisiloxane surfactants ((CH3)3SiO)2Si(CH3)(CH2)3(OCH2CH2)n OH (n = 6, 8, and 12), or BEn, are studied as a function of substrate properties by atomic force microscopy (AFM) imaging and force measurement. These trisiloxane surfactants are known as superwetters, which promote rapid spreading of dilute aqueous solutions on low-energy surfaces. This study also attempts to relate the BEn surface aggregate structures at the solid-liquid interface to their superwetting behavior. Four substrates are used in the study: muscovite mica, highly oriented pyrolytic graphite, and oxidized silicon wafer with and without a full monolayer of self-assembled n-octadecyltrichlorosilane (OTS). The concentration of BEn is fixed at 2 times the critical aggregation concentration (CAC). The BEn surfactants are only weakly attracted to hydrophilic surfaces, more on oxidized silicon than on mica. All three form ordinary planar monolayers on HOPG and OTS-covered oxidized silicon. The significance of surfactant adsorption on the AFM tip is investigated by comparing the force curves obtained by tips with and without thiol modification. The surface aggregate structures of the BEn surfactants correlate with their bulk structures and do not exhibit anomalous adsorption behavior. The adsorption behavior of the BEn superwetters is similar to that of the CmEn surfactants. Thus, our results confirm previous work showing that superwetting shares its main features with other classes of surfactants.

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery., Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury., Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p < 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically., Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.

Objectives: To examine the epidemiology and results of treatment of fractures of the distal humeral metaphysis., Design: Observational cohort study., Setting: An orthopaedic trauma unit, which provides all the fracture care for a well-defined catchment population., Patients/participants: A consecutive series of 320 patients with distal humeral fractures admitted to the unit between January 1988 and June 1997., Intervention: We adopted a protocol of open reduction and fixation of all displaced fractures (greater than 5 mm of displacement in any plane) in patients who were medically fit for anesthesia. Postoperative immobilization was a cylinder cast for 6 weeks. Patients with undisplaced fractures or who were medically unfit were also treated nonoperatively in cylinder casts for 6 weeks., Main Outcome Measurements: Epidemiological examination of patient subgroups and the incidence of complications of treatment., Results: The overall incidence of distal humeral fractures in adults during this time was 5.7 cases per 100,000 in the population per year with an almost equal male to female ratio. There was a bimodal age distribution, simple falls were the most common overall cause of fracture, and the majority of the fractures were extra-articular (AO/OTA type A) or complete articular fractures (AO/OTA type C). The risk of complications during treatment was generally low in most patients, and the majority healed their fractures uneventfully. Overall, 90.6% of fractures united within 12 weeks and just under half of the remaining 9.4% patients with union complications healed without requiring further operative intervention by 24 weeks. The risk of union complications was higher following high-energy injuries, open fractures, and nonoperative treatment. Although the AO/OTA classification was not predictive of union complications, the "low" transcondylar (type A2.3 and A3) and simple intercondylar fracture (type C1.3) configuration had a greater risk of union complications than the "high" subtype. The rate of infection, myositis ossificans, and other implant-related complications were higher following operative treatment of type C fractures than type A and B fractures., Conclusions: The epidemiology of a consecutive unselected series of adult distal humeral fractures is defined in this study. The majority of these fractures are best treated surgically by rigid open reduction and internal fixation, except for "low" Type A and C fractures, which have a higher risk of union complications. The role of total elbow arthroplasty to treat these more complex injuries requires further evaluation.

Purpose: The effects of oxygen reservoir and tear exchange are known for conventional hydrogel contact lenses. This study attempted to (1) confirm their presence in lenses of a silicone hydrogel (SH) material and (2) evaluate their individual and combined contributions to hypoxic relief of the cornea., Methods: Corneal oxygen uptake rates were measured polarographically for 10 OD corneas immediately after 300-sec periods (equivalent to 60+ blink cycles) of: (1) nonblink wear of a 0 Dk/L polymethylmethacrylate (PMMA) cap lens; (2) nonblink wear of that cap lens with a SH lens inserted between it and the cornea; (3) regular blinked wear of that same lens combination; (4) nonblinked wear of the SH lens alone; and (5) normal open-eye, non-lens wear. The rates for each eye had a ratio with its own baseline (no lens) rate, and the total sample mean was calculated for each condition from those individual eye means., Results: (1) Under nonblink conditions, a 28% reduction in corneal oxygen demand was observed when a SH lens was inserted under the PMMA cap lens versus without. (2) When regular blinking was added to that lens combination, corneal oxygen demand decreased another 8%, for a total of 36%. The combination of SH insertion and blinking did achieve a statistically significant difference (P<0.05 by the Dunnett test) from the nonblink, 0 Dk/L, maximum deprivation condition., Conclusion: The statistically significant hypoxia reduction observed with the SH lens insertion and blinking indicates the additive presence of two factors: (1) a lens reservoir effect caused by the SH lens and (2) a bulk-flow tear exchange effect caused by blinking. Their respective contributions to the reduction of corneal oxygen demand over the period studied were found to be in the ratio of 3.4:1.

We studied 28 patients with accelerated phase chronic myelogenous leukemia (CML) who were enrolled on the Novartis expanded access study 114. Diagnosis of accelerated phase CML was based on karyotypic evolution (n = 9) and hematologic criteria (n = 18). All patients were begun on 600 mg/day of imatinib mesylate. Dose reductions to 400 mg/day and then 300 mg/day were prescribed for an absolute neutrophil count (ANC) of <0.5/microl or a platelet count of <20,000/microl. Twenty-seven of the 28 patients continued treatment for a median of 34 weeks. Eleven patients developed thrombocytopenia following an average of 8.4 +/- 1.4 weeks of therapy. The onset of thrombocytopenia was associated with disease progression in one patient and a decline in bone marrow megakaryocytes in the other 10. Nine patients recovered to a platelet count of >20,000/microl after an average of 19.7 +/- 1.8 weeks. Patients who developed thrombocytopenia had a longer duration of disease (9.39 vs. 4.35 years; P < 0.01) and were more likely to be diagnosed with accelerated phase CML by hematologic criteria. Hematologic responses in patients with and without thrombocytopenia were comparable; however, 31.3% of patients without thrombocytopenia had a complete cytogenetic response compared to none of those with thrombocytopenia. Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate., (Copyright 2002 Wiley-Liss, Inc.)

Background: In some cases, rigid gas-permeable (RGP) contact lenses may be the best--or only--means of refractive correction. High Dk RGP materials have markedly reduced hypoxia under those lenses. With aspheric lens back surface designs, post-lens circulation may be enhanced as well by maximizing the provision of nutrients and the clearance of metabolic by-products, toxins, and debris, while minimizing the risk of lens binding., Methods: Performances of four aspheric back surface RGP designs were compared with a spherical optic zone and peripheral curve back surface reference design. Oxygen uptake rates were measured for each of 40 wearing combinations (five lens designs fitted to each of eight eyes) under non-blink and blink conditions for their effectiveness in reduction of post-lens hypoxia. Hypoxic reductions with blinking were scaled in exchange efficiency (EE) units, and used as relative indicators of post-lens tear exchange., Results: Combined exchange efficiency index (EE) scores (averaged responses across all eight eyes) for each of the five lens back surface designs ranged from a best overall performance of +13.9 EE units down to only +2.5 EE units, with the spherical reference design averaging +8.9 EE units. Tear pump efficiency of each of the eight eyes (averaged responses across all five lens designs) ranged from a high of +12.3 EE units down to -9.8 EE units (i.e., worse than the non-blink condition of 0 EE units). Among the 40 eye-lens back surface design combinations studied here, the highest exchange efficiency score registered was +28.4 EE units, the lowest being -13.8 EE units., Conclusions: Aspheric lens back surface and/or peripheral curve designs were found to vary significantly in their post-lens exchange efficiency performances, but no "universal problem-solver" design was found among the five we investigated.

Serine proteases play essential roles in a wide variety of cellular processes in endocrine cells. There is a growing interest in the roles of serine protease inhibitors, or serpins, as key regulators of their activity. We have cloned two neuroserpin cDNAs from a rat pituitary cDNA library and confirmed tissue plasminogen activator as a potential target for this inhibitor. We show that neuroserpin transcripts are expressed by endocrine cells in the adrenal and pituitary glands and that immunoreactive neuroserpin is stored in densely cored secretory granules in these cells. Overexpression of neuroserpin in an anterior pituitary corticotroph cell line results in the extension of neurite-like processes, suggesting that neuroserpin may play a role in cell communication, cell adhesion, and/or cell migration.

Neuroserpin is a serine protease inhibitor widely expressed in the developing and adult nervous systems and implicated in the regulation of proteases involved in processes such as synaptic plasticity, neuronal migration and axogenesis. We have analysed the effect of neuroserpin on growth factor-induced neurite outgrowth in PC12 cells. We show that small changes in neuroserpin expression result in changes to the number of cells extending neurites and total neurite length following NGF treatment. Increased expression of neuroserpin resulted in a decrease in the number of cells extending neurites and a reduction in total free neurite length whereas reduced levels of neuroserpin led to a small increase in the number of neurite extending cells and a significant increase in total free neurite length compared to the parent cell line. Neuroserpin also altered the response of PC12 cells to bFGF and EGF treatment. Neuroserpin was localised to dense cored secretory vesicles in PC12 cells but was unable to complex with its likely enzyme target, tissue plasminogen activator at the acidic pH found in these vesicles. These data suggest that modulation of neuroserpin levels at the extending neurite growth cone may play an important role in regulating axonal growth.

Serine protease inhibitors (serpins) are a family of structurally related proteins that play key roles in the regulation of proteolytic homeostasis. We have isolated a novel intracellular serpin, termed raPIT5a, from the rat pituitary gland. Northern blot analysis indicated raPIT5a mRNA expression in a range of tissues, including the adrenal gland and the brain. In situ hybridisation histochemistry revealed raPIT5a mRNA expression in specific cell populations in the rat pituitary gland, adrenal gland, and pancreas. Based on sequence similarities to other intracellular serpins, we predicted raPIT5a may inhibit the pro-apoptotic serine protease granzyme B. We confirmed this experimentally by identification of a stable inhibitory complex between granzyme B and raPIT5a. To determine whether granzyme B or granzyme B-related enzymes were expressed in the rat pituitary gland, we performed PCR using primers predicted to amplify granzyme B and two other published granzyme sequences. We identified rat natural killer protease-1 (RNKP-1), the rat homologue of granzyme B, and a novel putative serine protease highly similar to granzyme-like protein III (GLP III), which we termed GLP IIIa. These data suggest raPIT5a may regulate apoptosis in the pituitary by inhibition of granzyme B or GLP IIIa, or members of the caspase enzyme family which have similar substrate specificity. We have also identified expression of a second serpin, called neuroserpin, in pituitary tissue and found that it alters the morphology of the AtT20 corticotrope cell line, presumably through changes in cell adhesion. These results identify new roles for serpins in pituitary cell function.

We reviewed 286 consecutive patients with a fracture of a pubic ramus. The overall incidence was 6.9/100,000/year in the total population and 25.6/100,000/year in individuals aged over 60 years. The mean age of the patients was 74.7 years and 24.5% suffered from dementia. Women were affected 4.2 times more often than men. After injury, geriatric rehabilitation was frequently required and although most surviving patients returned to their original place of residence, their level of mobility was often worse. The overall survival rates at one and five years were 86.7% and 45.6%, respectively. Multiple logistic regression analysis showed that age and dementia were the only independent significant factors to be predictive of mortality (p < 0.05). Patients with a fracture of a pubic ramus had a significantly worse survival than an age-matched cohort from the general population (log-rank test, p < 0.001), but this was better than patients with a fracture of the hip during the first year after injury, although their subsequent mortality was higher. Five years after the fracture there was no significant difference in survival between the two groups.

The dielectric response of a simple, self emulsifying, system, based on a polysorbate and a medium chain length triglyceride, has been investigated as a function of the water content in the range 0 to 80% by weight. The low frequency capacitive dispersions have been characterised in terms of an electrode barrier layer dispersion, and the bulk conductance and capacitance have been quantified. It is shown that the barrier parameters are essentially insensitive to the water content, over concentrations from 2.5 to 75% by weight, and that the magnitude of the bulk emulsion conductance determines the form of the dispersions which can be observed.

Neuroserpin (NS) is a serine protease inhibitor (or serpin) that is widely expressed in the developing and adult nervous systems. It has been implicated in the regulation of proteases involved in processes such as synaptic plasticity, neuronal migration, and axogenesis. To aid in the characterization of this new serpin we have established a high-level expression system in Drosophila S2 cells and developed a purification strategy to obtain neuroserpin for functional studies. Suspension cultures of S2-NS cells secreted recombinant neuroserpin into the medium. High-level expression was maintained when the cells were switched to a nonselection serum-free medium for 3-4 days to facilitate protein purification. Recombinant neuroserpin was purified by sequential chromatography on Macroprep ceramic hydroxyapatite, Type I, POROS HQ20, Resource Q, and Superdex 75 HR 10/30 media. Two secreted forms of neuroserpin were observed with molecular weights of approximately 49 and approximately 50 kDa which may represent alternative glycosylation at three putative N-linked glycosylation sites. Amino acid sequence analysis indicated three NH(2)-terminal sequences. The major sequence was generated by cleavage at the Gly(18)-Ala(19) bond consistent with removal of an 18-amino-acid signal peptide. Two further sequences were identified each with one fewer amino acids at the NH(2)-terminus. All three NH(2)-terminal sequences were also identified by mass spectrometric analysis of neuroserpin following trypsin digestion. Mass spectrometry also confirmed the protein had an intact carboxyl terminus while complex formation assays indicated the inhibitor was functionally active. In summary, Drosophila S2 cells offered a nonlytic stable expression system for the continual production of neuroserpin in high-density suspension cultures., (Copyright 2001 Academic Press.)

Purpose: Interferometric methods have considerable potential for studying the thickness of layers of the human tear film and cornea because of their ability to make noninvasive, accurate, and rapid measurements. However, previous interferometric studies by Prydal and Danjo yielded tear thickness values near 40 and 11 microm, respectively, considerably greater than estimates made by invasive methods of 4 to 8 microm. Using a modified version of Danjo's method, interference effects from the tear film and cornea were studied, with the aim of correlation with known structure and optical properties of the cornea and hence determining the most probable value of tear film thickness., Methods: Reflectance spectra from the human cornea were measured at normal incidence. These spectra show oscillations whose maxima correspond to constructive interference between light reflected from the air surface and from some deeper surface. The frequency of these spectral oscillations is proportional to the thickness of the layer between the air surface and the second surface. Therefore, Fourier analysis of reflectance spectra can be used to determine the thickness of layers of the tear film and cornea. In the main experiment, 36 low-resolution spectra were obtained from six normal eyes for measuring thickness up to 100 microm. Control experiments included measurements of the time course of thickness changes and high-resolution spectra for measuring thickness up to 1000 microm., Results: For the main experiment, in the thickness range 1 to 100 microm, the strongest peak in the Fourier transform was near 3 microm (range, 1.5-4.7 microm) beneath the air surface. In the range 20 to 100 microm, the strongest peak was near 55 microm (range, 50-59 microm) for all 36 spectra; none were in Prydal's range near 40 microm. This 55-microm peak is consistent with a reflection from the basement membrane of the epithelium. Time course measurements after a blink show that the 3-microm peak is not an artifact. High-resolution spectra gave a peak near 510 microm, corresponding to the complete thickness of the cornea (plus tear film). This peak had a contrast similar to that of the 3-microm peak., Conclusions: These studies did not confirm Prydal's estimate of approximately 40 microm. Nor were there prominent peaks near Danjo's value of approximately 11 microm, except in cases of probable reflex tears. Because the reflection at the aqueous-mucus boundary would be expected to be weaker than that from the epithelial surface, the 3-microm peak is unlikely to correspond to the aqueous layer (rather than the complete tear film). The proposal that the 3-microm peak corresponds to a reflection from the front of the cornea is supported by the demonstration of a peak of similar contrast from the back of the cornea. Thus, the current evidence consistently supports a value of approximately 3 microm for the thickness of the human precorneal tear film.

Background: While the environment of the naturally closed eye substantially challenges the oxygen-dependent processes of the cornea, the presence of a contact lens further exacerbates those stresses. The purposes of this study are: (1) to describe responses of the human cornea under closed eye conditions to a wide range of Dk/t environments as ratios of their corresponding normal, open-eye (physiological) baseline rates; (2) to describe the difference ("hypoxic gap") function that separates those closed-eye responses from parallel responses for the open eye; and (3) to present predictive models for all three (closed-eye, open-eye, and difference) response functions in both graphical and mathematical forms., Methods: Oxygen uptake rates were measured polarographically: for the normal open eye and after both closed- and open-eye wear of six rigid contact lenses of transmissibilities ranging from 0 to 91 x 10(-9) (cm/sec)(ml O2/ml mmHg)., Results: Responses from the closed-eye and open-eye series to those six Dk/t levels were compared both graphically and statistically. Those response series were described by best-fit equations, from which a model for Dk/t effectiveness in meeting corneal oxygen needs under both closed- and open-eye conditions was developed., Conclusions: Response series for both closed and open eyes were found to be well described by natural log equations (R2 values > 0.99). Statistically, separation of those two series could be demonstrated (p < 0.05) by the Dk/t level of 12.8 x 10(-9) (cm/sec)(ml O2/ml mmHg). While, by the highest Dk/t level observed here of 91 x 10(-9) (cm/sec)(ml O2/ml mmHg), corneal responses for the open eye have already moderated down to just 1.5x the "ideal standard," closed-eye response rates are still averaging 2.7x that baseline. The difference ("hypoxic gap") function remaining between those closed- and open-eye curves appears to be stabilizing in its magnitude by 91 x 10(-9) (cm/sec)(ml O2/ml mmHg) as well.

Two cDNAs encoding the serine protease inhibitor (serpin) neuroserpin were cloned from a rat pituitary cDNA library (rNS-1, 2922 bp; rNS-2, 1599 bp). In situ hybridization histochemistry showed neuroserpin transcripts in the intermediate, anterior and posterior lobes of the pituitary gland and medullary cells in the adrenal gland. Expression of rNS-1 mRNA was restricted to selected cells in the pituitary gland. Analysis of purified secretory-granule fractions from pituitary and adrenal tissues indicated that neuroserpin was found in dense-cored secretory granules. This result suggested that endocrine neuroserpin may regulate intragranular proteases or inhibit enzymes following regulated secretion. To investigate the function of neuroserpin in endocrine tissues we established stable anterior pituitary AtT-20 cell lines expressing neuroserpin. Cells with increased levels of neuroserpin responded by extending neurite-like processes. Extracellular proteolysis by serine protease plasminogen activators has been suggested to regulate neurite outgrowth. As neuroserpin inhibits tissue plasminogen activator (tPA) in vitro, we measured plasminogen-activator levels. Zymographic analysis indicated that AtT-20 cells synthesized and secreted a plasminogen activator identical in size to tPA. A higher-molecular-mass tPA-neuroserpin complex was also observed in AtT-20-cell conditioned culture medium. tPA levels were similar in parent AtT-20 cells and a stable cell line with increased levels of neuroserpin. There was no accumulation of a tPA-neuroserpin complex. Together these results identify endocrine cells as an important source of neuroserpin. Moreover they suggest that neuroserpin is released from dense-cored secretory granules to regulate cell-extracellular matrix interactions through a mechanism that may not directly involve tPA.

Background: A bifocal rigid gas permeable (RGP) contact lens is now available that totally encapsulates an add segment of a different material within its inferior aspect. The purposes of this study were to determine the effects of the major lens and of its encapsulated segment region on the oxygen uptake rates of underlying cornea., Methods: Corneal oxygen uptake rates of 10 human corneas were measured--both centrally and inferiorly--for non-wearing conditions and then immediately after 300-second wearing periods of a polymethylmethacrylate (PMMA) lens and of this RGP-encapsulated segment bifocal contact lens. Corneal responses associated with these three environmental conditions were compared statistically (i.e., without the influence of blink-driven tear flow)., Results: Under the nonblinking conditions maintained (i.e., with oxygen availability restricted to lens transmissibility alone), central corneal hypoxia was found for the RGP bifocal lens to be only 47% of that induced by the PMMA (Dk/L = 0) condition, while the cornea under the encapsulated segment of the bifocal lens averaged 78% of the hypoxic response induced by that same condition. Central site responses were found to be significantly different for the bifocal and the PMMA lens (p < 0.001), as they were for the two inferior sites with these two lenses (p < 0.001). All lens-related responses were found to be significantly different from the no lens condition (p < 0.001)., Conclusions: Using Smith's model (JAOA, 1997) to estimate lens transmissibility, the major lens of this RGP bifocal design appears to meet approximately 80% of the Holden-Mertz daily-wear oxygen requirement--even without post-lens tear exchange, but only about 25% of that requirement appears to be met beneath the encapsulated segment region. Efficient supplementary infusion of oxygen under this lens by blink-driven tear exchange, then, is necessary to maintain optimal corneal health.

Introduced here are two predictive parameters, peDk/L and peDk. The prefix pe- (for physiologically effective) indicates that such values are estimates of lens transmissibility (Dk/L) and material permeability (Dk) and have been derived through a reverse application of the Residual Hypoxia model of Smith, relating corneal response (in hypoxic stress units) to lens transmissibility (Dk/L). Here, using independent databases, physiological responses to simple oxygen pathways (one layer, one material) but of unknown Dk value were entered into that model to estimate the Dk/L and (then by calculation) the Dk value of single vision rigid gas permeable (RGP) contact lenses. Also demonstrated was the application of this strategy for estimation of composite (integrated) Dk/L and Dk values of complex (multi-layer, multi-material) oxygen pathways, wherein one or more material Dk values and/or one or more local thickness are unknown.

We have cloned a novel serpin (raPIT5a) from a rat pituitary cDNA library which is structurally related to members of the ovalbumin subfamily of serine protease inhibitors. This new cDNA encodes a 374-amino acid protein, designated raPIT5a. raPIT5a was expressed in specific cells in the intermediate and anterior lobes of the pituitary. Recombinant raPIT5a was not secreted suggesting raPIT5a functions to inhibit intracellular proteases. Recombinant raPIT5a formed an SDS-stable complex with human granzyme B, a serine protease which induces apoptosis by activating members of the caspase enzyme family. These data suggest raPIT5a may have a role in regulating granzyme B or related enzymes and apoptosis in the pituitary gland.

Objective: The aim of the study was to assess the developmental outcome of neonatal survivors of hemolytic disease of the neonate treated with modern intrauterine transfusion techniques., Study Design: In this prospective, observational study, auditory evoked-response tests were performed in the nursery. Neurodevelopmental evaluation with the Gesell Developmental Schedules was performed between 9 and 18 months of corrected age to assess motor skills, language development, comprehension capacity, and social skills. The McCarthy Scales of Children's Abilities were administered between 36 and 62 months., Results: Forty children who survived severe fetal hemolytic disease were followed up until 62 months old. Demographic data included gestational age at first intrauterine transfusion (26.4 +/- 3.7 weeks), median number of intrauterine transfusions (4, range 1-8), lowest fetal hematocrit (20.2% +/- 7.8%), peak fetal bilirubin (7.1 +/- 2.1 mg/dL), incidence of hydrops fetalis (45%), and mean gestational age at delivery (35.6 +/- 2.2 weeks). One case of severe bilateral deafness and 1 case of right spastic hemiplegia were diagnosed. The Gesell Developmental Schedules score was assessed between 9 and 18 months of corrected age in 22 infants. The global developmental quotient was 101.9 +/- 9.5 (mean for normal population is 100). Regression analysis revealed no correlation between the global developmental quotient and gestational age at the first intrauterine transfusion, gestational age at birth, or the severity of the fetal hemolytic disease (fetal hematocrit, fetal bilirubin, presence of hydrops fetalis, total number of intrauterine transfusions, duration of neonatal phototherapy, and number of neonatal exchange transfusions). Eleven of the 40 children were followed up until they were 62 months old, and the McCarthy Scales of Children's Abilities were administered. The mean cognitive index was 107.6 +/- 9.4 (90-109 is considered average)., Conclusion: Despite severe fetal hemolytic disease, normal developmental outcome can be expected for children treated with intrauterine transfusions.

The effects of rigid contact lens material [polymethyl methyacrylate (PMMA) and itabisfluorofocon A] and prism ballasting (0, 1.5, 2.25, and 3 delta) on tear pump efficiency were studied by measuring corneal oxygen uptake rates on the right eyes of six human subjects under three conditions: (1) normal open eye; (2) after 5 min of static (without blinking) wear of the contact lens; and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lens. As expected, corneal oxygen uptake rates (i.e., demand for oxygen) measured with the itabisfluorofocon A material were significantly lower (p < 0.0001) than those measured with PMMA under both static and dynamic conditions. Under static conditions, no significant differences were found across materials among the corneal oxygen uptake rates associated with the four amounts of prism ballasting (p = 0.0514). However, under dynamic conditions, significant differences (p < 0.0001) were found across materials among corneal oxygen uptake rates associated with the four amounts of prism ballasting, with the lower amounts of prism ballasting being associated with lower corneal oxygen uptake rates. The changes in the measured corneal oxygen uptake rates from static to dynamic conditions, relative to those measured for the normal open eye, served as an index of tear pump efficiency. There were no significant differences in these changes for the prism amounts studied; however, static condition data were significantly higher than dynamic condition data for the 0 delta and 1.5 delta lenses only, whereas greater amounts of prism ballasting resulted in no reduction in oxygen uptake under dynamic conditions. In addition, significantly greater differences between static and dynamic condition data were found for the PMMA material than for itabisfluorofocon A.

Background: Lens transmissibility (Dk/L) and corneal relief from hypoxia are not linearly related. We describe graphically and by equations the relationship between corneal relief (scaled in oxygen shortfall units) and Dk/L across the transmissibility range of 1.2 to 189 x 10(-9) (cm/sec)(ml O2/ml mmHg)., Methods: Corneal responses to 28 Dk/L levels across the transmissibility range were expressed in oxygen shortfall units (osús), a relative scale of 100 steps bounded by each cornea's normal oxygen uptake rate with no contact lens in place (set = to 0 osús), and its maximum uptake rate for the open eye due to static PMMA lens wear (set = to 100), thus allowing the degree of hypoxic stress exhibited by all corneas to be compared on the same relative scale., Results: Responses of 11 human corneas to each of those 28 Dk/L steps were recorded across that entire transmissibility range, and their collective relationship described graphically., Conclusion: The graphic composite of all corneal responses to transmissibility steps across the Dk/L range of 1.2 to 189 X 10(-9) (cm/sec)(ml O2/ml mmHg) was found to be monotonic and continuous. While no single equation was found that optimally described (predicted) corneal responses across that entire spectrum, equations of the quadratic form fit limited domains of Dk/L (r2 values exceeding 90%) adequately for most laboratory and clinical applications.