NSF DARE-transforming modeling in neurorehabilitation: perspectives and opportunities from US funding agencies.

In recognition of the importance and timeliness of computational models for accelerating progress in neurorehabilitation, the U.S. National Science Foundation (NSF) and the National Institutes of Health (NIH) sponsored a conference in March 2023 at the University of Southern California that drew global participation from engineers, scientists, clinicians, and trainees. This commentary highlights promising applications of computational models to understand neurorehabilitation ("Using computational models to understand complex mechanisms in neurorehabilitation" section), improve rehabilitation care in the context of digital twin frameworks ("Using computational models to improve delivery and implementation of rehabilitation care" section), and empower future interdisciplinary workforces to deliver higher-quality clinical care using computational models ("Using computational models in neurorehabilitation requires an interdisciplinary workforce" section). The authors describe near-term gaps and opportunities, all of which encourage interdisciplinary team science. Four major opportunities were identified including (1) deciphering the relationship between engineering figures of merit-a term commonly used by engineers to objectively quantify the performance of a device, system, method, or material relative to existing state of the art-and clinical outcome measures, (2) validating computational models from engineering and patient perspectives, (3) creating and curating datasets that are made publicly accessible, and (4) developing new transdisciplinary frameworks, theories, and models that incorporate the complexities of the nervous and musculoskeletal systems. This commentary summarizes U.S. funding opportunities by two Federal agencies that support computational research in neurorehabilitation. The NSF has funding programs that support high-risk/high-reward research proposals on computational methods in neurorehabilitation informed by theory- and data-driven approaches. The NIH supports the development of new interventions and therapies for a wide range of nervous system injuries and impairments informed by the field of computational modeling. The conference materials can be found at https://dare2023.usc.edu/ .

Audit of ventriculoperitoneal shunt infections in paediatric patients, 2006-2013.

BACKGROUND: Infection following ventriculoperitoneal shunt placement remains a significant complication with an incidence of 3-27% cited in literature. Infections cause significant morbidity, and it is important that empirical antibiotic therapy for management is guided by accurate knowledge of prevailing aetiologies and local antibiotic sensitivity patterns. AIMS: To establish the incidence of shunt infections in our paediatric population, to identify the causative micro-organisms, and to determine the antibiotic resistance patterns of the responsible micro-organisms. METHODS: Retrospective data collection utilising existing databases in the Royal Hospital for Sick Children, Yorkhill, between 1 January 2006 and 30 September 2013. RESULTS: Total number of shunt operations was 308 with 28 episodes of infection involving 27 patients (male = 12, female = 15). The incidence of infection was 9%. In all, 79% of the episodes involved a single pathogen with 21% being mixed pathogens. Coagulase-negative staphylococci were the most common cause of infection (44%). Gram-positive sensitivity to flucloxacillin and gentamicin was noticeably low at 22% and 14%, respectively with 87% of coagulase-negative staphylococci resistant to gentamicin and 81% resistant to flucloxacillin. CONCLUSIONS: The changing spectrum of Gram-positive organisms has impacted on antibiotic sensitivity patterns, and our local prescribing policy has been adapted in order to manage shunt infections most effectively.

Single scan PC-MRI by alternating the velocity encoding gradient polarity between phase encoding steps.

The purpose of this study was to develop a faster approach to phase contrast magnetic resonance imaging. This article proposes a phase contrast imaging scheme called single scan phase contrast in which the polarity of the velocity-encoding gradient is alternated between phase encoding steps. In single scan phase contrast, ghost images due to moving spins form. The signal intensity of the ghost images is modulated by the sine of the motion-induce phase shift. Prior to image acquisition, the region of interest containing moving spins is identified, and the field of view is configured so to avoid overlap between the object in the image and the ghost image(s) due to motion in the region of interest. The image values of the region of interest and the ghost image are used to quantify velocity. At best, single scan phase contrast reduces the total acquisition time by a factor of two when compared to phase contrast. In this study, single scan phase contrast is validated against phase contrast in phantom and in vivo.

Improved early diagnosis of Pseudomonas aeruginosa by real-time PCR to prevent chronic colonisation in a paediatric cystic fibrosis population.

Early detection of Pseudomonas aeruginosa in children with cystic fibrosis is hampered by the need to process a sub-optimal specimen type, namely cough swabs, which are known to have a lower positive yield than sputa or more invasive samples. This delay in the detection of low levels of P. aeruginosa could potentially result in the loss of an opportunity to initiate early aggressive antibiotic therapy and result in chronic colonisation, with a poorer overall prognosis. Quantitative real-time PCR (qPCR) offers an opportunity to increase the detection rate of P. aeruginosa compared to traditional culture techniques. This study examined 500 cough swabs and 42 sputum samples from paediatric patients and showed that detection of P. aeruginosa could be increased in both sample types by 100% and 45% respectively. Overall the sensitivity was 100% and specificity of 58% when compared to culture as a gold standard. These results although initially promising require careful consideration both from a treatment and infection control standpoint as the significance of detection of very low levels of P. aeruginosa is unclear.

Coupling pediatric ventricle assist devices to the Fontan circulation: simulations with a lumped-parameter model.

In pediatric ventricular assist device (VAD) design, the process of matching device characteristics and dimensions to the relevant disease conditions poses a formidable challenge because the disease spectrum is more highly varied than for adult applications. One example arises with single-ventricle congenital defects, which demand palliative surgeries that create elevated systemic venous pressure and altered pulmonary hemodynamics. Substituting a mechanical pump as a right ventricle has long been proposed to eliminate the associated early and postoperative anomalies. A pulsatile lumped-parameter model of the single-ventricle circulation was developed to guide the preliminary design studies. Two special modules, the pump characteristics and the total cavopulmonary connection (TCPC) module, are introduced. The TCPC module incorporates the results of three-dimensional patient-specific computational fluid dynamics calculations, where the pressure drop in the TCPC anastomosis is calculated at the equal vascular lung resistance operating point for different cardiac outputs at a steady 60/40 inferior vena cava/superior vena cava flow split. Preliminary results obtained with the adult parameters are presented with no ventricle remodeling or combined larger-size single ventricle. A detailed literature review of single-ventricle function is provided. Coupling a continuous pump to the single-ventricle circulation brought both the pulmonary and systemic venous pressures back to manageable levels. Selected VADs provided an acceptable cardiac output trace of the single left ventricle, after initial transients. Remodeling of the systemic venous compliance plays a critical role in performance and is included in this study. Pulsatile operation mode with rotational speed regulation highlighted the importance of TCPC and pulmonary artery compliances. Four different pumps and three patient-specific anatomical TCPC pathologies were studied. Magnitudes of the equivalent TCPC resistances were found to be comparable to the vascular resistances of the normal baseline circulation, significantly affecting both the VAD design and hemodynamics.

Experimental immunisation and protection of guinea pigs with Vibrio cholerae toxoid and mucinases, neuraminidase and proteinase.

As measured by fluid accumulation in ileal loops, Vibrio cholerae mucinase complex, with or without toxoid, protected guinea pigs from challenges with V. cholerae live organisms and enterotoxin. The neuraminidase and proteinases of the complex were combined in modified oil emulsion or aluminum hydroxide adjuvants and the resultant vaccines given by the parenteral or oral routes. There was little difference between the two types of adjuvant. Control of stomach acidity improved oral vaccination. Animals injected intramuscularly (i.m.) with toxoid-containing vaccines were protected from challenge with cholera toxin (CT) whereas those given oral doses were not. Toxoid plus killed V. cholerae cells elicited a more effective protection against toxin challenge than killed V. cholerae cells alone. Vaccines containing mucinases, with or without toxoid, protected the animals from a live V. cholerae challenge. The anti-mucinase immune response may prevent adhesion of the V. cholerae cells and hence reduce delivery of toxin to receptors. These mucinases, neuraminidase and proteinases, may be useful components of acellular, toxoided cholera vaccines for human immunisation.