Universal logic with encoded spin qubits in silicon.

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors1. For many qubit technologies2-21, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances. Here we demonstrate an alternative approach to quantum computation that uses energy-degenerate encoded qubit states controlled by nearest-neighbour contact interactions that partially swap the spin states of electrons with those of their neighbours. Calibrated sequences of such partial swaps, implemented using only voltage pulses, allow universal quantum control while bypassing microwave-associated correlated error sources1,22-28. We use an array of six 28Si/SiGe quantum dots, built using a platform that is capable of extending in two dimensions following processes used in conventional microelectronics29. We quantify the operational fidelity of universal control of two encoded qubits using interleaved randomized benchmarking30, finding a fidelity of 96.3% ± 0.7% for encoded controlled NOT operations and 99.3% ± 0.5% for encoded SWAP. The quantum coherence offered by enriched silicon5-9,16,18,20,22,27,29,31-37, the all-electrical and low-crosstalk-control of partial swap operations1,22-28 and the configurable insensitivity of our encoding to certain error sources28,33,34,38 all combine to offer a strong pathway towards scalable fault tolerance and computational advantage.

Diagnosis of Acute Aortic Syndrome in the Emergency Department (DAShED) study: an observational cohort study of people attending the emergency department with symptoms consistent with acute aortic syndrome.

BACKGROUND: The diagnosis of acute aortic syndrome (AAS) is commonly delayed or missed in the ED. We describe characteristics of ED attendances with symptoms potentially associated with AAS, diagnostic performance of clinical decision tools (CDTs) and physicians and yield of CT aorta angiogram (CTA). METHODS: This was a multicentre observational cohort study of adults attending 27 UK EDs between 26 September 2022 and 30 November 2022, with potential AAS symptoms: chest, back or abdominal pain, syncope or symptoms related to malperfusion. Patients were preferably identified prospectively, but retrospective recruitment was also permitted. Anonymised, routinely collected patient data including components of CDTs, was abstracted. Clinicians treating prospectively identified patients were asked to record their perceived likelihood of AAS, prior to any confirmatory testing. Reference standard was radiological or operative confirmation of AAS. 30-day electronic patient record follow-up evaluated whether a subsequent diagnosis of AAS had been made and mortality. RESULTS: 5548 patients presented, with a median age of 55 years (IQR 37-72; n=5539). 14 (0.3%; n=5353) had confirmed AAS. 10/1046 (1.0%) patients in whom the ED clinician thought AAS was possible had AAS. 5/147 (3.4%) patients in whom AAS was considered the most likely diagnosis had AAS. 2/3319 (0.06%) patients in whom AAS was considered not possible did have AAS. 540 (10%; n=5446) patients underwent CT, of which 407 were CTA (7%). 30-day follow-up did not reveal any missed AAS diagnoses. AUROC (area under the receiver operating characteristic) curve for ED clinician AAS likelihood rating was 0.958 (95% CI 0.933 to 0.983, n=4006) and for individual CDTs were: Aortic Dissection Detection Risk Score (ADD-RS) 0.674 (95% CI 0.508 to 0.839, n=4989), AORTAs 0.689 (95% CI 0.527 to 0.852, n=5132), Canadian 0.818 (95% CI 0.686 to 0.951, n=5180) and Sheffield 0.628 (95% CI 0.467 to 0.788, n=5092). CONCLUSION: Only 0.3% of patients presenting with potential AAS symptoms had AAS but 7% underwent CTA. CDTs incorporating clinician gestalt appear to be most promising, but further prospective work is needed, including evaluation of the role of D-dimer. TRIAL REGISTRATION NUMBER: NCT05582967; NCT05582967.

Efficient Model-Based Anthropometry under Clothing Using Low-Cost Depth Sensors.

Measuring human body dimensions is critical for many engineering and product design domains. Nonetheless, acquiring body dimension data for populations using typical anthropometric methods poses challenges due to the time-consuming nature of manual methods. The measurement process for three-dimensional (3D) whole-body scanning can be much faster, but 3D scanning typically requires subjects to change into tight-fitting clothing, which increases time and cost and introduces privacy concerns. To address these and other issues in current anthropometry techniques, a measurement system was developed based on portable, low-cost depth cameras. Point-cloud data from the sensors are fit using a model-based method, Inscribed Fitting, which finds the most likely body shape in the statistical body shape space and providing accurate estimates of body characteristics. To evaluate the system, 144 young adults were measured manually and with two levels of military ensembles using the system. The results showed that the prediction accuracy for the clothed scans remained at a similar level to the accuracy for the minimally clad scans. This approach will enable rapid measurement of clothed populations with reduced time compared to manual and typical scan-based methods.

Pulmonary embolism management in the emergency department: part 2.

Pulmonary embolism (PE) can present with a range of severity. Prognostic risk stratification is important for efficacious and safe management. This second of two review articles discusses the management of high-, intermediate- and low-risk PE. We discuss strategies to identify patients suitable for urgent outpatient care in addition to identification of patients who would benefit from thrombolysis. We discuss specific subgroups of patients where optimal treatment differs from the usual approach and identify emerging management paradigms exploring new therapies and subgroups.

Longitudinal Degradation of Pavement Marking Detectability for Mobile LiDAR Sensing Technology in Real-World Use.

Recent advancements in vehicle automation and driver-assistance systems that detect pavement markings has increased the importance of the detectability of pavement markings through various sensor modalities across weather and road conditions. Among the sensing techniques, light detection and ranging (LiDAR) sensors have become popular for vehicle-automation applications. This study used low-cost mobile multi-beam LiDAR to assess the performance of several types of pavement marking materials installed on a limited-access highway in various conditions, and quantified the degradation in detection performance over three years. Four marking materials, HPS-8, polyurea, cold plastic, and sprayable thermoplastic, were analyzed in the current study. LiDAR reflectivity data extracted from a total of 210 passes through the test sections were analyzed. A new detectability score based on LiDAR intensity data was proposed to quantify the marking detectability. The results showed that the pavement marking detectability varied across the material types over the years. The results provide guidance for selecting materials and developing maintenance schedules when marking detectability by LiDAR is a concern.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

BACKGROUND: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. METHODS: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. RESULTS: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%-42%]); possible 26 out of 151 (17% [12%-24%]); and uncertain 9 out of 43, (20% [10%-36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%-53%]); migraine aura 4 out of 38 (11% [3%-25%]); non-TIA focal symptoms 16 out of 99 (16% [10%-25%]); and no focal features 1 out of 29 (3% [0%-18%]). After MRI, a further 14 (5% [95% CI, 3-8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3-62]; P<0.0001). CONCLUSIONS: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

Neurocognitive impact of Zika virus infection in adult rhesus macaques.

BACKGROUND: Zika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The objective of the study was to assess the neurocognitive impact of ZIKV infection in adult rhesus macaques. METHODS: Neurocognitive assessments were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen and modified Brinkman Board before and after subcutaneous ZIKV inoculation. Immune activation markers were measured in the blood and cerebral spinal fluid (CSF) by multiplex assay and flow cytometry. RESULTS: All animals (N = 8) had detectable ZIKV RNA in plasma at day 1 post-inoculation (PI) that peaked at day 2 PI (median 5.9, IQR 5.6-6.2 log10 genome equivalents/mL). In all eight animals, ZIKV RNA became undetectable in plasma by day 14 PI, but persisted in lymphoid tissues. ZIKV RNA was not detected in the CSF supernatant at days 4, 8, 14 and 28 PI but was detected in the brain of 2 animals at days 8 and 28 PI. Elevations in markers of immune activation in the blood and CSF were accompanied by a reduction in accuracy and reaction speed on the CANTAB in the majority of animals. CONCLUSIONS: The co-occurrence of systemic and CSF immune perturbations and neurocognitive impairment establishes this model as useful for studying the impact of neuroinflammation on neurobehavior in rhesus macaques, as it pertains to ZIKV infection and potentially other pathogens.

Pulmonary embolism diagnosis part 1: clinical assessment at the front door.

This first of two practice reviews addresses pulmonary embolism (PE) diagnosis considering important aspects of PE clinical presentation and comparing evidence-based PE testing strategies. A companion paper addresses the management of PE. Symptoms and signs of PE are varied, and emergency physicians frequently use testing to 'rule out' the diagnosis in people with respiratory or cardiovascular symptoms. The emergency clinician must balance the benefit of reassuring negative PE testing with the risks of iatrogenic harms from over investigation and overdiagnosis.

Telephone triage of young adults with chest pain: population analysis of NHS24 calls in Scottish unscheduled care.

BACKGROUND: Telephone triage is increasingly used to manage unscheduled care demand. Younger adults are frequent users, and commonly call with chest pain. We compared pathways of care in younger adults calling with chest pain, and associations of patient characteristics and telephone triage recommendation with hospital admission. METHODS: A retrospective study of all triage calls with chest pain to NHS24 advice line by people aged 15-34 years between 1 January 2015 and 31 December 2017 where chest pain was recorded as the call reason. Recommended outcome and subsequent use of services were determined using the continuous urgent care pathways (CUPs) database which records single episodes of care spanning multiple services. We determined the number of services involved, the proportion of patients with inpatient admission, those with an admission for an 'acute-and-serious' diagnosis, and the association between the triage call recommendation and these outcomes. RESULTS: There were 102 822 CUPs identified, with 1251 different combinations of services. The most common pathway was an NHS24 call then attendance at a primary care out-of-hours (PCOOH) centre, accounting for 38 643 (37.6%) CUPs. 9060 (8.8%) CUPs ended with hospital admission, 3030 (3.0%) the result of an 'acute-and-serious' diagnosis. 8453 (8.2%) were given 'self-care' advice and not referred further, while 46.9% ended at PCOOH and 15.2% at ED. 'Asthma, unspecified' was the most frequent 'acute-and-serious' diagnosis. Compared with people given self-care advice, referral to other services had increased odds of inpatient admission (adjusted OR (aOR) for ambulance called 28.7, 95% CI 22.6 to 36.3; for 1-hour in-home general practitioner (GP) visit arranged aOR 36.8, 95% CI 23.2 to 58.5) and for admission with an 'acute-and-serious' diagnosis (aOR ambulance called 23.9, 95% CI 16.2 to 35.4; aOR 1-hour GP visit 48.3, 95% CI 25.5 to 91.6). CONCLUSION: Chest pain triage by NHS24 appears safe, but care pathways can involve multiple service contacts. While acuity assigned to the call is strongly related to the odds of hospital admission and odds of an 'acute-and-serious' diagnosis, 'overtriage' means few patients are directed to self-care advice.

A parametric modeling of adult body shape in a supported seated posture including effects of age.

Statistical body shape models (SBSM) provide compact, flexible representations of body shape that can be implemented in design software. However, few SBSMs have been created to represent adults in supported seated postures that are relevant for the design of seated environments, and none has incorporated the effects of age. This paper presents an SBSM based on surface laser-scan data from 155 U.S. adults. The data were processed to obtain homologous mesh structure and symmetric geometry, and the processed data were statistically analysed using principal component analysis to obtain a compact representation of the data variance. Regression analysis was conducted to predict body size and shape from stature, body mass index, ratio of sitting height to stature, sex, and age. The resulting model allows rapid generation of realistic body models for applications, including product design, accommodation assessment, and safety system optimisation. The model is publicly accessible at HumanShape.org. Practitioner summary: This paper presents a statistical model that represents adult body shapes in a supported seated posture based on 3 D anthropometric measurements. This model is the first whole-body parametric model known to incorporate age effects based on data extending beyond 65 years of age.

Development of a Multiplex Bead Assay To Detect Immunoglobulin G Antibodies to Babesia duncani in Human Serum.

Babesia duncani is the causative agent of babesiosis in the western United States. The indirect fluorescent antibody (IFA) assay is the diagnostic test of choice for detection of B. duncani-specific antibodies. However, this test requires parasitized red blood cells harvested from infected hamsters, and test results are often difficult to interpret. To simplify serological testing for B. duncani, a proteomics approach was employed to identify candidate immunodiagnostic antigens. Several proteins were identified by electrospray ionization mass spectrometric analysis, and four recombinant protein constructs were expressed and used in a multiplex bead assay (MBA) to detect B. duncani-specific antibodies. Two antigens, AAY83295.1 and AAY83296.1, performed well with high sensitivities and specificities. AAY83295.1 had a higher sensitivity (100%) but lower specificity (89%) than AAY83296.1, which had a sensitivity of 90% and a specificity of 96%. Combining these two antigens did not improve the performance of the assay. This MBA could be useful for diagnosis, serosurveillance, and blood donor screening for B. duncani infection.

Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays.

INTRODUCTION: Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated. METHODS: After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed. RESULTS: FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer's reference interval. CONCLUSIONS: Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.

Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary ß3-subunit.

Voltage-gated sodium channels comprise an ion-selective α-subunit and one or more associated ß-subunits. The ß3-subunit (encoded by the SCN3B gene) is an important physiological regulator of the heart-specific sodium channel, Nav1.5. We have previously shown that when expressed alone in HEK293F cells, the full-length ß3-subunit forms trimers in the plasma membrane. We extend this result with biochemical assays and use the proximity ligation assay (PLA) to identify oligomeric ß3-subunits, not just at the plasma membrane, but throughout the secretory pathway. We then investigate the corresponding clustering properties of the α-subunit and the effects upon these of the ß3-subunits. The oligomeric status of the Nav1.5 α-subunit in vivo, with or without the ß3-subunit, has not been previously investigated. Using super-resolution fluorescence imaging, we show that under conditions typically used in electrophysiological studies, the Nav1.5 α-subunit assembles on the plasma membrane of HEK293F cells into spatially localized clusters rather than individual and randomly dispersed molecules. Quantitative analysis indicates that the ß3-subunit is not required for this clustering but ß3 does significantly change the distribution of cluster sizes and nearest-neighbor distances between Nav1.5 α-subunits. However, when assayed by PLA, the ß3-subunit increases the number of PLA-positive signals generated by anti-(Nav1.5 α-subunit) antibodies, mainly at the plasma membrane. Since PLA can be sensitive to the orientation of proteins within a cluster, we suggest that the ß3-subunit introduces a significant change in the relative alignment of individual Nav1.5 α-subunits, but the clustering itself depends on other factors. We also show that these structural and higher-order changes induced by the ß3-subunit do not alter the degree of electrophysiological gating cooperativity between Nav1.5 α-subunits. Our data provide new insights into the role of the ß3-subunit and the supramolecular organization of sodium channels, in an important model cell system that is widely used to study Nav channel behavior.

Thyroid homeostasis in B6C3F1 mice upon sub-chronic exposure to trifluoroiodomethane (CF3I).

Trifluoroiodomethane (CF3I) is a fire suppressant gas with potential for use in low global-warming refrigerant blends. Data from studies in rats suggest that the most sensitive health effect of CF3I is thyroid hormone perturbation, but the rat is a particularly sensitive species for disruption of thyroid homeostasis. Mice appear to be less sensitive than rats but still a conservative model with respect to humans. The purpose of this study was to test tolerance and thyroid response to CF3I in B6C3F1 male mice. Male mice were exposed to CF3I for 6 h per day, for 28 days, via whole body exposure at concentrations of 2500, 5000 and 10,000 ppm. A 16-day recovery period was included to evaluate reversibility. No adverse clinical signs were observed throughout the study, and body weights were unaffected by exposure. CF3I exposure had no effect on thyroid histology. An increase in relative thyroid weight was observed at 10,000 ppm on day 28 but not in a separate group of animals evaluated on day 29, and thyroid weight was not different from controls at 44 days. Slight and sporadic changes in serum triiodothyronine, thyroxine, and thyroid-stimulating hormone were observed but did not follow a consistent pattern with respect to timing, dose, or direction. Overall, exposure at up to 10,000 ppm (1.0%) of CF3I gas for 28 days produced no overt general toxicity and only transient, recoverable effects on thyroid weight and hormones at certain concentrations. On the basis of the effect of CF3I exposure on the thyroid, including evaluation of thyroid histopathology, the no observed adverse effect level for this study is 10,000 ppm. Considering the apparently greater toxicity reported in prior studies in male rats, our data suggest a species difference between rats and mice in terms of susceptibility to CF3I-induced thyroid hormone perturbation.

Establishing a Smartphone Ambulatory ECG Service for Patients Presenting to the Emergency Department with Pre-Syncope and Palpitations.

Background and Objectives: The Investigation of Palpitations in the ED (IPED) study showed that a smartphone-based event recorder increased the number of patients in whom an electrocardiogram (ECG) was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care and concluded that this safe, non-invasive and easy-to-use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope ambulatory care Clinic (SPACC) service. Materials and Methods: A clinical standard operating procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22 July 2019. Results: Between 22 July 2019 and 31 October 2019, 68 patients seen in the emergency departments (EDs) with palpitations or pre-syncope were referred to SPACC. Of those, 30 were male and 38 were female, and the mean age was 45.8 years old (SD 15.1) with a range from 18 years old to 80 years old. A total of 50 (74%) patients underwent full investigation. On the first assessment, seven (10%) patients were deemed to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics, or bigeminy. A symptomatic cardiac dysrhythmia was detected in six (8.8%) patients. Three patients had supraventricular tachycardia (4%), two had atrial fibrillation (3%), and one had atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based on ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Syncope Time Frames for Adverse Events after Emergency Department Presentation: An Individual Patient Data Meta-Analysis.

Background and Objectives: Knowledge of the incidence and time frames of the adverse events of patients presenting syncope at the ED is essential for developing effective management strategies. The aim of the present study was to perform a meta-analysis of the incidence and time frames of adverse events of syncope patients. Materials and Methods: We combined individual patients' data from prospective observational studies including adult patients who presented syncope at the ED. We assessed the pooled rate of adverse events at 24 h, 72 h, 7-10 days, 1 month and 1 year after ED evaluation. Results: We included nine studies that enrolled 12,269 patients. The mean age varied between 53 and 73 years, with 42% to 57% females. The pooled rate of adverse events was 5.1% (95% CI 3.4% to 7.7%) at 24 h, 7.0% (95% CI 4.9% to 9.9%) at 72 h, 8.4% (95% CI 6.2% to 11.3%) at 7-10 days, 10.3% (95% CI 7.8% to 13.3%) at 1 month and 21.3% (95% CI 15.8% to 28.0%) at 1 year. The pooled death rate was 0.2% (95% CI 0.1% to 0.5%) at 24 h, 0.3% (95% CI 0.1% to 0.7%) at 72 h, 0.5% (95% CI 0.3% to 0.9%) at 7-10 days, 1% (95% CI 0.6% to 1.7%) at 1 month and 5.9% (95% CI 4.5% to 7.7%) at 1 year. The most common adverse event was arrhythmia, for which its rate was 3.1% (95% CI 2.0% to 4.9%) at 24 h, 4.8% (95% CI 3.5% to 6.7%) at 72 h, 5.8% (95% CI 4.2% to 7.9%) at 7-10 days, 6.9% (95% CI 5.3% to 9.1%) at 1 month and 9.9% (95% CI 5.5% to 17) at 1 year. Ventricular arrhythmia was rare. Conclusions: The risk of death or life-threatening adverse event is rare in patients presenting syncope at the ED. The most common adverse events are brady and supraventricular arrhythmias, which occur during the first 3 days. Prolonged ECG monitoring in the ED in a short stay unit with ECG monitoring facilities may, therefore, be beneficial.

Lessons from a pilot for uncontrolled donation after circulatory death in the ED in the UK.

Worldwide there is a shortage of available organs for patients requiring transplants. However, some countries such as France, Italy and Spain have had greater success by allowing donations from patients with unexpected and unrecoverable circulatory arrest who arrive in the ED. Significant advances in the surgical approach to organ recovery from donation after circulatory death (DCD) led to the establishment of a pilot programme for uncontrolled DCD in the ED of the Royal Infirmary of Edinburgh. This paper describes the programme and discusses the lessons learnt.

Static, Dynamic, and Cognitive Fit of Exosystems for the Human Operator.

OBJECTIVE: To define static, dynamic, and cognitive fit and their interactions as they pertain to exosystems and to document open research needs in using these fit characteristics to inform exosystem design. BACKGROUND: Initial exosystem sizing and fit evaluations are currently based on scalar anthropometric dimensions and subjective assessments. As fit depends on ongoing interactions related to task setting and user, attempts to tailor equipment have limitations when optimizing for this limited fit definition. METHOD: A targeted literature review was conducted to inform a conceptual framework defining three characteristics of exosystem fit: static, dynamic, and cognitive. Details are provided on the importance of differentiating fit characteristics for developing exosystems. RESULTS: Static fit considers alignment between human and equipment and requires understanding anthropometric characteristics of target users and geometric equipment features. Dynamic fit assesses how the human and equipment move and interact with each other, with a focus on the relative alignment between the two systems. Cognitive fit considers the stages of human-information processing, including somatosensation, executive function, and motor selection. Human cognitive capabilities should remain available to process task- and stimulus-related information in the presence of an exosystem. Dynamic and cognitive fit are operationalized in a task-specific manner, while static fit can be considered for predefined postures. CONCLUSION: A deeper understanding of how an exosystem fits an individual is needed to ensure good human-system performance. Development of methods for evaluating different fit characteristics is necessary. APPLICATION: Methods are presented to inform exosystem evaluation across physical and cognitive characteristics.

The molecular mechanism of induction of unfolded protein response by Chlamydia.

The unfolded protein response (UPR) contributes to chlamydial pathogenesis, as a source of lipids and ATP during replication, and for establishing the initial anti-apoptotic state of host cell that ensures successful inclusion development. The molecular mechanism(s) of UPR induction by Chlamydia is unknown. Chlamydia use type III secretion system (T3SS) effector proteins (e.g, the Translocated Actin-Recruiting Phosphoprotein (Tarp) to stimulate host cell's cytoskeletal reorganization that facilitates invasion and inclusion development. We investigated the hypothesis that T3SS effector-mediated assembly of myosin-II complex produces activated non-muscle myosin heavy chain II (NMMHC-II), which then binds the UPR master regulator (BiP) and/or transducers to induce UPR. Our results revealed the interaction of the chlamydial effector proteins (CT228 and Tarp) with components of the myosin II complex and UPR regulator and transducer during infection. These interactions caused the activation and binding of NMMHC-II to BiP and IRE1α leading to UPR induction. In addition, specific inhibitors of myosin light chain kinase, Tarp oligomerization and myosin ATPase significantly reduced UPR activation and Chlamydia replication. Thus, Chlamydia induce UPR through T3SS effector-mediated activation of NMMHC-II components of the myosin complex to facilitate infectivity. The finding provides greater insights into chlamydial pathogenesis with the potential to identify therapeutic targets and formulations.

Approach to syncope in the emergency department.

Syncope is a common reason for ED attendance and it presents a major management challenge with regard to the appropriate workup and disposition. Nearly 50% of patients are admitted, and for many this is unnecessary; clinical decision rules have not proven to decrease unnecessary admissions. The European Society of Cardiology has recently developed guidance for managing syncope in the ED. This article highlights the key steps in evaluating syncope in the ED, factors involved in determining risk of a cardiac cause, and considerations for admission, observation or discharge.