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Hematologists evaluate alterations in blood cell enumeration and morphology to confirm the peripheral blood smear findings through manual microscopic examination. However, routine peripheral blood smear analysis is both time-consuming and labor-intensive. Here, we propose a smartphone-based autofluorescence microscopy (Smart-AM) system for imaging label-free blood smears at sub-cellular resolution and performing hematological analysis. Smart-AM enables rapid, high-quality, and label-free visualization of morphological features of different blood cells (leukocytes, erythrocytes, and thrombocytes) and abnormal variations in blood cells. Moreover, assisted with deep learning algorithms, this technique can automatically detect and classify different leukocytes with high accuracy, and transform the autofluorescence images into virtual Giemsa-stained images maintaining significant cellular features. The proposed technique is portable, cost-effective, and user-friendly, making it significant for broad point-of-care applications.

Lung cancer is one of the leading causes of cancer death worldwide. The diagnosis of lung cancer based on the analysis of formalin-fixed and paraffin-embedded (FFPE) tissues is laborious and time-consuming, failing to guide surgeons intraoperatively. Here we proposed a rapid histological imaging method, termed microscopy with ultraviolet single-plane illumination (MUSI), to enable rapidex-orin-vivoimaging of fresh and unprocessed tissues in a label-free and non-destructive manner. The MUSI system allows surgical specimens with large irregular surfaces to be screened at a speed of 0.5 mm2/s with a subcellular resolution, which is sufficient to provide immediate feedback to surgeons and pathologists for intraoperative decision-making. We demonstrate that MUSI can differentiate between different subtypes of human lung adenocarcinomas, revealing diagnostically important features that are comparable to the gold standard FFPE histology. As an assistive imaging platform, MUSI could facilitate the development of precise image-guided surgery and revolutionize the current practice in surgical pathology.

This study was performed to explore factors associated with adverse perinatal outcomes for second twins and to identify predictive factors for successful vaginal delivery of the second twin after vaginal delivery of the first twin.This 10-year retrospective study included 231 cases of twin pregnancies in which vaginal delivery of the second twin was attempted after vaginal delivery of the first twin. The relationships of obstetric characteristics with the composite adverse perinatal outcome of the second twin were analysed. Predictive factors for successful vaginal delivery of the second twin were also explored.Gestational age32 weeks was the only independent risk factor for the composite adverse perinatal outcome and neonatal intensive care unit admission for the second twin. A longer inter-twin delivery interval was associated with greater risk of caesarean delivery of the second twin, but it did not increase the risk of an adverse perinatal outcome. Non-vertex presentation of the second twin at delivery was independently associated with caesarean delivery (9.0% vs 2.0%, P=0.03). For second twins in breech presentation, caesarean delivery was associated with the presence of less experienced birth attendants.Among second twins born to mothers who had attempted vaginal delivery, adverse perinatal outcomes were mainly related to prematurity. The presence of more experienced birth attendants may contribute to successful vaginal delivery of the second twin, particularly for twins in non-vertex presentation.

Objective To investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) viral load and infection‐to‐delivery interval with maternal and cord serum concentrations of anti‐SARS‐CoV‐2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS‐CoV‐2 infection. Methods This was a prospective case series of consecutive pregnant women with laboratory‐confirmed SARS‐CoV‐2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT‐PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT‐PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS‐CoV‐2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection‐to‐delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation. Results Twenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID‐19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9–39.4) weeks. The median infection‐to‐delivery interval and infection duration were 41.5 (range, 2–187) days and 10.0 (range, 1–48) days, respectively. The median GA at delivery was 39.1 (range, 32.4–40.7) weeks and the median seroconversion interval was 14 (range, 1–19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti‐SARS‐CoV‐2 IgG. All neonatal NPS samples were negative for SARS‐CoV‐2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9–1.6). There was a negative correlation between infection‐to‐delivery interval and anti‐SARS‐CoV‐2 IgG concentrations in maternal (r = –0.6693, P = 0.0087) and cord (r = –0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = –0.4757, P = 0.0409). Conclusions In pregnant women who have recovered from COVID‐19, anti‐SARS‐CoV‐2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection‐to‐delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Optical-resolution photoacoustic microscopy (OR-PAM) has been widely used for imaging blood vessel and oxygen saturation of hemoglobin (sO2), providing high-resolution functional images of living animals in vivo. However, most of them require one or multiple bulky and costly pulsed lasers, hindering their applicability in preclinical and clinical settings. In this paper, we demonstrate a reflection-mode low-cost high-resolution OR-PAM system by using two cost-effective and compact laser diodes (LDs), achieving microvasculature and sO2 imaging with a high lateral resolution of ∼6 µm. The cost of the excitation sources has dramatically reduced by ∼20–40 times compared to that of the pulsed lasers used in state-of-the-art OR-PAM systems. A blood phantom study was performed to show a determination coefficient R2 of 0.96 in linear regression analysis. Experimental results of in vivo mouse ear imaging show that the proposed dual-wavelength LD-based PAM system can provide high-resolution functional images at a low cost.

Surgical margin analysis (SMA), an essential procedure to confirm the complete excision of cancerous tissue in tumor resection surgery, requires intraoperative diagnostic tools to avoid repeated surgeries due to a positive surgical margin. Recently, by taking the advantage of the high intrinsic optical absorption of DNA/RNA at 266 nm wavelength, ultraviolet photoacoustic microscopy (UV-PAM) has been developed to provide high-resolution histological images without labeling, showing great promise as an intraoperative tool for SMA. To enable the development of UV-PAM for SMA, here, a high-speed and open-top UV-PAM system is presented, which can be operated similarly to conventional optical microscopies. The UV-PAM system provides a high lateral resolution of 1.2 µm, and a high imaging speed of 55 kHz A-line rate with one-axis galvanometer mirror scanning. Moreover, to ensure UV-PAM images can be easily interpreted by pathologists without additional training, the original grayscale UV-PAM images are virtually stained by a deep-learning algorithm to mimic the standard hematoxylin- and eosin-stained images, enabling training-free histological analysis. Mouse brain slice imaging is performed to demonstrate the high performance of the open-top UV-PAM system, illustrating its great potential for SMA applications.

Non-visualisation of fetal gallbladder (NVFGB) is associated with chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis in Caucasian fetuses. We investigated the outcomes of fetuses with NVFGB in a Chinese cohort.This retrospective analysis included cases of NVFGB among Chinese pregnant women at five public fetal medicine clinics in Hong Kong from 2012 to 2019. We compared the incidences of subsequent gallbladder visualisation, chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis between cases of isolated NVFGB and cases of non-isolated NVFGB.Among 19 cases of NVFGB detected at a median gestational age of 21.3 weeks (interquartile range, 20.0-22.3 weeks), 10 (52.6%) were isolated and nine (47.4%) were non-isolated. Eleven (58.0%) cases had transient non-visualisation, four (21.0%) had gallbladder agenesis, three (15.8%) had chromosomal abnormalities (trisomy 18, trisomy 21, and 22q11.2 microduplication), one (5.2%) had biliary atresia, and none had cystic fibrosis. The incidence of serious conditions was significantly higher in the non-isolated group than in the isolated group (44.4% vs 0%; P=0.029); all three cases with chromosomal abnormalities and the only case of biliary atresia were in the non-isolated group, while all four cases with gallbladder agenesis were in the isolated group. The incidences of transient non-visualisation were similar (55.6% vs 60.0%; P=1.000).Isolated NVFGB is often transient or related to gallbladder agenesis. While investigations for chromosomal abnormalities and biliary atresia are reasonable in cases of NVFGB, testing for cystic fibrosis may be unnecessary in Chinese fetuses unless the NVFGB is associated with consistent ultrasound features, significant family history, or consanguinity.

Ultraviolet photoacoustic microscopy (UV-PAM) has been investigated to provide label-free and registration-free volumetric histological images for whole organs, offering new insights into complex biological organs. However, because of the high UV absorption of lipids and pigments in tissue, UV-PAM suffers from low image contrast and shallow image depth, hindering its capability for revealing various microstructures in organs. To improve the UV-PAM imaging contrast and imaging depth, here we propose to implement a state-of-the-art optical clearing technique, CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis), to wash out the lipids and pigments from tissues. Our results show that the UV-PAM imaging contrast and quality can be significantly improved after tissue clearing. With the cleared tissue, multilayers of cell nuclei can also be extracted from time-resolved PA signals. Tissue clearing-enhanced UV-PAM can provide fine details for organ imaging.

Histopathology based on formalin-fixed and paraffin-embedded tissues remains the gold standard for surgical margin assessment (SMA). However, routine pathological practice is lengthy and laborious, failing to provide immediate feedback to surgeons and pathologists for intraoperative decision-making. In this report, we propose a cost-effective and easy-to-use histological imaging method with speckle illumination microscopy (i.e., HiLo). HiLo can achieve rapid and non-destructive imaging of large and fluorescently-labelled resection tissues at an acquisition speed of 5 cm2/min with 1.3-μm lateral resolution and 5.8-μm axial resolution, demonstrating a great potential as an intraoperative SMA tool that can be used by surgeons and pathologists to detect residual tumors at surgical margins. It is experimentally validated that HiLo enables rapid diagnosis of different subtypes of human lung adenocarcinoma and hepatocellular carcinoma, producing images with remarkably recognizable cellular features comparable to the gold-standard histology. This work will facilitate the clinical translations of HiLo microscopy to improve the current standard-of-care.

Histopathology based on formalin-fixed and paraffin-embedded tissues has long been the gold standard for surgical margin assessment (SMA). However, routine pathological practice is lengthy and laborious, failing to guide surgeons intraoperatively. In this report, we propose a practical and low-cost histological imaging method with wide-field optical-sectioning microscopy (i.e., High-and-Low-frequency (HiLo) microscopy). HiLo can achieve rapid and non-destructive imaging of freshly-excised tissues at an extremely high acquisition speed of 5 cm2/min with a spatial resolution of 1.3 µm (lateral) and 5.8 µm (axial), showing great potential as an SMA tool that can provide immediate feedback to surgeons and pathologists for intraoperative decision-making. We demonstrate that HiLo enables rapid extraction of diagnostic features for different subtypes of human lung adenocarcinoma and hepatocellular carcinoma, producing surface images of rough specimens with large field-of-views and cellular features that are comparable to the clinical standard. Our results show promising clinical translations of HiLo microscopy to improve the current standard of care.

Objectives To review and compare pregnancy outcomes of patients undergoing history-indicated, ultrasound-indicated, or rescue cerclage. Design Case series with internal comparison. Setting A regional obstetric unit in Hong Kong. Patients Women undergoing cervical cerclage at Kwong Wah Hospital between 1 January 2001 and 31 December 2011. Interventions Cervical cerclage. Main outcome measures Pregnancy outcomes including miscarriage, gestational age at delivery, birth weight, and duration of pregnancy prolongation. Results Overall, 47 patients were included. Nine (19.1%) pregnancies resulted in miscarriage. The median gestational age at delivery was 35.7 weeks. Among the 23 patients who had history-indicated cerclage, only four (17.4%) had three or more previous second-trimester miscarriages or preterm deliveries. Among the 15 patients who had ultrasound-indicated cerclage, preoperative cervical length of ≤1.5 cm was associated with shorter prolongation of pregnancy, compared with that of >1.5 cm (median, 12.1 vs 18.4 weeks; P=0.009). Among the nine women who had rescue cerclage, those who underwent the procedure before 20 weeks of gestation delivered earlier than those underwent cerclage later (median, 22.5 vs 34.1 weeks; P=0.048). Conclusions Patients eligible for the Royal College of Obstetricians and Gynaecologists-recommended history-indicated cerclage remain few. The majority of patients may benefit from serial ultrasound monitoring of cervical length with or without ultrasound-indicated cerclage.

OBJECTIVES To evaluate the efficacy and safety of double balloon catheter for induction of labour in Chinese women with one previous caesarean section and unfavourable cervix at term. DESIGN Retrospective cohort study. SETTING A regional hospital in Hong Kong. PATIENTS Women with previous caesarean delivery requiring induction of labour at term and with an unfavourable cervix from May 2013 to April 2014. MAJOR OUTCOME MEASURES Primary outcome was to assess rate of successful vaginal delivery (spontaneous or instrument-assisted) using double balloon catheter. Secondary outcomes were double balloon catheter induction-to-delivery and removal-to-delivery interval; cervical score improvement; oxytocin augmentation; maternal or fetal complications during cervical ripening, intrapartum and postpartum period; and risk factors associated with unsuccessful induction. RESULTS All 24 Chinese women tolerated double balloon catheter well. After double balloon catheter expulsion or removal, the cervix successfully ripened in 18 (75%) cases. The improvement in Bishop score 3 (interquartile range, 2-4) was statistically significant (P

This article reports the feasibility study of miniaturizing probe-fed microstrip patch antennas by dielectric loading. The loading materials are barium tetratitanate ceramics of very high dielectric constant (er = 38, 80). It is shown that, simply through loading, the antenna sizes are greatly reduced; however, the antenna performances are deteriorated. For instance, the antenna gain becomes lower. Then enhancement of the antenna performances follows. A substrate–superstrate structure is used to recover the gain. Both the experiments and the finite-difference time-domain (FDTD) simulations demonstrate that the gain and impedance bandwidth can be retrieved such that they are comparable to those of conventional microstrip antennas loaded with low permittivity materials (er < 3). © 2006 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2006.

The use of very high permittivity ceramic materials (er = 38, 80) to miniaturize an aperture-coupled microstrip patch antenna is reported in this article. A loss of the antenna gain in such a technique is observed, and then a novel substrate-superstrate structure is developed to enhance the gain. The whole process of gain enhancement is analyzed by using the finite-difference time-domain (FDTD) method. The simulations are excellently correlated with the experiments. They validate that the loss of the antenna gain can be recovered up to that of conventional microstrip antennas loaded with low permittivity materials (er < 3). In addition, the performance comparison of the aperture-coupled microstrip antenna of very high permittivity with the probe-fed microstrip antenna of very high permittivity is presented. It is shown that the aperture-coupled antenna has wider impedance and radiation bandwidths than the probe-fed one while keeping the antenna gain at about the same level. © 2003 Wiley Periodicals, Inc. Int J RF and Microwave CAE 13: 154–160, 2003.

To determine current trends for different modes of delivery in twin pregnancies, factors affecting the mode of delivery, and associated outcomes.Retrospective cohort study.A public hospital in Hong Kong.All twin pregnancies booked at Kwong Wah Hospital during a 3-year period from 1 April 2006 to 31 March 2009.Of 197 sets of twins, 35 (18%) were delivered vaginally and 162 (82%) by caesarean section (47% were emergencies and 53% elective). In all, 32 (37%) of the elective and 21 (28%) of the emergency caesarean sections were in response to maternal requests. Vaginal delivery was more common in mothers with a history of vaginal delivery and monochorionic diamniotic twins. Women who conceived by assisted reproduction or those who had a tertiary education were more likely to deliver by caesarean section. The type of conception and the presentation of the second twin were statistically significant factors affecting maternal choice on the mode of delivery. Maternal age did not affect the choice of delivery mode. Except for the higher frequency of sepsis and cord blood acidosis in second twins delivered vaginally, there were no significant differences in neonatal morbidity between the groups that attempted vaginal delivery or requested caesarean sections. All the women who had compression sutures or hysterectomy to control massive postpartum haemorrhage were delivered by caesarean section.A high caesarean section rate observed in our cohort was associated with maternal requests for this mode of delivery. The type of conception and the presentation of the second twin were statistically significant factors affecting maternal choice on mode of delivery. Women's requests for caesarean delivery out of the concern for their babies are not supported by current evidence. In response to a woman with a twin pregnancy requesting caesarean delivery, the pros and cons of vaginal deliveries and caesarean sections should be fully explained before the woman's autonomy is respected.

To explore the preparedness of medical students towards advance directives and related end-of-life issues, and to examine background factors such as knowledge, attitudes, and experience concerning advance directives and related end-of-life issues.In 2007, 448 medical students in years 3 to 5 were surveyed at the Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. Their knowledge, attitudes, and experiences of advance directives and related end-of-life issues, and their self-perceived preparedness to discuss these matters with patients were evaluated.A total of 220 (49%) of the eligible students responded, of whom 79% supported the use of advance directives. Only 65 (30%) students were certain of what advance directives meant and 198 (90%) students felt that their knowledge of advance directives was inadequate. Also, 197 (90%) students felt unprepared about advance directives and end-of-life issues. Factors associated with positive attitude towards advance directives included religion and knowledge. No factors were found to be associated with self-perceived preparedness towards advance directives or end-of-life issues.Most of the medical students surveyed demonstrated a positive attitude towards advance directives and recognised the importance of advance directives. However, they felt that they were unprepared and lacking in knowledge and experience of advance directives and end-of-life issues. Wider range and more depth of education is needed to better equip medical students for future practice.

To study the success rate, predictors for success, and pregnancy outcomes after external cephalic version.Historical cohort study.Regional hospital, Hong Kong.All women who had singleton term breech pregnancies at term and opted for external cephalic version during 2001 and 2009. Their demographic data, clinical and ultrasound findings, procedure details, complications, and delivery outcomes were analysed.Predictive factors for successful external cephalic version.A total of 209 external cephalic versions were performed during the 9-year period. The success rate was 63% (75% for multiparous and 53% for nulliparous women). There was no significant complication. On univariate analysis, predictors of successful external cephalic version were: multiparity, unengaged presenting part, higher amniotic fluid index (≥ 10 cm), thin abdominal wall, low uterine tone, and easily palpable fetal head (subjective assessment by practitioners before external cephalic version). On multivariate analysis, only multiparity, non-engagement of the fetal buttock and thin maternal abdomen were associated with successful external cephalic version. In all, 69% of those who had successful external cephalic version succeeded in the first roll (P0.001), and 82% of the women with successful external cephalic versions had vaginal deliveries (93% in multiparous and 69% in nulliparous women). Uptake rate of external cephalic version was studied in the latter part of the study period (2006-2009). Whilst 735 women were eligible for external cephalic version, 131 women chose to have the procedure resulting in an uptake rate of 18%.External cephalic version was effective in reducing breech presentations at term and corresponding caesarean section rates, but the uptake rate was low. Further work should address the barriers to the low acceptance of external cephalic version. The results of this study could encourage women to opt for external cephalic version.

Obstetric cholestasis is associated with maternal morbidity and adverse foetal outcomes. No information on local incidence is available. We present our experience with eight consecutive cases of obstetric cholestasis diagnosed between January 2003 and December 2005 in a regional hospital in Hong Kong. Three patients presented with pruritus without rash, three with impaired liver function, and two with elevated blood pressure postpartum. Meconium-stained liquor was present in five patients and four had spontaneous preterm delivery (between 34 and 36 weeks). The higher the bile acid level, the more marked the prematurity (correlation coefficient, -0.771; P=0.025). All those presenting with itchiness delivered preterm. Two patients developed pre-eclampsia. The rates of labour induction and abdominal delivery were both 38%. Heightened awareness among clinicians is required to recognise patients with obstetric cholestasis. Affected pregnancies are associated with meconium passage and prematurity. In our locality, affected women may also have an increased risk of pre-eclampsia. In affected women, the bile acid level is useful in assessing the risk of prematurity.

To compare the efficacy of labour induction using sublingual misoprostol versus combined artificial rupture of membranes and oxytocin infusion for nulliparous women with a favourable cervix at term.Open randomised controlled trial.Regional hospital, Hong Kong.Fifty nulliparous women with a favourable cervix (Bishop score 6 or more) at term and indications for labour induction.With their informed consent, 100 eligible women were to be randomised to receive either sublingual misoprostol 50 micrograms every 4 hours for up to five doses or oxytocin infusion after artificial rupture of membranes. Interim analysis was planned at a sample size of 50.Vaginal delivery within 24 hours of induction.The study was terminated when interim analysis of the first 50 recruits showed that a significantly smaller proportion of misoprostol-treated women delivered vaginally within 24 hours of induction than in the conventional treatment group (68% vs 100%; relative risk, 0.68; 95% confidence interval, 0.51-0.91; P=0.009), although comparable numbers of women eventually delivered vaginally. The mean induction to vaginal delivery interval was 4.5 hours longer in the misoprostol group (P=0.027). After misoprostol treatment, all women went into labour. Forty percent of them delivered without oxytocin. There was no significant difference in uterine hyperstimulation rate, operative delivery rate, and neonatal outcomes. Maternal satisfaction was higher in the misoprostol group (92% vs 60%; relative risk, 1.53; 95% confidence interval, 1.09-2.16; P=0.008).Despite being well accepted by women, labour induction using this regimen of sublingual misoprostol is less effective in achieving vaginal delivery within 24 hours.

[1] With reference to a conventional air planar inverted-F antenna this paper describes the miniaturization of the planar inverted-F antenna by dielectric loading of barium tetratitanate ceramics of very high permittivity (er = 38, 80) at 1.8 GHz. It is found that a simple loading method can reduce the antenna size but at the cost of the antenna performance. For instance, the antenna gain becomes lower. Then a sophisticated loading approach based on a novel substrate-superstrate structure is developed to improve the antenna gain. The whole process of the gain enhancement is analyzed by using the finite difference time domain method. The simulations are excellently correlated with the experiments. They both show that the sophisticated loading technique can reduce the antenna size by four times and still maintains the comparable performance.

The inefficiency of detectors of low-energy photons permits a loophole in the experimental refutation of local hidden-variables theories by observations of polarization correlations. A specific local hidden-variables model of Clauser and Horne shows that a hypothetical selectivity of detectors can yield the counting rates predicted by quantum mechanics. We therefore derive a new Bell-type inequality, which takes detection inefficiency into account. The loophole can then be blocked by observing spin correlations of atom pairs in an electronic singlet state, if both spin analysis and detection are sufficiently efficient. We propose to create Na atom pairs in the electronic singlet state, by using the induced Raman effect to excite ${\mathrm{Na}}_{2}$ molecules in the electronic ground state $X^{1}{\ensuremath{\Sigma}}_{g}^{+}$ to the continuum of the electronic ground state. Two laser beams are to be used, one for excitation to a virtual intermediate state in $A^{1}{\ensuremath{\Sigma}}_{u}^{+}$, one to induce the downward transition to the final state. The ensemble needed to test the new inequality consists of those pairs which enter the respective collimating apertures of two Stern-Gerlach analyzers.