Dental health in children with phenylketonuria PKU and other inborn errors of amino acid metabolism managed by diet /

"Supported in part by Maternal and Child Health, Grant No. MCS-000252-16 and by contributions to Friends of Metabolic Research."

Phakometric measurement of ocular surface radii of curvature, axial separations and alignment in relaxed and accommodated human eyes

Measurements (autokeratometry, A-scan ultrasonography and video ophthalmophakometry) of ocular surface radii, axial separations and alignment were made in the horizontal meridian of nine emmetropes (aged 20-38 years) with relaxed (cycloplegia) and active accommodation (mean ± 95% confidence interval: 3.7 ± 1.1 D). The anterior chamber depth (-1.5 ± 0.3 D) and both crystalline lens surfaces (front 3.1 ± 0.8 D; rear 2.1 ± 0.6 D) contributed to dioptric vergence changes that accompany accommodation. Accommodation did not alter ocular surface alignment. Ocular misalignment in relaxed eyes is mainly because of eye rotation (5.7 ± 1.6° temporally) with small amounts of lens tilt (0.2 ± 0.8° temporally) and decentration (0.1 ± 0.1 mm nasally) but these results must be viewed with caution as we did not account for corneal asymmetry. Comparison of calculated and empirically derived coefficients (upon which ocular surface alignment calculations depend) revealed that negligible inherent errors arose from neglect of ocular surface asphericity, lens gradient refractive index properties, surface astigmatism, effects of pupil size and centration, assumed eye rotation axis position and use of linear equations for analysing Purkinje image shifts. © 2004 The College of Optometrists.

Non-invasive phakometric measurement of corneal and crystalline lens alignment in human eyes

We describe a non-invasive phakometric method for determining corneal axis rotation relative to the visual axis (β) together with crystalline lens axis tilt (α) and decentration (d) relative to the corneal axis. This does not require corneal contact A-scan ultrasonography for the measurement of intraocular surface separations. Theoretical inherent errors of the method, evaluated by ray tracing through schematic eyes incorporating the full range of human ocular component variations, were found to be larger than the measurement errors (β < 0.67°, α < 0.72° and d < 0.08 mm) observed in nine human eyes with known ocular component dimensions. Intersubject variations (mean ± S.D.: β = 6.2 ± 3.4° temporal, α = 0.2 ± 1.8° temporal and d = 0.1 ± 0.1 mm temporal) and repeatability (1.96 × S.D. of difference between repeat readings: β ± 2.0°, α ± 1.8° and d ± 0.2 mm) were studied by measuring the left eyes of 45 subjects (aged 18-42 years, 29 females and 16 males, 15 Caucasians, 29 Indian Asians, one African, refractive error range -7.25 to +1.25 D mean spherical equivalent) on two occasions. © 2005 The College of Optometrists.

Posterior retinal contour in adult human anisomyopia

PURPOSE. It is well documented that myopia is associated with an increase in axial length or, more specifically, in vitreous chamber depth. Whether the transverse dimensions of the eye also increase in myopia is relevant to further understanding of its development. METHODS. The posterior retinal surface was localized in two-dimensional space in both eyes of young adult white and Taiwanese-Chinese iso- and anisomyopes (N = 56), from measured keratometry, A-scan ultrasonography, and central and peripheral refraction (±35°) data, with the aid of a computer modeling program designed for this purpose. Anisomyopes had 2 D or more interocular difference in their refractive errors, with mean values in their more myopic eyes of -5.57 D and in their less myopic eyes of -3.25 D, similar to the means of the two isomyopic groups. The derived retinal contours for the more and less myopic eyes were compared by way of investigating ocular shape changes that accompany myopia, in the posterior region of the vitreous chamber. The presence and size of optic disc crescents were also investigated as an index of retinal stretching in myopia. RESULTS. Relative to the less myopic eyes of anisometropic subjects, the more myopic eyes were more elongated and also distorted into a more prolate shape in both the white and Chinese groups. However, the Chinese eyes showed a greater and more uniform relative expansion of the posterior retinal surface in their more myopic eyes, and this was associated with larger optic disc crescents. The changes in the eyes of whites displayed a nasal-temporal axial asymmetry, reflecting greater enlargement of the nasal retinal sector. CONCLUSIONS. Myopia is associated with increased axial length and a prolate shape. This prolate shape is consistent with the proposed idea that axial and transverse dimensions of the eye are regulated differently. The observations that ocular shape changes are larger but more symmetrical in Chinese eyes than in eyes of whites warrant further investigation.

The human factors of automatic speech recognition in control room systems

This thesis addresses the viability of automatic speech recognition for control room systems; with careful system design, automatic speech recognition (ASR) devices can be useful means for human computer interaction in specific types of task. These tasks can be defined as complex verbal activities, such as command and control, and can be paired with spatial tasks, such as monitoring, without detriment. It is suggested that ASR use be confined to routine plant operation, as opposed the critical incidents, due to possible problems of stress on the operators' speech.  It is proposed that using ASR will require operators to adapt a commonly used skill to cater for a novel use of speech. Before using the ASR device, new operators will require some form of training. It is shown that a demonstration by an experienced user of the device can lead to superior performance than instructions. Thus, a relatively cheap and very efficient form of operator training can be supplied by demonstration by experienced ASR operators. From a series of studies into speech based interaction with computers, it is concluded that the interaction be designed to capitalise upon the tendency of operators to use short, succinct, task specific styles of speech. From studies comparing different types of feedback, it is concluded that operators be given screen based feedback, rather than auditory feedback, for control room operation. Feedback will take two forms: the use of the ASR device will require recognition feedback, which will be best supplied using text; the performance of a process control task will require task feedback integrated into the mimic display. This latter feedback can be either textual or symbolic, but it is suggested that symbolic feedback will be more beneficial. Related to both interaction style and feedback is the issue of handling recognition errors. These should be corrected by simple command repetition practices, rather than use error handling dialogues. This method of error correction is held to be non intrusive to primary command and control operations. This thesis also addresses some of the problems of user error in ASR use, and provides a number of recommendations for its reduction.

The development of constrained source localisation algorithms for human brain imaging

This work sets out to evaluate the potential benefits and pit-falls in using a priori information to help solve the Magnetoencephalographic (MEG) inverse problem. In chapter one the forward problem in MEG is introduced, together with a scheme that demonstrates how a priori information can be incorporated into the inverse problem. Chapter two contains a literature review of techniques currently used to solve the inverse problem. Emphasis is put on the kind of a priori information that is used by each of these techniques and the ease with which additional constraints can be applied. The formalism of the FOCUSS algorithm is shown to allow for the incorporation of a priori information in an insightful and straightforward manner. In chapter three it is described how anatomical constraints, in the form of a realistically shaped source space, can be extracted from a subject’s Magnetic Resonance Image (MRI). The use of such constraints relies on accurate co-registration of the MEG and MRI co-ordinate systems. Variations of the two main co-registration approaches, based on fiducial markers or on surface matching, are described and the accuracy and robustness of a surface matching algorithm is evaluated. Figures of merit introduced in chapter four are shown to given insight into the limitations of a typical measurement set-up and potential value of a priori information. It is shown in chapter five that constrained dipole fitting and FOCUSS outperform unconstrained dipole fitting when data with low SNR is used. However, the effect of errors in the constraints can reduce this advantage. Finally, it is demonstrated in chapter six that the results of different localisation techniques give corroborative evidence about the location and activation sequence of the human visual cortical areas underlying the first 125ms of the visual magnetic evoked response recorded with a whole head neuromagnetometer.

Measurement of ocular component contributions to residual astigmatism in adult human eyes

The aim of this study was to determine whether an ophthalmophakometric technique could offer a feasible means of investigating ocular component contributions to residual astigmatism in human eyes. Current opinion was gathered on the prevalence, magnitude and source of residual astigmatism. It emerged that a comprehensive evaluation of the astigmatic contributions of the eye's internal ocular surfaces and their respective axial separations (effectivity) had not been carried out to date. An ophthalmophakometric technique was developed to measure astigmatism arising from the internal ocular components. Procedures included the measurement of refractive error (infra-red autorefractometry), anterior corneal surface power (computerised video keratography), axial distances (A-scan ultrasonography) and the powers of the posterior corneal surface in addition to both surfaces of the crystalline lens (multi-meridional still flash ophthalmophakometry). Computing schemes were developed to yield the required biometric data. These included (1) calculation of crystalline lens surface powers in the absence of Purkinje images arising from its anterior surface, (2) application of meridional analysis to derive spherocylindrical surface powers from notional powers calculated along four pre-selected meridians, (3) application of astigmatic decomposition and vergence analysis to calculate contributions to residual astigmatism of ocular components with obliquely related cylinder axes, (4) calculation of the effect of random experimental errors on the calculated ocular component data. A complete set of biometric measurements were taken from both eyes of 66 undergraduate students. Effectivity due to corneal thickness made the smallest cylinder power contribution (up to 0.25DC) to residual astigmatism followed by contributions of the anterior chamber depth (up to 0.50DC) and crystalline lens thickness (up to 1.00DC). In each case astigmatic contributions were predominantly direct. More astigmatism arose from the posterior corneal surface (up to 1.00DC) and both crystalline lens surfaces (up to 2.50DC). The astigmatic contributions of the posterior corneal and lens surfaces were found to be predominantly inverse whilst direct astigmatism arose from the anterior lens surface. Very similar results were found for right versus left eyes and males versus females. Repeatability was assessed on 20 individuals. The ophthalmophakometric method was found to be prone to considerable accumulated experimental errors. However, these errors are random in nature so that group averaged data were found to be reasonably repeatable. A further confirmatory study was carried out on 10 individuals which demonstrated that biometric measurements made with and without cycloplegia did not differ significantly.

A method for enhancing digital information displayed to computer users with visual refractive errors via spatial and spectral processing

This research pursued the conceptualization, implementation, and verification of a system that enhances digital information displayed on an LCD panel to users with visual refractive errors. The target user groups for this system are individuals who have moderate to severe visual aberrations for which conventional means of compensation, such as glasses or contact lenses, does not improve their vision. This research is based on a priori knowledge of the user's visual aberration, as measured by a wavefront analyzer. With this information it is possible to generate images that, when displayed to this user, will counteract his/her visual aberration. The method described in this dissertation advances the development of techniques for providing such compensation by integrating spatial information in the image as a means to eliminate some of the shortcomings inherent in using display devices such as monitors or LCD panels. Additionally, physiological considerations are discussed and integrated into the method for providing said compensation. In order to provide a realistic sense of the performance of the methods described, they were tested by mathematical simulation in software, as well as by using a single-lens high resolution CCD camera that models an aberrated eye, and finally with human subjects having various forms of visual aberrations. Experiments were conducted on these systems and the data collected from these experiments was evaluated using statistical analysis. The experimental results revealed that the pre-compensation method resulted in a statistically significant improvement in vision for all of the systems. Although significant, the improvement was not as large as expected for the human subject tests. Further analysis suggest that even under the controlled conditions employed for testing with human subjects, the characterization of the eye may be changing. This would require real-time monitoring of relevant variables (e.g. pupil diameter) and continuous adjustment in the pre-compensation process to yield maximum viewing enhancement.

A method for enhancing digital information displayed to computer users with visual refractive errors via spatial and spectral processing

This research pursued the conceptualization, implementation, and verification of a system that enhances digital information displayed on an LCD panel to users with visual refractive errors. The target user groups for this system are individuals who have moderate to severe visual aberrations for which conventional means of compensation, such as glasses or contact lenses, does not improve their vision. This research is based on a priori knowledge of the user's visual aberration, as measured by a wavefront analyzer. With this information it is possible to generate images that, when displayed to this user, will counteract his/her visual aberration. The method described in this dissertation advances the development of techniques for providing such compensation by integrating spatial information in the image as a means to eliminate some of the shortcomings inherent in using display devices such as monitors or LCD panels. Additionally, physiological considerations are discussed and integrated into the method for providing said compensation. In order to provide a realistic sense of the performance of the methods described, they were tested by mathematical simulation in software, as well as by using a single-lens high resolution CCD camera that models an aberrated eye, and finally with human subjects having various forms of visual aberrations. Experiments were conducted on these systems and the data collected from these experiments was evaluated using statistical analysis. The experimental results revealed that the pre-compensation method resulted in a statistically significant improvement in vision for all of the systems. Although significant, the improvement was not as large as expected for the human subject tests. Further analysis suggest that even under the controlled conditions employed for testing with human subjects, the characterization of the eye may be changing. This would require real-time monitoring of relevant variables (e.g. pupil diameter) and continuous adjustment in the pre-compensation process to yield maximum viewing enhancement.

Neural representations of social and non-social uncertainty in human decision making

The social landscape is filled with an intricate web of species-specific desired objects and course of actions. Humans are highly social animals and, as they navigate this landscape, they need to produce adapted decision-making behaviour. Traditionally social and non-social neural mechanisms affecting choice have been investigated using different approaches. Recently, in an effort to unite these findings, two main theories have been proposed to explain how the brain might encode social and non-social motivational decision-making: the extended common currency and the social valuation specific schema (Ruff & Fehr 2014). One way to test these theories is to directly compare neural activity related to social and non-social decision outcomes within the same experimental setting. Here we address this issue by focusing on the neural substrates of social and non-social forms of uncertainty. Using functional magnetic resonance imaging (fMRI) we directly compared the neural representations of reward and risk prediction and errors (RePE and RiPE) in social and non- social situations using gambling games. We used a trust betting game to vary uncertainty along a social dimension (trustworthiness), and a card game (Preuschoff et al. 2006) to vary uncertainty along a non-social dimension (pure risk). The trust game was designed to maintain the same structure of the card game. In a first study, we exposed a divide between subcortical and cortical regions when comparing the way these regions process social and non-social forms of uncertainty during outcome anticipation. Activity in subcortical regions reflected social and non-social RePE, while activity in cortical regions correlated with social RePE and non-social RiPE. The second study focused on outcome delivery and integrated the concept of RiPE in non-social settings with that of fairness and monetary utility maximisation in social settings. In particular these results corroborate recent models of anterior insula function (Singer et al. 2009; Seth 2013), and expose a possible neural mechanism that weights fairness and uncertainty but not monetary utility. The third study focused on functionally defined regions of the early visual cortex (V1) showing how activity in these areas, traditionally considered only visual, might reflect motivational prediction errors in addition to known perceptual prediction mechanisms (den Ouden et al 2012). On the whole, while our results do not support unilaterally one or the other theory modeling the underlying neural dynamics of social and non-social forms of decision making, they provide a working framework where both general mechanisms might coexist.

Errors in preparation and medication management in nursing professionals

The preparation and administration of medications is one of the most common and relevant functions of nurses, demanding great responsibility. Incorrect administration of medication, currently constitutes a serious problem in health services, and is considered one of the main adverse effects suffered by hospitalized patients. Objectives: Identify the major errors in the preparation and administration of medication by nurses in hospitals and know what factors lead to the error occurred in the preparation and administration of medication. Methods: A systematic review of the literature. Deined as inclusion criteria: original scientiic papers, complete, published in the period 2011 to May 2016, the SciELO and LILACS databases, performed in a hospital environment, addressing errors in preparation and administration of medication by nurses and in Portuguese language. After application of the inclusion criteria obtained a sample of 7 articles. Results: The main errors identiied in the pr eparation and administration of medication were wrong dose 71.4%, wrong time 71.4%, 57.2% dilution inadequate, incorrect selection of the patient 42.8% and 42.8% via inadequate. The factors that were most commonly reported by the nursing staff, as the cause of the error was the lack of human appeal 57.2%, inappropriate locations for the preparation of medication 57.2%, the presence of noise and low brightness in preparation location 57, 2%, professionals untrained 42.8%, fatigue and stress 42.8% and inattention 42.8%. Conclusions: The literature shows a high error rate in the preparation and administration of medication for various reasons, making it important that preventive measures of this occurrence are implemented.

Some problems and errors in cytogenetic biodosimetry

Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements, and others. Among the other factors influencing individual radioresistance are: radioadaptive response; bystander effect; levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilising effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionising radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for.

Neural Machine Translation in the Field of Law. Analysis and Evaluation against Human Reference of NMT Raw Outputs of an Atto Costitutivo of S.r.l. from Italian into German.

Artificial Intelligence (AI) is gaining ever more ground in every sphere of human life, to the point that it is now even used to pass sentences in courts. The use of AI in the field of Law is however deemed quite controversial, as it could provide more objectivity yet entail an abuse of power as well, given that bias in algorithms behind AI may cause lack of accuracy. As a product of AI, machine translation is being increasingly used in the field of Law too in order to translate laws, judgements, contracts, etc. between different languages and different legal systems. In the legal setting of Company Law, accuracy of the content and suitability of terminology play a crucial role within a translation task, as any addition or omission of content or mistranslation of terms could entail legal consequences for companies. The purpose of the present study is to first assess which neural machine translation system between DeepL and ModernMT produces a more suitable translation from Italian into German of the atto costitutivo of an Italian s.r.l. in terms of accuracy of the content and correctness of terminology, and then to assess which translation proves to be closer to a human reference translation. In order to achieve the above-mentioned aims, two human and automatic evaluations are carried out based on the MQM taxonomy and the BLEU metric. Results of both evaluations show an overall better performance delivered by ModernMT in terms of content accuracy, suitability of terminology, and closeness to a human translation. As emerged from the MQM-based evaluation, its accuracy and terminology errors account for just 8.43% (as opposed to DeepL’s 9.22%), while it obtains an overall BLEU score of 29.14 (against DeepL’s 27.02). The overall performances however show that machines still face barriers in overcoming semantic complexity, tackling polysemy, and choosing domain-specific terminology, which suggests that the discrepancy with human translation may still be remarkable.

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.