Introduction to the Issue on Physics and Applications of Laser Dynamics (IS-PALD 2017).

In this paper, we introduce the Optics Express feature issue of the 7th International Symposium on Physics and Applications of Laser Dynamics (IS-PALD). This issue consists of expanded papers related to oral and poster presentations. Selected papers represent the best of IS-PALD 2017.

The BMP2 variant L51P restores the osteogenic differentiation of human mesenchymal stromal cells in the presence of intervertebral disc cells.

Spinal fusion is hampered by the presence of remaining intervertebral disc (IVD) tissue and leads to spinal non-union. While the exact mechanism remains unknown, we hypothesise that factors preventing disc ossification, such as antagonists of the bone morphogenetic proteins (BMP), could be responsible for this process. The objective of this study was to investigate spinal non-union using an in vitro human model with a focus on the BMP signalling components and to identify factors contributing to the incomplete and delayed ossification. Human bone marrow-derived mesenchymal stromal cells (MSC) were cocultured with IVD cells in the presence of L51P, a BMP2 variant with osteoinductive potential. The ossification of MSC was evaluated by quantitative reverse transcription polymerase chain reaction (qPCR), alkaline phosphatase (ALP) activity and alizarin red staining. Endogenous expression of major BMP antagonists, namely Gremlin (GREM1), Noggin (NOG) and Chordin (CHRD) was detected in IVD-derived cells, with abundance in nucleus pulposus cells. Osteogenesis of MSC was hindered by IVD cells as shown by reduced alizarin red staining, ALP activity and qPCR. L51P, added to the cocultures, restored mineralisation, blocking the activity of the BMP antagonists secreted by IVD cells. It is possible that the BMP antagonists secreted by IVD cells are responsible for spinal non-unions. The inhibition of BMP antagonists with L51P may result in an efficient and more physiological osteoinduction rather than delivery of exogenous osteogenic factors. Therefore, L51P might represent an attractive therapeutic candidate for bone healing.

Impact of pharmacist-involved collaborative care on the clinical, humanistic and cost outcomes of high-risk patients with type 2 diabetes (IMPACT): a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: With the increasing prevalence of diabetes, the physician-centred model is challenged to deliver holistic care in Asia. Diabetes may be managed effectively within a multidisciplinary collaborative care model; however, evidence on its effectiveness in Asian patients is lacking. Therefore, the primary objective was to evaluate the clinical outcomes of multidisciplinary collaborative care vs physician-centred care in diabetes. The secondary objectives were to evaluate humanistic and economic outcomes among the two types of care. METHODS: This 6-month prospective, open-label, parallel-arm, randomized, controlled study was conducted at four outpatient healthcare institutions. High-risk patients aged ≥21 years with uncontrolled type 2 diabetes, polypharmacy and comorbidities were included. Patients with type 1 diabetes or those who were unable to communicate independently were excluded. The control arm received usual care with referrals to nurses and dietitians as needed. The intervention arm (multidisciplinary collaborative care) was followed up with pharmacists regularly, in addition to receiving the usual care. The primary outcomes included HbA1c, systolic blood pressure, low-density lipoprotein and triglycerides. The secondary outcomes included scores from the Problem Areas in Diabetes (PAID) and the Diabetes Treatment Satisfaction Questionnaires (DTSQ), and diabetes-related health service utilization rates and costs. RESULTS AND DISCUSSION: Of 411 eligible patients, 214 and 197 patients were randomized into the intervention and control arms, respectively. At 6 months, 141 patients in the intervention arm (65.9%) and 189 patients in the control arm (95.9%) completed the study. Mean HbA1c reduced from 8.6%±1.5% at baseline to 8.1%±1.3% at 6 months in the intervention arm (P=.04), with up to mean HbA1c improvement of 0.8% in patients with greater levels of uncontrolled glycemia. Whereas the mean HbA1c in the control arm remained unchanged (8.5%±1.4%) throughout the 6-month period. Improvements in PAID and DTSQ scores, reduction in physician workload and an average cost savings of US$91.01 per patient were observed in the intervention arm over 6 months. WHAT IS NEW AND CONCLUSIONS: The positive clinical, humanistic and economic outcomes highlighted the value of multidisciplinary collaborative care for Asian diabetic patients, thereby supporting the effectiveness of this approach in managing chronic diseases.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement.

Rare cause of jaundice in a post liver transplant patient.

A hepatitis B virus carrier suffering from acute flare of chronic hepatitis B infection underwent deceased-donor liver transplantation. He was put on the immunosuppressive agent tacrolimus. On routine follow-up, he was found to have abnormal liver function. Computed tomography scan of the abdomen did not show any dilatation of the biliary system. Liver biopsy showed scattered microabscesses, and a microgranuloma was detected. Endoscopic retrograde cholangiography was performed and a biliary anastomotic stricture (BAS) was noted. In addition, the Chinese liver fluke, Clonorchis sinensis, was discovered. Balloon dilatation and stenting were performed. The patient was given a course of praziquantel. His liver function improved and normalized. We present the case of a liver transplant recipient with cholangitis caused by C. sinensis infestation and infection and biliary obstruction resulting from BAS.

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux.

Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.

Clinicopathological study of renal biopsies after liver transplantation.

OBJECTIVE: To perform a clinicopathological study of patients having renal biopsies after liver transplantation. DESIGN: Case series. SETTING; Queen Mary Hospital, Hong Kong. PATIENTS: All post-liver transplantation patients who had a renal biopsy in the period from January 2000 to December 2010. RESULTS: Eleven renal biopsies were retrieved for review from 10 patients with liver transplantation. The male-to-female ratio was 9:1 (age range, 47-63 years). The median liver transplant-to-renal biopsy interval was 1590 (range, 102-3699) days. The predominant histological changes were interstitial fibrosis and tubular atrophy. Diabetic nephropathy (n=6) and immunoglobulin A nephropathy (n=4) were the commonest glomerulopathies. Only one patient had chronic calcineurin inhibitor nephrotoxicity. With a mean follow-up of 53 months, three patients died 2 to 53 months post-renal biopsy. All surviving patients had chronic renal impairment. Five patients developed end-stage renal failure and four had significant persistent proteinuria. CONCLUSION: Renal pathology was variable after liver transplantation; most biopsies showed complex renal lesions, whilst calcineurin inhibitor nephrotoxicity was rare. The recognition of kidney histology attributable to metabolic derangements after liver transplantation is potentially important in the interpretation of renal biopsy specimens and patient management. The renal outlook of this group of patients is guarded.

MDF-Net: A Multi-Scale Dynamic Fusion Network for Breast Tumor Segmentation of Ultrasound Images.

Breast tumor segmentation of ultrasound images provides valuable information of tumors for early detection and diagnosis. Accurate segmentation is challenging due to low image contrast between areas of interest; speckle noises, and large inter-subject variations in tumor shape and size. This paper proposes a novel Multi-scale Dynamic Fusion Network (MDF-Net) for breast ultrasound tumor segmentation. It employs a two-stage end-to-end architecture with a trunk sub-network for multiscale feature selection and a structurally optimized refinement sub-network for mitigating impairments such as noise and inter-subject variation via better feature exploration and fusion. The trunk network is extended from UNet++ with a simplified skip pathway structure to connect the features between adjacent scales. Moreover, deep supervision at all scales, instead of at the finest scale in UNet++, is proposed to extract more discriminative features and mitigate errors from speckle noise via a hybrid loss function. Unlike previous works, the first stage is linked to a loss function of the second stage so that both the preliminary segmentations and refinement subnetworks can be refined together at training. The refinement sub-network utilizes a structurally optimized MDF mechanism to integrate preliminary segmentation information (capturing general tumor shape and size) at coarse scales and explores inter-subject variation information at finer scales. Experimental results from two public datasets show that the proposed method achieves better Dice and other scores over state-of-the-art methods. Qualitative analysis also indicates that our proposed network is more robust to tumor size/shapes, speckle noise and heavy posterior shadows along tumor boundaries. An optional post-processing step is also proposed to facilitate users in mitigating segmentation artifacts. The efficiency of the proposed network is also illustrated on the "Electron Microscopy neural structures segmentation dataset". It outperforms a state-of-the-art algorithm based on UNet-2022 with simpler settings. This indicates the advantages of our MDF-Nets in other challenging image segmentation tasks with small to medium data sizes.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

BACKGROUND: There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS: A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS: A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION: Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.

The role of cryopreservation in the biomechanical properties of the intervertebral disc.

Implantation of intervertebral disc (IVD) allograft or tissue engineered disc constructs in the spine has emerged as an alternative to artificial disc replacement for the treatment of severe degenerative disc disease (DDD). Establishment of a bank of cryopreserved IVD allografts enables size matching and facilitates logistics for effective clinical management. However, the biomechanical properties of cryopreserved IVDs have not been previously reported. This study aimed to assess if cryopreservation with different concentrations of cryopreservant agents (CPA) would affect the dynamic viscoelastic properties of the IVD. Whole porcine lumbar IVDs (n = 40) were harvested and processed using various concentrations of CPA, 0 % CPA, 10 % CPA and 20 % CPA. The discs were cryopreserved using a stepwise freezing protocol and stored in liquid nitrogen. After four weeks of storage, the cryopreserved IVDs were quickly thawed at 37 °C for dynamic viscoelastic testing. The apparent modulus, elastic modulus (G'), viscous modulus (G") and loss modulus (G"/G') were calculated and compared to a fresh control group. Cryopreserved IVD without cryopreservants was significantly stiffer than the control. In the dynamic viscoelastic testing, cryopreservation with the use of CPA was able to preserve both G' and G" of an IVD. No significant differences were found between fresh IVD and IVD cryopreserved with 10 % CPA or 20 % CPA. This study demonstrated that CPAs at an optimal concentration could preserve the mechanical properties of the IVD allograft and can provide further credence for the application of long-term storage of IVD allografts for disc transplantation or tissue engineered construct applications.

Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience.

The issue of small-for-size graft (SFSG) containing the middle hepatic vein in right liver living donor liver transplantation from 1996 to 2008 (n = 320) was studied. Characteristics of donors, grafts and recipients were comparable between Era I (first 50 cases) and Era II (next 270 cases) except that the median model for end-stage liver disease (MELD) score was higher in Era I (29 vs. 24; p = 0.024). The median graft to standard liver volume ratio (G/SLV) in Era I was 49.0% (range, 32.8-86.2%), versus 49.3% (range, 28.4-89.4%) in Era II (p = 0.498). Hospital mortality rate, the study endpoint, dropped from 16.0% (8/50) in Era I to 2.2% (6/270) in Era II (p = 0.000). Univariate analysis showed that MELD score (p = 0.002), pretransplant hepatorenal syndrome (p = 0.000) and Era I (p = 0.000) were significant in hospital mortality. Logistic regression analysis showed that only Era I (relative risk 9.758; 95% confidence interval, 2.885-33.002; p = 0.000) was significant. In Era I, G/SLV<40% had a relative risk of 7.8 (95% confidence interval, 1.225-49.677; p = 0.030). The hospital mortality rates for G/SLV<40% were 50% (3/6) and 1.9% (1/52) in Era I and II respectively. In conclusion, through accumulation of experience, SFSG became less important as a factor in hospital mortality.

Challenges for Liver Transplantation During Recovery From the COVID-19 Pandemic: Insights and Recommendations.

The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many LT services worldwide reduced or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of LTs are likely to drop in the immediate post-COVID era. Prolonged and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients, and members of transplant teams. LT programs may have to revise existing strategies in selecting donors and recipients for transplants. Redesigning service provision, restructuring outpatient care, carefully screening and selecting donors and recipients, and performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services is to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling. This paper discusses the different elements affecting and the widespread impact of the COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the health care needs during this pandemic and beyond.

Melatonin content of the human pineal gland.

Gas chromatography with electron capture detection was used to quantitate melatonin in single human pineal glands. The sensitivity of this melatonin assay is in the low picogram range. A 24-hour rhythm of pineal melatonin content was observed.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>or=4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

Time-frequency analysis of click-evoked otoacoustic emissions by means of a minimum variance spectral estimation-based method.

This paper proposes a new minimum variance spectral estimation (MVSE)-based time-frequency analysis (TFA) technique for click-evoked otoacoustic emissions (CEOAEs). The MVSE is a popular spectrum analysis method which can yield a high frequency resolution compared to other nonparametric spectral analysis procedures. The conventional MVSE is extended to a TFA method by windowing the observation data to obtain a time-frequency representation for the signal under study. Inspired by the adaptive window selection process in wavelet transform and based on the time-frequency characteristics of CEOAEs, the window size of the windowed MVSE (WMVSE) is given a small value at high frequencies and a large value at low frequencies. The adaptive window size selection yields the proposed frequency-dependent WMVSE (FDWMVSE). The FDWMVSE method integrates the advantages of the adaptive window selection in wavelet transform with the fine frequency resolution of MVSE. Experimental results show that the FDWMVSE can achieve satisfactory time-frequency resolution and reveal meaningful time-frequency features when applied to synthesized and real CEOAEs.