The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Threshold-induced phase transitions in perceptrons

Error rates of a Boolean perceptron with threshold and either spherical or Ising constraint on the weight vector are calculated for storing patterns from biased input and output distributions derived within a one-step replica symmetry breaking (RSB) treatment. For unbiased output distribution and non-zero stability of the patterns, we find a critical load, α p, above which two solutions to the saddlepoint equations appear; one with higher free energy and zero threshold and a dominant solution with non-zero threshold. We examine this second-order phase transition and the dependence of α p on the required pattern stability, κ, for both one-step RSB and replica symmetry (RS) in the spherical case and for one-step RSB in the Ising case.

Digital video transmission over wireless networks

The advent of the Integrated Services Digital Network (ISDN) led to the standardisation of the first video codecs for interpersonal video communications, followed closely by the development of standards for the compression, storage and distribution of digital video in the PC environment, mainly targeted at CD-ROM storage. At the same time the second-generation digital wireless networks, and the third-generation networks being developed, have enough bandwidth to support digital video services. The radio propagation medium is a difficult environment in which to deploy low bit error rate, real time services such as video. The video coding standards designed for ISDN and storage applications, were targeted at low bit error rate levels, orders of magnitude lower than the typical bit error rates experienced on wireless networks. This thesis is concerned with the transmission of digital, compressed video over wireless networks. It investigates the behaviour of motion compensated, hybrid interframe DPCM/DCT video coding algorithms, which form the basis of current coding algorithms, in the presence of high bit error rates commonly found on digital wireless networks. A group of video codecs, based on the ITU-T H.261 standard, are developed which are robust to the burst errors experienced on radio channels. The radio link is simulated at low level, to generate typical error files that closely model real world situations, in a Rayleigh fading environment perturbed by co-channel interference, and on frequency selective channels which introduce inter symbol interference. Typical anti-multipath techniques, such as antenna diversity, are deployed to mitigate the effects of the channel. Link layer error control techniques are also investigated.

Noisy random Boolean formulae:a statistical physics perspective

Properties of computing Boolean circuits composed of noisy logical gates are studied using the statistical physics methodology. A formula-growth model that gives rise to random Boolean functions is mapped onto a spin system, which facilitates the study of their typical behavior in the presence of noise. Bounds on their performance, derived in the information theory literature for specific gates, are straightforwardly retrieved, generalized and identified as the corresponding macroscopic phase transitions. The framework is employed for deriving results on error-rates at various function-depths and function sensitivity, and their dependence on the gate-type and noise model used. These are difficult to obtain via the traditional methods used in this field.

On the robustness of random Boolean formulae

Random Boolean formulae, generated by a growth process of noisy logical gates are analyzed using the generating functional methodology of statistical physics. We study the type of functions generated for different input distributions, their robustness for a given level of gate error and its dependence on the formulae depth and complexity and the gates used. Bounds on their performance, derived in the information theory literature for specific gates, are straightforwardly retrieved, generalized and identified as the corresponding typical-case phase transitions. Results for error-rates, function-depth and sensitivity of the generated functions are obtained for various gate-type and noise models. © 2010 IOP Publishing Ltd.

Computing with noise: phase transitions in Boolean formulas

Computing circuits composed of noisy logical gates and their ability to represent arbitrary Boolean functions with a given level of error are investigated within a statistical mechanics setting. Existing bounds on their performance are straightforwardly retrieved, generalized, and identified as the corresponding typical-case phase transitions. Results on error rates, function depth, and sensitivity, and their dependence on the gate-type and noise model used are also obtained.

Phonological–lexical activation:a lexical component or anoutput buffer? Evidence from aphasic errors

Single word production requires that phoneme activation is maintained while articulatory conversion is taking place. Word serial recall, connected speech and non-word production (repetition and spelling) are all assumed to involve a phonological output buffer. A crucial question is whether the same memory resources are also involved in single word production. We investigate this question by assessing length and positional effects in the single word repetition and reading of six aphasic patients. We expect a damaged buffer to result in error rates per phoneme which increase with word length and in position effects. Although our patients had trouble with phoneme activation (they made mainly errors of phoneme selection), they did not show the effects expected from a buffer impairment. These results show that phoneme activation cannot be automatically equated with a buffer. We hypothesize that the phonemes of existing words are kept active though permanent links to the word node. Thus, the sustained activation needed for their articulation will come from the lexicon and will have different characteristics from the activation needed for the short-term retention of an unbound set of units. We conclude that there is no need and no evidence for a phonological buffer in single word production.

Adaptive electrical signal post-processing in optical communications systems

Improving bit error rates in optical communication systems is a difficult and important problem. The error correction must take place at high speed and be extremely accurate. We show the feasibility of using hardware implementable machine learning techniques. This may enable some error correction at the speed required.

Medication errors in older people with mental health problems:a review

Objective - To review and summarise published data on medication errors in older people with mental health problems. Methods - A systematic review was conducted to identify studies that investigated medication errors in older people with mental health problems. MEDLINE, EMBASE, PHARMLINE, COCHRANE COLLABORATION and PsycINFO were searched electronically. Any studies identified were scrutinized for further references. The title, abstract or full text was systematically reviewed for relevance. Results - Data were extracted from eight studies. In total, information about 728 errors (459 administration, 248 prescribing, 7 dispensing, 12 transcribing, 2 unclassified) was available. The dataset related almost exclusively to inpatients, frequently involved non-psychotropics, and the majority of the errors were not serious. Conclusions - Due to methodology issues it was impossible to calculate overall error rates. Future research should concentrate on serious errors within community settings, and clarify potential risk factors.

Characterization of time-resolved laser differential phase using 3D complementary cumulative distribution functions

An experimental method for characterizing the time-resolved phase noise of a fast switching tunable laser is discussed. The method experimentally determines a complementary cumulative distribution function of the laser's differential phase as a function of time after a switching event. A time resolved bit error rate of differential quadrature phase shift keying formatted data, calculated using the phase noise measurements, was fitted to an experimental time-resolved bit error rate measurement using a field programmable gate array, finding a good agreement between the time-resolved bit error rates.

Experiences in using a contingency factor-based validation methodology for spreadsheet DSS

The use of spreadsheets has become routine in all aspects of business with usage growing across a range of functional areas and a continuing trend towards end user spreadsheet development. However, several studies have raised concerns about the accuracy of spreadsheet models in general, and of end user developed applications in particular, raising the risk element for users. High error rates have been discovered, even though the users/developers were confident that their spreadsheets were correct. The lack of an easy to use, context-sensitive validation methodology has been highlighted as a significant contributor to the problems of accuracy. This paper describes experiences in using a practical, contingency factor-based methodology for validation of spreadsheet-based DSS. Because the end user is often both the system developer and a stakeholder, the contingency factor-based validation methodology may need to be used in more than one way. The methodology can also be extended to encompass other DSS.

Reduced attentional capacity, but normal processing speed and shifting of attention in developmental dyslexia: evidence from a serial task

We report the performance of a group of adult dyslexics and matched controls in an array-matching task where two strings of either consonants or symbols are presented side by side and have to be judged to be the same or different. The arrays may differ either in the order or identity of two adjacent characters. This task does not require naming – which has been argued to be the cause of dyslexics’ difficulty in processing visual arrays – but, instead, has a strong serial component as demonstrated by the fact that, in both groups, Reaction times (RTs) increase monotonically with position of a mismatch. The dyslexics are clearly impaired in all conditions and performance in the identity conditions predicts performance across orthographic tasks even after age, performance IQ and phonology are partialled out. Moreover, the shapes of serial position curves are revealing of the underlying impairment. In the dyslexics, RTs increase with position at the same rate as in the controls (lines are parallel) ruling out reduced processing speed or difficulties in shifting attention. Instead, error rates show a catastrophic increase for positions which are either searched later or more subject to interference. These results are consistent with a reduction in the attentional capacity needed in a serial task to bind together identity and positional information. This capacity is best seen as a reduction in the number of spotlights into which attention can be split to process information at different locations rather than as a more generic reduction of resources which would also affect processing the details of single objects.

Adaptive electrical signal post-processing in optical communications systems

Improving bit error rates in optical communication systems is a difficult and important problem. The error correction must take place at high speed and be extremely accurate. We show the feasibility of using hardware implementable machine learning techniques. This may enable some error correction at the speed required.

Multiple component patient safety intervention in English hospitals:controlled evaluation of second phase

Objective: To independently evaluate the impact of the second phase of the Health Foundation's Safer Patients Initiative (SPI2) on a range of patient safety measures. Design: A controlled before and after design. Five substudies: survey of staff attitudes; review of case notes from high risk (respiratory) patients in medical wards; review of case notes from surgical patients; indirect evaluation of hand hygiene by measuring hospital use of handwashing materials; measurement of outcomes (adverse events, mortality among high risk patients admitted to medical wards, patients' satisfaction, mortality in intensive care, rates of hospital acquired infection). Setting: NHS hospitals in England. Participants: Nine hospitals participating in SPI2 and nine matched control hospitals. Intervention The SPI2 intervention was similar to the SPI1, with somewhat modified goals, a slightly longer intervention period, and a smaller budget per hospital. Results: One of the scores (organisational climate) showed a significant (P=0.009) difference in rate of change over time, which favoured the control hospitals, though the difference was only 0.07 points on a five point scale. Results of the explicit case note reviews of high risk medical patients showed that certain practices improved over time in both control and SPI2 hospitals (and none deteriorated), but there were no significant differences between control and SPI2 hospitals. Monitoring of vital signs improved across control and SPI2 sites. This temporal effect was significant for monitoring the respiratory rate at both the six hour (adjusted odds ratio 2.1, 99% confidence interval 1.0 to 4.3; P=0.010) and 12 hour (2.4, 1.1 to 5.0; P=0.002) periods after admission. There was no significant effect of SPI for any of the measures of vital signs. Use of a recommended system for scoring the severity of pneumonia improved from 1.9% (1/52) to 21.4% (12/56) of control and from 2.0% (1/50) to 41.7% (25/60) of SPI2 patients. This temporal change was significant (7.3, 1.4 to 37.7; P=0.002), but the difference in difference was not significant (2.1, 0.4 to 11.1; P=0.236). There were no notable or significant changes in the pattern of prescribing errors, either over time or between control and SPI2 hospitals. Two items of medical history taking (exercise tolerance and occupation) showed significant improvement over time, across both control and SPI2 hospitals, but no additional SPI2 effect. The holistic review showed no significant changes in error rates either over time or between control and SPI2 hospitals. The explicit case note review of perioperative care showed that adherence rates for two of the four perioperative standards targeted by SPI2 were already good at baseline, exceeding 94% for antibiotic prophylaxis and 98% for deep vein thrombosis prophylaxis. Intraoperative monitoring of temperature improved over time in both groups, but this was not significant (1.8, 0.4 to 7.6; P=0.279), and there were no additional effects of SPI2. A dramatic rise in consumption of soap and alcohol hand rub was similar in control and SPI2 hospitals (P=0.760 and P=0.889, respectively), as was the corresponding decrease in rates of Clostridium difficile and meticillin resistant Staphylococcus aureus infection (P=0.652 and P=0.693, respectively). Mortality rates of medical patients included in the case note reviews in control hospitals increased from 17.3% (42/243) to 21.4% (24/112), while in SPI2 hospitals they fell from 10.3% (24/233) to 6.1% (7/114) (P=0.043). Fewer than 8% of deaths were classed as avoidable; changes in proportions could not explain the divergence of overall death rates between control and SPI2 hospitals. There was no significant difference in the rate of change in mortality in intensive care. Patients' satisfaction improved in both control and SPI2 hospitals on all dimensions, but again there were no significant changes between the two groups of hospitals. Conclusions: Many aspects of care are already good or improving across the NHS in England, suggesting considerable improvements in quality across the board. These improvements are probably due to contemporaneous policy activities relating to patient safety, including those with features similar to the SPI, and the emergence of professional consensus on some clinical processes. This phenomenon might have attenuated the incremental effect of the SPI, making it difficult to detect. Alternatively, the full impact of the SPI might be observable only in the longer term. The conclusion of this study could have been different if concurrent controls had not been used.

Investigating microphone efficacy for facilitation of mobile speech-based data entry

Despite being nominated as a key potential interaction technique for supporting today's mobile technology user, the widespread commercialisation of speech-based input is currently being impeded by unacceptable recognition error rates. Developing effective speech-based solutions for use in mobile contexts, given the varying extent of background noise, is challenging. The research presented in this paper is part of an ongoing investigation into how best to incorporate speechbased input within mobile data collection applications. Specifically, this paper reports on a comparison of three different commercially available microphones in terms of their efficacy to facilitate mobile, speech-based data entry. We describe, in detail, our novel evaluation design as well as the results we obtained.