Clinical practice - latest insights in optimizing the care of children with Down syndrome.

An essential part of the care of children with Down syndrome is secondary screening for comorbidity. It is well known that comorbidity frequently occurs in these children. A new update of the Dutch Down syndrome medical guideline was developed to create a sound evidence base for several of these conditions. We present the latest insights and recommendations from this Dutch medical guideline which are based on the most relevant literature currently available and developed with rigorous methodology. The main focus of this revision of the guideline was on obstructive sleep apnea and other airway problems and hematologic disorders, such as transient abnormal myelopoiesis, leukemia, and thyroid disorders. Conclusion: This is a short summary of the latest insights and recommendations from the updated Dutch medical guideline for children with Down syndrome.

On Senders's Models of Visual Sampling Behavior.

OBJECTIVE: We review the sampling models described in John Senders's doctoral thesis on "visual sampling processes" via a ready and accessible exposition. BACKGROUND: John Senders left a significant imprint on human factors/ergonomics (HF/E). Here, we focus on one preeminent aspect of his career, namely visual attention. METHODS: We present, clarify, and expand the models in his thesis through computer simulation and associated visual illustrations. RESULTS: One of the key findings of Senders's work on visual sampling concerns the linear relationship between signal bandwidth and visual sampling rate. The models that are used to describe this relationship are the periodic sampling model (PSM), the random constrained sampling model (RCM), and the conditional sampling model (CSM). A recent replication study that used results from modern eye-tracking equipment showed that Senders's original findings are manifestly replicable. CONCLUSIONS: Senders's insights and findings withstand the test of time and his models continue to be both relevant and useful to the present and promise continued impact in the future. APPLICATION: The present paper is directed to stimulate a broad spectrum of researchers and practitioners in HF/E and beyond to use these important and insightful models.

Shared control versus traded control in driving: a debate around automation pitfalls.

A major question in human-automation interaction is whether tasks should be traded or shared between human and automation. This work presents reflections-which have evolved through classroom debates between the authors over the past 10 years-on these two forms of human-automation interaction, with a focus on the automated driving domain. As in the lectures, we start with a historically informed survey of six pitfalls of automation: (1) Loss of situation and mode awareness, (2) Deskilling, (3) Unbalanced mental workload, (4) Behavioural adaptation, (5) Misuse, and (6) Disuse. Next, one of the authors explains why he believes that haptic shared control may remedy the pitfalls. Next, another author rebuts these arguments, arguing that traded control is the most promising way to improve road safety. This article ends with a common ground, explaining that shared and traded control outperform each other at medium and low environmental complexity, respectively. Practitioner summary: Designers of automation systems will have to consider whether humans and automation should perform tasks alternately or simultaneously. The present article provides an in-depth reflection on this dilemma, which may prove insightful and help guide design. Abbreviations: ACC: Adaptive Cruise Control: A system that can automatically maintain a safe distance from the vehicle in front; AEB: Advanced Emergency Braking (also known as Autonomous Emergency Braking): A system that automatically brakes to a full stop in an emergency situation; AES: Automated Evasive Steering: A system that automatically steers the car back into safety in an emergency situation; ISA: Intelligent Speed Adaptation: A system that can limit engine power automatically so that the driving speed does not exceed a safe or allowed speed.

Evaluating the Tobii Pro Glasses 2 and 3 in static and dynamic conditions.

Over the past few decades, there have been significant developments in eye-tracking technology, particularly in the domain of mobile, head-mounted devices. Nevertheless, questions remain regarding the accuracy of these eye-trackers during static and dynamic tasks. In light of this, we evaluated the performance of two widely used devices: Tobii Pro Glasses 2 and Tobii Pro Glasses 3. A total of 36 participants engaged in tasks under three dynamicity conditions. In the "seated with a chinrest" trial, only the eyes could be moved; in the "seated without a chinrest" trial, both the head and the eyes were free to move; and during the walking trial, participants walked along a straight path. During the seated trials, participants' gaze was directed towards dots on a wall by means of audio instructions, whereas in the walking trial, participants maintained their gaze on a bullseye while walking towards it. Eye-tracker accuracy was determined using computer vision techniques to identify the target within the scene camera image. The findings showed that Tobii 3 outperformed Tobii 2 in terms of accuracy during the walking trials. Moreover, the results suggest that employing a chinrest in the case of head-mounted eye-trackers is counterproductive, as it necessitates larger eye eccentricities for target fixation, thereby compromising accuracy compared to not using a chinrest, which allows for head movement. Lastly, it was found that participants who reported higher workload demonstrated poorer eye-tracking accuracy. The current findings may be useful in the design of experiments that involve head-mounted eye-trackers.

Why human factors science is demonstrably necessary: historical and evolutionary foundations.

We review the theoretical foundation for the need for human factors science. Over the past 2.8 million years, humans and tools have co-evolved. However, in the last century, technology is introduced at a rate that exceeds human evolution. The proliferation of computers and, more recently, robots, introduces new cognitive demands, as the human is required to be a monitor rather than a direct controller. The usage of robots and artificial intelligence is only expected to increase, and the present COVID-19 pandemic may prove to be catalytic in this regard. One way to improve overall system performance is to 'adapt the human to the machine' via task procedures, operator training, operator selection, a Procrustean mandate. Using classic research examples, we demonstrate that Procrustean methods can improve performance only to a limited extent. For a viable future, therefore, technology must adapt to the human, which underwrites the necessity of human factors science. Practitioner Summary: Various research articles have reported that the science of Human Factors is of vital importance in improving human-machine systems. However, what is lacking is a fundamental historical outline of why Human Factors is important. This article provides such a foundation, using arguments ranging from pre-history to post-COVID.

Development, prevention, and treatment of feeding tube dependency.

Enteral nutrition is effective in ensuring nutritional requirements and growth. However, when tube feeding lasts for a longer period, it can lead to tube dependency in the absence of medical reasons for continuation of tube feeding. Tube-dependent children are unable or refuse to start oral activities and they lack oral skills. Tube dependency has health-, psychosocial-, and economy-related consequences. Therefore, the transition to oral feeding is of great importance. However, this transition can be very difficult and needs a multidisciplinary approach. Most studies for treatment of tube dependency are based on behavioral interventions, such as family therapy, individual behavior therapy, neuro-linguistic programming, and parental anxiety reduction. Furthermore, oral motor therapy and nutritional adjustments can be helpful in tube weaning. The use of medication has been described in the literature. Although mostly chosen as the last resort, hunger-inducing methods, such as the Graz-model and the Dutch clinical hunger provocation program, are also successful in weaning children off tube feeding. CONCLUSION: The transition from tube to oral feeding is important in tube-dependent children but can be difficult. We present an overview for the prevention and treatment of tube dependency. What is known: • Longer periods of tube feeding can lead to tube dependency. • Tube weaning can be very difficult. What is new: • Weaning as soon as possible and therefore referral to a multidisciplinary team are recommended. • An overview of treatment options for tube dependency is presented in this article.

TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.

OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224. RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca(2+) sensitivity and altered cross-bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.

Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival.

BACKGROUND: Patients with peritoneal metastases (PMs) originating from colorectal carcinoma (CRC) are curatively treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC). We aim to improve patient selection for HIPEC by predicting MMC sensitivity. METHODS: The MMC sensitivity was determined for 12 CRC cell lines and correlated to mRNA expression of 37 genes related to the Fanconi anaemia (FA)-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC. Functionality of the FA-BRCA pathway in cell lines was assessed using a chromosomal breakage assay and western blot for key protein FANCD2. Bloom syndrome protein (BLM) was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines (n=12) and patient material (n=20). RESULTS: High sensitivity correlated with a low BLM (P=0.01) and BRCA2 (P=0.02) at mRNA expression level. However, FA-BRCA pathway functionality demonstrated no correlation to MMC sensitivity. In cell lines, weak intensity staining of BLM by IHC correlated to high sensitivity (P=0.04) to MMC. Low BLM protein expression was significantly associated with an improved survival in patients after CRS and HIPEC (P=0.04). CONCLUSIONS: Low BLM levels are associated with high MMC sensitivity and an improved survival after HIPEC.