Excess Heat Capacity in Mo/Au Transition Edge Sensor Bolometric Detectors.

Excess heat capacity in a bolometric detector has the consequence of increasing or leading to multiple device time constants. The Mo/Au bilayer transition edge sensor (TES) bolometric detectors initially fabricated for the high resolution mid-infrared spectrometer (HIRMES) exhibited two response thermalization scales, one of which is a few times longer than estimates based upon the properties of the bulk materials employed in the design. The relative contribution of this settling time to the overall time response of the detectors is roughly proportional to the pixel area, which ranges between ~0.3 and 2.6 mm2. Use of laser ablation to remove sections of the silicon membranes comprising the pixels results in a detector response with a smaller contribution from the secondary time constant. Additional information about the nature of this excess heat capacity is gleaned from glancing incidence x-ray diffraction, which reveals the presence of molybdenum silicides near the silicon surface which is a consequence of the bi-layer deposition. Quantitative analysis of the concentration of excess molybdenum, estimated with secondary ion mass spectroscopy, is commensurate to the additional heat capacity needed to explain the anomalous time response of the detectors.

Organizing lesbian/queer bathhouse events: Emerging forms of sexual experience.

Discussions of public sexual spaces in the social science literature have, until recently, been dominated by analyses of men's use of these spaces for erotic expression. In the late 1990s, feminist collectives began to explore the emancipatory potentials these spaces can have for lesbian sexualities. After a police raid on one such event called the "Pussy Palace," scholars in diverse disciplines began to explore how these events have both opened up and restricted erotic possibilities for lesbians, queer women, and trans* attendees. This article reviews the existing social science literature on lesbian and queer bathhouse events and highlights several key themes and subthemes that have dominated the discourse, including the importance that these spaces be recognized for their ability to both shape and be shaped by principles of community, safety, and sexual health/wellness.

Beyond either/or: Reading trans* lesbian identities.

Previous research has explored the affiliation and distancing strategies employed in published memoirs of gender transition. In this article, we are particularly interested in elucidating the ways in which individuals construct identities and characterize their sexualities, and how sociohistorical constraints might influence what is expressed with respect to this in personal narratives of transition. Using the memoirs of Lili Elbe (Hoyer, 1933) and Joy Ladin (2013) as conceptual brackets, this article investigates the complex relationship between the development and articulation of trans* identities and lesbian sexualities within the context of published memoirs of gender transition.

Metrology of infrared superconducting bolometers with a backshort.

We present the detailed metrology of a superconducting Transition-Edge Sensor (TES) absorber-coupled bolometer array bonded to a variable-delay backshort to form an integral field unit. The backshort is shaped as a wedge to continuously vary the electrical phase delay of the bolometer absorber reflective termination across the array. This resonant absorber termination structure is used to define a spectral response over a 4:1 bandwidth in the far-infrared, from ∼30 to 120 µm. The metrology of the backshort-bolometer array hybrid was achieved with a laser confocal microscope and a compact cryogenic system that provides a well-defined thermal (radiative and conductive) environment for the hybrid when cooled to ∼10 K. The results show the backshort free-space delays do not change with cooling. The estimated backshort slope is 1.58 milli-radians and within 0.3% of the targeted value. The sources of error in the free-space delay of the hybrid and optical cryogenic metrology implementations are discussed in detail. We also present measurements of the bolometer's single-crystal silicon membrane topography. The membranes deform and deflect out-of-plane under both warm and cold conditions. Intriguingly, the optically active area of the membranes tends to flatten when cold and repeatably achieve the same mechanical state over many thermal cycles; hence, no evidence for thermally-induced mechanical instability is observed. Most of the cold deformation is sourced from thermally-induced stress in the metallic layers comprising the TES element of the bolometer pixels. These results provide important considerations for the design of ultra-low-noise TES bolometers.

Shear behavior of human skull bones.

A shear-punch test (SPT) experimental method was developed to address the lack of shear deformation and failure response data for the human skull as a function of local bone microarchitecture. Improved understanding of skull deformation and fracture under varying stress-states helps implement mechanism-based, multi-axial material models for finite element analysis for optimizing protection strategies. Shear-punch coupons (N = 47 specimens) were extracted from right-parietal and frontal bones of three fresh-frozen-thawed human skulls. The specimens were kept as full through-thickness or segmented into the three skull constituent layers: the inner and outer cortical tables and the middle porous diploë. Micro-computed x-ray tomography (µCT) before and after SPT provided the bone volume fraction (BVF) as a function of depth for correlation to shear mechanisms in the punched volumes. Digital image correlation was used to track displacement of the punch above the upper die to minimize compliance error. Five full-thickness specimens were subjected to partial indentation loading to investigate the process of damage development as a function of BVF and depth. It was determined that BVF dominates the shear yield and ultimate strength of human skull bone, but the imposed uniaxial loading rate (0.001 and 0.1 s-1) did not have as strong a contribution (p = 0.181-0.806 > 0.05) for the shear yield and ultimate strength of the skull bone layer specimens. Shear yield and ultimate strength data were highly correlated to power law relationships of BVF (R2 = 0.917-0.949). Full-thickness and partial loaded SPT experiments indicate the diploë primarily dictates the shear strength of the intact structure.

DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Natural Language Processing of Radiology Reports in Patients With Hepatocellular Carcinoma to Predict Radiology Resource Utilization.

OBJECTIVE: Radiology is a finite health care resource in high demand at most health centers. However, anticipating fluctuations in demand is a challenge because of the inherent uncertainty in disease prognosis. The aim of this study was to explore the potential of natural language processing (NLP) to predict downstream radiology resource utilization in patients undergoing surveillance for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: All HCC surveillance CT examinations performed at our institution from January 1, 2010, to October 31, 2017 were selected from our departmental radiology information system. We used open source NLP and machine learning software to parse radiology report text into bag-of-words and term frequency-inverse document frequency (TF-IDF) representations. Three machine learning models-logistic regression, support vector machine (SVM), and random forest-were used to predict future utilization of radiology department resources. A test data set was used to calculate accuracy, sensitivity, and specificity in addition to the area under the curve (AUC). RESULTS: As a group, the bag-of-word models were slightly inferior to the TF-IDF feature extraction approach. The TF-IDF + SVM model outperformed all other models with an accuracy of 92%, a sensitivity of 83%, and a specificity of 96%, with an AUC of 0.971. CONCLUSIONS: NLP-based models can accurately predict downstream radiology resource utilization from narrative HCC surveillance reports and has potential for translation to health care management where it may improve decision making, reduce costs, and broaden access to care.

The mechanical response of commercially available bone simulants for quasi-static and dynamic loading.

Bone is a complex hierarchal structured material with varying porosity and mechanical properties. In particular, human cranial bone is essentially a natural composite consisting of low porosity outer and inner tables and a cancellous interior, or diploë. Experimental studies of biomechanically accurate cranial bone analogues are of high importance for biomechanical, forensics, and clinical researchers, which could improve the understanding and prevention of traumatic injury. Many reported studies use commercially available bone surrogates to draw biomechanical and forensics conclusions; however, their mechanical properties are not tabulated over a range of strain rates. This study elucidates the mechanical viability of three leading commercially available bone surrogates, i.e. Synbone, Sawbone, and Bonesim, over a large range of strain rates (10-3 to 103 s-1). Quasi-static compression testing was conducted using a universal testing machine and a Split-Hopkinson Pressure bar system equipped with high-speed video was used to determine the dynamic mechanical behavior of these materials. Micro-computed X-ray tomography (XRT) were performed on each material to investigate their pore structures and distributions. All materials exhibited strain rate dependent strength behavior, particularly at high loading rates (≥103 s-1). The Young's modulus was found to increase with strain rate from 10-3 to 10-1 s-1 for transversely and longitudinally loaded surrogate materials except for Synbone and the higher density Bonesim. The higher density Bonesim was determined to be the most suitable cranial bone simulant tested based on a combination of transverse Young's Modulus (1500 MPa), yield strength (19 MPa), ultimate strength (49 MPa), and ultimate strain (17%). These materials show limited promise for applications where the measured elastic properties and strengths are of interest.

Birth outcomes in women with gestational diabetes managed by lifestyle modification alone: The PANDORA study.

AIMS: To assess outcomes of women in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort with gestational diabetes mellitus (GDM) managed by lifestyle modification compared with women without hyperglycaemia in pregnancy. METHODS: Indigenous (n = 97) and Europid (n = 113) women managed by lifestyle modification were compared to women without hyperglycaemia (n = 235). Multivariate linear and logistic regressions assessed whether GDM-lifestyle women had poorer outcomes compared to women without hyperglycaemia. RESULTS: Women with GDM-lifestyle had higher body mass index and lower gestational weight gain than women without hyperglycaemia. On univariate analysis, gestational age at delivery was lower and induction rates were higher in women with GDM-lifestyle than without hyperglycaemia. On multivariable regression, GDM-lifestyle was associated with lower gestational age at delivery (by 0.73 weeks), lower birthweight z-score (by 0.26, p = 0.007), lower likelihood of large for gestational age (LGA) [OR (95% CI): 0.55 (0.28, 1.02), p = 0.059], and greater likelihood of labour induction [2.34 (1.49, 3.66), p < 0.001] than women without hyperglycaemia. CONCLUSION: Women with GDM managed by lifestyle modification had higher induction rates and their offspring had lower birthweight z-scores, with a trend to lower LGA than those without hyperglycaemia in pregnancy. Further studies are indicated to explore reasons for higher induction rates.

Indigenous healthcare worker involvement for Indigenous adults and children with asthma.

BACKGROUND: Asthma education is regarded as an important step in the management of asthma in national guidelines. Racial and socio-economic factors are associated with markers of asthma severity, including recurrent acute presentations to emergency health facilities. Worldwide, indigenous groups are disproportionately represented in the severe end of the asthma spectrum. Appropriate models of care are important in the successful delivery of services, and are likely contributors to improved outcomes for people with asthma. OBJECTIVES: To determine whether involvement of an indigenous healthcare worker (IHW) in comparison to absence of an IHW in asthma education programmes, improves asthma related outcomes in indigenous children and adults with asthma. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles. The latest search was in December 2006. SELECTION CRITERIA: All randomised controlled trials comparing involvement of an indigenous healthcare worker (IHW) in comparison to absence of an IHW in asthma education programmes for indigenous people with asthma. DATA COLLECTION AND ANALYSIS: Two independent review authors selected data for inclusion, a single author extracted the data. Both review authors independently assessed study quality. We contacted authors for further information. As it was not possible to analyse data as "intention-to-treat", we analysed data as "treatment received". MAIN RESULTS: Only a single study was applicable for this review, and included 24 children randomised to an asthma education programme involving an IHW, compared to a similar intervention without an IHW. Twenty two of these children completed the trial. Only one outcome (asthma knowledge in children, mean difference of 3.30 units, 95% CI 1.07 to 5.53) significantly favoured the IHW involvement group. However, although not statistically significant, all the outcomes favoured the group that had IHW involvement in the asthma education program. There were no studies in adults. AUTHORS' CONCLUSIONS: The involvement of IHW in asthma programs targeted for their own ethnic group in one small trial was beneficial for some but not all asthma outcomes. Thus there is insufficient data to be confident that the involvement of IHW is beneficial in all settings. Nevertheless, given the complexity of health outcomes and culture as well as the importance of self-determination for indigenous peoples, the practice of including IHW in asthma education programs for indigenous children and adults with asthma is justified, but should be subject to further randomised controlled trials.

Preconception care for women with type 2 diabetes mellitus: A mixed-methods study of provider knowledge and practice.

AIMS: Preconception care may decrease adverse pregnancy outcomes associated with pre-existing diabetes mellitus. Aboriginal Australians are at high risk of type 2 diabetes mellitus (T2DM), with earlier onset. We explored practitioner views on preconception care delivery for women with T2DM in the Northern Territory, where 31% of births are to Aboriginal women. METHODS: Mixed-methods study including cross-sectional survey of 156 health practitioners and 11 semi-structured interviews. RESULTS: Practitioners reported low attendance for preconception care however, 51% provided counselling on an opportunistic basis. Rural/remote practitioners were most likely to find counselling feasible. The majority (69%) utilised appropriate guidelines and addressed lifestyle modifications including smoking (81%), weight management (79%), and change medications appropriately such as ceasing ACE inhibitors (69%). Fewer (40%) prescribed the recommended dose of folate (5mg) or felt comfortable recommending delaying pregnancy to achieve optimal preconception glucose control (42%). Themes identified as barriers to care included the complexity of care setting and infrequent preconception consultations. There was a focus on motivation of women to make informed choices about conception, including birth spacing, timing and contraception. Preconception care enablers included cross-cultural communication, a multi-disciplinary care team and strong client-based relationships. CONCLUSIONS: Health practitioners are keen to provide preconception counselling and reported knowledge of evidence-based guidelines. Improvements are needed in recommending high dose folate and optimising glucose control. Cross-cultural communication and team-based care were reported as fundamental to successful preconception care in women with T2DM. Continued education and policy changes are required to support practitioners in opportunities to enhance pregnancy planning.

Cost-effectiveness of androgen suppression therapies in advanced prostate cancer.

BACKGROUND: The costs and side effects of several antiandrogen therapies for advanced prostate cancer differ substantially. We estimated the cost-effectiveness of antiandrogen therapies for advanced prostate cancer. METHODS: We performed a cost-effectiveness analysis using a Markov model based on a formal meta-analysis and literature review. The base case was assumed to be a 65-year-old man with a clinically evident, local recurrence of prostate cancer. The model used a societal perspective and a time horizon of 20 years. Six androgen suppression strategies were evaluated: diethylstilbestrol (DES), orchiectomy, a nonsteroidal antiandrogen (NSAA), a luteinizing hormone-releasing hormone (LHRH) agonist, and combinations of an NSAA with an LHRH agonist or orchiectomy. Outcome measures were survival, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. RESULTS: DES, the least expensive therapy, had a discounted lifetime cost of $3600 and the lowest quality-adjusted survival, 4.6 QALYs. At a cost of $7000, orchiectomy was associated with 5.1 QALYs, resulting in an incremental cost-effectiveness ratio of $7500/QALY relative to DES. All other strategies-LHRH agonists, NSAA, and both combined androgen blockade strategies-had higher costs and lower quality-adjusted survival than orchiectomy. These results were sensitive to the quality of life associated with orchiectomy and the efficacy of combined androgen blockade, and they changed little when prostate-specific antigen results were used to guide therapy. Under a wide range of other assumptions, the cost-effectiveness of orchiectomy relative to DES was consistently less than $20 000/QALY. Androgen suppression therapies were most cost-effective if initiated after patients became symptomatic from prostate metastases. CONCLUSIONS: For men who accept it, orchiectomy is likely to be the most cost-effective androgen suppression strategy. Combined androgen blockade is the least economically attractive option, yielding small health benefits at high relative costs.

Promoters containing ATF-binding sites are de-regulated in cells that express the EWS/ATF1 oncogene.

Chromosomal translocations that fuse the N-terminal region of the Ewings sarcoma oncogene (EWS) to the C-terminal region (including the DNA-binding domain) of the cellular transcription factor ATF1 are associated with a tumour type termed malignant melanoma of soft parts (MMSP). It is envisioned that transformation by the EWS/ATF1 fusion protein results from aberrant transcriptional regulation of genes that are normally regulated by ATF1. To examine this hypothesis we have expressed exogenous EWS-ATF1 in JEG3 cells and tested its ability to activate several promoters that contain binding sites for ATF1. We show that EWS-ATF1 is a strong constitutive activator of some promoters tested but represses others. Significantly, the ability of particular promoters to be activated by EWS/ATF1 in JEG3 cells correlates with promoter activity in two MMSP-derived cell lines (SU-CCS-1 and DTC1). Our results therefore provide evidence that endogenous EWS/ATF1 can de-regulate transcription and that this capacity may contribute to transformation in MMSP.

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

Elevation of melatonin in chicken retina by 5-hydroxytryptophan: differential light/dark responses.

Melatonin is synthesized in the chicken retina under the influence of a circadian clock, which also regulates the expression of tryptophan hydroxylase (TPH) and serotonin N-acetyltransferase (AA-NAT). In order to examine the role of substrate supply in the rhythmic synthesis of melatonin in chicken retina, tryptophan and 5-hydroxytryptophan were administered day and night in light or darkness. When administered systemically at night in darkness, 5-hydroxytryptophan, but not tryptophan, dramatically stimulates melatonin levels in the chick retina in a dose-dependent manner. Intraocular administration of 5-hydroxytryptophan also increases melatonin levels locally, indicating a retinal site of action of the serotonin precursor. The effect of 5-hydroxytryptophan is much greater at night, when TPH and AA-NAT activities are high, than during the day, when the enzyme activities are low. Similarly, unexpected light exposure at night, which inactivates AA-NAT, significantly reduces the ability of 5-hydroxytryptophan to increase retinal melatonin levels. The results suggest that TPH, but not AA-NAT or other enzymes in the melatonin biosynthetic pathway, is saturated with substrate in situ. The rate of melatonin production appears to be a function of the concentration of serotonin, which is regulated by TPH, and by the level of activity of AA-NAT.

A system for quantitative morphological measurement and electronic modelling of neurons: three-dimensional reconstruction.

A system for accurately reconstructing neurones from optical sections taken at high magnification is described. Cells are digitised on a 68000-based microcomputer to form a database consisting of a series of linked nodes each consisting of x, y, z coordinates and an estimate of dendritic diameter. This database is used to generate three-dimensional (3-D) displays of the neurone and allows quantitative analysis of the cell volume, surface area and dendritic length. Images of the cell can be manipulated locally or transferred to an IBM 3090 mainframe where a wireframe model can be displayed on an IBM 5080 graphics terminal and rotated interactively in real time, allowing visualisation of the cell from all angles. Space-filling models can also be produced. Reconstructions can also provide morphological data for passive electrical simulations of hippocampal pyramidal cells.

Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit.

In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 mumol/kg x h) or ascorbate (0.1%) for 10 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha 2-adrenoceptors were determined. 1. The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h. 2. Alpha 2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha 2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha 2-adrenoceptor number and the platelet alpha 2-adrenoceptor mediated aggregatory response. 3. The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (-)[125I]iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly beta 1-adrenoceptors) but not in lymphocytes (possessing mainly beta 2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs.

E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-ca rboxylate sesquihydrate) is a highly selective and potent inhibitor of type V phosphodiesterase(PDE5). The in vitro and in vivo effect of E4021 on platelet function was evaluated, using echistatin, a potent disintegrin, as a positive reference agent. E4021 inhibits aggregatory response to collagen in washed human platelets (IC50 = 5 microM, vs. 0.14 microM with echistatin). In the ex vivo-platelet aggregation assay using whole blood from treated guinea pigs, E4021 (9 mg/kg i.v.) showed a moderate inhibition (43%) against collagen (0.125 microg/ml), whereas echistatin (250 microg/kg i.v.) exerted a 88% inhibition. The absence of endothelium-derived factors (NO) may account for the moderate in vitro and ex vivo antiplatelet activity of E4021. In an in vivo model of reversible platelet aggregation elicited by collagen (100 microg/kg i.v.), both E4021 and echistatin attenuated the intrapulmonary platelet accumulation in guinea pigs (-36% and -44%, respectively). In addition, E4021 (9 mg/kg i.v.) and echistatin (250 microg/kg i.v.) caused a similar inhibition of platelet adhesion at sites of microfilament-induced vascular injury in guinea pigs (52% and 65%, respectively). The two agents in combination did not show additive effect, suggesting that E4021 inhibits platelet activation and impairs interactions of adhesion receptors with matrix proteins. E4021 caused a selective increase in cGMP concentrations in the platelets isolated from treated guinea pigs: cAMP was not affected. It is concluded that the antiplatelet activity of E4021 is mediated through cGMP mechanism by virtue of selective inhibition of PDE5 in the platelets.

Functional, psychological, and satisfaction outcomes of laser in situ keratomileusis for high myopia.

PURPOSE: To identify factors that motivate patients to seek laser in situ keratomileusis (LASIK) treatment for myopia and establish subjective levels of functional improvement and satisfaction across a range of indices after LASIK surgery. SETTING: The Corneal Diseases and Excimer Laser Research Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland. METHODS: In this questionnaire-based, cross-sectional study, an anonymous 34-item questionnaire was forwarded to 50 consecutive patients in a prospective study who had had LASIK for high myopia by a single surgeon at a single center. The questionnaire used visual analog scales, anchored at each end by an adjectival descriptor. The mean preoperative myopia was -10.7 diopters +/- 4.4 (SD). Seventy-six percent of eyes (83% of patients) achieved post-LASIK uncorrected visual acuity (UCVA) of 6/12 or better; 1 eye lost 2 lines of corrected Snellen visual acuity. RESULTS: A 98% reply rate was achieved. The most common motivating factor for pursuing LASIK was to improve UCVA (88%); only 21% rated improved cosmesis as an important motive. Most patients (81% to 100%) reported functional improvement across the spectrum of visual tasks assessed, although 8.8% reported difficulty with nighttime driving. Ninety-six percent felt their UCVA was as good as anticipated, 97.9% were satisfied with the speed of visual improvement, 93.8% achieved the goals for which they had surgery, 97.9% reported an improved quality of life, and 97.9% were satisfied with the overall outcome of LASIK. CONCLUSIONS: Using an anonymous, wide-ranging questionnaire, high levels of functional improvement and satisfaction with the speed of visual recovery and outcome were reported by patients after LASIK for high myopia. Nighttime driving symptoms of variable severity were, however, noted by 8.8% of patients, despite high levels of satisfaction with other aspects of visual function.

Safety and predictability of laser in situ keratomileusis enhancement by flap reelevation in high myopia.

PURPOSE: To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment following primary procedures for high myopia and astigmatism. SETTING: Corneal Diseases and Excimer Laser Research Unit, Department of Ophthalmology, University of Dundee, Dundee, United Kingdom. METHODS: This prospective observational study of retreatment comprised a cohort of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group (P < .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the stromal bed. RESULTS: The mean follow-up after retreatment was 12.8 +/- 5.1 months (range 1.5 to 24 months; 19 eyes >/=6 months, 13 eyes > or = 12 months). The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at 1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow-up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter statistically between 1 week and subsequent times. The mean UCVA improved from 6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%, 75.0%, and 95.8% of eyes, respectively. No significant complications that led to a loss of best corrected visual acuity were encountered, although retreatment procedures were more uncomfortable than primary procedures and self-limiting; epithelial ingrowth that did not threaten vision was common, and 2 patients complained of nighttime visual symptoms. CONCLUSIONS: Retreatment of residual myopia by reelevating the flap was relatively safe and predictable, with a low risk of sight-threatening complications. However, longer term studies may be required to detect late complications.