Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Carbohydrate intake and glycemic index affect substrate oxidation during a controlled weight cycle in healthy men.

BACKGROUND/OBJECTIVES: Because both, glycemic index (GI) and carbohydrate content of the diet increase insulin levels and could thus impair fat oxidation, we hypothesized that refeeding a low GI, moderate-carbohydrate diet facilitates weight maintenance. SUBJECTS/METHODS: Healthy men (n=32, age 26.0±3.9 years; BMI 23.4±2.0 kg/m(2)) followed 1 week of controlled overfeeding, 3 weeks of caloric restriction and 2 weeks of hypercaloric refeeding (+50, -50 and +50% energy requirement) with low vs high GI (41 vs 74) and moderate vs high CHO intake (50% vs 65% energy). We measured adaptation of fasting macronutrient oxidation and the capacity to supress fat oxidation during an oral glucose tolerance test. Changes in fat mass were measured by quantitative magnetic resonance. RESULTS: During overfeeding, participants gained 1.9±1.2 kg body weight, followed by a weight loss of -6.3±0.6 kg and weight regain of 2.8±1.0 kg. Subjects with 65% CHO gained more body weight compared with 50% CHO diet (P<0.05) particularly with HGI meals (P<0.01). Refeeding a high-GI diet led to an impaired basal fat oxidation when compared with a low-GI diet (P<0.02), especially at 65% CHO intake. Postprandial metabolic flexibility was unaffected by refeeding at 50% CHO but clearly impaired by 65% CHO diet (P<0.05). Impairment in fasting fat oxidation was associated with regain in fat mass (r=0.43, P<0.05) and body weight (r=0.35; P=0.051). CONCLUSIONS: Both higher GI and higher carbohydrate content affect substrate oxidation and thus the regain in body weight in healthy men. These results argue in favor of a lower glycemic load diet for weight maintenance after weight loss.

Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome.

Body composition is related to various physiological and pathological states. Characterization of individual body components adds to understand metabolic, endocrine and genetic data on obesity and obesity-related metabolic risks, e.g. insulin resistance. The obese phenotype is multifaceted and can be characterized by measures of body fat, leg fat, liver fat and skeletal muscle mass rather than by body mass index. The contribution of either whole body fat or fat distribution or individual fat depots to insulin resistance is moderate, but liver fat has a closer association with (hepatic) insulin resistance. Although liver fat is associated with visceral fat, its effect on insulin resistance is independent of visceral adipose tissue. In contrast to abdominal fat, appendicular or leg fat is inversely related to insulin resistance. The association between 'high fat mass + low muscle mass' (i.e. 'sarcopenic adiposity') and insulin resistance deserves further investigation and also attention in daily clinical practice. In addition to cross-sectional data, longitudinal assessment of body composition during controlled under- and overfeeding of normal-weight healthy young men shows that small decreases and increases in fat mass are associated with corresponding decreases and increases in insulin secretion as well as increases and decreases in insulin sensitivity. However, even under controlled conditions, there is a high intra- and inter-individual variance in the changes of (i) body composition; (ii) the 'body composition-glucose metabolism relationship' and (iii) glucose metabolism itself. Combining individual body components with their related functional aspects (e.g. the endocrine, metabolic and inflammatory profiles) will provide a suitable basis for future definitions of a 'metabolically healthy body composition'.

A model of the internal control system within the superior colliculus.

This paper describes a mathematical model devised to help explain experimental observations involving the role of the superior colliculus in the generation of saccades. Specifically, the superior colliculus has long been known to be involved in production of the error signal that determines the location to which the eyes are moved. The superior colliculus is normally modeled only in terms of its final output, neglecting the processes that must occur within the superior colliculus in order to create that signal. This model includes treatment of the lateral inhibition system and the sequence of activity in populations of neurons in the superficial, intermediate, and deeper layers of the superior colliculus. Influence from the cerebellum and nuclei of the mesencephalon are included in the model to demonstrate the effect of external influences on the operation of the superior colliculus. The model demonstrates one possible function of the moving hill hypothesis as an intracollicular control system for the generation of saccades. The purpose of the development of this model is to stimulate discussion on the more precise performance of the superior colliculus in the saccadic eye movement system.

Dynamic system modeling of the 3-D oculomotor plant. The 1st step in discerning ocular motor control.

This paper describes the design and development of a 3-D ocular motor plant. The 3-D model is an expansion of the Linear Homeomorphic Saccadic Eye Movement Model reported by Enderle et. al., which describes the dynamics of horizontal eye movements about a single axis. In addition to its predecessor, the 3-D model incorporates both vertical and torsional components of the ocular plant, along with recent findings of mid-orbital constraints referred to as muscle pulleys. Insight of ocular motor control, as well as diagnosis of strabismus, would benefit from such a model.

Improving design project experiences through improved assessment practices.

This paper is offered as an introduction to the ways in which improved foci on educational outcomes associated with engineering design project experiences may lead to: (a) improvements in the learning of engineering students and consequently, (b) improved knowledge, design and technology to benefit individuals in need. Strategies to improve learning outcomes of design experiences include clearly articulating what it is that we want students to know and achieve, having detailed means of assessing each of the learning outcomes we target, communicating about the assessment process with students from the start of their design experiences, and providing thorough evaluative feedback to students to foster learning while we still have access to them. This paper is based on ongoing work within the National Science Foundation (NSF) Senior Design Projects to Aid Persons with Disabilities program. Readers are invited to collaborate in further efforts in this area.

Multi-position eye movement detection system.

A device that records saccadic eye movements in any X-Y position is presented in this paper. Eye movements are recorded using infrared optoelectronics mounted on hemispherical shaped eyepieces, which in turn are mounted on goggles styled after an ophthalmologist's test frames. A computer controlled, wall mounted light bank facilitates targeting for eye movements. Output from the device is sent to a PC type computer and stored in the hard disk using a data acquisition board. The user interface is Windows based and the output from the goggles are represented as a trace map of plotted points. This output can also be saved or printed for future analysis and reference. The device is designed with reference to standard ISO design methodology, and subject safety and final product usage have been reviewed following ISO analysis procedures. Accuracy in tracking of eye movements is maintained by utilizing a twenty-four channel detection system, hemispherically mounted and lensed optoelectronics to reduce cross-talk due to incident light, and signal processing that attenuates incident light as well as ambient light. Also, a reset feature is included to maintain equal baseline control. An automatic switching device is included in the test frame to allow the device to "warm up," assuring that equal IR power is delivered for each subject tested. The IR units in the goggles are also modular in case replacement is required.

The design and development of a biosensor to measure the concentration of meconium in amniotic fluid.

Meconium aspiration syndrome occurs in 0.2% to 1% of all deliveries and has a mortality rate as high as 18%. The disease is responsible for 2% of all perinatal deaths. Meconium may be classified as being thick or thin, but this assessment is normally performed visually by clinicians. A "meconiumcrit" analysis has been developed to objectively define the concentration of meconium. However, this analysis does not provide real-time continuous readings. This study focused on the design and development of a sensor to provide an objective, continuous, real-time assessment of meconium thickness. Meconium has an absorption spectrum centered at 410 nm and observes Beer's law. Blue light centered at 430 nm was delivered through meconium solutions, and a photodiode translated the strength of the incoming light into a voltage. This voltage was analyzed by a microcontroller to determine the concentration of meconium.

Use of timelines in senior design--an efficient project management tool for faculty.

An important part of any multi-tasked project or undertaking is a work plan. Large contractors with multi-year design projects use a work plan to schedule resources and identify critical design decisions; a smaller company may map out the course and order of work as well as schedule resources. Either way, the work plan is an indispensable tool that assists the project manager in the planning and timely execution of the project. Introduced is the concept of the timeline (or work plan) and its utilization in an Undergraduate Senior Design Course by both Faculty and Student as a Project Management Tool and device from which to chart student progress towards completion of course requirements. Discussed are examples of student project planning and comments with regards to the effectiveness of project planning for the student as well as a discussion of how this device has assisted faculty in charting student progress towards project completion, meeting course requirements, and grading. Project and Time Management issues described in this paper are through the Senior Design Program at the University of Connecticut (UCONN) with National Science Foundation Senior Design Projects to Aid Persons with Disabilities and industry-sponsored projects [1].

Using a multidisciplinary team approach in biomedical engineering senior design.

Under Criterion 4, the Professional Component of the Accreditation Board for Engineering and Technology (ABET) Engineering Criteria 2000, a curriculum culminating in a major design experience is required. In addition, under Criterion 3, program graduates must demonstrate an ability to function on multidisciplinary teams. This paper describes some team related issues in senior design at University of Connecticut (UConn) with National Science Foundation (NSF) Senior Design Projects to Aid Persons with Disabilities and industry-sponsored projects. While these Criteria can both be satisfied in a senior design course sequence, it is not the most desirable method to achieve satisfactory results. Effective teamwork involves skills that may be learned in classes and training sessions. It is best achieved through team experiences in a series of courses, ideally beginning the freshman year.

Eye tracker.

A device that records saccadic eye movements, the Eye Tracker, is presented in this paper. The Eye Tracker utilizes infra-red technology mounted on fully adjustable goggles to follow eye movements targeted by either a goggles mounted HUD type display or a wall mounted light bank. Output from the goggles is remotely sent to a PC type computer, which leads to device portability. The goggles can also maintain output data in an internal memory for latter download. The user interface is Windows based with the output from the goggles represented as a trace map or plotted points. This output can also be saved or printed for future reference. The user interface can be used on any PC type computer. The device is designed with reference to standard ISO design methodology. Safety in design and final product usage has also been addressed with reference to standard ISO type procedures. Device accuracy is maintained by precise construction of the IR units in the goggles and tight control of cross talk between each IR device plus filtering of ambient light signals. Also, a reset feature is included to maintain equal baseline control. An automatic switching device is included in the goggles to allow the Eye Tracker to "warm up," assuring that equal IR power is delivered for each subject tested. The IR units in the goggles are also modular in case replacement is required.

First year experience at the University of Connecticut with NSF design projects to aid persons with disabilities.

This paper provides an overview of the first year experience at University of Connecticut (UConn) with National Science Foundation (NSF) Senior Design Projects to Aid Persons with Disabilities. Devices and software to aid persons with disabilities often need custom modification, are prohibitively expensive, or even nonexistent. Much of the disabled community does not have access to custom modification of available devices, and other benefits of current technology. Moreover, when available, engineering and support salaries make the cost of any custom modifications beyond the reach of most disabled individuals. The NSF in 1988 started to provide a mechanism whereby student engineers at universities throughout the United States designed and constructed devices for persons with disabilities. This program combined the academic requirement of a design experience with enhanced educational opportunities for students, and improved the quality of life for disabled individuals. Students and university faculty provided, through their normal ABET accredited senior design class, engineering time to design and build the device or software, and the NSF provided funds, competitively awarded to universities, for supplies, equipment and fabrication costs for the design projects. Described in this report are first year experiences at UConn with this NSF program including lecture topics, site visits to clients and project selection, required reports and the WWW, course structure and organization.

Tele-talk: a communication device for the persons with hearing disabilities.

Tele-Talk is a device designed to allow a person with hearing disabilities to communicate using the telephone, with a minimum of effort and without requiring a multitude of special equipment. This device provides a previously unavailable link for the hearing disabled to communicate directly over telephone lines. Tele-Talk has the extra capability of operating in live conference situations using microphone input. Today, most devices designed for the hearing-impaired are dependent on both communicants' owning/operating identical set-ups. If an accessory item is missing or misplaced, communication breaks down. Tele-Talk answers the need to permit transparent hearing assistance via the telephone.

Saccade derivative filters and their clinical implications.

A saccade model is used to evaluate the accuracy of three derivative algorithms, the two-point central difference derivative filter, band-limited derivative filter and median derivative filter. Noise contaminated saccade simulations are used to compare the known velocity and acceleration waveforms with estimates from each of the three algorithms. The median derivative filter, a nonlinear differentiating digital filter, provides the best velocity estimates from an eye position signal. This filter has no impulse response function, eliminates Gibb's phenomena evident in all linear filters, and is easy to implement.

A WEB based approach in biomedical engineering design education.

As part of the accreditation process for university engineering programs, students are required to complete a minimum number of design credits in their course of study, typically at the senior level. Many call this the capstone course. Engineering design is a course or series of courses that bring together concepts and principles that students learn in their field of study--it involves the integration and extension of material learned in their major toward a specific project. Most often, the student is exposed to system-wide analysis, critique and evaluation for the first time. Design is an iterative, decision making process in which the student optimally applies previously learned material to meet a stated objective. At the University of Connecticut, students work in teams of 3-4 members and work on externally sponsored projects. To facilitate working with sponsors, a WEB based approach is used for reporting the progress on projects. Students are responsible for creating their own WEB sites that support both html and pdf formats. Students provide the following deliverables: weekly progress reports, project statement, specifications, project proposal, interim report, and final report. A senior design homepage also provides links to data books and other resources for use by students. We are also planning distance learning experiences between two campuses so students can work on projects that involve the use of video conferencing.

Effects of cerebellar lesions on saccade simulations.

Experimental studies involving cerebellar lesions have been important tools for learning about the operation of the saccadic eye movement system. These studies have been used to further develop a neural network model for horizontal saccadic eye movement control. The neural control mechanism is first order time optimal, initiated by the deep layers of the superior colliculus and terminated by the cerebellar fastigial nucleus. The neural circuit consists of neurons in the paramedian pontine reticular formation (burst, tonic and pause cells), the vestibular nucleus, abducens nucleus, oculomotor nucleus, cerebellum, substantia nigra, nucleus reticularis tegmenti pontis, the thalamus, the deep layers of the superior colliculus and the oculomotor plant for each eye. Agonist burst cell activity is initiated with maximal firing due to an error between the target and eye position, and continues until the internal eye position in the cerebellar vermis reaches the desired position, then decays to zero. The cerebellar vermis is responsible for adapting the duration of maximal firing based on the initial position of the eye. There are two sets of neural integrators in the neural network. One operates within the cerebellar vermis to predict the width of the pulse, and the other within the paramedian pontine reticular formation to maintain the eyes at their destination. Antagonist neural activity is inhibited during the agonist burst activity. After the agonist burst, antagonist neural activity rises with a stochastic rebound burst and from input from the fastigial nucleus, then falls to a tonic firing level necessary to keep the eye at its destination. The onset of the antagonist tonic firing is stochastic, weakly coordinated with the end of the agonist burst, and under cerebellar control. A common mechanism of action is described, based on cerebellar gating, through the fastigial nucleus, that explains a number of different saccadic eye movement types, including dynamic overshoot, glissadic overshoot and undershoot, and undershoot. A linear homeomorphic oculomotor muscle model is used in the simulations of the operation of the neural network. Each of the neural sites in the model fire similar to experimental data, and simulate fast eye movements.

Application of robust data processing methods to the analysis of eye movements.

We have developed a robust, nonlinear differentiating digital filter for the estimation of eye velocity from an eye-position signal. This filter is equally applicable to a large variety of other biomedical signals. The filter is implemented by taking an odd number of two-point differences around the point of interest and then selecting the median difference. Dividing the median difference by the time interval yields the derivative of the input signal. The Robust Differentiator (RD) is a classic order-statistic filter consisting of a bank of linear filters (the two-point differences) followed by the median operation to select one difference for the derivative calculation. The RD has no impulse response function and eliminates the "ringing" that is typical of all linear filters. The RD not only performs better than the FIR differentiating filters for impulse noise but is equally effective for both broad-band and narrow-band Gaussian noise. The RD "bandwidth" is adjustable by selecting the interval for the two-point differences.

GENESIS as a neural network modeling tool for saccadic eye movements.

Interest in exploring the computational properties of networks of parallel distributed processing elements has increased due to studies of the structure and function of biological neural networks. Much of the current research involves numerical simulations of these types of networks. GENESIS (GEneral NEtwork SImulation System) and XODUS (X-based Ouput and Display Utility for Simulators) are a result of that interest. The two systems combined provides a standardized and flexible means of constructing neural networks. The structure of GENESIS follows the actual biological network much more closely than artificial neural networks. This paper presents a simple simulation of the cable properties of a dendritic cable consisting of twenty compartments and one soma. The results of the simulation are then compared to actual cable metrics.

Eye tracking performance variability in a homogeneous population.

Pursuit tracking eye movements were recorded and analyzed from a group of US Air Force Pilot Candidates (PCs). The PCs ranged in age from 21 to 27 with a median age of 23. All were college graduates and recently passed a Flying Class I physical exam. These PCs comprise a highly motivated, intelligent group of young subjects. Pursuit tracking was assessed by having the subjects track a small spot of green light moving sinusoidally in the horizontal plane at frequencies from 0.2 to 1.0 Hz in 0.2 Hz increments. Peak-to-peak target amplitude was 40 degrees. Eye movements were recorded using an infrared reflectance device. Eye movements were separated into smooth pursuit (SP) and saccadic (SA) components. Tracking performance was evaluated by computing the gain and asymmetry of the SP component and the percentage of tracking movements contributed by the SA component. Both mean values and variance of the tracking performance of the PCs were not found to be statistically different from a group consisting of both flying and nonflying Air Force personnel.