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e18725 Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR14) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts’ characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.

Purpose Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population. Patients and Methods A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses. Results A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%. Conclusions The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies.

Advanced urothelial cancer (aUC) is invariably lethal and standard of care, platinum-based chemotherapy has changed little over the past 25 years. However, the past 5 years have been transformational with the advent of immunotherapies and targeted therapies. In this review, the authors focus on the therapies that are showing the greatest promise and have changed, or will imminently impact, the treatment landscape of aUC. Checkpoint inhibition is showing deep and durable responses in some patients and trial activity is concentrated on identifying the most suitable position within the treatment paradigm along with the most appropriate patients and therapeutic combinations. Novel targeted therapies in aUC are gaining renewed interest with nectin-4 antibody drug conjugates and fibroblast growth factor receptor inhibitors, both receiving recent regulatory approvals. Bispecific antibodies, capable of binding to two targets at the same time, are also showing promise. This review discusses the preclinical data, the relevant past, and present clinical trials along with regulatory status to provide a concise overview of the current and impending treatment options for aUC.

Dysfunctional performance monitoring has been proposed as a potential neurocognitive biomarker of various internalising psychopathological symptoms, such as anxiety, depressive, and obsessive-compulsive symptoms. Given the overlapping neurophysiological findings and high rates of comorbidity amongst these internalising symptoms, an important research gap pertains to the specificity of performance monitoring to each of these symptoms. The aim of the present study was to examine the effects of anxiety, depressive, and obsessive-compulsive symptoms on performance monitoring in healthy adults. The sample consisted of 50 participants, with ages ranging from 18 to 33 years (M = 22.82, SD = 3.84). The Depression, Anxiety, and Stress Scales-21 and the Obsessive Compulsive Inventory-Revised were administered to assess the various internalising symptoms. An arrow flanker task was administered to elicit error responses whilst electrophysiological data were recorded from the scalp. Performance monitoring was indexed by the error-related negativity and correct response negativity. Bivariate correlations revealed that the three internalising symptoms were not associated with error-related negativity or correct response negativity amplitudes. However, a regression model revealed that greater levels of anxiety symptoms were uniquely associated with larger error-related negativity amplitude after controlling for depressive symptoms. In addition, greater levels of depressive symptoms were uniquely associated with smaller error-related negativity amplitude. Another regression model revealed that greater levels of depressive symptoms were uniquely associated with smaller correct response negativity amplitude after controlling for anxiety symptoms. These findings suggest that performance monitoring differentially associates with anxiety and depressive symptoms amongst healthy adults, providing some evidence of specificity for each respective symptoms.

Over the years, the field of bioprinting has attracted attention for its highly automated fabrication system that enables the precise patterning of living cells and biomaterials at pre-defined positions for enhanced cell-matrix and cell-cell interactions. Notably, vat polymerization (VP)-based bioprinting is an emerging bioprinting technique for various tissue engineering applications due to its high fabrication accuracy. Particularly, different photo-initiators (PIs) are utilized during the bioprinting process to facilitate the crosslinking mechanism for fabrication of high-resolution complex tissue constructs. The advancements in VP-based printing have led to a paradigm shift in fabrication of tissue constructs from cell-seeding of tissue scaffolds (non-biocompatible fabrication process) to direct bioprinting of cell-laden tissue constructs (biocompatible fabrication process). This paper, presenting a first-time comprehensive review of the VP-based bioprinting process, provides an in-depth analysis and comparison of the various biocompatible PIs and highlights the important considerations and bioprinting requirements. This review paper reports a detailed analysis of its printing process and the influence of light-based curing modality and PIs on living cells. Lastly, this review also highlights the significance of VP-based bioprinting, the regulatory challenges and presents future directions to transform the VP-based printing technology into imperative tools in the field of tissue engineering and regenerative medicine. The readers will be informed on the current limitations and achievements of the VP-based bioprinting techniques. Notably, the readers will realize the importance and value of highly-automated platforms for tissue engineering applications and be able to develop objective viewpoints towards this field. Accepted version

Microbiological analysis of food traditionally involves examination of a representative sample for the presence, numbers, and types of microorganisms and/or their products, and is necessary to assess safety, spoilage, quality, suitability, and shelf-life of food. Conventional methods for the detection, isolation, and enumeration of foodborne microorganisms mostly rely on the cultural methods involving growth of microorganisms. Identification and characterization of spoilage or pathogenic microorganisms is based on enrichment-serology involving pre- and selective enrichment, selective and differential plating, confirmation, and strain typing. Conventional methods which are usually simple, reliable, and well-established are often regarded as the “Gold standard”. However, they are labor and material intensive, imprecise, time-consuming, retrospective, and often subjective in nature. During the past 40 years, advances in the areas of immunology, molecular biology, computer science, miniaturization, and automation have resulted in the development of many microbiological methods for rapid detection, enumeration, and characterization of foodborne microorganisms, especially emerging pathogens. These methods include modified conventional methods, microscopy- based methods, immunology-based methods, nucleic acid-based methods, molecular methods, and biosensors, and microarray-based methods. More recently, genomic-based methods for characterization of pathogens have been used by the regulatory agencies for investigating foodborne illness outbreaks and recalls of food contaminated with pathogens such as Salmonella and Listeria. These improved diagnostic technologies reduce the total time needed to detect, isolate, enumerate, identify, and characterize pathogenic microorganisms. While the rapid methods are labor- and time saving and yield accurate results with high degree of sensitivity and specificity, they require specific and often proprietary material, consumables, equipment, software, and trained analysts. In this chapter, the conventional and rapid methods used today in food microbiology are discussed.

In a recent report by risk assessment experts on the identification of food safety priorities using the Delphi technique, foodborne viruses were recognized among the top rated food safety priorities and have become a greater concern to the food industry over the past few years. Food safety experts agreed that control measures for viruses throughout the food chain are required. However, much still needs to be understood with regard to the effectiveness of these controls and how to properly validate their performance, whether it is personal hygiene of food handlers or the effects of processing of at risk foods or the interpretation and action required on positive virus test result. This manuscript provides a description of foodborne viruses and their characteristics, their responses to stress and technologies developed for viral detection and control. In addition, the gaps in knowledge and understanding, and future perspectives on the application of viral detection and control strategies for the food industry, along with suggestions on how the food industry could implement effective control strategies for viruses in foods. The current state of the science on epidemiology, public health burden, risk assessment and management options for viruses in food processing environments will be highlighted in this review., Highlights • Foodborne virus outbreaks carry both a heavy public health and economic burden • Reliable detection of viruses in food matrixes remains a challenge • Current process validations are hampered by difficulty in cultivating viruses. • Classical approaches to risk assessment are possible, if the appropriate methodologies are developed. • Risk assessments are based on general principles and research is needed to support these assessments. • Research effort, needs to be undertaken to understand the ecology, behaviour and transmission of foodborne viruses from the farm and to the consumer.

Osteoporosis is the most commonly encountered metabolic bone disease, and metabolic bone-disease clinics have been established to assist in the diagnosis and treatment of uncommon causes of low bone-mineral density. Hypophosphatemia leading to metabolic bone disease may be encountered, and an understanding of phosphate homeostasis can aid in the diagnosis. Two cases of hypophosphatemia leading to low bone-mineral densities were seen at the University of Alabama at Birmingham Osteoporosis Clinic. We developed a diagnostic algorithm, and the laboratory values of each patient were tested with the algorithm. The algorithm, incorporating the use of a spot urine phosphate and spot urine creatinine level at the time of initial serum metabolic profile evaluation, accurately determined the cause of hypophosphatemia in each case.

Primary ADT (pADT) monotherapy is used significantly for patients with clinically localised disease in Asia and is acceptable even by guidelines, especially in intermediate- and high-risk disease. This occurs despite controversy in the West and data suggesting association with adverse effects, notably cardiovascular events. We therefore sought to assess the impact of pADT on all-cause mortality and prostate cancer-specific mortality (PCSM) in Asian men with high-risk and unfavourable intermediate-risk PCa. With cancer registry data, men from a single centre in Singapore with clinically localised high-risk/unfavourable intermediate-risk PCa diagnosed between 2004 and 2014 and either treated conservatively with no therapy or started on pADT within 1 year of diagnosis were followed up through January 2017. Patients with non-localised PCa (clinical stage T4, regional/distant lymph node involvement, metastases), or receipt of local therapy (radical prostatectomy/radiotherapy) were excluded. The primary outcomes of all-cause mortality and PCSM were analysed with Cox proportional hazards regression models. Three hundred and forty Asian men were analysed, and 177 (52.1%) were started on pADT, with mean age of 77 (49–98) years. There were 119 deaths in the cohort, and 68 (38.4%) occurred in patients treated with pADT (median follow-up, 4.4 years). After adjusting for comorbidities and clinical characteristics, pADT did not provide benefit to all-cause mortality, PCSM or cardiovascular mortality. For clinically localised unfavourable intermediate-risk and high-risk PCa, starting pADT within 12 months of diagnosis is not associated with improved 5-year all-cause mortality or PCSM compared to patients treated conservatively with no therapy and should be discouraged due to lack of mortality benefit.

Consumer boycotts are triggered by egregious events, but the literature has not distinguished the level of egregiousness from consumers’ preferences or disutility associated with a given level of egregiousness, nor has the literature studied how these two components of egregiousness affect boycott intensity. We provide a model of market-level boycotts that distinguishes the two egregiousness components. Consistent with the predictions of our model, the market-level intensity of consumer boycotting of BP-branded gasoline, which was triggered by the BP Deepwater Horizon oil spill, increased with the spill’s egregiousness level, approximated by the officially reported daily amount of oil leaked into the ocean and by other measures (i.e., the duration of the spill and the intensity of media coverage), and with consumers’ disutility from egregiousness, approximated by an area’s environmentalism and its proximity to the Gulf of Mexico. This paper was accepted by J. Miguel Villas-Boas, marketing.

This case focuses on marketing public policy and legislation issues in the business environment. The Commonwealth Government of Australia wants to impose mandatory warning labels for fast-food served by quick-service chainrestaurants like McDonald’s. These warnings are to appear on fast-food packaging to warn diners of the possible harms arising from consuming fast-food. This is similar to the warnings that are used in Australia on tobacco product packages. This highlights a turning point where legislators appear to be heeding calls of vocal pressure groups to curb and legislate the industry’s activities. The loudest calls have appeared in well-publicized legal cases and film documentaries like Super-Size Me. McDonald’s has been well-aware of these challenges. The company continues to respond and fight legal challenges on these points. As a result, the company has improved its supply chain, employees’ work-conditions, their treatment of animals, their stores, food and customer service to offer leaner, healthier and more upmarket products. The few vocal critics who have secured media coverage seem to rely on sensationalizing the issue — e.g., eating McDonald’s for 30 days makes you fat. They seem to ignore the results from other experiments where people who ate suitable portions of McDonald’s food for the same 30 day period actually lost weight. Other challenges that have been found to be lies in courts of law include allegations of animal cruelty, unsafe food and food that makes people obese. Yet the public continue to believe these allegations. Can the industry do more, or do something different, to change people’s minds?

Objective: Despite high-grade intravesical prostatic protrusion (IPP) being closely related to bladder outlet obstruction (BOO), up to 21% of patients with low IPP remain obstructed. This study evaluates the characteristics and urodynamic findings of men with small prostates and low IPP. Methods: One hundred and fourteen men aged >50 years old with lower urinary tract symptoms (LUTS) were assessed with symptoms, uroflowmetry, serum prostate-specific antigen (PSA), transabdominal ultrasound measurement of prostate volume (PV), IPP and post-void residual urine (PVRU). All patients underwent pressure flow studies. Patients with PV

Chlorine and PAA spray reduced MNV and

Tumor-induced osteomalacia is a rare cause of acquired hypophosphatemia due to the paraneoplastic overproduction of fibroblast growth factor-23. Unlike many causes of osteomalacia, tumor-induced osteomalacia is curable by resection of the offending tumor. If a patient has a tumor that is unidentifiable, unresectable, or makes the decision to forgo surgery, medical treatment is recommended. Burosumab (KRN23) is a fully human monoclonal antibody against fibroblast growth factor-23 that was recently approved for the treatment of X-linked hypophosphatemia. We present a case of tumor-induced osteomalacia due to two somatostatin receptor avid meningiomas. The patient initially was wheelchair bound due to symptoms of diffuse bone and muscle pain with recurrent traumatic and nontraumatic fractures. Serum phosphate was 1.8mg/dL (reference range: 2.4-5.0mg/dL) with no other laboratory or historical cause. Workup revealed two widely separated intracranial meningiomas with typical magnetic resonance imaging characteristics. The duplicity of tumors precluded safe surgery and the potential delay in, or lack of, efficacy using radiosurgery prompted the treatment team to opt for medical treatment. Burosumab was initiated resulting in improvement in pain symptoms and mobility. Serum phosphate normalized. Trials are ongoing to assess the utility of burosumab in the treatment of tumor-induced osteomalacia.

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Cognitive fatigue is a psychological state characterised by feelings of tiredness and impaired cognitive functioning arising from high cognitive demands. This paper examines the recent research progress on the assessment of cognitive fatigue and provides informed recommendations for future research. Traditionally, cognitive fatigue is introspectively assessed through self-report or objectively inferred from a decline in behavioural performance. However, more recently, researchers have attempted to explore the biological underpinnings of cognitive fatigue to understand and measure this phenomenon. In particular, there is evidence indicating that the imbalance between sympathetic and parasympathetic nervous activity appears to be a physiological correlate of cognitive fatigue. This imbalance has been indexed through various heart rate variability indices that have also been proposed as putative biomarkers of cognitive fatigue. Moreover, in contrast to traditional inferential methods, there is also a growing research interest in using data-driven approaches to assessing cognitive fatigue. The ubiquity of wearables with the capability to collect large amounts of physiological data appears to be a major facilitator in the growth of data-driven research in this area. Preliminary findings indicate that such large datasets can be used to accurately predict cognitive fatigue through various machine learning approaches. Overall, the potential of combining domain-specific knowledge gained from biomarker research with machine learning approaches should be further explored to build more robust predictive models of cognitive fatigue. Ministry of National Development (MND) National Research Foundation (NRF) Published version This research/project is supported by the National Research Foundation, Singapore, and Ministry of National Development, Singapore under its Cities of Tomorrow R&D Programme (CoT Award: COT-V4-2020-1). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the view of National Research Foundation, Singapore and Ministry of National Development, Singapore.

Advanced wafer-level packaging (WLP) techniques, mainly driven by high performance applications in memory and mobile market, have been adopted for large-scale manufacturing in recent years. Temporary wafer bonding and debonding technology has been widely studied and developed over the last decade for use in various WLP technologies, such as package-on-package (PoP), fan-out integration, and 2.5-D and 3-D integration using through-silicon-via (TSV). Temporary bonding technology enables handling of thinned substrates ( In this study, a series of formulations based on polar thermoplastics were developed for temporary wafer bonding applications. These materials target high temperature survivability and improved adhesion to prevent the premature delamination during downstream wafer processing. All of these materials provide high thermal stability up to 250°C or higher, and are able to be bonded to carrier wafers treated with release layers, which can be selectively debonded by either mechanical or laser release after backside processing. The material left on device wafer after debonding can be easily cleaned using common industrial solvents. Wafers bonded with these materials demonstrate lower overall stack total thickness variation (TTV < 5 μm) after grinding and have successfully passed a 200°C PECVD process without any delamination during grinding and PECVD processes.

With increasing demand for mobile devices to be lighter and thinner and consume less power while operating at high speed and high bandwidth, many equipment suppliers and assembly participants have invested great efforts to achieve fine-line fan-out wafer-level packaging (FOWLP). However, the inherent warp of reconstituted wafers, which can contribute to poor die placement accuracy and/or delamination at the interface of the build-up layer and carrier, remains a major challenge. In this study, the interactions among laser release layer, glass carrier, and build-up layer were evaluated for optimization of redistribution layer (RDL)–first FOWLP as a foundation to move toward fine-line FOWLP. In this study, a series of experiments incorporating glass carrier, laser release layer, and build-up layers were carried out to determine the optimal setup for RDL-first FOWLP. First, glass carriers (300 mm × 300 mm × 0.7 mm) with coefficients of thermal expansion of 3 and 8 ppm/°C were treated with 150-nm laser release layers. After deposition of 0.1 μm of sacrificial material on the glass carrier, 8-μm build-up layers were coated and patterned by lithography to electroplate Cu interconnections with a density of approximately 10% of the surface area. Subsequent to die attachment, molding compound was applied on top to form a 200-μm protective overcoat. The reconstituted wafer was then separated from the glass carrier through a laser ablation process using a 308-nm laser to complete the design of experiments (DOE). An experiment to study the correlation of glass carrier, laser release layer, build-up layers, and molding compound in RDL-first FOWLP processes is discussed to address full process integration on 300-mm glass substrates. The combination of glass carrier, laser release layer, build-up layer, and molding compound will pave the way for realizing cost-effective RDL-first FOWLP on panel-size substrates.

Aim To develop and internally validate two nomograms for predicting the probability of overall and clinically-significant prostate cancer on initial biopsy in a Singaporean population. Methods Data were collected from men undergoing initial prostate biopsy at a single center. The indications for biopsy were serum prostate-specific antigen (PSA) ≥4.0 ng/mL or suspicious digital rectal examination (DRE) findings. Men with PSA >30 ng/mL were excluded. Age, PSA, prostate volume (PV) and DRE were predictors included in our logistic regression model and used to construct two nomograms for overall prostate cancer and clinically-significant (Gleason sum ≥7) cancer detection. Predictive accuracies of our nomograms were assessed using area under curve (AUC) of their receiver–operator characteristic curves. Internal validation was performed using the bootstrap method. Our nomograms were compared to a model based on PSA alone using AUC and decision curve analysis (DCA). Results Out of 672 men analyzed, our positive biopsy rate was 26.2% (n = 176), of which 63.6% (n = 112) had clinically significant disease. Age, PSA, PV and DRE status were all independent risk factors for both overall prostate cancer detection as well as clinically-significant cancer detection (all P < 0.05). Our nomogram outperformed serum PSA for both overall and clinically-significant cancer detection (0.736 vs 0.642, P < 0.001 and 0.793 vs 0.696, P < 0.001, respectively). Using DCA, our nomograms had superior net benefit and net reduction in biopsy rate compared to PSA alone. Conclusions Our nomograms have been shown to be superior to PSA alone, on both AUC and DCA. However, it warrants external validation.

Human allergic reactions to peanut proteins and the associated risk of life-threatening anaphylaxis requires vigilant management of peanuts in food processing. Processed forms of peanuts with attenuated antigenicity and less severe immunogenic responses may lower the risk. Molecular subfractions of raw (UP), blanched (BP) and roasted (RP) peanuts were prepared including water-insoluble (P1), water-soluble high mass (30kDa, P2) and water-soluble low mass (30kDa, P3) fractions. Products were screened by measuring binding to IgG (polyclonal antibody against peanut allergen) and IgE (sera from peanut-allergic donors, RAST3). The results showed that IgE titres were highest for total extracts of RP, particularly for P3 fractions of UP and RP, and were affected by further heating. Antigenicity was also modulated by heating in the presence of either peanut oil or non-peanut food ingredients (lactose, coconut oil). Results support several alternative methods for regulating peanut antigenicity using food processing approaches but require further substantiation in larger numbers of allergic and control donor sera.

Vascular networks have an important role to play in transporting nutrients, oxygen, metabolic wastes and maintenance of homeostasis. Bioprinting is a promising technology as it is able to fabricate complex, specific multi-cellular constructs with precision. In addition, current technology allows precise depositions of individual cells, growth factors and biochemical signals to enhance vascular growth. Fabrication of vascularized constructs has remained as a main challenge till date but it is deemed as an important stepping stone to bring organ engineering to a higher level. However, with the ever advancing bioprinting technology and knowledge of biomaterials, it is expected that bioprinting can be a viable solution for this problem. This article presents an overview of the biofabrication of vascular and vascularized constructs, the different techniques used in vascular engineering such as extrusion-based, droplet-based and laser-based bioprinting techniques, and the future prospects of bioprinting of artificial blood vessels.

Low-moisture foods (LMFs) have been defined as those food products with a water activity (aw) less than 0.85 and are generally considered less susceptible to microbial spoilage and the growth of foodborne pathogens. However, in recent years, outbreaks linked to LMFs have increased, with Salmonella spp., Bacillus cereus, Cronobacter sakazakii, Clostridium spp., Escherichia coli O157:H7, non-O157 E. coli, and Staphylococcus aureus being the principal pathogens involved. Because of the new concerns raised as a result of recent outbreaks, new approaches need to be developed to control foodborne pathogens in LMFs. This review summarizes the recent research on novel inactivation methods suitable for use on LMFs. Among the methods discussed are the nonthermal inactivation methods as well as other novel methods such as radio-frequency and microwave heating. Additional research is needed to evaluate older technologies and develop new technologies, either alone or in combination, to understand the mechanisms of inactivation.

As requirements increase for mobile devices to be lighter and thinner and to operate at high speed and high bandwidth, innovations in wafer-level packaging have evolved to 3-D structures, such as package-on-package (PoP), fan-out integration, and through-silicon-via (TSV) interposer architectures. However, wafer-level packaging is still considered to be costly and slow in throughput due to wafer size limitations. In this study, temporary bonding and debonding processes using mechanical or laser release technologies were applied in the fabrication process of an integrated embedded glass interposer as a foundation for 3-D integrated circuit (IC) packaging on panel-level packaging. Glass interposers having dimensions of 10 mm × 10 mm and a thickness of 120 μm were fabricated. The interposers had through-glass vias (TGVs) 25 μm in diameter and 3000 I/O pads of copper under-bump metallization (UBM) and were designed as a nearly full-array type. The interposers were supported by a temporary bonding material on silicon or glass wafers and embedded by built-up dielectric material on which fan-out redistribution circuit layers were deposited. For forming the pattern of the redistribution layer, a UV laser was used to form 75-μm-diameter blind vias, and conductive interconnections were made by a semi-additive process (SAP) using photolithography and electrolytic copper. The process of building up layers from the glass interposer to form an embedded fan-out interposer can eliminate a joining process required by traditional 2.5-D IC integration. Finally, the embedded fan-out carrier is separated from the glass or silicon wafer through a laser debonding process. An experiment to study the correlation of bonding material and release material with built-up lamination in backside processes will be discussed in this paper to address full process integration on panel-size substrates. The combination of temporary bonding technology with mechanical or laser release technologies will pave the way for realizing cost-effective 3-D IC packaging on panel-level substrates.

Objective Despite being the third commonest cancer in Singaporean men, there is a dearth of basic data on the detection rate of prostate cancer and post-procedure complication rates locally using systematic 12-core biopsy. Our objective is to evaluate prostate cancer detection rates using 12-core prostate biopsy based on serum prostate specific antigen (PSA) levels and digital rectal examination (DRE) findings in Singaporean men presenting to a single tertiary centre. The secondary objective is to evaluate the complication rates of transrectal prostate biopsies. Methods We retrospectively examined 804 men who underwent first transrectal-ultrasound (TRUS) guided 12-core prostate biopsies from January 2012 to April 2014. Prostate biopsies were performed on men presenting to a tertiary institution when their PSA levels were ≥4.0 ng/mL and/or when they had suspicious DRE findings. Results Overall prostate cancer detection rate was 35.1%. Regardless of DRE findings, patients were divided into four subgroups based on their serum PSA levels: 0–3.99 ng/mL, 4.00–9.99 ng/mL, 10.00–19.99 ng/mL and ≥20.00 ng/mL and their detection rates were 9.5%, 20.9%, 38.4% and 72.3%, respectively. The detection rate of cancer based on suspicious DRE findings alone was 59.2% compared to 36.5% based on serum PSA cut-off of 4.0 ng/mL alone. The post-biopsy admission rate for sepsis was 1.5%. Conclusion In conclusion, using contemporary 12-core biopsy methods, the local prostate cancer detection rate based on serum PSA and DRE findings has increased over the past decade presumably due to multiple genetic and environmental factors. Post-biopsy sepsis remains an important complication worldwide.

Infection with human norovirus (HuNoV) is considered a common cause of foodborne illness worldwide. Foodborne HuNoV outbreaks may result from consumption of food contaminated by an infected food handler in the foodservice environment, in which bare-hand contact, lack of hand washing, and inadequate cleaning and disinfection are common contributing factors. The goal of this study was to examine cross-contamination of a HuNoV surrogate, murine norovirus (MNV-1), during common procedures used in preparing fresh produce in a food service setting, including turning water spigots, handling and chopping Romaine lettuce, and washing hands. MNV-1 transfer % was log-transformed to achieve a normal distribution of the data and enable appropriate statistical analyses to be performed. MNV-1 transfer coefficients varied by surface type, and a greater affinity for human hands and chopped lettuce was observed. For example, greater transfer was observed from a contaminated stainless steel spigot to a clean hand (24% or 1.4-log transfer %) compared to transfer from hand to spigot (0.6% or -0.2-log transfer %). During the chopping of Romaine lettuce, MNV-1 was transferred from either a contaminated cutting board (25% or 1.4-log transfer %) or knife (~100% or 2.0-log transfer %) to lettuce at a significantly greater rate (p>0.05) than from contaminated lettuce to the board (2.1% or 0.3-log transfer %) and knife (1.2% or 0.06-log transfer %). No significant difference (p>0.05) in MNV-1 transfer coefficients was observed between bare hands and Romaine lettuce during handling. For handwashing trials, only one hand was inoculated with MNV-1 prior to washing. The handwashing methods included rubbing hands under tap water for at least 5s (average 2.8-log reduction) or washing hands for at least 20s with liquid soap (average 2.9-log reduction) or foaming soap (average 3.0-log reduction), but no statistical difference between these reductions was achieved (p>0.05). Despite the reductions of MNV-1 observed, residual virions were detected on both hands after washing in every replicate trial. This observation reveals that virions are transferred from one hand to the other during washing with and without soap. Each transfer scenario was repeated at least 9 times, and the data gathered indicate that MNV-1 transfers readily between common surfaces during food preparation. These data are important for the development of quantitative risk analyses, and will assist in the development of appropriate intervention strategies for enteric viruses in food preparation.

This paper presents a preliminary investigation ofusing motion detection algorithms in a commercial drone aspart of a surveillance system. Frame differencing is used in thealgorithm as it is an effective and an efficient way for detectingand tracking moving objects. We explore ways in which thedrone can make decisions autonomously, based on informationextracted from moving objects in views and for applicationssuch as agriculture, hunting, public safety and land surveying.

Human papilloma virus (HPV) infects keratinocytes of the skin and mucous membranes, and is associated with the induction of cutaneous warts and malignancy. Warts can induce significant morbidity and disability but most therapies, including cryotherapy, laser, and radiofrequency devices showlowefficacy and induce discomfort through tissue destruction. Microwaves are readily capable of passing through highly keratinised skin to deliver energy and induce heating of the tissue in a highly controllable, uniform manner. To determine the effects of microwave on cutaneous HPV infection. We undertook a pilot study of microwave therapy to the skin in 32 consecutive individuals with 52 recalcitrant long-lived viral cutaneous warts. Additionally, we undertook a molecular characterisation of the effects of microwaves on the skin. Tissue inflammation was minimal, but 75.9% of lesions cleared which compares favourably with previous studies showing a clearance rate of 23-33% for cryotherapy or salicylic acid. We show that microwaves specifically induce dendritic cell cross-presentation of HPV antigen to CD8+ T cells and suggest that IL-6 may be important for DC IRF1 and IRF4 modulation to enhance this process. Keratinocyte-skin dendritic cell cross-talk is integral to host defence against HPV infections, and this pilot study supports the concept of microwave induction of anti-HPV immunity which offers a promising approach for treatment of HPV-induced viral warts and potentially HPV-related cancers.

Fan-out wafer-level-packaging (FO-WLP) technology is developed with the advantages of smaller package size, higher Input/Output (I/O) counts, lower cost, and better performance. In this study, the FO-WLP technology is applied to TSV-less inter-connection technology of 2.5D IC packaging and a novel RDL-first wafer level packaging is demonstrated. Firstly, a pre-coated laser release layer at the interface of RDL and carrier wafer is used for the separation of the reconfigured wafer and carrier wafer with laser de-bonding technology. Since release layer material is the key factor for de-bonding, these materials are evaluated to determine the quality. Test chips are flip-chip bonded onto a carrier wafer with 2 layers of RDL and passivation, following by wafer molding process. Wafers reveal a warp surface due to chemical material shrinkage and CTE mismatch during post mold curing. Warpage of molded wafer is needed to be optimized for equipment handling and the warpage characterization is collected to analyze by different processes. To examine the quality of the structure, electrical measurement is carried out and their respective results are presented.

Studies comparing the dosimetric effects of high- and low-energy photons to treat prostate cancer using 3-dimensional conformal and intensity modulated radiation therapy have yielded mixed results. With the advent of newer radiation delivery systems like volumetric modulated arc therapy (VMAT), the impact of changing photon energy is readdressed.Sixty-five patients treated for prostate cancer at our institution from 2011 to 2012 underwent CT simulation. A target volume encompassing the prostate and entire seminal vesicles was treated to 50.4 Gy, followed by a boost to the prostate and proximal seminal vesicles to a total dose of 81 Gy. The VMAT plans were generated for 6-MV and 10-MV photons under identical optimization conditions using the Eclipse system version 8.6 (Varian Medical Systems, Palo Alto, CA). The analytical anisotropic algorithm was used for all dose calculations. Plans were normalized such that 98% of the planning target volume (PTV) received 100% of the prescribed dose. Dose-volumetric data from the treatment planning system was recorded for both 6-MV and 10-MV plans, which were compared for both the entire cohort and subsets of patients stratified according to the anterior-posterior separation.Plans using 10-MV photons had statistically significantly lower relative integral dose (4.1%), gradient measure (4.1%), skin Dmax (16.9%), monitor units (13.0%), and bladder V(30) (3.1%) than plans using 6-MV photons (P.05). There was no difference in rectal dose, high-dose-region bladder dose, PTV coverage, or conformity index. The benefit of 10-MV photons was more pronounced for thicker patients (anterior-posterior separation21 cm) for most parameters, with statistically significant differences in bladder V(30), bladder V(65), integral dose, conformity index, and monitor units.The main dosimetric benefits of 10-MV as compared with 6-MV photons are seen in thicker patients, though for the entire cohort 10-MV plans resulted in a lower integral dose, gradient measure, skin Dmax, monitor units, and bladder V(30), possibly at the expense of higher rectum V(81).

Purpose The Leibovich model was updated to prognosticate oncological outcomes in postnephrectomy nonmetastatic renal cell carcinoma (RCC) for each major histological subtype including clear cell (ccRCC), papillary (papRCC), and chromophobe RCC. We evaluated its performance in an independent population of predominantly Asian patients from Singapore. Materials and Methods Nine hundred and forty two binephric patients with nonmetastatic unilateral RCC treated with radical/partial nephrectomy from 1990 to 2015 from Singapore were retrospectively reviewed. Based on the Leibovich model, ccRCC patients were scored from 0 to 25 and papRCC patients divided into 3 risk groups. Primary outcomes of progression-free survival (PFS) and cancer-specific survival (CSS) were assessed with the Kaplan–Meier method. Receiver operating characteristic curves and calibration plots were obtained to determine discrimination and calibration respectively. Results Eight hundred and twenty nine patients (88%) had ccRCC where 16.2% experienced disease progression while 11.9% died of RCC over a median follow-up of 76 (42–117) months. There was good discrimination (c-index 0.81 for PFS, 0.83 for CSS) and calibration (PFS calibration-in-the-large 0.002 and calibration slope 0.99, CSS calibration-in-the-large 0.005 and calibration slope 0.96). One hundred and thirteen patients (12%) had papRCC, where 18.6% progressed while 14.2% died from RCC over a median follow-up of 69.5 (36.0–112.0) months. Discrimination was slightly weaker (c-index 0.72 for PFS, 0.74 for CSS), and the model was only calibrated for CSS (calibration-in-the-large 0.002, calibration slope 0.98), not for PFS (calibration-in-the-large 0.09, calibration slope 1.93). Conclusions The updated Leibovich score is applicable for prognostication of progression and death in both ccRCC and papRCC, even when applied to an independent population of Asian patients. Further validation is required to ensure accuracy in prognosticating PFS for papRCC.

Evaluated was the effectiveness of programed materials developed to present elementary college physics experiments in mechanics to non-science college majors. The group working with the materials were compared with a group receiving instruction in a conventional lecture-demonstration situation. No significant differences were detected between the groups on a final examination, a laboratory performance test, and a written laboratory test. Inferences drawn included (1) tactile training can be merged effectively with programed learning, (2) manipulative skills can be taught effectively with programed materials, (3) laboratory performance tests increase the variability of the grades and are effective research instruments in evaluating instructional outcomes, and (4) students participate equally as well in class and laboratory activities when using programed materials for laboratory instruction as when instructed in the laboratory by a conventional method. Subjective evaluations indicated favorable student reactions to the method, less confusion in the laboratory, better individual work, and little evidence of boredom and monotony. Moreover, it was felt that manipulative responses of the students gave the instructor feedback for laboratory learning effectiveness. (GR)

Smoking remains the most preventable cause of early mortality and ill health in Aboriginal people. The Aboriginal Health & Medical Research Council of New South Wales has developed the Aboriginal Tobacco Resistance and Control (ATRAC) Yarning Tool with a range of key stakeholders, to contribute to reducing the prevalence of smoking in Aboriginal communities. The Yarning Tool was adapted from the ATRAC Framework and aims to promote the meaningful discussion, planning and strengthening of tobacco resistance and control activities using a continuous quality improvement (CQI) approach. CQI provides an opportunity to closer align current health service practice with evidence. The Yarning Tool was piloted using focus group testing across four Aboriginal Community Controlled Health Services (ACCHSs) and three Local Health Districts. Purposive sampling was used to ensure that services engaged were from a diverse range of settings, with representation from metropolitan, regional and rural areas, and services with varying degrees of tobacco control capacity. Overall, feedback on the Yarning Tool and its potential use was positive. Pilot participants consistently reported that the Yarning Tool brought staff from a range of positions together to focus on tackling tobacco for the service and community. The pilot participants agreed that the Yarning Tool could be practical for the planning and reviewing stages of a CQI activity, and recommended that the tool should be completed every 6 months. The Yarning Tool is a simple tool to guide the ATRAC Framework principles into practice, and provides a platform to support Aboriginal community-led efforts, and coordination and integration of tobacco control efforts. The tool shows promise as a mechanism to encourage ACCHSs and other relevant services to use a CQI approach to reduce tobacco use in Aboriginal communities.

We present Above Water - a digital/physical hybrid game to inform people about the available strategies to cope with two types of Anxiety Disorders - Generalized Anxiety Disorder and Panic Disorder. The game teaches players about existing treatments. This hybrid game is designed to inspire players to share their experiences and develop their own personal narrative. The document also outlines an assessment strategy to study the game and determine its effectiveness as a game for health. The game is designed to educate non-institutionalized individuals with clinical anxiety and panic disorder. Potential players may be diagnosed, seeking intervention information, or a supportive friend.