Interferometric time-stretch microscopy for ultrafast quantitative cellular and tissue imaging at 1 μm

Quantitative phase imaging (QPI) has been proven to be a powerful tool for label-free characterization of biological specimens. However, the imaging speed, largely limited by the image sensor technology, impedes its utility in applications where high-throughput screening and efficient big-data analysis are mandated. We here demonstrate interferometric time-stretch (iTS) microscopy for delivering ultrafast quantitative phase cellular and tissue imaging at an imaging line-scan rate >20 MHz-orders-of-magnitude faster than conventional QPI. Enabling an efficient time-stretch operation in the 1-mum wavelength window, we present an iTS microscope system for practical ultrafast QPI of fixed cells and tissue sections, as well as ultrafast flowing cells (at a flow speed of up to 8 ms). To the best of our knowledge, this is the first time that time-stretch imaging could reveal quantitative morphological information of cells and tissues with nanometer precision. As many parameters can be further extracted from the phase and can serve as the intrinsic biomarkers for disease diagnosis, iTS microscopy could find its niche in high-throughput and high-content cellular assays (e.g., imaging flow cytometry) as well as tissue refractometric imaging (e.g., whole-slide imaging for digital pathology).published_or_final_versio

Asymmetric-detection time-stretch optical microscopy (ATOM) for ultrafast high-contrast cellular imaging in flow

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Narrow-linewidth idler generation in fiber four-wave mixing and parametric amplification by dithering two pumps in opposition of phase

Wide-bandwidth and high-gain fiber optical parametric amplifiers (OPAs) have been demonstrated recently. Their application as all-optical wavelength converters has been hampered by pump-induced converted-signal spectrum broadening, due to the required pump phase modulation. In this paper, we theoretically investigate and experimentally demonstrate a technique to cancel the converted-signal broadening by using four-wave mixing (FWM) or parametric amplification with two pumps phase-modulated 180° out of phase. The resulting converted-signal quality is comparable to that of the output signal.link_to_subscribed_fulltex

The development and validation of a knowledge, attitude and behaviour questionnaire to assess undergraduate evidence-based practice teaching and learning

Objectives: Most evidence-based practice (EBP) educational assessment tools evaluated to date have focused on specific knowledge components or technical skills. Other important potential barriers to the adoption of EBP, such as attitudinal, perceptual and behavioural factors, have yet to be studied, especially in the undergraduate setting. Therefore, we developed and validated a knowledge, attitude and behaviour questionnaire designed to evaluate EBP teaching and learning in an undergraduate medical curriculum. Methods: We derived the questionnaire from a comprehensive literature review, informed by international and local experts and a Year 5 student focus group. We determined its factor structure and refined and validated the questionnaire according to the responses of a cohort of Year 5 and a combined group of Years 2 and 3 students using principal components factor analysis with varimax rotation. Factor reliability was computed using Cronbach's alpha coefficient. We assessed construct validity by correlating the factors with other measures of EBP activity and examined responsiveness through paired t-test of the pre/post factor mean scores. Results: A 43-item questionnaire was developed. Four factors were identified from both student groups. The overall questionnaire as well as each factor had high construct validity (Cronbach's alpha > 0.7 for each scale). No significant correlations were found between the 4 factors, confirming their orthogonality. Positive correlations, however, resulted between factor mean scores and other EBP activities. The responsiveness of the questionnaire was satisfactory. Conclusion: A reliable knowledge, attitude and behaviour measure of EBP teaching and learning appropriate for undergraduate medical education has been developed and validated.link_to_subscribed_fulltex

Health care consequences of cesarean birth during the first 18 months of life

OBJECTIVE: Elective cesarean delivery is increasingly common. The potential effects of surgical delivery in an unselected sample of infants beyond the immediate neonatal period remain poorly defined. METHODS: We carried out an 18-month follow-up of a population-based cohort of 8327 Hong Kong Chinese infants born in 1997. The main outcome measures were utilization of outpatient visits and hospitalizations, categorized by doctor-diagnosed causes as reported by parents. RESULTS: Among term singleton infants, there was no association of cesarean (compared with vaginal) birth with subsequent hospital admission (adjusted odds ratio = 0.92; 95% confidence interval = 0.79-1.08) or with above versus below the median number of outpatient episodes (1.10; 0.96-1.26) in the first 18 months of life. There were weak positive associations with afebrile gastrointestinal, respiratory, skin and a few other conditions. CONCLUSION: Cesarean birth is not associated with hospitalization or outpatient care overall during the first 18 months after adjustment for confounders. We cannot rule out isolated associations with minor morbidities. © 2007 Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex

Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians

Objective Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates. Study design and setting Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK$20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475). Results The final prepayment response rate was 82.9$42.7, prepayment with three mailings at HK$66.5 and prepayment with three mailings and telephone follow-up at HK$112.1 per responder recruited (US$1=HK$7.8). Conclusion The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings. © 2004 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Evaluation of a handheld clinical decision support tool for evidence-based learning and practice in medical undergraduates

INTRODUCTION: Handheld computers (PDAs) uploaded with clinical decision support software (CDSS) have the potential to facilitate the adoption of evidence-based medicine (EBM) at the point-of-care among undergraduate medical students. Further evaluation of the usefulness and acceptability of these tools is required. METHODS: All 169 Year 4 undergraduate medical students at the University of Hong Kong completed a post-randomised controlled trial survey. Primary outcome measures were CDSS/PDA usefulness, satisfaction, functionality and utilisation. Focus groups were also conducted to derive complementary qualitative data on the students' attitudes towards using such new technology. RESULTS: Overall, the students found the CDSS/PDA useful (mean score = 3.90 out of 6, 95% confidence interval (CI) = 3.78, 4.03). They were less satisfied with the functional features of the CDSS (mean score = 3.45, 95% CI = 3.32, 3.59) and the PDA (mean score = 3.51 95% CI = 3.40, 3.62). Utilisation was low, with the average frequency of use less than once per week. Although students reported a need for information in patient care at least once daily, they infrequently used the CDSS in a clinical setting (20.4 ± 10.4% of the time), with an average information retrieval success rate of 37.6 ± 22.1% requiring 63.7 ± 86.1 seconds. Multivariable regression shows that higher perceived CDSS/PDA usefulness was associated with more supportive faculty attitudes, greater knowledge of EBM, better computer literacy skills and increased use in a clinical setting. Greater satisfaction with the CDSS/PDA was associated with increased use in a clinical setting and higher successful search rates. Qualitative results were consistent with these quantitative findings and yielded additional information on students' underlying feelings that may explain the observations. CONCLUSIONS: While PDAs uploaded with the CDSS are able to provide students with better access to high quality information, improvements in faculty attitudes, students' knowledge of EBM and computer literacy skills, and having the CDSS specially designed for undergraduate use are essential to increasing student adoption of such point-of-care tools.link_to_subscribed_fulltex

Non-attendance and effective equity of access at four public specialist outpatient centers in Hong Kong

This study tests whether socio-economic status (SES), at either the individual or ecologic levels, exerts a direct impact on non-attendance or an indirect impact on attendance through longer waiting time for appointments and/or doctor-shopping behavior at four public specialist outpatient centers in Hong Kong. We collected information through three main sources, namely patients' referral letters, telephone interviews with both open- and closed-ended questions (e.g. doctor-shopping data) and hospital administrative databases from a total of 6495 attenders and non-attenders enrolled from July 2000 through October 2001. Individual-level SES was measured by education, occupation and monthly household income. Tertiary planning unit (TPU)-level SES data consisted of proportion unemployed, proportion with tertiary education, median income and Gini coefficient. Direct effects of SES on non-attendance were examined by logistic regression. Indirect contributions mediated through waiting time and doctor-shopping were analyzed by structural equation modeling. We found that SES, at the individual or ecologic level, did not exert a direct effect on non-attendance. Instead, TPU-level SES contributed positively to waiting time (β=0.06±0.03, p=0.048), i.e. worse-off neighborhoods (and those with greater income inequality) had a shorter waiting time. Individual-level SES was also directly associated with the likelihood of doctor-shopping (β=0.16±0.02, p<0.001), i.e. the poor were less likely to doctor-shop. Both waiting time (β=0.12±0.02, p<0.001) and doctor-shopping (β=0.37±0.02, p<0.001) were significantly related to non-attendance. Our findings suggest a highly equitable specialist ambulatory care public system in Hong Kong. Health care resources are appropriately targeted at the socially indigent, and the poor are not discriminated against and pushed to seek alternative sources of care by the system. These results should be confirmed using a prospective design. © 2005 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Physicians' perceptions towards the impact of and willingness to pay for clinical computerization in Hong Kong

Background and objectives: We evaluated factors associated with physicians' perceptions towards the effects of computers on health care and on current levels of computerization in their practice. We also performed a contingent valuation to quantify physicians' perceived benefits from computerization in a hypothetical ambulatory, solo clinic. Methods: We surveyed 949 representative physicians in Hong Kong by post. Factor analysis was performed to summarize similar items into categories. Multivariable log-linear regression models were employed to assess the relationships between different factor scores and the number of functions computerized. We elicited their willingness-to-pay (WTP) for three defined computer systems using contingent valuation techniques. WTP values were estimated using econometric modeling by both, parametric and geometric methods. Sociodemographic, attitudinal, and practice-related predictors of WTP were estimated through regression analyses. Results: Factor analysis revealed a three-factor solution which explained 53% of total variance. The overall mean score (mean=3.51±0.45) showed a generally positive attitude towards the effects of computers on health care. Respondents with a higher level of computer knowledge had significantly higher mean overall (P=0.002) and factor scores for all three factors (P<0.01). Higher factor scores on the effects of computers on patient care and clinicians (P=0.006) and on the health system (P=0.032) were associated with a higher number of functions computerized. The parametric median WTP values for computerizing administrative, clinical, and both sets of functions were HK$21,205 (US$ 2719), HK$34,231 (US$ 4389), and HK$45,720 (US$ 5862), respectively, which were lower than the estimates obtained from demand curves using the geometric method [HK$43,286 (US$ 5549), HK$59,570 (US$ 7637), and HK$84,623 (US$ 10,849), respectively]. Doctors with higher incomes were willing to pay more to computerize the clinic, with strong dose-response gradients demonstrated. Those who worked in corporate settings were also more likely to accept higher WTP values. Conclusions: Our findings confirm that better knowledge about computers is contributory to a more positive attitude towards the effects of computers on health care, which is in turn significantly associated with higher levels of actual computerization in clinical practice. WTP values represent the likelihood, in monetary terms, of translating doctors' perceived benefits from computerization into investment action. © 2004 Elsevier Ireland Ltd. All rights reserved.link_to_subscribed_fulltex

A newborn with a 790 kb chromosome 17p13.3 microduplication presenting with aortic stenosis, microcephaly and dysmorphic facial features - Is cardiac assessment necessary for all patients with 17p13.3 microduplication?

While deletion of chromosome 17p13.3 (encompassing PAFAH1B1 and YWHAE genes) is known to result in Miller-Dieker syndrome (OMIM 247200), 17p13.3 microduplication gives rise to a condition commonly associated with developmental delay and autism spectrum disorder. We report a Chinese newborn presenting with dysmorphic features, microcephaly and valvar aortic stenosis, who was confirmed to have a 790 kb microduplication in chromosome 17p13.3 by array comparative genomic hybridization (aCGH). The patient passed away at 4 months of age with presumably life-threatening event associated with his cardiac condition. From literature review, congenital heart diseases of various kinds were identified in up to 20% of patients with 17p13.3 microduplication. We propose cardiac assessment should be part of the comprehensive evaluation of these patients. © 2012 Elsevier Masson SAS.link_to_subscribed_fulltex