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Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Industry Alignment Fund – Pre-positioning Programme Background Epicardial adipose tissue (EAT) is the visceral fat deposit within the pericardium that surrounds the heart and the coronary arteries. EAT volume measured from non-contrast CT (NCCT) has been demonstrated to be significantly associated with adverse cardiovascular risk,1 particularly in patients with coronary artery disease.2 However, routine measurement of EAT volume is still challenging in clinical practice, as it is a tedious manual process and prone to human error. Purpose We aimed to develop a fully automated AI toolkit (i.e., AI EAT) for the quantification of EAT from routine NCCT scans and assess its performance in reference to clinical ground truth. Methods This is a multicenter study which performs CT scans in 5000 Asian Admixture patients (APOLLO study NCT05509010). In the current stage of this study, NCCT data analysis were conducted in 551 patients with 26,037 images. AI EAT was developed via a novel deep learning framework using an ensemble region-based UNet. The region-based UNet uses 2 component UNet models to perform segmentation of pericardium at the apex region and non-apex region (middle and basal). EAT volume was obtained by automated thresholding of the voxels (-190 to -30 Hounsfield Unit) within the pericardium (Figure 1). The network was trained in 501 patients with 23,712 NCCT images and tested in 50 patients with 2,325 NCCT images. The performance of AI EAT was evaluated with respect to clinical ground truth using Dice similarity coefficient (DSC), Pearson correlation, and Bland-Altman analysis. Results The AI EAT quantification process took less than 10 seconds per subject, compared with 20-30 minutes for expert readers. Compared to clinical ground truth, our AI EAT achieved a DSC of 0.96±0.01 and 0.91±0.02 for pericardium and EAT segmentations, respectively. There was strong agreement between the AI EAT and clinical ground truth in deriving the EAT volume (r=0.99, P Conclusion End-to-end deep learning system accurately quantifies epicardial adipose tissue in standard NCCT images without manual segmentation.

Accessing cyclic carbonate monomers on a large scale is critical for the development of any new carbonate-based materials platform. The synthesis of carbonate monomers can be a challenging and tedi...

Accessing cyclic carbonate monomers on large scales is critical for development of any new carbonate-based material platform. This is particularly important in the context of using automated experimental systems for materials synthesis, which can often require large inputs of starting materials. However, the synthesis of carbonate monomers can be a challenging and tedious endeavor, requiring multiple synthetic steps and purifications. To address this, we report a drastically improved and scalable process for the synthesis of carbonate monomers via a two-step route that avoids the use of hazardous phosgene or chloroformate reagents. The cyclic carbonate monomers can be obtained in high yields and with minimal need for chromatographic purification. This process enables rapid access to a broad array of functional groups on the carbonate monomer and monomers generated from procedure can readily be polymerized via ring-opening polymerization.

Background Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. Methods The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. Results The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. Conclusion The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

Carbon and oxygen burning reactions, in particular, $^{12}$C+$^{12}$C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-$\gamma$ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for $^{12}$C+$^{12}$C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed., Comment: accepted for publication in Phys. Rev. Lett

Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature.Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared.We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation.Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the β^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Introduction of hydrophilic components, particularly amines and zwitterions, onto a degradable polymer platform, while maintaining precise control over the polymer composition, has been a challenge. Recognizing the importance of these hydrophilic residues in multiple aspects of the nanobiomedicine field, herein, a straightforward synthetic route to access well-defined amphiphilic and hydrophilic degradable block copolymers from diethanolamine-derived functional eight-membered N-substituted aliphatic cyclic carbonates is reported. By this route, tertiary amine, secondary amine, and zwitterion residues can be incorporated across the polymer backbone. Demonstration of pH-responsiveness of these hydrophilic residues and their utility in the development of drug-delivery vehicles, catered for the specific requirements of respective model drugs (doxorubicin and diclofenac sodium salt) are shown. As hydrophilic components in degradable polymers play crucial roles in the biological interactions, these materials offers opportunities to expand the scope and applicability of aliphatic cyclic carbonates. Our approach to these functional polycarbonates will expand the range of biocompatible and biodegradable synthetic materials available for nanobiomedicine, including drug and gene delivery, antimicrobials, and hydrophilic polymers as poly(ethylene glycol) (PEG) alternatives.

Summary The use of topical antiseptics in the treatment of atopic dermatitis (AD) has previously been explored. However, no triclosan-containing leave-on emollient has been evaluated previously, to our knowledge. The aims of this study were to assess the safety and efficacy of an emollient containing triclosan compared with the emollient alone (vehicle) for the treatment of AD. Eligible patients with mild to moderate AD were randomized to receive either the study cream or vehicle. All patients also received a low-potency corticosteroid cream to use during the treatment phase of the study if necessary. Patients were assessed for severity according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of corticosteroid used, patient assessment of cream, and adverse events (AEs). In total, 60 patients received either the study cream or vehicle, and an intention-to-treat analysis was performed. At day 14, there was a significant decrease in SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day 27, although there was an improved mean reduction from baseline, this was no longer significant (P > 0.05). Only four patients had mild treatment-related AEs. The mean total amount of topical steroid applied by the patients using the study was significantly lower than that used by controls (P = 0.40). Triclosan-containing leave-on emollient was safe and highly acceptable to patients. However, the overall benefit on day 27 was not significant. Nevertheless, the amount of topical steroid used by patients was significantly less with the study cream than with the vehicle, thus further studies are needed to confirm its steroid-sparing effect.

In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability. In addition, the macromolecular antimicrobial is less likely to induce resistance as it acts via a membrane-lytic mechanism. The polymer is not cytotoxic toward mammalian cells with LD50 of 99.0 ± 11.6 mg kg-1 in mice through i.v. injection. In an S. aureus blood stream infection mouse model, the polymer removes bacteria from the blood more rapidly than the antibiotic Augmentin. At the effective dose, the polymer treatment does not damage liver and kidney tissues or functions. In addition, blood electrolyte balance remains unchanged after the treatment. The low cost of starting materials, ease of synthesis, nontoxicity, broad spectrum activity with fast killing kinetics, and in vivo antimicrobial activity make these macromolecular antimicrobials ideal candidates for prevention of sepsis and treatment of infections.

Early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is crucial. In this retrospective study, 581 infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks, or who did not fit these criteria but were judged to be at increased risk, were screened for ROP. ROP developed in 159 (27.4%). The incidence of ROP appeared to be inversely proportional to birth weight and gestational age. Infants with a birth weight below 750 g had a significantly higher risk of developing stage 3 and 4 ROP. The mean age at detection was 7.6 ± 1.6 weeks. Nearly all of the ROP cases and all of the stage 3 and 4 cases were detected between the 5th and 10th week. Because screening should be focused on these visionthreatening stages, ophthalmic examinations should be concentrated in, but not limited to, the period between the 5th and the 10th postnatal week.

1. The pharmacokinetics of trimethoprim (TMP) following intra-aortic administration were investigated in rainbow trout. 2. The disposition kinetics for TMP were best described by a three-compartment open model. The disappearance of TMP from fish blood was characterized by rapid and pronounced distribution phases and a slow terminal elimination phase. 3. In contrast with pharmacokinetic data of TMP in mammals, the present study documented a long terminal elimination t1/2(36.1 h), large Vdss(5980 ml/kg) and small Clb(2.4 ml/min/kg) for TMP in rainbow trout, thus illustrating the slow biotransformation and elimination capacity, particularly the strong 'holding' capacity (storage) for the drug in trout. 4. The pharmacokinetic profiles in the present study indicated no dose dependency of TMP following three different bolus doses (5, 10 and 50 mg/kg). Hence, the first-order kinetic assumption was verified. 5. Urinary excretion of TMP was a minor elimination route in trout (14.4% dose).

To evaluate the effectiveness of CT and MRI at 0.5 T in the diagnosis and staging of retinoblastoma, we studied 11 patients in whom retinoblastoma was clinically suspected. Nine of the eleven had surgically proven retinoblastoma; in the other two a diagnosis of Coats' disease was made. MRI was not as specific as CT for diagnosing retinoblastoma, due to its lack of sensitivity in detecting calcification; it did, however, have superior contrast resolution. On MRI, Coats' disease was reliably diagnosed and easily differentiated from retinoblastoma. Moreover, the greater ability of MRI to differentiate subretinal fluid from tumour also confers high accuracy in measuring tumour size. CT is still the study of choice in the diagnosis of retinoblastoma, but when MRI is available, it should be performed for better differentiation from lesions such as Coats' disease.

Dermatofibrosarcoma protuberans (DFSP) has conventionally been treated with wide local excision. More recently Mohs micrographic surgery (MMS) has been advocated.To assess our departmental experience with DFSP in the context of a literature review relating to DFSP treated with MMS.This was a case review of 35 patients with DFSP treated between 1998 and 2009 with MMS using paraffin-embedded sections.Seventeen patients required one horizontal layer to clear their tumour, 10 patients needed two and eight patients needed three layers or more. The median preoperative clinical size was 6 cm(2) (range 0·75-54·8) and the median postoperative wound size was 46·8 cm(2) (range 4-145·2). Tumour persistence has not been observed in any of our patients after a median follow-up duration of 29·5 months (range 6-146).We present 35 DFSP patients, none of whom showed persistent tumour after treatment with 'slow' MMS using paraffin sections. We advocate MMS as the treatment of choice for DFSP, especially for tumours over the head and neck region where tissue conservation is particularly important.

Scrotal pyoderma gangrenosum is uncommon. We present a 17-year-old Chinese male patient with newly diagnosed Crohn's disease presenting with scrotal pyoderma gangrenosum. Biopsy and other investigations were done to diagnose and look for associated diseases of pyoderma gangrenosum. Treatment with high-dose prednisolone failed. Subsequent treatment with oral cyclosporine was successful.

Clinical and microscopic pigmentation may affect the treatment outcomes in basal cell carcinoma. However, there have not been any in-depth histopathological comparisons between clinically pigmented and non-pigmented basal cell carcinomas with regards to microscopic melanization. The aims of our study were to determine the proportion of pigmented basal cell carcinomas presenting to the National Skin Centre in Singapore, to characterize the histological pattern of melanization and to perform a semi-quantitative analysis of the degree of microscopic melanization of the tumours. Patients with clinical features and histologically confirmed basal cell carcinomas were recruited. Demographic data and clinical characteristics were recorded and basal cell carcinoma sections were examined for histological subtype and pattern of melanization. Twenty-five Chinese patients with 30 basal cell carcinomas were recruited. Three of the five clinically non-pigmented and all of the clinically pigmented basal cell carcinomas had microscopic evidence of melanization. Microscopic melanization in clinically non-pigmented basal cell carcinomas was present only focally or in the centre of the tumour mass. Both groups of basal cell carcinomas may be colonized by melanocytes. Two morphological types of melanocytes, a dendritic and round cell type, were identified. Future research is required to evaluate if the degree of microscopic melanization influences the treatment outcome of basal cell carcinomas.

A 53-year-old woman presented with a chronic, non-healing painless ulcer over her right clavicular area of a two-month duration. Skin biopsy, microbiological and radiological investigations confirmed the diagnosis of scrofuloderma arising from an underlying tuberculous infection of her acromioclavicular joint. She was treated successfully with anti-tuberculosis therapy with complete healing of the ulcer. Awareness of this uncommon presentation of osteoarticular tuberculosis may assist in earlier diagnosis.

The breakout reaction 15O(alpha,gamma)19Ne, which regulates the flow between the hot CNO cycle and the rp process, is critical for the explanation of the burst amplitude and periodicity of x-ray bursters. We report on the first successful measurement of the critical alpha-decay branching ratios of relevant states in 19Ne populated via 19F(3He,t)19Ne. Based on the experimental results and our previous lifetime measurements of these states, we derive the first experimental rate of 15O(alpha,gamma)19Ne. The impact of our experimental results on the burst pattern and periodicity for a range of accretion rates is analyzed.

An experimental design was employed in the investigation of the impact of two status cues, language style and source expertise, on people’s perceptions of online political discussants and their intentions and motivations to participate in local online political discussion fora. Specifically, the colloquial form of Singapore English, known as Singlish, was manipulated, together with information about the expertise of a discussant, in a 2 3 2 between-subjects factorial design, with the discussion issue manipulated as a within-subjects variable. Eighty undergraduates, 42 male and 38 female, participated in the study. Overall, the results of this study provide very limited support for the significant effects of status cues on perceptions and participation. The implications of the results of this study for theories of computer-mediated communication and linguistics in the context of the Internet are discussed. Published version

Probabilistic packet marking (PPM) has been proposed for the identification of the true sources of spoofed IP packets typically used in denial of service (DoS) attacks. However, PPM suffers from high combination overhead and large false positives under large scale DDoS attacks. In this paper, we propose to use an entropy-minimization clustering technique to solve the limitations in PPM scheme. This technique is used to divide the attack traffics into clusters based on shared bottleneck. Consequently, it reduces the combination overhead and false positive. Our technique also preserves the advantages of the PPM scheme, as it works with any type of traffic (TCP, UDP, etc). It does not generate any new network traffic and it utilizes only the information at the IP layer. We have carried out theoretical analysis and simulation studies using ns-2 software to evaluate the proposed technique. Our results demonstrated that our approach gives significant higher precision and lower combination overhead for attack paths reconstruction under large scale DDoS.

Mechanical ventilation (MV) during exacerbation of asthma or chronic obstructive pulmonary disease (COPD) is unequivocally needed when apnoea, cardiorespiratory arrest, coma, hypoxia or treatment failure is present. The need is less clear when the patient can respond, has intact airway reflexes and spontaneous respiration. In this situation, acidosis is an important factor in the decision to institute MV. This study aimed to provide a clinical means of identifying patients with acute respiratory acidosis (ARA) in a setting where blood gas analysis is unavailable. We undertook a prospective, observational study of consecutive patients who presented to two emergency departments with severe and life-threatening exacerbation of asthma or COPD. Each underwent clinical assessment, treatment and blood gas analysis. The outcome measure was ARA or mixed ARA and metabolic acidosis. A total of 127 episodes in patients aged 15-90 years (65.3% males and 34.7% females) were included in the study. Of these, 62.2% had asthma and 37.8% had COPD; 71.7% had life-threatening and 28.3% had severe attacks. Overall, the adjusted odds ratio (and 95% confidence intervals) for predictors of ARA were 7.09 (1.79-28.06) for drowsiness, 4.11 (1.31-12.88) for flushing, 3.34 (1.01-11.02) for having COPD and 2.86 (1.01-8.07) for intercostal retractions. In conclusion, with drowsiness, the likelihood of ARA is about seven times higher. The presence of flushing, COPD and intercostal retractions also increase the risk of ARA.

Acute pulmonary thromboembolism (PE) has been considered rare among Asians. We aim to describe the frequency and clinical features of this condition in a hospital in Singapore. Among patients admitted by the Emergency Department (ED), comparisons were made between those primarily diagnosed in the ED and those who were not.Retrospective review of all cases of radiologically proven acute PE over a 20-month period.Sixty-two patients were identified. The mean age was 61.5 +/- 18.0 years with a female to male ratio of 1.8:1. There were more Malays compared to other races. There were also more Caucasians, given the proximity of the hospital to the airport and the inclusion of tourists. The commonest symptoms were dyspnoea and chest pain, while the commonest signs were tachycardia and tachypnoea. Prolonged immobilisation was the commonest risk factor. Electrocardiographic S1Q3T3 pattern was seen in more patients compared to Western studies. Cardiomegaly was the commonest chest X-ray finding. Thirty-two patients were identified to have a source of embolisation. Overall mortality rate was 21%. The ED diagnosed 36% of the cases. Alternative admitting diagnoses were predominantly ischaemic heart disease and pneumonia. The group diagnosed in the ED were notably female (P = 0.044), Caucasian (P = 0.002) and had prolonged immobilisation (P = 0.025) prior to the onset of PE.Acute PE is not as rare here as previously thought. Clinical features reveal more similarities than differences compared to other studies in the literature. We advocate a high index of suspicion for earlier diagnosis in the ED.

We report two cases of acute toluene poisoning occurring during parquet flooring. Inhalation is the major route of absorption in the workplace, owing to the high volatility of the compound. Such patients should be monitored closely for respiratory distress, central nervous system (CNS) depression and cardiac arrhythmias. Both our patients manifested signs of CNS depression and one had bronchospasm aborted by salbutamol Industries using toluene must ensure that precautions like adequate ventilation are taken to protect their workers.

We studied the appearance of retinoblastoma on unenhanced and gadolinium-enhanced images and the accuracy of tumour staging with MR imaging. The MR images were obtained in 18 children with retinoblastoma and compared with histopathological findings after enucleation. The MR imaging included T1-weighted and dual-echo T2-weighted images before, and T1-weighted images after, gadopentetate dimeglumine injection. The contrast between tumour and ipsilateral vitreous strongly increased (57 %) after gadolinium on T1-weighted images (p = 0.004). Tumour was strongly hypointense as compared with ipsilateral vitreous in all patients using heavily T2-weighted (TE = 120 ms) images (p = 0.001). The estimated T2 of tumour (mean 96 + 14 ms) did not correlate with histological grading or degree of calcification. Unenhanced T1-weighted MR images rightfully excluded extrascleral growth in 16 of 16 cases, but its presence was confirmed after enucleation in only one of 2 abnormal MR scans. Invasion of the optic nerve behind the cribriform plate was confirmed in 2 of 3 abnormal gadolinium-enhanced MR scans, but also in 1 of the 15 cases in which MR images were normal. The T2-weighted images were useful in assessing retinal detachment. We conclude that heavily T2-weighted images, unenhanced T1-weighted images and gadolinium-enhanced T1-weighted MR images are complementary in characterizing and staging retinoblastoma.

The purpose of this retrospective study is to investigate the influence of 45 Gy megavoltage external beam radiotherapy on the occurrence of second primary tumours in hereditary- and non-hereditary retinoblastoma patients. Eighty-seven hereditary and 19 non-hereditary patients were irradiated for retinoblastoma. The follow-up of the hereditary patients ranged from 4-23 years (mean 12.4 years), of the non-hereditary patients from 6-23 years (mean 12 years). In the hereditary group 4 patients developed a second primary tumour (2 rhabdomyosarcoma, 1 osteosarcoma, 1 malignant histiocytoma), and 5 patients developed a pineoblastoma. Three second primary tumours were situated inside the radiation field. The latency period ranged from 1.5 to 18 years (mean 4.8 years). None of the non-hereditary patients developed a second primary tumour. The actuarially calculated probability of being free from second primary tumours was 96.9% at 10 years and 89.4% at 20 years (pineoblastoma excluded). The survival was 91.2% at 10 years and 84.2% at 20 years (pineoblastoma excluded). From this study it is suggested that external beam irradiation has a potentiating effect in patients, with the genetic predispopsition for retinoblastoma and who are more susceptible to second primary malignancies.

We report a case of an unusual giant congential tumor presenting in a newborn infant as a large exophytic mass emerging from the left orbit. After enucleation orbital recurrence developed within 14 days. No anti-tumor treatment was given and the child died at the age of 4 weeks. The histopathological and cytogenetical analysis of the tumor is presented. The tumor was diagnosed as a retinoblastoma but we could not exclude the possibility of a neuroblastoma. (C) 1994 Wiley-Liss, Inc.

The possibility of significant antitumor activity associated with hyperthermia was first documented by Busch, who reported the disappearance of a facial sarcoma following high fever in a patient with erysipelas (Busch 1866). In the last decade interest has been rekindled in the clinical application of this modality because numerous reports and comprehensive reviews have indicated that there may be a significant advantage in the use of heat alone, or combined with radiation or cytotoxic drugs, to enhance the killing of tumor cells (Hall 1988; Overgaard 1989).

In 1975–1987 at least 84 children developed blindness or impaired vision due to retinopathy of prematurity (ROP) in the Netherlands. Neonatal data were obtained on 74 (86%). Unexpectedly most children (40 i.e. 54%) had been in level I and II hospitals after birth. Screening for ROP had been either insufficient or not timed according to present recommendations in 33 out of 40 children in level I and II hospitals and 25 out of 34 in level III hospitals. As the number of children with ROP has not changed appreciably over the last 40 years, while birth rates in the Netherlands have steadily decreased, the incidence of blindness/impaired vision due to ROP has probably increased. In the current population at risk of ROP which differs considerably from the one during the first epidemic, the disease may not be completely preventable. We conclude that improvements in screening procedures and timely treatment are crucial in order to improve the present situation.