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L1Base: from functional annotation to prediction of active LINE-1 elements.

L1Base is a dedicated database containing putatively active LINE-1 (L1) insertions residing in human and rodent genomes that are as follows: (i) intact in the two open reading frames (ORFs), full-length L1s (FLI-L1s) and (ii) intact ORF2 but disrupted ORF1 (ORF2-L1s). In addition, due to their regulatory potential, the full-length (>6000 bp) non-intact L1s (FLnI-L1s) were also included in the database. Application of a novel annotation methodology, L1Xplorer, allowed in-depth annotation of functional sequence features important for L1 activity, such as transcription factor binding sites and amino acid residues. The L1Base is available online at http://l1base.molgen.mpg.de. In addition, the data stored in the database can be accessed from the Ensembl web browser via a DAS service (http://l1das.molgen.mpg.de:8080/das).

Animals↗

Perifoveal laser treatment for subfoveal choroidal new vessels in age-related macular degeneration. Results of a randomized clinical trial.

In a controlled clinical trial, 160 eyes underwent "perifoveal" laser photocoagulation. All patients had age-related macular degeneration and subfoveal neovascularization (0.5 to 2.5 disc diameters), without detectable fibrous tissue, and visual acuity from 20/100 to 20/1000. At least 1 year of follow-up has been completed in 127 eyes. Visual acuity was maintained or improved in 12 (20.3%) of 59 untreated eyes vs 28 (41.1%) of 68 treated eyes (P = .04). Reading visual acuity (J4) with the use of low-vision aids was retained in 28 untreated eyes (47.4%) vs 50 treated eyes (73.5%) (P less than .01). Automated static perimetry showed an increased scotomatous area and/or depth with eccentric fixation in all but four patients. A flat atrophic scar was achieved in 53 of 68 treated eyes. Statistical analysis indicated that perifoveal photocoagulation has been effective in the short-term preservation of visual acuity.

Aged↗

Instrument to measure the heat convection coefficient on the endothelial surface of arteries and veins.

The primary objective of the paper was to present the design and analysis of an instrument to measure the heat convection coefficient h on the endothelial surfaces of arteries and veins. An invasive thermistor probe was designed to be inserted through the vessel wall and positioned on the endothelial surface. Electrical power was supplied to the thermistor by a constant temperature anemometry circuit. Empirical calibrations were used to relate electrical measurements in the thermistor to the h at the endothelial surface. As the thermal processes are strongly dependent on baseline blood temperature, the instrument was calibrated at multiple temperatures to minimise this potentially significant source of error. Three different sizes of thermistor were evaluated to optimise accuracy and invasiveness, and the smallest thermistors provided the best results. The sensitivity to thermistor position was evaluated by testing the device at multiple locations, varying both depth of thermistor penetration and position along the vessel. Finally, the measurement accuracy of the instrument was determined for the range of h from 430 to 4200 W m(-2)K, and the average error of the reading was 4.9% for the smallest thermistor. Although the instrument was designed specifically for measurements in the portal vein to obtain useful data for current numerical modelling, the device can be used in any large vessel.

Catheter Ablation↗

Efficacy of dapiprazole.

A study was performed to evaluate the clinical usefulness of dapiprazole in a private clinical setting. This study was unmasked, but used one eye of each subject as a control. Thirty consecutive subjects were given dapiprazole as directed by the manufacturer. The administration of dapiprazole followed bilateral dilation for routine fundus examination. Subjects were dilated using one drop each of proparacaine 0.5%, tropicamide 1.0%, and phenylephrine 2.5%. Pupil diameter, amplitude of accommodation, and conjunctival injection were evaluated. Each of these three variables was measured (1) before instillation of the diagnostic agents, (2) before the instillation of diapiprazole, and (3) at 30, 60, 120, and 180 min after the final instillation of dapiprazole. The average pupillary recovery time for dapiprazole-treated eyes was similar to previously published data. Accommodation also showed significant recovery, with comfortable reading ability returning after approximately 30 min. The design of our study did not permit us to determine what portion of accommodation recovery was attributable to alpha ciliary muscle effect and what portion resulted from the increased depth of field that was due to the pupillary constriction. All of our subjects exhibited conjunctival hyperemia after the administration of dapiprazole. This side effect persisted through the entire 180-min observation period that followed dapiprazole administration.

Accommodation, Ocular↗

Inter- and intra-examiner variability using standard and constant force periodontal probes.

Current methods of measuring periodontal probing depths at specified sites by clinical means are subject to wide variation both within and between examiners. This paper reports an investigation into the influence of a constant-force periodontal probe on intra- and inter-examiner variability when measuring probing depths. 30 sites in 10 patients with untreated chronic adult type periodontitis were examined by 2 operators, firstly using a standard periodontal pocket probe then with a constant force probe. Neither examiner was aware of the others readings and were thus blind in relation to one another. Comparison of the recordings of the 2 operators using the standard probes showed significant differences between the operators (p less than 0.01) but this difference became insignificant when the constant force probe was used. One operator had a significant variation between his standard and constant force measurements (p less than 0.01), but the other did not. Overall there was a maximum variation of +/- 1 mm in 79.9% of recordings using the standard probe and this agreement was increased to 100% with the use of the constant pressure probe.

Adult↗

Correlation of hemodynamic variables with transcutaneous PO2 measurements in critically ill adult patients.

Transcutaneous oxygen (PtcO2) monitoring with miniaturized heated electrodes has been shown to continuously track arterial oxygen tension (PaO2) noninvasively in stable infants. However, the correlation between the two is less marked in unstable adults, and PtcO2 appears to be additionally influenced by perfusion. The ability of PtcO2 to detect alterations in cardiac index (CI) was evaluated in 19 critically ill adult patients. The PtcO2 was found to be influenced by the PaO2, the CI, and local vascular tone, with a rapid response time to changes in these variables. All instances of improvement in PtcO2 readings were associated with improvement in PaO2 or hemodynamic status. Because of its high sensitivity, continuous noninvasive PtcO2 monitoring should allow reduction in routine PaO2 and CI determinations. However, a decrease in PtcO2 requires immediate in-depth evaluation of the patient's PaO2 and CI because of its lack of specificity.

Adult↗

[Measuring depth perception in stereoamblyopia by using a suprathreshold stimulus].

BACKGROUND: Stereotests based on random distribution pattern (global stereopsis) show disadvantages when giving larger disparation, because subjects with limited fusion-ability do not recognize them, while realistic shapes of objects (contour stereopsis) are usually fused. Because of this random dot tests can not always be utilized to verify subnormal stereo-ability. SUBJECTS AND METHODS: This paper describes a way of testing stereo-ability not by approaching stereo-angle-thresholds but by presenting supra-threshold stimuli and evaluating the emphasized subjective "elevation level" readings. With this method I examined normosensoric healthy subjects and compared them to subjects with different binocular defects. RESULTS AND CONCLUSIONS: The subjective sensations correlate well with the clinical impression of what those patients, known at the department for long periods, should be able to differentiate. There is no evidence that healthy people are fully competent while "cured" strabismus cases should be incompetent. Indeed a gradual decrease of stereo-ability is seen. We strive for a really simple finger test in terms of subjective depth perception as a quick halfprecise office check.

Adolescent↗

Use of an intracranial near-infrared probe for localization during stereotactic surgery for movement disorders.

Localization of targets during stereotactic surgery is frequently accomplished by identification of the boundaries between the gray matter of various nuclei and the surrounding white matter. The authors describe an intracranial probe developed for this purpose, which uses near-infrared (NIR) light. The probe fits through standard stereotactic holders and emits light at its tip. The scattered light is detected and analyzed by a spectrometer, with the slope of the trailing portion of the reflectance curve used as the measurement value. Near-infrared readings were obtained during 27 neurosurgical procedures. The first three operations were temporal lobectomies, with values obtained from tracks in the resected specimen and resection bed. In the next five procedures, the probe was inserted stereotactically to a depth of 1 to 2 cm with measurements obtained every 1 mm. The probe was then used in 19 stereotactic procedures for movement disorders, obtaining measurements every 0.5 to 1 mm to target depths of 6 to 8 cm to interrogate subcortical structures. The NIR signals were correlated to distances beneath the cortical surface measured on postoperative computerized tomography or magnetic resonance imaging by using angle correction and three-dimensional reconstruction techniques. The NIR values for white and gray matter obtained during the lobectomies were significantly different (white matter 2.5+/-0.37, gray matter 0.82+/-0.23 mean +/- standard deviation). The NIR values from the superficial stereotactic tracks showed initial low values corresponding to cortical gray matter and high values corresponding to subcortical white matter. There was good correlation between the NIR signals and postoperative imaging in the 19 stereotactic cases. Dips due to adjacent sulci, a plateau of high signal due to subcortical white matter, a dip in the NIR signal during passage through the ventricle, dips due to the caudate nucleus, and peaks due to the white matter capsule between ventricle and thalamus were constant features. The putamen-capsule boundary and the lamina externa and interna of the globus pallidus could be distinguished in three cases. Elevated signals corresponding to the thalamic floor were seen in 10 cases. Nuances such as prior lesions and nonspecific white matter changes were also detected. There was no incidence of morbidity associated with use of the probe. Data acquisition was straightforward and the equipment required for the studies was inexpensive. The NIR probe described in this article seems to be able to detect gray-white matter boundaries around and within subcortical structures commonly encountered in stereotactic functional neurosurgery. This simple, inexpensive method deserves further study to establish its efficacy for stereotactic localization.

Brain↗

[Potential role of gravity in computerized tomography in neoplasms].

PURPOSE: The possible evolution of the usual CT signs in oncology makes the logical premise of our experience. Our goal was to transform instrumental findings in information richer in clinical yield, in compliance with the guidelines of the National Cancer Institute (Bethesda, Md, USA). MATERIAL AND METHODS: Our study was developed over a 3-year period and involved 432 selected patients with primary neoplasms. The lesions were in pulmonary, gastroenteric and genitourinary sites and stages differed (T2/T3, N0/N3, M0/M1); the Karnofsky score ranged 60-90. We integrated the tumor staging obtained with CT with gravitational tests by means of simple changes in the position of forced decubitus resulting in procubitus and triclinium-like positions (right and left lateral decubitus). We restudied only the cT class of each lesion, looking for a better depiction of the lesion-adjacent, fat, and compared the results the examinations in the standard versus the modified decubitus. Judgements were relative to the technical quality of the modified examination and to the potential impact of these findings on the following pTNM staging. RESULTS: In our 432 patients and only relative to the cT parameter, CT with standard decubitus correctly staged 312 lesions (mean accuracy: 72.2%) versus 352 for CT with modified decubitus (mean accuracy: 81.5%). Improvements were more marked in gastric (22.9% of 48 cases), vesical (23% of 26 cases) and colic (22.3% of 76 cases) lesions, and less marked in pulmonary (10.6% of 132 cases), ovarian (14% of 71 cases) and endometrial (17.1% of 70 cases) lesions. The routine application of pTNM verifications to CT staging helped show the most frequent causes of cTNM mistaging in solid lesions which, in most of the T2/T3 classes, involve the direct spread to an adjacent organ and the depth of invasion of adjacent structures. CONCLUSIONS: The combination and comparison of cTNM with pTNM are useful not only for final tumor staging but also to assess the pretreatment diagnostic accuracy of CT studies. Introducing gravitational tests and reading examinations in pairs improved lesion location, which is the most important technical information for subsequent prognosis and treatment and can help decrease pre-/post-treatment management costs.

Aged↗

[What do you actually see? Visual impairments and their simulation for well-seeing subjects].

Most physicians know little about how persons with limited vision perceive something. Sometimes, simple technical aids can make it possible to get an idea as to what a visual disorder means to the person involved. Examples of this are the wearing of glasses of varying positive power and light transmittance, or the study of case histories, paintings and photographic simulations. Among the latter are a woman who painted what she 'saw' with her removed eye, an anophthalmic man who painted from memory, and the painting of a protanopic artist who chose colours by reading the labels on the paint tubes. Thus one may gain insight in disturbances such as phantom images, diminished visual acuity and visual field loss, metamorphopsia, diplopia, dazzling, and visual agnosia. And also in disturbed image fusion, in depth and stereoscopic vision, dark adaptation and colour vision, as well as diminishing visual functions at high age. This article contains colour illustrations that simulate the disturbances.

Aging↗

Effects of pressure on whole blood glucose measurements using the Bayer Glucometer 4 blood glucose meter.

The effect of pressure was investigated on the readings of whole blood glucose obtained from the Bayer Glucometer 4 blood glucose meter which uses the hexokinase enzymatic reaction. Sixteen subjects (eight normal and eight insulin-dependent diabetics) were exercised in a hyperbaric chamber at a depth of 3.7 atm abs. Venous blood samples were monitored at regular intervals for whole blood glucose concentration as measured by a Glucometer 4 inside the chamber. The blood samples were immediately placed in an airlock and taken to 1 atm abs, where whole blood glucose concentrations were measured using an identical instrument. The remaining blood was then analyzed in duplicate for serum glucose concentration using standard laboratory methods. The results show a significant difference between whole blood glucose concentrations measured at pressure and those measured at atmospheric pressure. Significant differences are also observed between whole blood glucose concentrations measured under pressure and serum blood glucose concentrations measured at atmospheric pressure.

Adult↗

An interdisciplinary course in the basic sciences for senior medical and PhD students.

Integrating clinical and basic sciences throughout the medical school curriculum has become a major objective of various innovations in medical education. While early clinical exposure has evolved as an efficient means of introducing clinical studies in the preclinical years, interdisciplinary integration of basic sciences during the clinical years remains a challenge. The authors describe their three years of experience with an interdisciplinary course designed to demonstrate the continuum of medical information from the clinic to the basic sciences. In this course, sixth-year medical students are required to choose one of three to four different one-week programs, each of which requires them to conduct an in-depth investigation of a defined clinical topic. Program coordinators are encouraged to work in clinician-basic scientist teams and to use a variety of teaching methods, with an emphasis on tutored individual and group learning based on critical readings of original papers. Coordinators are also encouraged to enable graduate research students to participate. From 1998 to 2000, students participated in nine programs, seven of which were coordinated by interdisciplinary teams. Several clinical and basic science disciplines were represented in each program, and various teaching methods were used. Graduate students participated in two of the programs. Evaluation of the programs (a debriefing discussion as well as short written evaluations) indicated moderate to good achievement of the course objectives.

Curriculum↗

White polystyrene as a substitute for water in high energy photon dosimetry.

White polystyrene (C8H8 with 2 wt. % to TiO2) has been compared to water using photon beams with nominal accelerating potential of 4 MV, 6 MV, 15 MV and 25 MV. The absolute reading and hence the measured absorbed dose is found to be up to 3% lower in white polystyrene which can be taken into account by using a correction factor. From these data differences in relative measurements (TMR or percentage depth dose) can be calculated showing differences of less than 0.7% normalized to maximum dose. Since the correction factor shows a dependence on photon energy and field size the use of a common scaling factor is not possible. The effect on photon dosimetry is discussed.

Biophysical Phenomena↗

Measurements of ionisation in water, polystyrene and a 'solid water' phantom material for electron beams.

Measurements of central axis depth ionisation curves and ionisation at ionisation maximum were carried out in water, clear polystyrene and a commercially available 'solid water' phantom material. Flat and cylindrical chambers were used for electron beams of 5-10 MeV. Displacements for the cylindrical chambers were determined, indicating a recommended value of 0.55 times cavity radius (without perturbation corrections). The use of a single scaling parameter is considered for converting depth ionisation curves obtained in plastic to those in water. This is shown to be valid within 2 mm at these energies and for these materials. Ionisation ratios between water and polystyrene are presented, i.e. correction factors for converting ionisation readings in the plastic to readings in water required for electron dosimetry determinations. These show 3% differences on average at these energies, ionisation in water being higher. Variations were observed with chamber wall material and chamber type. Measurements in the solid water material showed it to be a better water substitute than polystyrene for electron dosimetry in this energy range, although still significantly different from a true water phantom. Experiments at 10 MeV on the effect of charge storage on chamber reading in polystyrene, as a result of previous irradiation with electron beams, were carried out, indicating that such effects have negligible influence on the ionisation ratios reported.

Electrons↗

Quantitative estimation of attenuation in ultrasound video images: correlation with histology in diffuse liver disease.

RATIONALE AND OBJECTIVES: To determine the relationship between the attenuation of backscatter intensity in B-scan images of the liver and diffuse liver disease in order to assess the usefulness of this method in providing quantitative objective characterization of diffuse liver diseases in general and in fatty liver in particular. METHODS: Twenty-four healthy volunteers and 28 patients with elevated liver enzyme levels who underwent liver biopsy were included in this study. An automatic far-field slope (FFS) algorithm that estimates the decrease in amplitude of the backscattered echo as a function of beam depth was implemented on the noncompensated image that was acquired on a commercial phased-array ultrasound system fitted to a custom-built interface card. The images were processed at a work-station. All scans were acquired repeatedly, read, and graded blindly by experienced ultrasound radiologists. Histology obtained via needle biopsy was reviewed without knowledge of the ultrasound findings. RESULTS: Analysis of the FFS data for fatty infiltration in all patient groups yielded a sensitivity of 67%, a specificity of 77%, a positive predictive value (PPV) of 77%, negative predictive value (NPV) of 67%, and an accuracy of 71%. The mean score of the ultrasound reviewers showed a sensitivity of 82%, a specificity of 66%, a PPV% of 68%, an NPV of 81%, and an accuracy of 72%. Normal FFS values (false-negative) were found in five patients with proved fatty infiltration. All of these patients had coexistent moderate to severe hepatic inflammation. However, FFS data in patients with uncomplicated (pure) fatty infiltration revealed a sensitivity of 100%, a specificity of 80%, a PPV of 89%, an NPV of 100%, and an accuracy of 92%. The best ultrasound score yielded a sensitivity of 100%, a specificity of 60%, a PPV of 80%, an NPV of 100%, and an accuracy of 85% in the same patients. CONCLUSIONS: The data demonstrate an excellent sensitivity (100%) of the FFS values in patients with uncomplicated fatty infiltration. This was also the only group of patients in whom the FFS score was superior to the radiologists' best score. The FFS method can be used as a tool to follow up the response to a clinical or research treatment and to obtain standardization of pattern interpretation independently of the individual reader.

Adolescent↗

Re-writing motherhood: researching women's experiences of learning to mother for the first time.

OBJECTIVE: The aim of this paper was to examine one woman's experience and memory of learning to mother during pregnancy and the first postnatal year. DESIGN: Narratives of experience and memory were elicited through three in-depth interviews: during the third trimester of pregnancy; at four to six weeks postpartum; and, when the infant was nine months old. Feminist poststructural approaches informed the interview process. Through discourse analysis the detail of this woman's experiences was read closely in terms of the constructions, tensions, gaps, absences and contradictions as she reflected on what and how she learned to mother. SETTING: The woman was interviewed in her home. PARTICIPANTS: The larger research study from which the data in this article are drawn was an extended interview study of 15 women over a 12-month period. RESULTS: The close analysis of the data exemplifies the outcomes of the larger study from which it was drawn, in its demonstration of the complex and often contradictory processes of maternal learning. An understanding of this complexity is argued to be an essential condition for effective and inclusive nursing and midwifery intervention. CONCLUSIONS: Norms of 'good' mothering have been traditionally narrow within nursing literature. Although this is changing, these norms still serve to shape and also restrict possible positions women can take up to make sense of their experience. They provide background to the complex, and sometimes contradictory, processes of learning that take place during the perinatal period.

Adolescent↗

Critical subjective measurement of amplitude of accommodation.

The use of fixed print size to measure amplitude of accommodation by the push-up method will result in a range of angular sizes of the print at the nearpoint for patients with different amplitudes. We investigated the effect of this on measured amplitude of accommodation in 60 subjects aged 25 to 45 years. We designed a near-vision chart, based on the Bailey-Lovie near-vision charts, but for which the letter sizes on adjacent lines are varied so that the difference between the inverse of letter sizes is constant (dioptric scale) rather than the geometric ratio between letters on adjacent lines being constant (logarithmic scale). Using this new chart, we compared the amplitudes obtained using N5 print (N5 Blur method) and with two critical methods for which the print of interest was always close to threshold acuity. This was achieved by having patients' attention drawn to a smaller line of letters every time the chart was moved closer in half-diopter steps. The N5 Blur method gave considerably higher amplitude measures than the two critical methods, but the mean differences decreased markedly as age increased: 1.8 to 2.2 D for a 25- to 29-year-old group to 0.7 to 0.8 D for a 40- to 45-year-old group. We believe that the use of fixed size print for measuring amplitude of accommodation by the push-up method gives overestimations that are more marked the higher the amplitude. This occurs because smaller measuring distances that accompany the higher amplitudes will increase angular size and consequently depth-of-focus (in dioptric terms).(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗

Underestimation of intraocular lens power for cataract surgery after myopic photorefractive keratectomy.

OBJECTIVE: To assess the validity of corneal power measurement and standard intraocular lens power (IOLP) calculation after photorefractive keratectomy (PRK). DESIGN: Nonrandomized, prospective, cross-sectional, clinical study. PARTICIPANTS: A total of 31 eyes of 21 females and 10 males with a mean age at the time of surgery of 32.3 +/- 6.6 years (range, 24.4-49.5 years). INTERVENTION: Subjective refractometry, standard keratometry, TMS-1 corneal topography analysis, and pachymetry were performed before and 15.8 +/- 10.4 months after PRK for myopia (n = 24, -1 .5 to -8.0 diopters [D], mean -5.4 +/- 1.9 D) or myopic astigmatism (n = 7, sphere -2.0 to -7.5 D, mean -4.4 +/- 1.9 D; cylinder -1.0 to -3.0 D, mean -1.9 +/- 0.7 D). The IOLP calculations were done using two different formulas (SRK/T and HAIGIS). MAIN OUTCOME MEASURES: Keratometric power (K) and topographic simulated keratometric power (TOPO) as measured (Kmeas, TOPOmeas) and as calculated according to the change of power of the anterior corneal surface or according to the spherical equivalent change after PRK (Kcalc, TOPOcalc), IOLP for emmetropia, and postoperative ametropia for calculated corneal powers were assessed in a model. RESULTS: After PRK, mean Kmeas and TOPOmeas were significantly greater (0.4-1.4 D, maximum 3.3 D) than mean KRcalc and TOPOcalc (P < 0.0001). On average, the relative flattening of the cornea after PRK was underestimated by 14% to 30% (maximum, 83%) depending on the method of calculation. The mean theoretical IOLP after PRK ranged from + 17.4 D (SRK/T, TOPOmeas) to +20.9 D (HAIGIS, Kcalc) depending on the calculation method for corneal power and IOLP calculation formula used. For both formulas, IOLP values using keratometric readings were significantly higher (>1 D) than IOLP values using topographic readings (P < 0.0001). The theoretically induced mean refractive error after cataract surgery ranged from +0.4 to +1.4 (maximum, +3.1) D. Corneal power overestimation and IOLP underestimation correlated significantly with the spherical equivalent change after PRK (P = 0.001) and the intended ablation depth during PRK (P = 0.004). CONCLUSIONS: To avoid underestimation of IOLP and hyperopia after cataract surgery following PRK, measured corneal power values must be corrected. The calculation method using spherical equivalent change of refraction at the corneal plane seems to be the most appropriate method. In comparison with this method, direct power measurements underestimate corneal flattening after PRK by 24% on average. Use of conventional topography analysis seems to increase the risk of error. However, because this study is retrospective and theoretical, there is still a need for a large prospective investigation to validate the authors' findings.

Adult↗