Disease Behaviour Classification: A pragmatic model for predicting outcomes in Interstitial Lung Disease.

BACKGROUND AND OBJECTIVE: The interstitial lung diseases (ILD) are a heterogenous group of disorders with similar clinical presentation, but widely varying prognoses. The use of a pragmatic disease behaviour classification (DBC), first proposed in international guidelines in 2013, categorises diseases into five behavioural classes based on their predicted clinical course. This study aimed to determine the prognostic utility of the DBC in an ILD cohort. METHODS: Consecutive patients presented at the weekly multidisciplinary meeting (MDM) of a specialist ILD centre were included. MDM consensus was obtained for diagnosis and DBC category (1-5). Baseline and serial clinical and physiological data were collected over the study period (median 3.9 years, range 0-5.4 years). The relationship between DBC and prognostic outcomes was explored. RESULTS: 137 ILD patients, [64 (47%) female] were included with mean age 67.0 ± 1.1 years, baseline FVC% 72.7 ± 1.7, and baseline DLco% 57.8 ± 1.6%. Patients were stratified into DBC by consensus at MDM: DBC1 n = 0 (0%), DBC2 n = 16 (12%), DBC3 n = 10 (7.3%), DBC4 n = 55 (40%), and DBC5 n = 56 (41%). On univariable Cox regression, increasing DBC class was associated with poorer progression-free survival (HR 1.6, 95% CI 1.2-2.0, p < 0.001). On multivariable Cox regression, DBC remained predictive of PFS when combined with age and gender (HR 1.4, 95% CI 1.1-1.9, p = 0.011), baseline FVC% (HR 1.5, 95% CI 1.1-1.8, p = 0.003) and ILD diagnosis (HR 1.6, 95% CI 1.2-2.2, p < 0.0001). CONCLUSION: DBC as determined at ILD multidisciplinary meeting may be a useful prognostic tool for the management of ILD patients.

Acceptability and feasibility of the World Health Organization's Caregiver Skills Training Programme (WHO CST) delivered via eLearning, videoconferencing, and in-person hybrid modalities in Hong Kong.

Background: Local children with developmental disabilities were deprived of learning opportunities due to recent social and health incidents, resulting in elevating challenging behaviors and familial conflicts. This study explored the acceptability and feasibility of the World Health Organization's Caregiver Skills Training Programme (WHO CST) in alternative delivery modes under new normal and post COVID-19 period. Method: CST was delivered via eLearning (EL), videoconferencing (VC), and in-person hybrid (IP) modes to 34 parent-child dyads, being randomly assigned to modes of asynchronous non-interfering EL (n = 9), synchronous with online coaching VC (n = 7), synchronous with in-person coaching IP (n = 9) and Wait-list Control WLC (n = 9). Data from two standardized scales of General Health Questionnaire (GHQ-12) and Strengths and Difficulties Questionnaire (SDQ), and Post-session and Home Visit Feedback Form by Caregivers that included both structured and open-ended questions were collected before and after intervention. Both quantitative and qualitative approaches were used in studying the collected data. Results: High levels of acceptability and feasibility of the training programme were supported by ratings on comprehensiveness and relevance, agreement with their personal values, duration, and usefulness. IP and VC groups yielded more positive changes than EL and WLC groups with 3, 16, 13, and -3% in General Health Questionnaire (GHQ-12), -13, -15, -6 and 0% in Difficulties-total, and 36.5, 35.5, 5.8 and 2.4% in Prosocial Scale at Strengths and Difficulties Questionnaire (SDQ) for EL, VC, IP, and WLC groups respectively from baseline to 12 weeks after intervention. Results from two standardized scales echoed with qualitative observations that the programme helped improve caregivers' well-being, child's communication, and behaviors across intervention groups. Conclusions: Current findings revealed that CST delivered in three alternative modes were acceptable and feasible, and yielded positive impacts toward both caregivers and children. In-person coaching, and skill-practicing sessions were effective in mitigating child's challenging behaviors while personal interaction, either face-to-face or virtual, is a significant factor in uplifting caregivers' well-being, whereas the self-learning model was appreciated by the busy caregivers. In clinical practice, needs and goals of families and the constraints of remote interventions at the settings should be balanced.

Translation and validation of the Reaction to Impairment and Disability Inventory for Chinese population in Hong Kong.

PURPOSE: This study translated the reaction to impairment and disability inventory (RIDI) to Chinese and validated it for use in Hong Kong. METHODS: We conducted an instrument validation of the Chinese RIDI, with a sample of 244 persons with CID. The research questionnaire collected demographic information, illness-related variables, the Chinese version of RIDI (C-RIDI), and measures of resilience and well-being. We examined the factor structure, internal consistency, convergent validity, and criterion-related validity of the C-RIDI. RESULTS: The C-RIDI has good content validity and no major changes to the translated items were needed for the use in Hong Kong. For factor structure, we replicated the results of Livneh et al. The C-RIDI has two second-order factors of adaptive and nonadaptive scales, which interact with the two denial subscales. Internal consistency of the subscales is satisfactory except for the three-item denial subscales. Correlations of the C-RIDI subscales with illness-related variables, resilience, and mental well-being are consistent with our hypotheses and provide support for the convergent and criterion-related validity of the scale. CONCLUSIONS: The C-RIDI has satisfactory psychometric properties. The study results support its internal consistency, convergent validity, criterion-related validity, and factorial validity.IMPLICATIONS FOR REHABILITATIONEmotional adjustment to chronic illness and disability is a key determinant of illness self-management, mental well-being, and quality of life.The study translated the reaction to impairment and disability inventory into Chinese and conducted a psychometric evaluation of the translated instrument.The Chinese RIDI had a similar second-order factor structure as in the validation studies of the English version, and result of this confirmatory factor analysis support the theory underlying the design of the RIDI.The Chinese RIDI had satisfactory convergent and criterion-related validity and internal consistency, and is ready for application in rehabilitation practice and research in the Chinese context.

Performance of a new symptom checker in patient triage: Canadian cohort study.

BACKGROUND: Computerized algorithms known as symptom checkers aim to help patients decide what to do should they have a new medical concern. However, despite widespread implementation, most studies on symptom checkers have involved simulated patients. Only limited evidence currently exists about symptom checker safety or accuracy when used by real patients. We developed a new prototype symptom checker and assessed its safety and accuracy in a prospective cohort of patients presenting to primary care and emergency departments with new medical concerns. METHOD: A prospective cohort study was done to assess the prototype's performance. The cohort consisted of adult patients (≥16 years old) who presented to hospital emergency departments and family physician clinics. Primary outcomes were safety and accuracy of triage recommendations to seek hospital care, seek primary care, or manage symptoms at home. RESULTS: Data from 281 hospital patients and 300 clinic patients were collected and analyzed. Sensitivity to emergencies was 100% (10/10 encounters). Sensitivity to urgencies was 90% (73/81) and 97% (34/35) for hospital and primary care patients, respectively. The prototype was significantly more accurate than patients at triage (73% versus 58%, p<0.01). Compliance with triage recommendations in this cohort using this iteration of the symptom checker would have reduced hospital visits by 55% but cause potential harm in 2-3% from delay in care. INTERPRETATION: The prototype symptom checker was superior to patients in deciding the most appropriate treatment setting for medical issues. This symptom checker could reduce a significant number of unnecessary hospital visits, with accuracy and safety outcomes comparable to existing data on telephone triage.

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; DlCO, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).

The detrimental impacts of negative age stereotypes on the episodic memory of older adults: does social participation moderate the effects?

BACKGROUND: Older adults' cognitive abilities can be impaired through priming of negative age stereotypes. However, it is unclear whether the effects of negative priming can be extended to episodic memory, which is believed to be the most age-sensitive type among the long-term memory systems, in Asian populations. Social participation has recently emerged as a potential protective factor for maintaining the cognitive function of older adults. The purpose of this study was to examine the effects of negative age stereotype priming on episodic memory and the moderating role of social participation in the priming effect. METHODS: A total of 105 community-dwelling older adults residing in Hong Kong were randomly allocated to two experimental conditions. Participants were primed either with negative age stereotype words (n = 53) or neutral words (n = 52) using an implicit priming task. Episodic memory performance was assessed using the Hong Kong List Learning Task (HKLLT), which includes total learning, two delayed recalls and a recognition task. Analysis of covariance (ANCOVA) was used to assess group differences in the priming task and memory performance, while a series of moderation analyses were performed to examine the moderating effects of social participation. RESULTS: The group that received negative age stereotype priming performed significantly worse than the group that received neutral words in their episodic memory test. Additional analyses showed that socially active individuals might be less prone to the effects of negative age stereotypes for the recognition task only. CONCLUSIONS: Older adults who are more socially active might be more immune to the effects of negative age stereotype priming on episodic memory. These results provide initial support for the hypothesis that social participation might act as an effective strategy to ward against negative age stereotype priming. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04202120 (first posted December 17, 2019), (Retrospectively registered).

Sense of Community Mediating Between Age-Friendly Characteristics and Life Satisfaction of Community-Dwelling Older Adults.

The growth of age-friendly community initiatives underscores a paradigmatic shift from the individual to the community, addressing dynamic transactions between people and the environment they are living in. The purpose of the present study is to address the gap in existing research by examining the psycho-social effects of the sense of community in mediating between WHO domains of age-friendliness and the life satisfaction of older adults. Data were obtained from 898 participants in Hong Kong. Path analysis was conducted. Two AFC domains, Social Participation as well as Community Support and Health Services, were found to be associated with life satisfaction. Sense of community was found to mediate between these two domains and life satisfaction. The implications of these findings are discussed with reference to developing opportunities in social participation of older adults and enhancing community/health support services in the context of developing sustainability in the community.

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. METHODS: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. FINDINGS: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. INTERPRETATION: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. FUNDING: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus.

Cryobiopsy versus open lung biopsy in the diagnosis of interstitial lung disease (COLDICE): protocol of a multicentre study.

Introduction: Transbronchial lung cryobiopsy (TBLC) is a novel, minimally invasive technique for obtaining lung tissue for histopathological assessment in interstitial lung disease (ILD). Despite its increasing popularity, the diagnostic accuracy of TBLC is not yet known. The COLDICE Study (Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease allianCE) aims to evaluate the agreement between TBLC and surgical lung biopsy sampled concurrently from the same patients, for both histopathological and multidisciplinary discussion (MDD) diagnoses. Methods and analysis: This comparative, multicentre, prospective trial is enrolling patients with ILD requiring surgical lung biopsy to aid with their diagnosis. Participants are consented for both video-assisted thoracoscopic surgical (VATS) biopsy and TBLC within the same anaesthetic episode. Specimens will be blindly assessed by three expert pathologists both individually and by consensus. Each tissue sample will then be considered in conjunction with clinical and radiological data, within a centralised MDD. Each patient will be presented twice in random order, once with TBLC data and once with VATS data. Meeting participants will be blinded to the method of tissue sampling. The accuracy of TBLC will be assessed by agreement with VATS at (1) histopathological analysis and (2) MDD diagnosis. Data will be collected on interobserver agreement between pathologists, interobserver agreement between MDD participants, and detailed clinical and procedural characteristics. Ethics and dissemination: The study is being conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice and Australian legislation for the ethical conduct of research. Trial registration number: ACTRN12615000718549.

Telephone-based behavioral activation intervention for dementia family caregivers: Outcomes and mediation effect of a randomized controlled trial.

OBJECTIVES: The study examined the effects of a telephone-administered psycho-education with behavioral activation intervention (TBA) for family caregivers of person's with Alzheimer's dementia to reduce levels of depressive symptoms and burden and to enhance relationship satisfaction with the care-recipient METHODS: A double-blinded randomized trial compared TBA with telephone-based psycho-education with general monitoring (TGM). Ninety-six dementia caregivers were randomized. Both conditions received four weekly psycho-education sessions led by a social worker. TBA participants then received eight bi-weekly behavioral activation practice sessions delivered by paraprofessionals. TGM participants received eight bi-weekly monitoring sessions by paraprofessionals. RESULTS: As compared to TGM, TBA participants reported significantly larger reductions in depressive symptoms and burden and larger improvement in relationship satisfaction. Self-efficacy for controlling upsetting thoughts was found to have a partial meditation effect between TBA and the reduction of depressive symptoms. Qualitative feedback suggested that TBA participants expressed unique gains in awareness and developing new ways of reappraising the caregiving situation. CONCLUSION: TBA was an effective intervention to reduce depressive symptoms and burden as well as to enhance relationship satisfaction in dementia caregivers. PRACTICE IMPLICATIONS: The use of telephone and trained paraprofessionals can enhance the accessibility and sustainability of behavioral activation intervention for dementia family caregivers.

The Longer-Term Psychosocial Development of Adolescents: Child Development Accounts and the Role of Mentoring.

Objective: To examine the long-term development of adolescents who participated in the Child Development Fund (CDF), which was a community intervention that consisted of Child Development Accounts (CDAs) and mentorship components. Design: This was an evaluative study of the CDF community intervention and was conducted between January and June 2016 in Hong Kong. Participants: A total of 902 adolescents from low socioeconomic backgrounds participated in this study (552 in the CDF and 350 in the comparison group). All CDF participants completed the 3-year CDF program between 2011 and 2015. Main outcome measures: We assessed different developmental aspects of the adolescents, including health in terms of health-related quality of life; behavioral problems; attitude in terms of hope; cognitive capacity in terms of schooling; and social aspects in terms of social support. Results: Compared to the non-participants, the CDF participants appeared to have fewer behavioral problems, higher levels of perceived social support, higher levels of hope, better understanding of academic subjects, higher levels of motivation to study, fewer school withdrawal behaviors, and better quality of life related to social functioning. The male gender moderated the program's effect on hope. Results also show that higher levels of mentorship quality moderated the program's effect on social support, hope, self-perceived understanding of academic subjects, and motivation to study. Conclusion: Adolescents who participated in the CDF program appeared to perform better than the non-participants in regard to behavioral, academic, attitudinal, and social aspects. Good quality of mentorship had a positive influence on the program's effects. The CDF appears to be a promising program offering long-term and multi-dimensional benefits to participants.

Incidence of clinically relevant medication errors in the era of electronically prepopulated medication reconciliation forms: a retrospective chart review.

BACKGROUND: To reduce medication discrepancies (unintended differences between a patient's outpatient and inpatient medication regimens), Canadian institutions have implemented medication reconciliation forms that are prepopulated with outpatient medication dispensing data. These may prompt prescribers to reorder discontinued medications or continue newly contraindicated medications. Our objective was to evaluate the incidence of medication discrepancies and errors of commission after the implementation of such forms. METHODS: This retrospective chart review included patients previously enrolled in an observational study in which a research pharmacist prospectively collected best-possible medication histories in the emergency department. Research assistants uninvolved with the parent study compared medication orders written in the first 48 hours after admission with the research pharmacist's best-possible medication history to identify medication discrepancies and errors of commission, defined as inappropriate medication continuations and reordering of previously stopped medications. An independent panel adjudicated the clinical significance of the errors. RESULTS: Of 151 patients, 71 (47.0% [95% confidence interval (CI) 39.2-54.9]) were exposed to 112 medication errors on admission. Of the 112 errors, 24 (21.4% [95% CI 14.9-29.9]) were clinically significant. Errors of commission accounted for 24.1% (27/112 [95% CI 17.3-32.8]) of all errors; 10 (37.0% [95% CI 18.8-55.2]) of the errors of commission were clinically significant. INTERPRETATION: Medication errors were common after the implementation of electronically prepopulated medication reconciliation forms. Prospective research is required to examine the impact of prepopulated medication reconciliation forms and ensure they do not facilitate errors of commission.

Age-Friendliness and Life Satisfaction of Young-Old and Old-Old in Hong Kong.

Age-friendliness, promoted by the World Health Organization (WHO), aims to enable and support individuals in different aspects of life for fostering life satisfaction and personal well-being as they age. We identified specific aspect(s) of age-friendliness associated with life satisfaction and examined similarities and differences in age-friendliness and life satisfaction in young-old and old-old adults. Six hundred and eighty-two ageing adults were asked to complete a survey questionnaire consisting of the Age-friendly City Scale, Satisfaction with Life Scale, and sociodemographic variables. Multiple linear regression analysis was used to examine the effects of various domains of age-friendliness on life satisfaction among the young-old adults (aged 65 to 74, n = 351) and the old-old adults (aged 75 to 97, n = 331). Common domains associated with life satisfaction in both young-old and old-old groups were transportation and social participation. Community and health services were associated with life satisfaction for the young-old group only. On the other hand, civic participation and employment was significantly associated with the old-old group only. Social participation is important for the young-old and the old-old. Ageing older adults can be a resource to the society. Implications for promoting and implementing age-friendliness were discussed in the context of successful and productive ageing and the need for a more refined taxonomy of social activities.

The development of mentoring-relationship quality, future-planning style, and career goal setting among adolescents from a disadvantaged background.

Our behaviors are regulated by our perception of the future based on past experiences and knowledge. Children from a disadvantaged background might encounter obstacles more frequently when they plan their future. It is possible that a good relationship with an adult volunteer who provides assistance and guidance in the disadvantaged youth's development may facilitate their future-planning style and career goal setting. The present study investigated the role of a good mentoring relationship in promoting a disadvantaged youth's future-planning style and goal-setting ability. It focused on children from a disadvantaged background who participated in the Child Development Fund (CDF) in Hong Kong. In the study, 187 CDF participants (93 with high mentoring-relationship quality [MRQ] and 94 with low MRQ) and 208 comparison group participants were able to complete all four times of the survey. Repeated-measures analyses of covariance showed that Group main effects were observed for both future-planning style, F(2, 374) = 5.92, p < .01, and career goal-setting self-efficacy, F(2, 376) = 6.07, p < .01. Main Time effect was also found for the latter, F(3, 1128) = 7.99, p < .01. A significant Group × Time interaction effect was observed for future-planning style only, F(5.78, 1081.21) = 2.17, p < .05. Our results suggest that participants with high MRQ outperformed the comparison group in both future-planning style and career goal-setting self-efficacy. Multiple regression analyses revealed that mean MRQ score accounted for 3.9% (p < .01) of the variance in future-planning style and 4.1% (p < .01) of the variance in career goal-setting self-efficacy, supporting the role of a good mentoring relationship. Mentors have introduced new resources to the disadvantaged youths with high MRQ and have promoted the development of various skills through modeling.

Blood flow in intracranial aneurysms treated with Pipeline embolization devices: computational simulation and verification with Doppler ultrasonography on phantom models.

PURPOSE: The aim of this study was to validate a computational fluid dynamics (CFD) simulation of flow-diverter treatment through Doppler ultrasonography measurements in patient-specific models of intracranial bifurcation and side-wall aneurysms. METHODS: Computational and physical models of patient-specific bifurcation and sidewall aneurysms were constructed from computed tomography angiography with use of stereolithography, a three-dimensional printing technology. Flow dynamics parameters before and after flow-diverter treatment were measured with pulse-wave and color Doppler ultrasonography, and then compared with CFD simulations. RESULTS: CFD simulations showed drastic flow reduction after flow-diverter treatment in both aneurysms. The mean volume flow rate decreased by 90% and 85% for the bifurcation aneurysm and the side-wall aneurysm, respectively. Velocity contour plots from computer simulations before and after flow diversion closely resembled the patterns obtained by color Doppler ultrasonography. CONCLUSION: The CFD estimation of flow reduction in aneurysms treated with a flow-diverting stent was verified by Doppler ultrasonography in patient-specific phantom models of bifurcation and side-wall aneurysms. The combination of CFD and ultrasonography may constitute a feasible and reliable technique in studying the treatment of intracranial aneurysms with flow-diverting stents.

Vector projectile imaging: time-resolved dynamic visualization of complex flow patterns.

Achieving non-invasive, accurate and time-resolved imaging of vascular flow with spatiotemporal fluctuations is well acknowledged to be an ongoing challenge. In this article, we present a new ultrasound-based framework called vector projectile imaging (VPI) that can dynamically render complex flow patterns over an imaging view at millisecond time resolution. VPI is founded on three principles: (i) high-frame-rate broad-view data acquisition (based on steered plane wave firings); (ii) flow vector estimation derived from multi-angle Doppler analysis (coupled with data regularization and least-squares fitting); (iii) dynamic visualization of color-encoded vector projectiles (with flow speckles displayed as adjunct). Calibration results indicated that by using three transmit angles and three receive angles (-10°, 0°, +10° for both), VPI can consistently compute flow vectors in a multi-vessel phantom with three tubes positioned at different depths (1.5, 4, 6 cm), oriented at different angles (-10°, 0°, +10°) and of different sizes (dilated diameter: 2.2, 4.4 and 6.3 mm; steady flow rate: 2.5 mL/s). The practical merit of VPI was further illustrated through an anthropomorphic flow phantom investigation that considered both healthy and stenosed carotid bifurcation geometries. For the healthy bifurcation with 1.2-Hz carotid flow pulses, VPI was able to render multi-directional and spatiotemporally varying flow patterns (using a nominal frame rate of 416 fps or 2.4-ms time resolution). In the case of stenosed bifurcations (50% eccentric narrowing), VPI enabled dynamic visualization of flow jet and recirculation zones. These findings suggest that VPI holds promise as a new tool for complex flow analysis.

Cerebral ischemic injury is enhanced in a model of oculodentodigital dysplasia.

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant disease that results in visible developmental anomalies of the limbs, face, eyes and teeth. Recently analysis of human connexin43 (Cx43) DNA sequences has revealed a number of different missense, duplication and frame shift mutations resulting in this phenotype. A mouse model of this disorder has been created with a missense point mutation of the glycine amino acid at position 60 to serine (G60S). Heterozygote +/G60S mice exhibit a similar ODDD phenotype as observed in humans. In addition to the malformations listed above, ODDD patients often have neurological findings. In the brain, Cx43 is highly expressed in astrocytes and has been shown to play a role in neuroprotection. We were interested in determining the effect of the +/G60S mutation following stroke. Four days after middle cerebral artery occlusion the volume of infarct was larger in mice with the +/G60S mutation. In astrocyte-neuron co-cultures, exposure to glutamate also resulted in greater cellular death in the +/G60S mutants. Protein levels of Cx43 in the mutant mouse were found to be reduced when compared to the normal tissue. Cx43 protein was observed as a continual line of small punctate aggregates in the plasma membrane with increased intracellular localization, which is distinct from the larger plaques seen in the normal mouse astrocytes. Functionally, primary +/G60S astrocytes exhibited reduced gap junctional coupling and increased hemichannel activity, which may underlie the mechanism of increased damage during stroke. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.

Design of anthropomorphic flow phantoms based on rapid prototyping of compliant vessel geometries.

Anatomically realistic flow phantoms are essential experimental tools for vascular ultrasound. Here we describe how these flow phantoms can be efficiently developed via a rapid prototyping (RP) framework that involves direct fabrication of compliant vessel geometries. In this framework, anthropomorphic vessel models were drafted in computer-aided design software, and they were fabricated using stereolithography (one type of RP). To produce elastic vessels, a compliant photopolymer was used for stereolithography. We fabricated a series of compliant, diseased carotid bifurcation models with eccentric stenosis (50%) and plaque ulceration (types I and III), and they were used to form thin-walled flow phantoms by coupling the vessels to an agar-based tissue-mimicking material. These phantoms were found to yield Doppler spectrograms with significant spectral broadening and color flow images with mosaic patterns, as typical of disturbed flow under stenosed and ulcerated disease conditions. Also, their wall distension behavior was found to be similar to that observed in vivo, and this corresponded with the vessel wall's average elastic modulus (391 kPa), which was within the nominal range for human arteries. The vessel material's acoustic properties were found to be sub-optimal: the estimated average acoustic speed was 1801 m/s, and the attenuation coefficient was 1.58 dB/(mm·MHz(n)) with a power-law coefficient of 0.97. Such an acoustic mismatch nevertheless did not notably affect our Doppler spectrograms and color flow image results. These findings suggest that phantoms produced from our design framework have the potential to serve as ultrasound-compatible test beds that can simulate complex flow dynamics similar to those observed in real vasculature.