Stiffness Analysis and Experiment of a Novel 5-DoF Parallel Kinematic Machine Considering Gravitational Effects

In order to carry out high-precision machining of aerospace structural components with large size, thin wall and complex surface, this paper proposes a novel parallel kinematic machine (PKM) and formulates its semi-analytical theoretical stiffness model considering gravitational effects that is verified by stiffness experiments. From the viewpoint of topology structure, the novel PKM consists of two substructures in terms of the redundant and overconstrained parallel mechanisms that are connected by two interlinked revolute joints. The theoretical stiffness model of the novel PKM is established based upon the virtual work principle and deformation superposition principle after mapping the stiffness models of substructures from joint space to operated space by Jacobian matrices and considering the deformation contributions of interlinked revolute joints to two substructures. Meanwhile, the component gravities are treated as external payloads exerting on the end reference point of the novel PKM resorting to static equivalence principle. This approach is proved by comparing the theoretical stiffness values with experimental stiffness values in the same configurations, which also indicates equivalent gravity can be employed to describe the actual distributed gravities in an acceptable accuracy manner. Finally, on the basis of the verified theoretical stiffness model, the stiffness distributions of the novel PKM are illustrated and the contributions of component gravities to the stiffness of the novel PKM are discussed.

Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown.

METHODS: In a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality.

RESULTS: In total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality.

CONCLUSION: Aspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.

Automated image analysis for experimental investigations of salt water intrusion in coastal aquifers

A novel methodology has been developed to quantify important saltwater intrusion parameters in a sandbox style experiment using image analysis. Existing methods found in the literature are based mainly on visual observations, which are subjective, labour intensive and limits the temporal and spatial resolutions that can be analysed. A robust error analysis was undertaken to determine the optimum methodology to convert image light intensity to concentration. Results showed that defining a relationship on a pixel-wise basis provided the most accurate image to concentration conversion and allowed quantification of the width of mixing zone between the saltwater and freshwater. A large image sample rate was used to investigate the transient dynamics of saltwater intrusion, which rendered analysis by visual observation unsuitable. This paper presents the methodologies developed to minimise human input and promote autonomy, provide high resolution image to concentration conversion and allow the quantification of intrusion parameters under transient conditions.

Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead and Oligo gene expression data

BACKGROUND: Urothelial pathogenesis is a complex process driven by an underlying network of interconnected genes. The identification of novel genomic target regions and gene targets that drive urothelial carcinogenesis is crucial in order to improve our current limited understanding of urothelial cancer (UC) on the molecular level. The inference of genome-wide gene regulatory networks (GRN) from large-scale gene expression data provides a promising approach for a detailed investigation of the underlying network structure associated to urothelial carcinogenesis.

METHODS: In our study we inferred and compared three GRNs by the application of the BC3Net inference algorithm to large-scale transitional cell carcinoma gene expression data sets from Illumina RNAseq (179 samples), Illumina Bead arrays (165 samples) and Affymetrix Oligo microarrays (188 samples). We investigated the structural and functional properties of GRNs for the identification of molecular targets associated to urothelial cancer.

RESULTS: We found that the urothelial cancer (UC) GRNs show a significant enrichment of subnetworks that are associated with known cancer hallmarks including cell cycle, immune response, signaling, differentiation and translation. Interestingly, the most prominent subnetworks of co-located genes were found on chromosome regions 5q31.3 (RNAseq), 8q24.3 (Oligo) and 1q23.3 (Bead), which all represent known genomic regions frequently deregulated or aberated in urothelial cancer and other cancer types. Furthermore, the identified hub genes of the individual GRNs, e.g., HID1/DMC1 (tumor development), RNF17/TDRD4 (cancer antigen) and CYP4A11 (angiogenesis/ metastasis) are known cancer associated markers. The GRNs were highly dataset specific on the interaction level between individual genes, but showed large similarities on the biological function level represented by subnetworks. Remarkably, the RNAseq UC GRN showed twice the proportion of significant functional subnetworks. Based on our analysis of inferential and experimental networks the Bead UC GRN showed the lowest performance compared to the RNAseq and Oligo UC GRNs.

CONCLUSION: To our knowledge, this is the first study investigating genome-scale UC GRNs. RNAseq based gene expression data is the data platform of choice for a GRN inference. Our study offers new avenues for the identification of novel putative diagnostic targets for subsequent studies in bladder tumors.

Colorectal cancer risk following adenoma removal: a large prospective population-based cohort study

Background: Randomised controlled trials have demonstrated significant reductions in colorectal cancer (CRC) incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing CRC risk in routine clinical practice. The aim of this investigation was to quantify CRC risk following polypectomy in a large prospective population-based cohort study.

Methods: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland (NI) were identified via electronic pathology reports received to the NI Cancer Registry (NICR). Patients were matched to the NICR to detect CRC and deaths up to 31st December 2010. CRC standardised incidence ratios (SIRs) were calculated and Cox proportional hazards modelling applied to determine CRC risk.

Results: During 44,724 person-years of follow-up, 193 CRC cases were diagnosed amongst 6,972 adenoma patients, representing an annual progression rate of 0.43%. CRC risk was significantly elevated in patients who had an adenoma removed (SIR 2.85; 95% CI: 2.61 to 3.25) compared with the general population. Male sex, older age, rectal site and villous architecture were associated with an increased CRC risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess CRC risk.

Conclusions: CRC risk was elevated in individuals following polypectomy for adenoma, outside of screening programmes.

Impact: This finding emphasises the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma.

Network Connectivity Proxy: Architecture, Implementation, and Performance Analysis

Several studies in the last decade have pointed out that many devices, such as computers, are often left powered on even when idle, just to make them available and reachable on the network, leading to large energy waste. The concept of network connectivity proxy (NCP) has been proposed as an effective means to improve energy efficiency. It impersonates the presence of networked devices that are temporally unavailable, by carrying out background networking routines on their behalf. Hence, idle devices could be put into low-power states and save energy. Several architectural alternatives and the applicability of this concept to different protocols and applications have been investigated. However, there is no clear understanding of the limitations and issues of this approach in current networking scenarios. This paper extends the knowledge about the NCP by defining an extended set of tasks that the NCP can carry out, by introducing a suitable communication interface to control NCP operation, and by designing, implementing, and evaluating a functional prototype.

Gleason Upgrading with Time in a Large Prostate Cancer Active Surveillance Cohort

PURPOSE: We report the percentage of patients on active surveillance who had disease pathologically upgraded and factors that predict for upgrading on surveillance biopsies.

MATERIALS AND METHODS: Patients in our active surveillance database with at least 1 repeat prostate biopsy were included. Histological upgrading was defined as any increase in primary or secondary Gleason grade on repeat biopsy. Multivariate analysis was used to determine baseline and dynamic factors associated with Gleason upgrading. This information was used to develop a nomogram to predict for upgrading or treatment in patients electing for active surveillance.

RESULTS: Of 862 patients in our cohort 592 had 2 or more biopsies. Median followup was 6.4 years. Of the patients 20% were intermediate risk, 0.3% were high risk and all others were low risk. During active surveillance 31.3% of cases were upgraded. On multivariate analysis clinical stage T2, higher prostate specific antigen and higher percentage of cores involved with disease at the time of diagnosis predicted for upgrading. A total of 27 cases (15% of those upgraded) were Gleason 8 or higher at upgrading, and 62% of all 114 upgraded cases went on to have active treatment. The nomogram incorporated clinical stage, age, prostate specific antigen, core positivity and Gleason score. The concordance index was 0.61.

CONCLUSIONS: In this large re-biopsy cohort with medium-term followup, most cases have not been pathologically upgraded to date. A model predicting for upgrading or radical treatment was developed which could be useful in counseling patients considering active surveillance for prostate cancer.

Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma:analysis of a clinic-based population

Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history.

High-resolution genetic analysis reveals extensive gene flow within the jellyfish Pelagia noctiluca (Scyphozoa) in the North Atlantic and Mediterranean Sea

Despite the importance of gelatinous zooplankton as components of marine ecosystems, both ecologically and socio-economically, relatively little is known about population persistence or connectivity in jellyfish. In the present study, we employed a combination of nuclear microsatellite markers and sequence data from the mitochondrial cytochrome oxidase I (COI) gene to determine levels and patterns of population genetic structuring in the holoplanktonic jellyfish Pelagia noctiluca across the northeast Atlantic Ocean and Mediterranean Sea. Our results indicate a high degree of connectivity in P. noctiluca, with little evidence of geographical structuring of genetic variation. A small but significant differentiation of Atlantic Ocean and Mediterranean stocks was detected based on the microsatellite data, but no evidence of differentiation was observed with the mtDNA, probably due to the higher power of the microsatellites to detect low levels of genetic structuring. Two clearly distinct groups of genotypes were observed within the mtDNA COI, which probably diverged in the early Pleistocene, but with no evidence of geographical structuring. Palaeodistribution modelling of P. noctiluca at the Last Glacial Maximum (LGM; ca. 21 KYA) indicated large areas of suitable habitat south of the species’ current-day distribution, with little reduction in area. The congruent evidence for minimal genetic differentiation from the nuclear microsatellites and the mtDNA, coupled with the results of the palaeodistribution modelling, supports the idea of long-term population stability and connectivity, thus providing key insights into the population dynamics and demography of this important species

Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies

Purpose: Researchers have demonstrated associations between trauma and psychosis. Childhood trauma, in particular, appears to be an important determinant. Recently, bullying has become considered a traumatic experience in its own right. This review aims to analyse research with prospective designs, which will enable conclusions about whether or not bullying causes psychosis.

Methods: A systematic review of the literature was carried out independently by two reviewers. Eligibility and quality assessment criteria were applied. A meta-analysis and narrative synthesis were then completed.

Results: Ten studies met inclusion criteria. Four used data from the same large database, and were combined as one. The majority provided confirmation that bullying appears to cause later development of psychosis. A meta-analysis yielded an unadjusted odds ratio (OR) of 2.148 [95% confidence interval (CI) 1.140–4.044].

Conclusions: The studies reviewed here suggest that bullying does predict the later development of psychotic symptoms. What is lacking from the literature is adequate investigation into other potential mediating factors. The current review highlights the significant role of bullying within this complex interaction. Potential mediating variables are explored, including a dose–response effect for the severity and frequency of victimization. Suggestions for targeting intervention are also suggested alongside clinical implications and recommendations for future research.

Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes

BACKGROUND: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes.

METHODS: We performed GWAS of empirically derived positive and negative symptom scales in Irish cases from multiply affected pedigrees and a larger, independent case-control sample, subsequently combining these into a large Irish meta-analysis. In addition to single-SNP associations, we considered gene-based and pathway analyses to better capture convergent genetic effects, and to facilitate biological interpretation of these findings. Replication and testing of aggregate genetic effects was conducted using an independent European-American sample.

RESULTS: Though no single marker met the genome-wide significance threshold, genes and ontologies/pathways were significantly associated with negative and positive symptoms; notably, NKAIN2 and NRG1, respectively. We observed limited overlap in ontologies/pathways associated with different symptom profiles, with immune-related categories over-represented for negative symptoms, and addiction-related categories for positive symptoms. Replication analyses suggested that genes associated with clinical presentation are generalizable to non-Irish samples.

CONCLUSIONS: These findings strongly support the hypothesis that modifier loci contribute to the etiology of distinct Scz symptom profiles. The finding that previously implicated "risk loci" actually influence particular symptom dimensions has the potential to better delineate the roles of these genes in Scz etiology. Furthermore, the over-representation of distinct gene ontologies/pathways across symptom profiles suggests that the clinical heterogeneity of Scz is due in part to complex and diverse genetic factors.

Geostatistical Fisher discriminant analysis

A geostatistical version of the classical Fisher rule (linear discriminant analysis) is presented.This method is applicable when a large dataset of multivariate observations is available within a domain split in several known subdomains, and it assumes that the variograms (or covariance functions) are comparable between subdomains, which only differ in the mean values of the available variables. The method consists on finding the eigen-decomposition of the matrix W-1B, where W is the matrix of sills of all direct- and cross-variograms, and B is the covariance matrix of the vectors of weighted means within each subdomain, obtained by generalized least squares. The method is used to map peat blanket occurrence in Northern Ireland, with data from the Tellus
survey, which requires a minimal change to the general recipe: to use compositionally-compliant variogram tools and models, and work with log-ratio transformed data.

Secure D2D Communication in Large-Scale Cognitive Cellular Networks: A Wireless Power Transfer Model

In this paper, we investigate secure device-to-device (D2D) communication in energy harvesting large-scale cognitive cellular networks. The energy constrained D2D transmitter harvests energy from multiantenna equipped power beacons (PBs), and communicates with the corresponding receiver using the spectrum of the primary base stations (BSs). We introduce a power transfer model and an information signal model to enable wireless energy harvesting and secure information transmission. In the power transfer model, three wireless power transfer (WPT) policies are proposed: 1) co-operative power beacons (CPB) power transfer, 2) best power beacon (BPB) power transfer, and 3) nearest power beacon (NPB) power transfer. To characterize the power transfer reliability of the proposed three policies, we derive new expressions for the exact power outage probability. Moreover, the analysis of the power outage probability is extended to the case when PBs are equipped with large antenna arrays. In the information signal model, we present a new comparative framework with two receiver selection schemes: 1) best receiver selection (BRS), where the receiver with the strongest channel is selected; and 2) nearest receiver selection (NRS), where the nearest receiver is selected. To assess the secrecy performance, we derive new analytical expressions for the secrecy outage probability and the secrecy throughput considering the two receiver selection schemes using the proposed WPT policies. We presented Monte carlo simulation results to corroborate our analysis and show: 1) secrecy performance improves with increasing densities of PBs and D2D receivers due to larger multiuser diversity gain; 2) CPB achieves better secrecy performance than BPB and NPB but consumes more power; and 3) BRS achieves better secrecy performance than NRS but demands more instantaneous feedback and overhead. A pivotal conclusion- is reached that with increasing number of antennas at PBs, NPB offers a comparable secrecy performance to that of BPB but with a lower complexity.

Endothelial cell loss and surgically induced astigmatism after sutureless large-incision manual cataract extraction (SLIMCE).

OBJECTIVES:

To describe a modified manual cataract extraction technique, sutureless large-incision manual cataract extraction (SLIMCE), and to report its clinical outcomes.

METHODS:

Case notes of 50 consecutive patients with cataract surgery performed using the SLIMCE technique were retrospectively reviewed. Clinical outcomes 3 months after surgery were analyzed, including postoperative uncorrected visual acuity, best-corrected visual acuity, intraoperative and postoperative complications, endothelial cell loss, and surgically induced astigmatism using the vector analysis method.

RESULTS:

At the 3-month follow-up, all 50 patients had postoperative best-corrected visual acuity of at least 20/60, and 37 patients (74%) had visual acuity of at least 20/30. Uncorrected visual acuity was at least 20/68 in 28 patients (56%) and was between 20/80 and 20/200 in 22 patients (44%). No significant intraoperative complications were encountered, and sutureless wounds were achieved in all but 2 patients. At the 3-month follow-up, endothelial cell loss was 3.9%, and the mean surgically induced astigmatism was 0.69 diopter.

CONCLUSIONS:

SLIMCE is a safe and effective manual cataract extraction technique with low rates of surgically induced astigmatism and endothelial cell loss. In view of its low cost, SLIMCE may have a potential role in reducing cataract blindness in developing countries.

Heterogeneous error-resilient scheme for spectral analysis in ultra-low power wearable electrocardiogram devices

Wearable devices performing advanced bio-signal analysis algorithms are aimed to foster a revolution in healthcare provision of chronic cardiac diseases. In this context, energy efficiency is of paramount importance, as long-term monitoring must be ensured while relying on a tiny power source. Operating at a scaled supply voltage, just above the threshold voltage, effectively helps in saving substantial energy, but it makes circuits, and especially memories, more prone to errors, threatening the correct execution of algorithms. The use of error detection and correction codes may help to protect the entire memory content, however it incurs in large area and energy overheads which may not be compatible with the tight energy budgets of wearable systems. To cope with this challenge, in this paper we propose to limit the overhead of traditional schemes by selectively detecting and correcting errors only in data highly impacting the end-to-end quality of service of ultra-low power wearable electrocardiogram (ECG) devices. This partition adopts the protection of either significant words or significant bits of each data element, according to the application characteristics (statistical properties of the data in the application buffers), and its impact in determining the output. The proposed heterogeneous error protection scheme in real ECG signals allows substantial energy savings (11% in wearable devices) compared to state-of-the-art approaches, like ECC, in which the whole memory is protected against errors. At the same time, it also results in negligible output quality degradation in the evaluated power spectrum analysis application of ECG signals.