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RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb).We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort.Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431-3p down-regulation and miR-1303 up-regulation accompanied with corresponding changes in their predicted target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431-3p mimic/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431-3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively.This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431-3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.

Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) reduces blood loss and improves hemodynamics. Complete occlusion results in distal ischemia, limiting its use for prolonged care. This study evaluated two next-generation partial REBOA (pREBOA) catheters and their ability to achieve targeted distal aortic flow. Materials and methods Swine underwent hemorrhagic shock, complete aortic occlusion, controlled continuous balloon deflation, and targeted distal perfusion (TDP; 300-mL/min) phases. They were randomized into three groups (n = 6/group), one managed with the current ER-REBOA (ER), and two with the new pREBOA technologies: a bilobed (BL) device and a semicompliant pREBOA-PRO (PRP). Hemodynamics including flow rates and mean arterial pressures at the carotid artery and infrarenal aorta were recorded. Results Hemodynamics were comparable between groups during hemorrhage and complete occlusion phases. During the controlled continuous balloon deflation phase, the distal aortic flow rate strongly correlated with percent balloon volume in BL and PRP groups, suggesting a precise control of distal perfusion. The slope of flow-balloon-volume curves was greater in the ER group than BL and PRP groups, indicating the change in distal aortic flow rate was more sensitive to the balloon volume (less titratable) when using ER. During the TDP phase, variation in distal aortic flow and mean arterial pressure with respect to the target flow was lower in ER and PRP groups, than the BL group. Conclusions Pressure-regulated occlusion using the next-generation pREBOA catheters is more controlled than the first-generation ER-REBOA catheter and allow for targeted and precise distal perfusion.

In this work, by capping a macrolactam ring at the C-terminus of a de novo-designed peptide, namely zp80, we have constructed a small peptide library via the solid phase peptide synthesis for screening. Eight peptides bearing different aspartic acid-rich macrolactam rings but the same linear (IIRR)

Atmospheric particulate matter, especially in urban and industrial environments, can act as a source of different organic pollutants that can pose significant health impacts to residents. However, the pollution status and transport mechanisms of fine particle-bound polycyclic aromatic hydrocarbons (PAHs) in indoor and outdoor environments are uncertain. This study aimed to determine the spatial distribution and morphological characteristics of fine particle-bound PAHs and analyze the factors (source contributions and backward trajectories) that influence their concentrations. The results showed that mean concentrations of 16 PAHs were higher in indoor dust as compared to outdoor dust. In addition, the lowest concentrations of the 16 PAHs were found on the 11-20th floor, with smoking householdsnonsmoking households (except Nap, Acy, and Ace). The 2-3 ring PAHs were more prominent in households with cooking activities. The particle size distribution showed that most of the particles were62 μm in diameter, indicating that the indoor particles were smaller in size. Furthermore, the range of δ13C values in the outdoor dust (-30.17 ~ -28.63 ‰) samples was significantly lower than in indoor dust (-28.29 ~ -22.53 ‰). The results based on diagnostic ratios, positive matrix factorization (PMF) analysis and backward trajectory model analysis suggested that the sources of PAHs in indoor and outdoor dust were mixed, originated both locally and from neighboring provinces transported over long distances, especially concentrated in the Yangtze River Delta area. Finally, carcinogenic risk values for indoor dust were greater than those for outdoor dust. Therefore, it is recommended that local governments and industries with high PAH emissions should implement proper protocols to monitor and minimize the pollution levels of PAHs in the urban industrial environment in order to mitigate their health risks.

Multiobjective interval linear programming (MOILP) is one of the most important approaches to real-world optimization problems involving multiple conflicting objectives under imprecision or uncertainty. From the viewpoint of order vector space, this paper aims to solve MOILP problems with an admissible order. We first extend the concept of admissible order on the set of intervals and study some properties of admissible order vector space. We then employ an admissible order and interval ordered weighted aggregation (OWA) operator to transform a MOILP problem into an interval weighted sum scalarization multiobjective optimization problem whose solution can be derived by solving several related real-valued programming problems, and the Pareto optimal solution of this MOILP problem can likewise be obtained. Then, we introduce the W-efficient solutions and axial solutions of the MOILP problem to account for decision makers’ preferences as partial information. Two simple examples and two real-life problems are employed to illustrate and substantiate our conceptual arguments.

Background: Adult asthma is phenotypically heterogeneous with unclear etiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. Methods: Environmental risk was evaluated by assessing the records of National Health Insurance Research database (NHIRD) and residence-based air pollution [PM2.5 and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)], integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-SNE integrating 18 clinical and demographic variables. Findings: In the NHIRD dataset, a modest increase in the relative risk with time-lag effect for emergency (N=209,837) and outpatient visits (N=638,538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH originated from multiple sources, posing a significant risk for current asthma and its severity, correlating with the level of oxidative stress markers, notably Ne-(hexanoyl)-lysine (HEL) as a marker of response in both cases and controls. Further, levels of circulating sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) were found to discriminate asthma, correlating with the levels of exposure to PAH and metals, respectively, and both correlating with a panel of circulating inflammatory markers. Stratification of the combined datasets by 6 phenotypic clusters among 1,163 asthmatic subjects and those with comorbid T2DM revealed cluster-selective environmental risks and biosignatures. Interpretation: These results suggest the potential contribution of environmental factors, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity. Funding Information: This work was supported, in part, by grants from National Health Research Institutes, Taiwan (EOPP10-014, EOSP07-014 and NHRI-102A1-PDCO-03010201) and Ministry of Health, Taiwan (EODOH01), National Science Council (NSC 102-2314-B-037-052), Ministry of Health (EODOH01), Ministry of Science and Technology (MOST 103-2320-B-110-001), and Academic Sinica (BM-102021170), Taiwan. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: All eligible subjects were enrolled in the study after signing the informed consent approved by the respective recruitment hospitals.

Being a class of vitamin A's main derivatives, retinoic acids (RAs) are important to animals' growth and development. Previous studies demonstrated that exposure of excessive amounts of RAs would lead to malformation and abnormal development in aquatic animals such as amphibians and fishes. Currently, there are only limited toxicity data of RAs available for freshwater species, while those for marine species are seriously lacking. This study aimed to fill such data gap by conducting toxicity tests on six marine species (i.e., one microalga, four invertebrates and one fish) towards the exposure to all-trans-RA (at-RA), which is the most widely distributed RA in the environment. Results showed that the embryo of medaka fish Oryzias melastigma was the most sensitive towards the exposure of at-RA while the gastropod Monodonta labio was the least sensitive. A species sensitivity distribution (SSD) was constructed based on the experimental results generated from the present study. An interim marine-specific predicted no-effect concentration (PNEC) of at-RA was derived at 2300 ng/L. By computing the hazard quotients using the interim marine-specific PNEC and available measured and predicted concentrations of RAs, we found the current levels of RAs posed no immediate risks to the marine environment of Hong Kong. The interim marine-specific PNEC was more than 500-fold of freshwater-specific PNEC (i.e., 3.93 ng/L), indicating that marine species were generally less sensitive than their freshwater counterparts towards RAs. This was the first study to document the concentration-response of various marine species towards at-RA exposure and construct the marine-specific SSD for assessing the ecological risk of at-RA towards the marine environment. Since various forms of RAs and their metabolites often coexist in aquatic environments, further studies should investigate their combined toxicity to an array of marine species of different trophic levels with consideration of chronic exposure scenarios.

Background: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. Two common procedures are loop electrosurgical excision procedure (LEEP) and ‘cold knife cone biopsy’ (CKC), yet no randomised trials have compared these modalities. We aimed to compare margins status, specimen size and fragmentation after LEEP and CKC. Methods: The EXCISE Trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC by computer generated random numbers. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. Findings: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. All patients were included in the analysis. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p=1.00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p=.00). There were no differences in grade three complications (p=.65). Interpretation: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardised protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted. Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR registration number ACTRN12617000132347). Funding Statement: Australia New Zealand Gynaecological Oncology Group [#FNR2016/03]. Declaration of Interests: PAC and CDHW have received honoraria from Seqirus unrelated to this work. All other authors declare no competing interests. Ethics Approval Statement: Ethical approval for the study was granted by the St John of God Healthcare Human Research Ethics Committee (Reference number #1137) and approvals were obtained at all participating sites.

Purpose To evaluate the cost-effectiveness of a nurse-led care program for breast cancer patients receiving outpatient-based chemotherapy. Method An open-label, single-center randomized controlled trial was conducted. Patients receiving the nurse-led care and those receiving the routine care were compared in terms of quality of life, as well as in health service utilizations and total cost of care. A cost-utility analysis was conducted. Results A total of 124 patients were recruited. The data of 116 subjects who completed the study were used for the cost-utility analysis. There were 81 unscheduled hospital visits and 43 hospital admissions. The common reasons for utilizing health services were infections and fevers, skin problems, digestive system problems, and mouth/teeth/throat problems. There were no differences in health service utilizations between the nurse-led and routine care groups for subjects receiving four-cycle chemotherapy. For those receiving six-cycle chemotherapy, the estimated number of emergency department visits was 2.188 times (95% Confidence Interval, 1.051 to 4.554) higher for the routine care group when compared with the nurse-led care group (p = .038). The incremental cost-utility ratios were £8856 and £18,936 per quality-adjusted life year gained for subjects receiving four-cycle and six-cycle chemotherapy, respectively. Conclusions Cancer patients make unscheduled health service visits when receiving outpatient-based chemotherapy, which leads to increased health service costs. The nurse-led care reduces emergency departments visits made by breast cancer patients undergoing six-cycle adjuvant chemotherapy . For breast cancer patients undergoing four-cycle chemotherapy and six-cycle chemotherapy, the nurse-led care could be cost-effective.

ObjectiveAlthough endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival.MethodsIn a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid).ResultsAfter a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31–3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20–7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21–7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC.ConclusionOur findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.

Travel behaviour has been studied for decades to guide transportation development and management, with the support of traditional data collected by travel surveys. Recently, with the development of information and communication technologies (ICT), we have entered an era of big data, and many sources of novel data, including mobile phone data, have emerged and been applied to travel behaviour research. Compared with traditional travel data, mobile phone data have many unique features and advantages, which attract scholars in various fields to apply them to travel behaviour research, and a certain amount of progress has been made to date. However, this is only the beginning, and mobile phone data still have great potential that needs to be exploited to further advance human mobility studies. This paper provides a review of existing travel behaviour studies that have applied mobile phone data, and presents the progress that has been achieved to date, and then discusses the potential of mobile phone data in advancing travel behaviour research and raises some challenges that need to be dealt with in this process.

This paper proposes a method to compress deep neural networks (DNNs) based on interpretability. For a trained DNN model, the activation maximization technique is first used to visualize every filter of the DNN model. Then, a single-layer filter pruning approach is introduced from what is learned by visualization. The entire DNN model is compressed layer by layer by using the single-layer filter pruning method in which the compression of the current layer is based on the compression of the preceding layers. Importantly, in addition to effective compression, the proposed method renders a better interpretation of the deep learning process. With a 60 % compression rate of the VGG-16, our method achieves 0.8429 Top-1 accuracy under CIFAR-10, with a slight accuracy drop of only 0.0322, and the storage space of the model can be compressed to 9.42 Mb. For a modern DNN model such as ResNet50, our visualization-based filter pruning method is significantly better than other pruning strategies in different convolutional layers under different compression rates and the larger ImageNet dataset. After pruning, the computation cost and storage requirement of the DNN can be significantly reduced, which means that complex DNN models can be easily implemented in small mobile devices, thus enabling the efficient use of DNNs in the Internet of Things technologies.

The authors regret that Donal Brennan was missing from the author list. The details shown above are now correct with Dr Brennan included. Dr. Brennan contributed to conceptualisation and data curation and final review of manuscript. Dr. Brennan does not have any conflicts to disclose. The authors would like to apologise for any inconvenience caused.

The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked . m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC. Refereed/Peer-reviewed

The epicenter motion direction carries important information about the seismogenic dynamics but, to our knowledge, lacks systematic study. In this work, we studied the earthquake process from this perspective. To grasp the feature in directional information, we proposed a new descriptor, i.e., the direction of motion change defined as the difference in azimuths between two consecutive earthquake events. For the aftershock sequences of the Landers and the Northridge Earthquakes, the regional earthquake catalogs of south China, southern California, and New Zealand, and the corresponding aftershock depleted catalogs, we studied the distribution and long-range correlation of the direction of motion change. Similar results are found for the aftershock and regional earthquake process even if aftershocks depleted from the catalogs: Both of them hold a tendency for successive events to migrate in opposite directions along fault zones and show no long-range correlation, rendering plausibly a fundamental characteristic governed by seismogenic dynamics. For aftershocks, the phenomenon is conjectured to be the alternate release of residual stress at both ends of the fissures. With regard to regional earthquakes, the underlying physics and mechanisms are not very clear. It should be something related to the seismodynamic process, such as stress configuration modified by earthquakes. The study from this new perspective of directional information is believed to benefit a better understanding of the earthquake process.

A retrospective review for enchondroma in the hand which had undergone operative treatment is presented. Twenty patients were treated operatively over a 10-year period. A total of 70% of the patients presented with pathological fracture. Enchondromas were most commonly located in the little finger (65%) and proximal phalange (60%). Enchondromas presented with pathological fractures and were treated definitively after the fracture had healed, except for one patient with open reduction, internal fixation of fracture, and bone grafting. All 20 patients underwent curettage of the enchondroma. In the same operative occasion, 16 patients received bone grafting, three patients received bone substitutes, and one had received bone cement. Fourteen (70%) of the patients suffered no major postoperative complications. Postoperative stiffness was encountered in seven patients. A secondary operation for relief of postoperative stiffness was performed in three patients. Factors were assessed for their risk of resulting in postoperative stiffness and occurrence of secondary operation. Factors included sex, age, pathological fracture, location of lesion, and preoperative stiffness. Only preoperative stiffness was a statistically significant risk factor contributing to postoperative stiffness and occurrence of a secondary operation.

The low take-home baby rate in older women in Australia (5.8%) undergoing IVF (5.8%) is linked to the depletion of the ovarian reserve of primordial follicles. Oocyte depletion causes an irreversible change to ovarian function. We found that the young patient FSH receptor and LH receptor expression profile on the granulosa cells collected from different size follicles were similar to the expression profile reported in natural cycles in women and sheep. This was reversed in the older patients with poor ovarian reserve. The strong correlation of BMPR1B and FSH receptor density in the young was not present in the older women; whereas, the LH receptor and BMPR1B correlation was weak in the young but was strongly correlated in the older women. The reduced fertilisation and pregnancy rate was associated with a lower LH receptor density and a lack of essential down-regulation of the FSH and LH receptor. The mechanism regulating FSH and LH receptor expression appears to function independently, in vivo, from the dose of FSH gonadotrophin, rather than in response to it. Restoring an optimum receptor density may improve oocyte quality and the pregnancy rate in older women.

Tick-borne disease in dogs is common in South-east Asia and includes babesiosis and ehrlichiosis. These diseases can be largely prevented by compliant use of tick preventive products. This study investigated knowledge of ticks and tick-borne disease and use of tick preventive agents by a large sample of dog owners in Hong Kong. A total of 492 valid questionnaires were completed by owners attending veterinary practices, approached by researchers at common dog-walking areas, or targeted via local social media sites for pet owners. A high proportion of respondents were aware of tick-borne disease (79%) and this correlated well with use of preventive products. However, 18% of owners did not use any protection, mainly due to lack of knowledge of the risk of disease. Targeted advice stressing the importance of tick protection use and frequent follow-up at veterinary clinics could help reduce the risk of tick-borne disease. It would be beneficial if veterinarians provided training of frontline staff at the clinics to ensure they provide essential information to clients in an easily understandable format.

We introduce the notion of granular reduct in formal fuzzy contexts.We proposed methods of granular reduct in the sense of reducing attributes.We examined the relationship between granular reduct and classification reduct. Knowledge reduction is one of the key issues in knowledge discovery and data mining. During the construction of a concept lattice, it has been recognized that computational complexity is a major obstacle in deriving all the concept from a database. In order to improve the computational efficiency, it is necessary to preprocess the database and reduce its size as much as possible. Focusing on formal fuzzy contexts, we introduce in the paper the notions of granular consistent sets and granular reducts and propose granular reduct methods in the sense of reducing the attributes. With the proposed approaches, the attributes that are not essential to all the object concepts can be removed without loss of knowledge and, consequently, the computational complexity of constructing the concept lattice is reduced. Furthermore, the relationship between the granular reducts and the classification reducts in a formal fuzzy context is investigated.

Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Several modeling approaches have been developed for simulating ambient PAHs, but no hourly intra-urban spatial data are currently available. The aim of this study is to develop a new modeling strategy in simulating, on an hourly basis, grid-scale PM2.5-PAH levels. PM and PAHs were collected over a one-year time frame through an established air quality monitoring network within a metropolitan area of Taiwan. Multivariate linear regression models, in combination with correlation analysis and PAH source identification by principal component analysis (PCA), were performed to simulate hourly grid-scale PM2.5-PAH concentrations, taking criteria pollutants and meteorological variables selected as possible predictors. The simulated levels of 72-h personal exposure were found to be significantly (R=0.729**, p

The performance degradation and durability of a Li-ion battery is a major concern when it is operated under radiation conditions, for instance, in deep space exploration, in high radiation field, or rescuing or sampling equipment in a post-nuclear accident scenario. This paper examines the radiation effects on the electrode and electrolyte materials separately and their effects on a battery's capacity loss and resistance increase. A 60 Co irradiator (34.3 krad/h) was used to provide 0.8, 4.1, and 9.8 Mrad dose to LiFePO 4 electrodes and 0.8, 1.6, and 5.7 Mrad to 1 M LiPF 6 in 1:1 wt% EC:DMC electrolytes. This study shows that the coin cells assembled with irradiated components have higher failure rate (ca. 70%) than that of control group (ca. 14%). A significant battery capacity fade post irradiation was observed. The electrolyte also shows a darkened color a few weeks or months after irradiation. The discovery of this latent effect may be significant because a battery may degrade significantly even showing no sign of degradation immediately after exposure. We investigated electrolyte composition by Fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, and nuclear magnetic resonance spectroscopy prior and post irradiation. Polymerization reactions and HF formation are considered as the cause of the discoloration.

Feature extraction has been a major area of research in remote sensing, and fractal feature is a natural characterization of complex objects across scales. Extending on the modified triangular prism (MTP) method, we systematically discuss three factors closely related to the estimation of fractal dimensions of remotely sensed images. They are namely the (F1) number of steps, (F2) step size, and (F3) estimation accuracy of the facets' areas of the triangular prisms. Differing from the existing improved algorithms that separately consider these factors, we simultaneously take all factors to construct three new algorithms, namely the modification of the eight-pixel algorithm, the four corner and the moving-average MTP. Numerical experiments based on 4000 generated images show their superior performances over existing algorithms: our algorithms not only overcome the limitation of image size suffered by existing algorithms but also obtain similar average fractal dimension with smaller standard deviation, only 50% for images with high fractal dimensions. In the case of real-life application, our algorithms more likely obtain fractal dimensions within the theoretical range. Thus, the fractal nature uncovered by our algorithms is more reasonable in quantifying the complexity of remotely sensed images. Despite the similar performance of these three new algorithms, the moving-average MTP can mitigate the sensitivity of the MTP to noise and extreme values. Based on the numerical and real-life case study, we check the effect of the three factors, (F1)-(F3), and demonstrate that these three factors can be simultaneously considered for improving the performance of the MTP method. HighlightsEmployment of three critical factors to estimate the fractal dimensions of remotely sensed imageries.Construction of new algorithms to simultaneously consider the factors.More reasonable and effective unraveling of the fractal nature of imageries.

Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients.

One of the key issues of knowledge discovery and data mining is knowledge reduction. Attribute reduction of formal contexts based on the granules and dominance relation are first reviewed in this paper. Relations between granular reduts and dominance reducts are investigated with the aim to establish a bridge between the two reduction approaches. We obtain meaningful results showing that granule-based and dominance-relation-based attribute reducts and attribute characteristics are identical. Utilizing dominance reducts and attribute characteristics, we can obtain all granular reducts and attribute characteristics by the proposed approach. In addition, we establish relations between dominance classes and irreducible elements, and present some judgment theorems with respect to the irreducible elements.

The multifractal properties of daily rainfall time series at the stations in Pearl River basin of China over periods of up to 45 years are examined using the universal multifractal approach based on the multiplicative cascade model and the multifractal detrended fluctuation analysis (MF-DFA). The results from these two kinds of multifractal analyses show that the daily rainfall time series in this basin have multifractal behavior in two different time scale ranges. It is found that the empirical multifractal moment function $K(q)$ of the daily rainfall time series can be fitted very well by the universal mulitifractal model (UMM). The estimated values of the conservation parameter $H$ from UMM for these daily rainfall data are close to zero indicating that they correspond to conserved fields. After removing the seasonal trend in the rainfall data, the estimated values of the exponent $h(2)$ from MF-DFA indicate that the daily rainfall time series in Pearl River basin exhibit no long-term correlations. It is also found that $K(2)$ and elevation series are negatively correlated. It shows a relationship between topography and rainfall variability., 16 pages, 7 figures, 1 table, accepted by Physica A

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorized as: Women with LLL (n=68), women with LLS (n=177) and women without LLL or LLS (n=394). Multivariable-adjusted generalized linear models were used to compare women's physical and mental QoL by LLL status. Results On average, women were 65years of age and 4years after diagnosis. Women with LLL had clinically lower physical QoL ( M =41.8, SE =1.4) than women without LLL or LLS ( M =45.1, SE =0.8, p =.07), however, their mental QoL was within the normative range ( M =49.6; SE =1.1 p =1.0). Women with LLS had significantly lower physical ( M =41.0, SE =1.0, p =.003) and mental QoL ( M =46.8; SE =0.8, p M =50.6, SE =0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3–5years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women's QoL.

HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort.Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann-Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression analyses.Median CA125 and HE4 levels were higher in stage III and IV tumours (p0.001) and in tumours with outer-half myometrial invasion (p0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC)=0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC=0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR=2.40, 95% CI 1.19-4.83, p=0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR=2.86, 95% CI 1.25-6.51, p=0.012).These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.

In this paper, we introduce the notion of formal decision context as an extension of formal contexts by employing the notion of decision information table. We use formal concept analysis to formulate an approach to extract ''if-then'' rule from formal decision contexts. We also construct a knowledge-lossless method for complexity reduction in formal decision contexts so that the maximum rules extracted from the reduced formal decision contexts are identical to that extracted from the initial decision formal contexts. More specifically, we develop the discernibility matrix and the discernibility function in formal decision contexts to compute all of the attribute reductions without loss of knowledge.

Visual classification method has been proposed as a learning strategy for pattern classification problem. In this paper, we show the strong convergence property of this method. In particular, the method is shown to converge to the Bayesian estimator, i.e., the learning error of the method is convergent to the posterior expected minimal value. The performance of the method has also been theoretically evaluated to comply with the human visual sensation and perception principle. The method is successfully used to some practical remote sensing and disease diagnosis applications. The experimental results all verify the validity and effectiveness of the theoretical conclusions.

In this paper, a general framework for the study of dual fuzzy rough approximation operators determined by a fuzzy implication operator I in infinite universes of discourse is investigated. Lower and upper approximations of fuzzy sets with respect to a fuzzy approximation space in infinite universes of discourse are first introduced. Properties of I-fuzzy rough approximation operators are then examined. An operator-oriented characterization of fuzzy rough sets is further proposed, that is, I-fuzzy rough approximation operators are defined by axioms. Different axiom sets of lower and upper I-fuzzy set-theoretic operators guarantee the existence of different types of fuzzy relations which produce the same operators. Finally, a comparative study of I-fuzzy rough sets with fuzzy topological spaces is presented. It is proved that there exists a one-to-one correspondence between the set of all reflexive and T-transitive fuzzy approximation spaces and the set of all fuzzy Alexandrov spaces such that the lower and upper I-fuzzy rough approximation operators in a fuzzy approximation space are, respectively, the fuzzy interior and closure operators in a fuzzy topological space. We defined I-fuzzy rough approximation operators determined by a fuzzy implication operator I by using constructive approach.We gave the operator-oriented characterization of I-fuzzy rough approximation operators.We presented the topological structures of I-fuzzy rough sets.

A new method is proposed in this paper to learn overcomplete dictionary from signals. Differing from the current methods that enforce uniform sparsity constraint on the coefficients of each input signal, the proposed method attempts to impose global sparsity constraint on the coefficient matrix of the entire signal set. This enables the proposed method to fittingly assign the atoms of the dictionary to represent various signals and optimally adapt to the complicated structures underlying the entire signal set. By virtue of the sparse coding and sparse PCA techniques, a simple algorithm is designed for the implementation of the method. The efficiency and the convergence of the proposed algorithm are also theoretically analyzed. Based on the experimental results implemented on a series of signal and image data sets, the capability of the proposed method is substantiated in original dictionary recovering, signal reconstructing and salient signal structure revealing.

Dempster-Shafer theory of evidence has been employed as a major method for reasoning with multiple evidence. The Dempster's rule of combination is however incapable of managing highly conflicting evidence coming from different information sources at the normalization step. Extending current rules, we incorporate the ideas of group decision-making into the theory of evidence and propose an integrated approach to automatically identify and discount unreliable evidence. An adaptive robust combination rule that incorporates the information contained in the consistent focal elements is then constructed to combine such evidence. This rule adjusts the weights of the conjunctive and disjunctive rules according to a function of the consistency of focal elements. The theoretical arguments are supported by numerical experiments. Compared to existing combination rules, the proposed approach can obtain a reasonable and reliable decision, as well as the level of uncertainty about it.

Human beings often observe objects or deal with data hierarchically structured at different levels of granulations. In this paper, we study optimal scale selection in multi-scale decision tables from the perspective of granular computation. A multi-scale information table is an attribute-value system in which each object under each attribute is represented by different scales at different levels of granulations having a granular information transformation from a finer to a coarser labelled value. The concept of multi-scale information tables in the context of rough sets is introduced. Lower and upper approximations with reference to different levels of granulations in multi-scale information tables are defined and their properties are examined. Optimal scale selection with various requirements in multi-scale decision tables with the standard rough set model and a dual probabilistic rough set model are discussed respectively. Relationships among different notions of optimal scales in multi-scale decision tables are further analyzed.

This paper proposes a general framework for the study of interval-valued information systems by integrating the variable-precision-dominance-based rough set theory with inclusion measure theory. By introducing a α -dominance relation based on inclusion measures between two interval numbers, we propose a variable-precision-dominance-based rough set approach based on the substitution of indiscernibility relation by the α -dominance relation. The knowledge discovery framework is formulated for interval-valued information systems. Furthermore, knowledge reduction of interval-valued decision systems based on the variable-precision-dominance-based rough set model is postulated. Relationships between these reducts and discernibility matrices are also established to substantiate knowledge reduction in the variable-precision-dominance-based rough set model.

Nonlinear dimensionality reduction of data lying on multi-cluster manifolds is a crucial issue in manifold learning research. An effective method, called the passage method, is proposed in this paper to alleviate the disconnectivity, short-circuit, and roughness problems ordinarily encountered by the existing methods. The specific characteristic of the proposed method is that it constructs a globally connected neighborhood graph superimposed on the data set through technically building the smooth passages between separate clusters, instead of supplementing some rough inter-cluster connections like some existing methods. The neighborhood graph so constructed is naturally configured as a smooth manifold, and hence complies with the effectiveness condition underlying manifold learning. This theoretical argument is supported by a series of experiments performed on the synthetic and real data sets residing on multi-cluster manifolds.

Investigating long-range correlation by the Hurst exponent, H , is crucial in the study of time series. Recently, empirical-mode-decomposition-based arbitrary-order Hilbert spectral analysis (EMD-HSA) has been proposed to numerically obtain without proof a scaling relationship, generated from the amplitude–frequency distribution, related to H . We propose a formalism to empirically study EMD-HSA, to deduce its scaling exponent ξ ( q ) from the perspective of EMD-based arbitrary-order Hilbert marginal spectrum (EMD-HMS), and to numerically compare the results with the expected H . EMD-HSA and EMD-HMS experiments show that, by incompletely removing (quasi-)periodic trends, the sunspot series should have an H value around 0.12.

Traumatic brain injury (TBI) results in enduring motor and cognitive dysfunction. Although gait disturbances have been documented among TBI patients, few studies have profiled gait abnormalities in animal models of TBI. We sought to obtain a comprehensive longitudinal analysis of gait function following severe penetrating ballistic-like brain injury (PBBI) in rats. Rats were subjected to either unilateral frontal PBBI, probe insertion alone, or sham surgery. Sensorimotor performance was assessed using the CatWalk automated gait analysis system. Baseline measurements were taken 3 days prior to injury and detailed analysis of gait was performed at 1, 3, 7, 14, and 28 days post-injury. Both PBBI and probe-inserted rats displayed altered static and dynamic gait parameters that were primarily evident during the early (

The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis-negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively). This may be explained by relatively small sample sizes in earlier studies but could also reflect difficulties in accurately classifying high-grade ovarian malignancies. In the current study, we investigated KRAS and BRAF mutations in 78 low-grade (FIGO grade 1 and 2) endometrioid adenocarcinomas and compared the results with the presence of endometriosis in the tumor-associated ovary and/or in other pelvic sites. KRAS mutations were identified in 12 (29%) of 42 endometriosis-associated endometrioid adenocarcinomas with satisfactory analysis but in only 1 (3%) of 29 tumors in which endometriosis was not identified. BRAF mutation was identified only in a single endometriosis-associated case. These findings support the hypothesis that endometriosis-associated and independent endometrioid adenocarcinoma may develop via different molecular pathways and that KRAS mutations have an important role only in the former tumors. In contrast, BRAF mutations do not appear to have a significant role in either endometrioid adenocarcinoma subgroup. This may be relevant to future targeted therapies in patients with high-stage or recurrent disease and indicate that histopathologists should carefully examine endometrioid adenocarcinoma specimens, including nonneoplastic tissues, for the presence of endometriosis.

While brain oxygen tension (PbtO(2)) monitoring is an important parameter for evaluating injury severity and therapeutic efficiency in severe traumatic brain injury (TBI) patients, many factors affect the monitoring. The goal of this study was to identify the effects of FiO(2) (fraction of inspired oxygen) on PbtO(2) in uninjured anesthetized rats and measure the changes in PbtO(2) following penetrating ballistic-like brain injury (PBBI). Continuous PbtO(2) monitoring in uninjured anesthetized rats showed that PbtO(2) response was positively correlated with FiO(2) (0.21-0.35) but PbtO(2) remained stable when FiO(2) was maintained at ∼0.26. Importantly, although increasing FiO(2) from 0.21 to 0.35 improved P(a)O(2), it concomitantly reduced pH levels and elevated P(a)CO(2) values out of the normal range. However, when the FiO(2) was maintained between 0.26 and 0.30, the pH and P(a)O(2) levels remained within the normal or clinically acceptable range. In PBBI rats, PbtO(2) was significantly reduced by ∼40% (16.9 ± 1.2 mm Hg) in the peri-lesional region immediately following unilateral, frontal 10% PBBI compared to sham rats (28.6 ± 1.7 mm Hg; mean ± SEM, p