A Protocol for the Secure Linking of Registries for HPV Surveillance

In order to monitor the effectiveness of HPV vaccination in Canada the linkage of multiple data registries may be required. These registries may not always be managed by the same organization and, furthermore, privacy legislation or practices may restrict any data linkages of records that can actually be done among registries. The objective of this study was to develop a secure protocol for linking data from different registries and to allow on-going monitoring of HPV vaccine effectiveness.A secure linking protocol, using commutative hash functions and secure multi-party computation techniques was developed. This protocol allows for the exact matching of records among registries and the computation of statistics on the linked data while meeting five practical requirements to ensure patient confidentiality and privacy. The statistics considered were: odds ratio and its confidence interval, chi-square test, and relative risk and its confidence interval. Additional statistics on contingency tables, such as other measures of association, can be added using the same principles presented. The computation time performance of this protocol was evaluated.The protocol has acceptable computation time and scales linearly with the size of the data set and the size of the contingency table. The worse case computation time for up to 100,000 patients returned by each query and a 16 cell contingency table is less than 4 hours for basic statistics, and the best case is under 3 hours.A computationally practical protocol for the secure linking of data from multiple registries has been demonstrated in the context of HPV vaccine initiative impact assessment. The basic protocol can be generalized to the surveillance of other conditions, diseases, or vaccination programs

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities

A quantitative systems view of the spindle assembly checkpoint

The idle assembly checkpoint acts to delay chromosome segregation until all duplicated sister chromatids are captured by the mitotic spindle. This pathway ensures that each daughter cell receives a complete copy of the genome. The high fidelity and robustness of this process have made it a subject of intense study in both the experimental and computational realms. A significant number of checkpoint proteins have been identified but how they orchestrate the communication between local spindle attachment and global cytoplasmic signalling to delay segregation is not yet understood. Here, we propose a systems view of the spindle assembly checkpoint to focus attention on the key regulators of the dynamics of this pathway. These regulators in turn have been the subject of detailed cellular measurements and computational modelling to connect molecular function to the dynamics of spindle assembly checkpoint signalling. A review of these efforts reveals the insights provided by such approaches and underscores the need for further interdisciplinary studies to reveal in full the quantitative underpinnings of this cellular control pathway

Laser Doppler blood flow imaging using a CMOS imaging sensor with on-chip signal processing

The first fully integrated 2D CMOS imaging sensor with on-chip signal processing for applications in laser Doppler blood flow (LDBF) imaging has been designed and tested. To obtain a space efficient design over 64 × 64 pixels means that standard processing electronics used off-chip cannot be implemented. Therefore the analog signal processing at each pixel is a tailored design for LDBF signals with balanced optimization for signal-to-noise ratio and silicon area. This custom made sensor offers key advantages over conventional sensors, viz. the analog signal processing at the pixel level carries out signal normalization; the AC amplification in combination with an anti-aliasing filter allows analog-to-digital conversion with a low number of bits; low resource implementation of the digital processor enables on-chip processing and the data bottleneck that exists between the detector and processing electronics has been overcome. The sensor demonstrates good agreement with simulation at each design stage. The measured optical performance of the sensor is demonstrated using modulated light signals and in vivo blood flow experiments. Images showing blood flow changes with arterial occlusion and an inflammatory response to a histamine skin-prick demonstrate that the sensor array is capable of detecting blood flow signals from tissue

Improving face recognition in age-related macular degeneration via caricaturing

Purpose : Patients with age-related macular degeneration (AMD) have difficulty recognising faces and facial expressions. We examined if this could be improved using an image enhancement procedure derived from high-level cortical coding of faces in a perceptual 'face-space', namely caricaturing. Caricaturing exaggerates the ways in which the shape information in an individual face differs from the average. We tested whether caricaturing would improve face identity perception in AMD patients, and facial expression recognition in a simulation of AMD (normal-sighted young adults shown blurred faces). Methods : To test identity perception, 12 Caucasian AMD patients (mean age 81, range 67-92, 8 females) with mild through severe stages of AMD performed a rating task using monocular vision. Using four levels of caricaturing (0, 20, 40 and 60% exaggeration), and 26 young adult Caucasian faces, participants rated how different two people's faces appeared when compared in pairs. To test expression recognition, 45 Caucasian normal-sighted undergraduates (mean age 22, 36 females) labelled expressions (as happy, sad, anger, fear, disgust, surprise) using two blur levels (50 and 70) to mimic the appearance of different severities of AMD and four levels of caricaturing (0, 40, 80, 100% exaggeration). Results : For identity, a total of 19 eyes were included in AMD patients with visual acuities (VA) ranging from 6/6 to 6/360. Analysing individual eyes, a significant caricature advantage (at p<.05) was seen in 9/9 (100%) eyes with mild AMD (6/6 to 6/15), 3/6 (50%) eyes with moderate AMD (6/24 to 6/30), and 2/4 (50%) eyes with severe AMD (6/75 and 6/360). No change with caricaturing was found for one patient (both eyes; VA 6/19 and 6/24) and in 3 individual eyes (6/60, 6/120 and 6/360). For expression, caricaturing significantly improved expression recognition (at p<.01) at both blur levels (simulating approximately moderate and severe AMD) with accuracy improved by approximately 7% (e.g., for severe blur, 44% correct in expression labelling without caricaturing, 51% with 100% exaggeration). Conclusions : Caricaturing can significantly improve perceived differences in facial identity in patients with mild AMD and some patients with moderate and severe AMD. It also significantly improves expression recognition in simulated AMD conditions with normal-sighted young adults, suggesting it should also be useful for expression recognition in patients

Impacts of impaired face perception on social interactions and quality of life in age-related macular degeneration:A qualitative study and new community resources

Aims Previous studies and community information about everyday difficulties in age-related macular degeneration (AMD) have focussed on domains such as reading and driving. Here, we provide the first in-depth examination of how impaired face perception impacts social interactions and quality of life in AMD. We also develop a Faces and Social Life in AMD brochure and information sheet, plus accompanying conversation starter, aimed at AMD patients and those who interact with them (family, friends, nursing home staff). Method Semi-structured face-to-face interviews were conducted with 21 AMD patients covering the full range from mild vision loss to legally blind. Thematic analysis was used to explore the range of patient experiences. Results Patients reported faces appeared blurred and/or distorted. They described recurrent failures to recognise others' identity, facial expressions and emotional states, plus failures of alternative non-face strategies (e.g., hairstyle, voice). They reported failures to follow social nuances (e.g., to pick up that someone was joking), and feelings of missing out ('I can't join in'). Concern about offending others (e.g., by unintentionally ignoring them) was common, as were concerns of appearing fraudulent ('Other people don't understand'). Many reported social disengagement. Many reported specifically face-perception-related reductions in social life, confidence, and quality of life. All effects were observed even with only mild vision loss. Patients endorsed the value of our Faces and Social Life in AMD Information Sheet, developed from the interview results, and supported future technological assistance (digital image enhancement). Conclusion Poor face perception in AMD is an important domain contributing to impaired social interactions and quality of life. This domain should be directly assessed in quantitative quality of life measures, and in resources designed to improve community understanding. The identity-related social difficulties mirror those in prosopagnosia, of cortical rather than retinal origin, implying findings may generalise to all low-vision disorders.This research was supported by Australian Research Council grants CE110001021 (www.ccd.edu.au; EM, JL, AD) and DP150100684 (EM), National Health and Medical Research Council Project Grant 1063458 (https://www.nhmrc.gov.au/ TM, ER and FS), Rebecca Cooper Medical Foundation Grant (FS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Improving face identity perception in age-related macular degeneration via caricaturing

Abstract Patients with age-related macular degeneration (AMD) have difficulty recognising people’s faces. We tested whether this could be improved using caricaturing: an image enhancement procedure derived from cortical coding in a perceptual ‘face-space’. Caricaturing exaggerates the distinctive ways in which an individual’s face shape differs from the average. We tested 19 AMD-affected eyes (from 12 patients; ages 66–93 years) monocularly, selected to cover the full range of vision loss. Patients rated how different in identity people’s faces appeared when compared in pairs (e.g., two young men, both Caucasian), at four caricature strengths (0, 20, 40, 60% exaggeration). This task gives data reliable enough to analyse statistically at the individual-eye level. All 9 eyes with mild vision loss (acuity ≥ 6/18) showed significant improvement in identity discrimination (higher dissimilarity ratings) with caricaturing. The size of improvement matched that in normal-vision young adults. The caricature benefit became less stable as visual acuity further decreased, but caricaturing was still effective in half the eyes with moderate and severe vision loss (significant improvement in 5 of 10 eyes; at acuities from 6/24 to poorer than <6/360). We conclude caricaturing has the potential to help many AMD patients recognise faces