Distributed Hypothesis Testing with Privacy Constraints.

We revisit the distributed hypothesis testing (or hypothesis testing with communication constraints) problem from the viewpoint of privacy. Instead of observing the raw data directly, the transmitter observes a sanitized or randomized version of it. We impose an upper bound on the mutual information between the raw and randomized data. Under this scenario, the receiver, which is also provided with side information, is required to make a decision on whether the null or alternative hypothesis is in effect. We first provide a general lower bound on the type-II exponent for an arbitrary pair of hypotheses. Next, we show that if the distribution under the alternative hypothesis is the product of the marginals of the distribution under the null (i.e., testing against independence), then the exponent is known exactly. Moreover, we show that the strong converse property holds. Using ideas from Euclidean information theory, we also provide an approximate expression for the exponent when the communication rate is low and the privacy level is high. Finally, we illustrate our results with a binary and a Gaussian example.

A theoretical and numerical study on the mechanics of vibro-acoustic modulation.

Vibro-acoustic modulation (VAM) is a form of a non-destructive testing technique used in nonlinear acoustic methods for the detection of defects. It comprises of exciting the structure with a dual frequency sinusoidal signal and studying the interaction of this wave with the underlying defect. In this work a theoretical study on the mechanics of VAM is presented for a generic material body. The roles of different types of defect on the response of the material are analyzed. The theoretical analysis shows the origins of the nonlinear frequencies in the form of higher harmonics and sidebands commonly observed in the output response of VAM excitation. In addition, the analysis provides insights on the relationships between the magnitudes of the nonlinear responses and those of the input vibrations, and on the physical origins of the nonlinear responses. For a physical visualization of the nonlinear vibrations associated with the theory a finite element analysis of VAM is also performed. The model looks into the plausibility of using VAM for the mapping of damage in physical structures. The model is also used to investigate the effects of the defect size and defect depth on the nonlinear mechanism of VAM.

Synthesis and high-throughput processing of polymeric hydrogels for 3D cell culture.

3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.

Treatment of Acute Sore Throat in Malaysia: A Consensus of Multidisciplinary Recommendations Using Modified Delphi Methodology.

Introduction: Using antibiotics in the treatment of acute sore throats has been linked with antimicrobial resistance (AMR) and needs to be addressed. The consensus sought to improve diagnostic accuracy, decrease unwarranted antibiotic prescriptions and enhance patient outcomes. Methods: A multidisciplinary panel of nine experts reviewed published literature and discussed current practices in managing sore throat. Ten evidence-based statements on sore throat and AMR, diagnostic accuracy and antibiotic prescribing, and symptomatic therapy were developed. A modified Delphi exercise was then carried out. A consensus was reached if at least 70% of the group agreed with the statement. Results: All 10 statements for managing acute sore throat achieved consensus. The major concern of AMR caused by improper antibiotic prescribing, particularly in cases of viral sore throat, was recognized. This underscores the need for improved diagnostic tools, such as the McIsaac score, to reduce needless antibiotic prescriptions. To improve patient satisfaction, effective pain management using non-antibiotic alternatives such as paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and flurbiprofen throat lozenges was recommended. Pain and inflammation can be adequately managed with low-dose NSAIDs. The potential benefits of topical NSAIDs were acknowledged for their milder safety profile than oral formulations. Conclusion: A consensus was achieved on the use of a clinical diagnostic tool, prudent use of antibiotics, and symptomatic therapy in acute sore throat management. The McIsaac score and point-of-care testing (POCT) for the presence of group A beta-hemolytic Streptococcus (GABHS) can aid in the decision-making process for antibiotic use, reducing needless prescriptions. The mainstay of therapy is symptomatic treatment, which includes the use of NSAIDs.

Widespread impact of HLA restriction on immune control and escape pathways of HIV-1.

The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine.

ARIA Care Pathways 2019: Next-Generation Allergic Rhinitis Care and Allergen Immunotherapy in Malaysia.

An increase in the prevalence of allergic rhinitis (AR) worldwide presents a significant burden to the health care system. An initiative was started in Europe designated as Allergic Rhinitis and Its Impact on Asthma (ARIA) to develop internationally applicable guidelines by utilising an evidence-based approach to address this crucial issue. The efforts are directed at empowerment of patients for self-management, the use of digital mobile technology to complement and personalise treatment, and establishment of real-life integrated care pathways (ICPs). This guideline includes aspects of patients' and health care providers' management and covers the main areas of treatment for AR. The model provides better real-life health care than the previous traditional models. This review summarises the ARIA next-generation guideline in the context of the Malaysian health care system.

Effects of Relative Positions of Defect to Inclusion on Nanocomposite Strength.

It is generally accepted that material inhomogeneity causes stress concentrations at the interface and thus reduces the overall strength of a composite. To overcome this reduction in strength, some groups experimented on coating the nanoinclusions with a layer of rubbery material, aiming for higher energy absorption. However, representative volume element (RVE) nanocomposite models, established with randomly distributed core-shell nanoparticles and single nanoparticle cells, show that the enhancement in strength observed in some experiments remains elusive computationally. By including a pre-existing crack in the matrix of the RVE, the stress concentration at the crack tip is reduced for cases where the nanoparticle and precrack are aligned away from the loading direction. This suggests that stress concentrations around inherent defects in materials can sometimes be reduced by adding nanoparticles to improve material strength. The effect is reversed if the crack and nanoparticle are aligned towards the loading direction. Parametric studies were also carried out in terms of the relative stiffness of the nanoparticle to the matrix and crack length. Validation tests were performed on 3D RVEs with an elliptical crack as the initial defect, and the results match with the 2D findings.

Distributionally Robust and Multi-Objective Nonnegative Matrix Factorization.

Nonnegative matrix factorization (NMF) is a linear dimensionality reduction technique for analyzing nonnegative data. A key aspect of NMF is the choice of the objective function that depends on the noise model (or statistics of the noise) assumed on the data. In many applications, the noise model is unknown and difficult to estimate. In this paper, we define a multi-objective NMF (MO-NMF) problem, where several objectives are combined within the same NMF model. We propose to use Lagrange duality to judiciously optimize for a set of weights to be used within the framework of the weighted-sum approach, that is, we minimize a single objective function which is a weighted sum of the all objective functions. We design a simple algorithm based on multiplicative updates to minimize this weighted sum. We show how this can be used to find distributionally robust NMF (DR-NMF) solutions, that is, solutions that minimize the largest error among all objectives, using a dual approach solved via a heuristic inspired from the Frank-Wolfe algorithm. We illustrate the effectiveness of this approach on synthetic, document and audio data sets. The results show that DR-NMF is robust to our incognizance of the noise model of the NMF problem.

Complications of Immediate versus Delayed DIEP Reconstruction: A Meta-Analysis of Comparative Studies.

PURPOSE: The setting regarding the ideal timing for deep inferior epigastric perforator flap (DIEP) reconstruction remains unclear. Immediate breast reconstruction (IBR) is performed at the same time as mastectomy, while delayed breast reconstruction (DBR) is performed at any time after mastectomy except immediately. We compared both strategies to assess whether IBR or DBR should be performed to reduce postoperative adverse events. METHODS: A systematic review of PubMed, Embase, Medline, Cochrane, and Web of Science was conducted, aiming at articles comparing the recipient site outcomes of IBR versus DBR with DIEP. We used the Mantel-Haenszel method with a fixed effects model. Results were expressed as the OR with a 95% CI. RESULTS: Two retrospective and two prospective studies were identified involving 5784 DIEPs (1744 immediate and 4040 delayed). We showed a significant difference in favor of IBR for wound healing issues (OR = 0.57, 95% CI 0.41, 0.77; p = 0.0003). However, no significant differences for hematoma, infection, fat necrosis, partial flap loss, and total flap loss rate were seen. CONCLUSIONS: Despite variability in the choice of the ideal time for breast reconstruction and outcomes reported among studies, immediate DIEP surgery appears to be a reliable setting with less delayed healing issues.

Lightweight, Fiber-Damage-Resistant, and Healable Bio-Inspired Glass-Fiber Reinforced Polymer Laminate.

Glass-Fiber-Reinforced Polymer (GFRP) laminates are widely used in the automotive and marine industries such as auto bodies and boat hulls. Decreasing the weight and improving the reparability of GFRP parts will cut down material usage, fuel consumption and repair costs. This study shows a bio-inspired helicoidal stacking configuration that significantly improves the impact performance and fiber damage resistance of GFRP laminates. For similar impact performance in terms of perforation energy, the helicoidal GFRP laminate is 20% lighter than the conventional quasi-isotropic GFRP laminate. Upon impact, delaminations and matrix splits link-up and grow extensively throughout the helicoidal laminate. This effectively reduces fiber damage and improves impact performance. Because helicoidal GFRP laminates are resistant to fiber damage and composite healing agents can effectively repair non-fiber damage, embedding healing agents into helicoidal GFRP results in lightweight, inexpensive and healable laminates.

Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study.

RATIONALE: The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. OBJECTIVES: To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. METHODS: In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). MEASUREMENTS AND MAIN RESULTS: A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001). CONCLUSIONS: IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.

Effectiveness of bilateral single-hinged knee bracing in osteoarthritis: A finite element study.

Effectiveness of knee braces remains to be identified. Therefore, the purpose of this study was to investigate the effectiveness of bilateral single-hinged knee bracing in knee osteoarthritis (OA) using finite element (FE) method. A three-dimensional FE model consisted of main model (knee-brace structure) and submodel (strap-muscle system) was developed. The submodel was used to convert the elastic strap-muscle interaction into an equivalent stiffness value required by the main model. Adding 100 N · mm/rad torsion spring to the brace with 5 kPa strap pressure lowered maximum von Mises stress in the knee OA components at a flexion angle greater than or equal to 90°. Separately, employing 10% brace pre-tension to the brace with 5 kPa strap pressure started to reduce stresses at a flexion angle of 70°. The configuration involving a combination of 10% brace pre-tension and 300 N · mm/rad torsion spring with 30 kPa strap tightness produced stress reduction over the entire range from 0° to 100° flexion angle. The basic bilateral single-hinged knee brace has shown to reduce stresses in the knee OA at high flexion angles only. Compared to the torsion spring, the brace pre-tension has shown to provide more significant benefits (i.e. stress reduction at lower flexion angles). The most sophisticated effects were achieved when the torsion spring was used in combination with the brace pre-tension. These two features can be potentially used for the development of an active knee brace if they can be modulated at different flexion angles or during the gait cycle.

An Interpretable Intensive Care Unit Mortality Risk Calculator.

Mortality risk is a major concern to patients who have just been discharged from the intensive care unit (ICU). Many studies have been directed to construct machine learning models to predict such risk. Although these models are highly accurate, they are less amenable to interpretation and clinicians are typically unable to gain further insights into the patients' health conditions and the underlying factors that influence their mortality risk. In this paper, we use patients' profiles extracted from the MIMIC-III clinical database to construct risk calculators based on different machine learning techniques such as logistic regression, decision trees, random forests, k-nearest neighbors and multilayer perceptrons. We perform an extensive benchmarking study that compares the most salient features as predicted by various methods. We observe a high degree of agreement across the considered machine learning methods; in particular, age, blood urea nitrogen level and the indicator variable - whether the patient is discharged from the cardiac surgery recovery unit are commonly predicted to be the most salient features for determining patients' mortality risks. Our work has the potential to help clinicians interpret risk predictions.

A Covalently Crosslinked Ink for Multimaterials Drop-on-Demand 3D Bioprinting of 3D Cell Cultures.

In vitro 3D cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here, a versatile ink comprising a 4-arm poly(ethylene glycol) (PEG)-based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second is reported. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a novel drop-on-demand 3D bioprinting platform, designed specifically for producing 3D cell cultures, consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D cell cultures comprising multiple hydrogel environments in one structure in a standard 96-well plate format. The platform's compatibility for biological applications is validated using pancreatic ductal adenocarcinoma cancer (PDAC) and human dermal fibroblast cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

Stress response envelopes of intact tibiofemoral joint and knee osteoarthritis.

The purpose of this study was to determine stress envelopes for an intact tibiofemoral joint and to study how they vary with knee loading, external-internal rotation, varus-valgus rotation and cartilage degradation (osteoarthritis) using the finite element method. The envelopes were presented in terms of knee flexion angle. The maximum von Mises stress for all tibiofemoral joint components increased with increasing the axial compressive force magnitude. Menisci exhibited the highest magnitude of maximum von Mises stress as compared to the femoral and tibial cartilages. In a range of flexion angles between 0° and 100°, the medial meniscus exhibited the highest maximum von Mises stress than the lateral meniscus and the stress in medial meniscus tended to increase with increasing the flexion angle. External-internal and varus-valgus rotations changed the stress distribution: higher stress on lateral compartment but lower stress on medial compartment, and conversely. The internal rotation provided more extreme effect than the external rotation. For the knee osteoarthritis, cartilage degradation (early stage) caused maximum von Mises stress to increase on the intact menisci revealing that knee osteoarthritis could also cause meniscal tear. The late osteoarthritis caused the maximum von Mises stress to increase on the calcified cartilage and subchondral bone.

High density mechanical energy storage with carbon nanothread bundle.

The excellent mechanical properties of carbon nanofibers bring promise for energy-related applications. Through in silico studies and continuum elasticity theory, here we show that the ultra-thin carbon nanothreads-based bundles exhibit a high mechanical energy storage density. Specifically, the gravimetric energy density is found to decrease with the number of filaments, with torsion and tension as the two dominant contributors. Due to the coupled stresses, the nanothread bundle experiences fracture before reaching the elastic limit of any individual deformation mode. Our results show that nanothread bundles have similar mechanical energy storage capacity compared to (10,10) carbon nanotube bundles, but possess their own advantages. For instance, the structure of the nanothread allows us to realize the full mechanical energy storage potential of its bundle structure through pure tension, with a gravimetric energy density of up to 1.76 MJ kg-1, which makes them appealing alternative building blocks for energy storage devices.

Synthesis and evaluation of functionalized isoindigos as antiproliferative agents.

A series of functionalized isoindigos structurally related to meisoindigo (1-methylisoindigo), a therapeutic agent used for the treatment of a form of leukemia, were synthesized and evaluated for antiproliferative activities on a panel of human cancer cells. Two promising compounds (1-phenpropylisoindigo and 1-(p-methoxy-phenethyl)-isoindigo) that were more potent than meisoindigo and comparable to 6-bromoindirubin-3'-oxime on leukemic K562 and liver HuH7 cells were identified. Structure-activity relationships showed the importance of keeping one of the lactam NH in an unsubstituted state. Substitution of the other lactam NH with aryl or arylalkyl side chains retained or improved activity in most instances. An intact exocyclic double bond was also essential, possibly to maintain planarity and rigidity of the isoindigo scaffold. None of the compounds were found to inhibit CDK2 in an in vitro assay, in spite of reports linking the antiproliferative activities of meisoindigo and other isoindigos to CDK2 inhibition. Hence, these functionalized isoindigos disrupted cell growth and proliferation by other mechanistic pathways that did not involve CDK2 inhibition.

Mechanical properties and buckling behaviors of condensed double-walled carbon nanotubes.

Molecular dynamics (MD) simulations are performed on condensed double-walled carbon nanotubes (CDWCNTs) to investigate the effects of compressed interwall spacings on their mechanical properties, in particular their buckling behavior under axial compression, torsion and bending. In CDWCNTs, the inner and outer nanotubes have diameters that are closer to each other than the nanotubes of conventional double-walled carbon nanotubes (DWCNTs). This leads to a smaller interwall spacing. The mechanical properties of the CDWCNTs, such as Young's modulus, interwall shear modulus, and the buckling strain under axial compression, torsion and bending are found to be greatly enhanced when compared with those of conventional DWCNTs. The enhancement is found to be inversely proportional to the interwall spacing.

One-dimensional iron-cyclopentadienyl sandwich molecular wire with half metallic, negative differential resistance and high-spin filter efficiency properties.

We present a theoretical study on a series of novel organometallic sandwich molecular wires (SMWs), which are constructed with alternating iron atoms and cyclopentadienyl (Cp) rings, using DFT and nonequilibrium Green's function techniques. It is found that that the SMWs are stable, flexible structures having half-metallic (HM) properties with 100% negative spin polarization near the Fermi level in the ground state. Some SMWs of finite size show a nearly perfect spin filter effect (SFE) when coupled between ferromagnetic electrodes. Moreover, their I-V curves exhibit negative differential resistance (NDR), which is essential for certain electronic applications. The SMWs are the first linear molecules with HM, high SFE, and NDR and can be easily synthesized. In addition, we also analyze the underlying mechanisms via the transmission spectra and spin-dependent calculations. These findings strongly suggest that the SMWs are promising materials for application in molecular electronics.