A retrospective observational study of vCare: a virtual emergency clinical advisory and transfer service in rural and remote Australia.

BACKGROUND: Provision of critical care in rural areas is challenging due to geographic distance, smaller facilities, generalist skill mix and population characteristics. Internationally, the amalgamation telemedicine and retrieval medicine services are developing to overcome these challenges. Virtual emergency clinical advisory and transfer service (vCare) is one of these novel services based in New South Wales, Australia. We aim to describe patient encounters with vCare from call initiation at the referring site to definitive care at the accepting site. METHODS: This retrospective observational study reviewed all patients using vCare in rural and remote Australia for clinical advice and/or inter-hospital transfer for higher level of care between February and March 2021. Data were extracted from electronic medical records and included remoteness of sites, presenting complaint, triage category, camera use, patient characteristics, transfer information, escalation of therapeutic intervention and outcomes. Data were summarised using cross tabulation. RESULTS: 1,678 critical care patients were supported by vCare, with children (12.5%), adults (50.6%) and older people (36.9%) evenly split between sexes. Clinicians mainly referred to vCare for trauma (15.1%), cardiac (16.1%) and gastroenterological (14.8%) presentations. A referral to vCare led to an escalation of invasive intervention, skill, and resources for patient care. vCare cameras were used in 19.8% of cases. Overall, 70.5% (n = 1,139) of patients required transfer. Of those, 95.1% were transferred to major regional hospitals and 11.7% required secondary transfer to higher acuity hospitals. Of high-urgency referrals, 42.6% did not receive high priority transport. Imaging most requested included CT and MRI scans (37.2%). Admissions were for physician (33.1%) and surgical care (23.3%). The survival rate was 98.6%. CONCLUSION: vCare was used by staff in rural and remote facilities to support decision making and care of patients in a critical condition. Issues were identified including low utilisation of equipment, heavy reliance on regional sites and high rates of secondary transfer. However, these models are addressing a key gap in the health workforce and supporting rural and remote communities to receive care.

An overview of the process, progress, and outcomes of a National Center for Accelerated Innovation: The Boston Biomedical Innovation Center Experience.

Implementation of clinically useful research discoveries in the academic environment is challenged by limited funding for early phase proof-of-concept studies and inadequate expertise in product development and commercialization. To address these limitations, the National Institutes of Health (NIH) established the National Centers for Accelerated Innovations (NCAI) program in 2013. Three centers competed successfully for awards through this mechanism. Here, we present the experience of one such center, the Boston Biomedical Innovation Center (B-BIC), and demonstrate its remarkable success at the translation of innovations to clinical application and commercialization, as well as skills development and education.

The 24-h savings of adaptation to novel movement dynamics initially reflects the recall of previous performance.

Humans rapidly adapt reaching movements in response to perturbations (e.g., manipulations of movement dynamics or visual feedback). Following a break, when reexposed to the same perturbation, subjects demonstrate savings, a faster learning rate compared with the time course of initial training. Although this has been well studied, there are open questions on the extent early savings reflects the rapid recall of previous performance. To address this question, we examined how the properties of initial training (duration and final adaptive state) influence initial single-trial adaptation to force-field perturbations when training sessions were separated by 24 h. There were two main groups that were distinct based on the presence or absence of a washout period at the end of day 1 (with washout vs. without washout). We also varied the training duration on day 1 (15, 30, 90, or 160 training trials), resulting in 8 subgroups of subjects. We show that single-trial adaptation on day 2 scaled with training duration, even for similar asymptotic levels of learning on day 1 of training. Interestingly, the temporal force profile following the first perturbation on day 2 matched that at the end of day 1 for the longest training duration group that did not complete the washout. This correspondence persisted but was significantly lower for shorter training durations and the washout subject groups. Collectively, the results suggest that the adaptation observed very early in reexposure results from the rapid recall of the previously learned motor recalibration but is highly dependent on the initial training duration and final adaptive state.NEW & NOTEWORTHY The extent initial readaptation reflects the recall of previous motor performance is largely unknown. We examined early single-trial force-field adaptation on the second day of training and distinguished initial retention from recall. We found that the single-trial adaptation following the 24-h break matched that at the end of the first day, but this recall was modified by the training duration and final level of learning on the first day of training.

XX/XY Sex Chromosomes in the South American Dwarf Gecko (Gonatodes humeralis).

Sex-specific genetic markers identified using restriction site-associated DNA sequencing, or RADseq, permits the recognition of a species' sex chromosome system in cases where standard cytogenetic methods fail. Thus, species with male-specific RAD markers have an XX/XY sex chromosome system (male heterogamety) while species with female-specific RAD markers have a ZZ/ZW sex chromosome (female heterogamety). Here, we use RADseq data from 5 male and 5 female South American dwarf geckos (Gonatodes humeralis) to identify an XX/XY sex chromosome system. This is the first confidently known sex chromosome system in a Gonatodes species. We used a low-coverage de novo G. humeralis genome assembly to design PCR primers to validate the male-specificity of a subset of the sex-specific RADseq markers and describe how even modest genome assemblies can facilitate the design of sex-specific PCR primers in species with diverse sex chromosome systems.

The absence or temporal offset of visual feedback does not influence adaptation to novel movement dynamics.

Delays in transmitting and processing sensory information require correctly associating delayed feedback to issued motor commands for accurate error compensation. The flexibility of this alignment between motor signals and feedback has been demonstrated for movement recalibration to visual manipulations, but the alignment dependence for adapting movement dynamics is largely unknown. Here we examined the effect of visual feedback manipulations on force-field adaptation. Three subject groups used a manipulandum while experiencing a lag in the corresponding cursor motion (0, 75, or 150 ms). When the offset was applied at the start of the session (continuous condition), adaptation was not significantly different between groups. However, these similarities may be due to acclimation to the offset before motor adaptation. We tested additional subjects who experienced the same delays concurrent with the introduction of the perturbation (abrupt condition). In this case adaptation was statistically indistinguishable from the continuous condition, indicating that acclimation to feedback delay was not a factor. In addition, end-point errors were not significantly different across the delay or onset conditions, but end-point correction (e.g., deceleration duration) was influenced by the temporal offset. As an additional control, we tested a group of subjects who performed without visual feedback and found comparable movement adaptation results. These results suggest that visual feedback manipulation (absence or temporal misalignment) does not affect adaptation to novel dynamics, independent of both acclimation and perceptual awareness. These findings could have implications for modeling how the motor system adjusts to errors despite concurrent delays in sensory feedback information.NEW & NOTEWORTHY A temporal offset between movement and distorted visual feedback (e.g., visuomotor rotation) influences the subsequent motor recalibration, but the effects of this offset for altered movement dynamics are largely unknown. Here we examined the influence of 1) delayed and 2) removed visual feedback on the adaptation to novel movement dynamics. These results contribute to understanding of the control strategies that compensate for movement errors when there is a temporal separation between motion state and sensory information.

Using a nursing productivity committee to achieve cost savings and improve staffing levels and staff satisfaction.

Challenged by rising costs, higher registered nurse vacancy rates and declining staff morale, a Nursing Productivity Committee was formed to analyze productive and nonproductive hours and seek improvements in our staffing models and scheduling processes. The changes implemented led to lower nurse to patient ratios, better control of labor costs, elimination of agency staff, greater staff satisfaction, and introduction of new technologies. Nurse managers, nursing supervisors, and frontline staff are now more knowledgeable and empowered to use creative solutions to manage their budgets and schedules in these times of fluctuating census and varying vacancy rates.

Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis.

Airway surface liquid (ASL) absorption is initiated by Na+ entry via epithelial Na+ channels (ENaC), which establishes an osmotic gradient that drives fluid from the luminal to serosal airway surface. We and others have recently reported that a protease/anti-protease balance regulates ENaC in human airway epithelial cells (HAEC) and provides a mechanism for autoregulation of ASL volume. In cystic fibrosis (CF), this balance is disturbed, leading to constitutive proteolytic activation of ENaC and the pathological Na+ hyperabsorption characteristic of this airway disease. Prostasin is a glycosylphosphatidylinositol-anchored serine protease that activates ENaC and is expressed on the surface epithelium lining the airway. In this report we present evidence that prostasin expression is regulated by the ASL volume, allowing for increased proteolytic activation of ENaC when the ASL volume is high. Prostasin activity is further regulated by the cognate serpin protease nexin-1 (PN-1), which is expressed in HAEC and inhibits Na+ absorption by forming an inactive complex with prostasin and preventing the proteolytic processing of prostasin. Whereas these mechanisms regulate prostasin expression in response to ASL volume in non-CF epithelia, HAEC cultured from CF patients express >50% more prostasin on the epithelial surface. These findings suggest that a proteolytic cascade involving prostasin, an upstream prostasin-activating protease, and PN-1 regulate Na+ absorption in the airway and that abnormal prostasin expression contributes to excessive proteolytic activation of ENaC in CF patients.

Hepatocyte growth factor and other fibroblast secretions modulate the phenotype of human bronchial epithelial cells.

The luminal airway surface is lined with epithelial cells that provide a protective barrier from the external environment and clear inhaled pathogens from the lung. To accomplish this important function, human bronchial epithelial (HBE) cells must be able to rapidly regenerate a mucociliary layer of cells following epithelial injury. Whereas epithelial-fibroblast interactions are known to modulate the airway architecture during lung development and repair, little is known about how these two cells interact. Using a primary HBE and lung fibroblast coculture system, we demonstrate that 1) subepithelial fibroblasts provide a suitable environment for differentiation of HBE cells into a polarized ciliated phenotype despite being cultured in media that induces terminal squamous differentiation and growth arrest in the absence of fibroblasts, 2) HBE cells cocultured with subepithelial fibroblasts exhibit augmented ciliogenesis, accelerated wound repair, and diminished polarized ion transport compared with cells grown in control conditions, and 3) hepatocyte growth factor (HGF) is important for subepithelial fibroblast modulation of HBE cell differentiation. These results provide a model to study fibroblast modulation of epithelial phenotype and indicate that HGF secreted by subepithelial fibroblasts contributes to HBE cell differentiation.

Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: a mechanism for sodium hyperabsorption in cystic fibrosis.

Efficient clearance of mucus and inhaled pathogens from the lung is dependent on an optimal airway surface liquid (ASL) volume, which is maintained by the regulated transport of sodium and chloride across the airway epithelium. Accumulating evidence suggests that impaired mucus clearance in cystic fibrosis (CF) airways is a result of ASL depletion caused by excessive Na(+) absorption through the epithelial sodium channel (ENaC). However, the cellular mechanisms that result in increased ENaC activity in CF airways are not completely understood. Recently, proteases were shown to modulate the activity of ENaC, but the relevance of this mechanism to the physiologic regulation of ASL volume is unknown. Using primary human airway epithelial cells, we demonstrate that: (i) protease inhibitors are present in the ASL and prevent the activation of near-silent ENaC, (ii) when the ASL volume is increased, endogenous protease inhibitors become diluted, allowing for proteolytic activation of near-silent channels, and (iii) in CF, the normally present near-silent pool of ENaC is constitutively active and the alpha subunit undergoes increased proteolytic processing. These findings indicate that the ASL volume modulates the activity of ENaC by modification of the serine protease-protease inhibitor balance and that alterations in this balance contribute to excessive Na(+) absorption in cystic fibrosis.

Chronic aeroallergen during infancy enhances eotaxin-3 expression in airway epithelium and nerves.

We have documented that exposure of rhesus monkeys to house dust mite aeroallergen during postnatal development resulted in significant recruitment of eosinophils into the airway mucosa (Clin Exp Allergy 33:1686-1694, 2003). Because eosinophils were not uniformly distributed throughout the five conducting airway generations examined, we speculated that trafficking within anatomic microenvironments of the lung is mediated by differential chemokine expression. To address this question, we used quantitative real-time RT-PCR to evaluate the related eosinophilic chemokines, eotaxin (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26) within isolated airways of infant monkey lung. Overall, chemokine mRNA expression levels in house dust mite-exposed airways were as follows: eotaxin-3 > eotaxin > eotaxin-2. Immunofluorescence staining for eotaxin-3 and CC chemokine receptor 3 (CCR3) showed positive cells within epithelium and peripherally located nerve fiber bundles of the airway wall. Epithelial volume of eotaxin-3 within the trachea correlated with epithelial volume of major basic protein. CCR3+ and MHC Class II+ dendritic cells, but not eosinophils or mast cells, co-localized within eotaxin-3+ nerve fiber bundles. We conclude that localized expression of eotaxin-3 plays an important role in the recruitment of diverse CCR3+ cell populations to different anatomic microenvironments within the infant airway in response to chronic allergen exposure.

A critical role for eosinophils in allergic airways remodeling.

Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma.