Working Memories for Storage and Recall of Arbitrary Temporal Sequences

A working memory model is described that is capable of storing and recalling arbitrary temporal sequences of events, including repeated items. These memories encode the invariant temporal order of sequential events that may be presented at widely differing speeds, durations, and interstimulus intervals. This temporal order code is designed to enable all possible groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system.

Store Working Memory Networks for Storage and Recall of Arbitrary Temporal Sequences

Neural network models of working memory, called Sustained Temporal Order REcurrent (STORE) models, are described. They encode the invariant temporal order of sequential events in short term memory (STM) in a way that mimics cognitive data about working memory, including primacy, recency, and bowed order and error gradients. As new items are presented, the pattern of previously stored items is invariant in the sense that, relative activations remain constant through time. This invariant temporal order code enables all possible groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system. Such a competence is needed to design self-organizing temporal recognition and planning systems in which any subsequence of events may need to be categorized in order to to control and predict future behavior or external events. STORE models show how arbitrary event sequences may be invariantly stored, including repeated events. A preprocessor interacts with the working memory to represent event repeats in spatially separate locations. It is shown why at least two processing levels are needed to invariantly store events presented with variable durations and interstimulus intervals. It is also shown how network parameters control the type and shape of primacy, recency, or bowed temporal order gradients that will be stored.

Soft sediment ecology of Lough Hyne Marine Reserve - spatial and temporal patterns

Distribution of soft sediment benthic fauna and the environmental factors affecting them were studied, to investigate changes across spatial and temporal scales. Investigations took place at Lough Hyne Marine Reserve using a range of methods. Data on the sedimentation rates of organic and inorganic matter were collected at monthly intervals for one year at a number of sites around the Lough, by use of vertical midwater-column sediment traps. Sedimentation of these two fractions were not coupled; inorganic matter sedimentation depended on hydrodynamic and weather factors, while the organic matter sedimentation was more complex, being dependent on biological and chemical processes in the water column. The effects of regular hypoxic episodes on benthic fauna due to a natural seasonal thermocline were studied in the deep Western Trough, using camera-equipped remotely-operated vehicle to follow transects, on a three-monthly basis over one year. In late summer, the area below the thermocline of the Western Trough was devoid of visible fauna. Decapod crustaceans were the first taxon to make use of ameliorating oxygen conditions in autumn, by darting below the thermocline depth, most likely to scavenge. This was indicated by tracks that they left on the surface of the Trough floor. Some species, most noticeably Fries’ goby Lesueurigobius friesii, migrated below the thermocline depth when conditions were normoxic and established semi-permanent burrows. Their population encompassed all size classes, indicating that this habitat was not limited to juveniles of this territorial species. Recolonisation by macrofauna and burrowing megafauna was studied during normoxic conditions, from November 2009 to May 2010. Macrofauna displayed a typical post-disturbance pattern of recolonisation with one species, the polychaete Scalibregma inflatum, occurring at high abundance levels in March 2010. In May, this population had become significantly reduced and a more diverse community was established. The abundance of burrowing infauna comprising decapods crabs and Fries’ gobies, was estimated by identifying and counting their distinctive burrow structures. While above the summer thermocline depth, burrow abundance increased in a linear fashion, below the thermocline depth a slight reduction of burrow abundance occurred in May, when oxygen conditions deteriorated again. The majority of the burrows occurring in May were made by Fries’ gobies, which are thought to encounter low oxygen concentrations in their burrows. Reduction in burrow abundance of burrowing shrimps Calocaris macandreae and Callianassa subterranea (based on descriptions of burrow structures from the literature), from March to May, might be related to their reduced activity in hypoxia, leading to loss of structural burrow maintenance. Spatial and temporal changes to macrofaunal assemblage structures were studied seasonally for one year across 5 sites in the Lough and subject to multivariate statistical analysis. Assemblage structures were significantly correlated with organic matter levels in the sediment, the amounts of organic matter settling out of the water column one month before macrofaunal sampling took place as well as current speed and temperature. This study was the first to investigate patterns and processes in the Lough soft sediment ecology across all 3 basins on a temporal and spatial scale. An investigation into the oceanographic aspects of the development, behaviour and break-down of the summer thermocline of Lough Hyne was performed in collaboration with researchers from other Irish institutions.

Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol

Background: The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. Methods/Aims: This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre. A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. Conclusion: The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.

Early nutrition and eczema in infancy

Eczema prevalence rates among Irish infants are unreported, despite eczema being the most common inflammatory condition of infancy. Maternal and infant nutritional status including vitamin D and other fat-soluble vitamins as well as early infant feeding have been linked with eczema initiation and development. Therefore, early nutrition could be a potential modifiable risk factor. The objective of this thesis was to prospectively describe early infant feeding and complementary feeding practices, to evaluate infant vitamin D supplementation practice, to quantify cord serum 25-hydroxyvitamin D [25(OH)D] and propose reference intervals for vitamin D metabolites, to report eczema prevalence and explore the potential role of infant nutrition and eczema. These research needs were investigated through the Cork BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact with Neurological and Nutritional Endpoints) Birth Cohort Study (n 2137). This thesis was the first comprehensive report from the birth cohort, therefore it was important to describe the cohort sociodemographic profile. Although socio-demographic characteristics compared well with national data, there was an over-representation of educated mothers which may limit the generalizability of the results. From August 2008 through November 2011, comprehensive postnatal assessments were completed at day 2 and at 2, 6, 12 and 24 months. Breastfeeding rates were low, while complementary feeding practices were broadly compliant with national guidelines. The implementation of a national infant vitamin D supplementation policy had a major impact on supplementation practice. Low levels of serum 25(OH)D were universal among Irish neonates. Eczema is a complex and multifaceted disease, which is increasing globally. This was the first report of eczema prevalence data among Irish infants which compared with international reports. Given the high prevalence and considerable burden eczema has on the lives of sufferers, intensive research efforts to identify a cause and therapeutic strategies to prevent/reduce eczema was re-emphasized in this thesis.

Nutrition, growth and body composition in preterm infants

The goal of neonatal nutrition in the preterm infant is to achieve postnatal growth and body composition approximating that of a normal fetus of the same postmenstrual age and to obtain a functional outcome comparable to infants born at term. However, in clinical practice such a pattern is seldom achieved, with growth failure and altered body composition being extensively reported. The BabyGrow preterm nutrition study was a longitudinal, prospective, observational study designed to investigate nutrition and growth in 59 preterm infants following the implementation of evidence-based nutrition guidelines in the neonatal unit at Cork University Maternity Hospital. Nutrient delivery was precisely measured during the entire hospital stay and intakes were compared with current international recommendations. Barriers to nutrient delivery were identified across the phases of nutritional support i.e. exclusive parenteral nutrition and transition (establishment of enteral feeds) phases of nutrition and nutritional strategies to optimise nutrient delivery were proposed according to these phases. Growth was measured from birth up to 2 months corrected age and body composition was assessed in terms of fat mass and lean body mass by air displacement plethysmography (PEA POD) at 34 weeks gestation, term corrected age and 2 months corrected age. Anthropometric and body composition data in the preterm cohort were compared with a term reference group from the Cork BASELINE Birth Cohort Study (n=1070) at similar time intervals. The clinical and nutritional determinants of growth and body composition during the neonatal period were reported for the first time. These data have international relevance, informing authoritative agencies developing evidence-based practice guidelines for neonatal nutritional support. In the future, the nutritional management of preterm infants may need to be individualised to consider gestational age, birth weight as well as preterm morbidity.

Quaternary geology of the German North Sea and Western Irish Sea Mud Belt: revised stratigraphies, geotechnical properties, sedimentology and anthropogenic impacts

The climatic development of the Mid to Late Quaternary (last 400,000 years) is characterised by fluctuation between glacial and interglacial periods leading to the present interglacial, the Holocene. In comparison to preceding periods it was believed the Holocene represented a time of relative climatic stability. However, recent work has shown that the Holocene can be divided into cooler periods such as the Little Ice Age alternating with time intervals where climatic conditions ameliorated i.e. Medieval Warm Period, Holocene Thermal Optimum and the present Modern Optimum. In addition, the Holocene is recognised as a period with increasing anthropogenic influence on the environment. Onshore records recording glacial/interglacial cycles as well as anthropogenic effects are limited. However, sites of sediment accumulation on the shallow continental shelf offer the potential to reconstruct these events. Such sites include tunnel valleys and low energy, depositional settings. In this study we interrogated the sediment stratigraphy at such sites in the North Sea and Irish Sea using traditional techniques, as well as novel applications of geotechnical data, to reconstruct the palaeoenvironmental record. Within the German North Sea sector a combination of core, seismic and in-situ Cone Penetration Testing (CPT) data was used to identify sedimentary units, place them within a morphological context, relate them to glacial or interglacial periods stratigraphically, and correlate them across the German North Sea. Subsequently, we were able to revise the Mid to Late Quaternary stratigraphy for the North Sea using this new and novel data. Similarly, Holocene environmental changes were investigated within the Irish Sea at a depositional site with active anthropogenic influence. The methods used included analyses on grain-size distribution, foraminifera, gamma spectrometry, AMS 14C and physical core logging. The investigation revealed a strong fluctuating climatic signal early in the areas history before anthropogenic influence affects the record through trawling.

A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

VISION OF EQUINOX FOR ORCHESTRA

The artistic play of light seen on a pyramid in some Mayan ruins located in Cancun, Mexico provided the inspiration for Vision of Equinox. On both the spring and autumn equinox days, the sunlight projected on the pyramid forms a shape which looks like a serpent moving on the stairway of the pyramid. Vision of Equinox was composed with an image of light as the model for the artistic transfiguration of sound. The light image of sound changes its shape in each stage of the piece, using the orchestra in different ways - sometimes like a chamber ensemble, sometimes like one big instrument. The image of light casting on a pyramid is expressed by descending melodic lines that can be heard several times in the piece. At the final climax of the work, a complete and embodied artistic figure is formed and stated, expressing the appearance of the Mayan god Quetzalcoatl, the serpent, in my own imagination. The light and shadow which comprise this pyramid art are treated as two contrasting elements in my composition and become the two main motives in this piece. To express these two contrasting elements, I picked the numbers "5" and "2," and used them as "key numbers" in this piece. As a result, the intervals of a fifth and a second (sometimes inverted as a seventh) are the two main intervals used in the structure. The interval of a fifth was taken into account for the construction of the pyramid, which has five points of contact. The interval of a second was selected as a contrasting sonority to the fifth. Further, the numbers "5" and "2" are used as the number of notes which form the main motives in this piece; quintuplets are used throughout this piece, and the short motive made by two sixteenth notes is used as one of the main motives in this piece. Moreover, the shape of the pyramid provided a concept of symmetry, which is expressed by the setting of a central point of the music (pitch center) as well as the use of retrograde and inversion in this piece.

Prediction in dynamic models with time-dependent conditional variances

This paper considers forecasting the conditional mean and variance from a single-equation dynamic model with autocorrelated disturbances following an ARMA process, and innovations with time-dependent conditional heteroskedasticity as represented by a linear GARCH process. Expressions for the minimum MSE predictor and the conditional MSE are presented. We also derive the formula for all the theoretical moments of the prediction error distribution from a general dynamic model with GARCH(1, 1) innovations. These results are then used in the construction of ex ante prediction confidence intervals by means of the Cornish-Fisher asymptotic expansion. An empirical example relating to the uncertainty of the expected depreciation of foreign exchange rates illustrates the usefulness of the results. © 1992.

A cross-site, comparative effectiveness study of an integrated HIV and substance use treatment program.

Co-occurrence of HIV and substance abuse is associated with poor outcomes for HIV-related health and substance use. Integration of substance use and medical care holds promise for HIV patients, yet few integrated treatment models have been reported. Most of the reported models lack data on treatment outcomes in diverse settings. This study examined the substance use outcomes of an integrated treatment model for patients with both HIV and substance use at three different clinics. Sites differed by type and degree of integration, with one integrated academic medical center, one co-located academic medical center, and one co-located community health center. Participants (n=286) received integrated substance use and HIV treatment for 12 months and were interviewed at 6-month intervals. We used linear generalized estimating equation regression analysis to examine changes in Addiction Severity Index (ASI) alcohol and drug severity scores. To test whether our treatment was differentially effective across sites, we compared a full model including site by time point interaction terms to a reduced model including only site fixed effects. Alcohol severity scores decreased significantly at 6 and 12 months. Drug severity scores decreased significantly at 12 months. Once baseline severity variation was incorporated into the model, there was no evidence of variation in alcohol or drug score changes by site. Substance use outcomes did not differ by age, gender, income, or race. This integrated treatment model offers an option for treating diverse patients with HIV and substance use in a variety of clinic settings. Studies with control groups are needed to confirm these findings.

Variation in the type and frequency of postoperative invasive Staphylococcus aureus infections according to type of surgical procedure.

OBJECTIVE: To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study. SETTING: Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia. PATIENTS: Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures. METHODS: We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate. RESULTS: In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures. CONCLUSION: The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

Major and minor music compared to excited and subdued speech.

The affective impact of music arises from a variety of factors, including intensity, tempo, rhythm, and tonal relationships. The emotional coloring evoked by intensity, tempo, and rhythm appears to arise from association with the characteristics of human behavior in the corresponding condition; however, how and why particular tonal relationships in music convey distinct emotional effects are not clear. The hypothesis examined here is that major and minor tone collections elicit different affective reactions because their spectra are similar to the spectra of voiced speech uttered in different emotional states. To evaluate this possibility the spectra of the intervals that distinguish major and minor music were compared to the spectra of voiced segments in excited and subdued speech using fundamental frequency and frequency ratios as measures. Consistent with the hypothesis, the spectra of major intervals are more similar to spectra found in excited speech, whereas the spectra of particular minor intervals are more similar to the spectra of subdued speech. These results suggest that the characteristic affective impact of major and minor tone collections arises from associations routinely made between particular musical intervals and voiced speech.

Using fractal downscaling of satellite precipitation products for hydrometeorological applications

The objective of spatial downscaling strategies is to increase the information content of coarse datasets at smaller scales. In the case of quantitative precipitation estimation (QPE) for hydrological applications, the goal is to close the scale gap between the spatial resolution of coarse datasets (e.g., gridded satellite precipitation products at resolution L × L) and the high resolution (l × l; L»l) necessary to capture the spatial features that determine spatial variability of water flows and water stores in the landscape. In essence, the downscaling process consists of weaving subgrid-scale heterogeneity over a desired range of wavelengths in the original field. The defining question is, which properties, statistical and otherwise, of the target field (the known observable at the desired spatial resolution) should be matched, with the caveat that downscaling methods be as a general as possible and therefore ideally without case-specific constraints and/or calibration requirements? Here, the attention is focused on two simple fractal downscaling methods using iterated functions systems (IFS) and fractal Brownian surfaces (FBS) that meet this requirement. The two methods were applied to disaggregate spatially 27 summertime convective storms in the central United States during 2007 at three consecutive times (1800, 2100, and 0000 UTC, thus 81 fields overall) from the Tropical Rainfall Measuring Mission (TRMM) version 6 (V6) 3B42 precipitation product (~25-km grid spacing) to the same resolution as the NCEP stage IV products (~4-km grid spacing). Results from bilinear interpolation are used as the control. A fundamental distinction between IFS and FBS is that the latter implies a distribution of downscaled fields and thus an ensemble solution, whereas the former provides a single solution. The downscaling effectiveness is assessed using fractal measures (the spectral exponent β, fractal dimension D, Hurst coefficient H, and roughness amplitude R) and traditional operational scores statistics scores [false alarm rate (FR), probability of detection (PD), threat score (TS), and Heidke skill score (HSS)], as well as bias and the root-mean-square error (RMSE). The results show that both IFS and FBS fractal interpolation perform well with regard to operational skill scores, and they meet the additional requirement of generating structurally consistent fields. Furthermore, confidence intervals can be directly generated from the FBS ensemble. The results were used to diagnose errors relevant for hydrometeorological applications, in particular a spatial displacement with characteristic length of at least 50 km (2500 km2) in the location of peak rainfall intensities for the cases studied. © 2010 American Meteorological Society.

Variation in use of surveillance colonoscopy among colorectal cancer survivors in the United States.

BACKGROUND: Clinical practice guidelines recommend colonoscopies at regular intervals for colorectal cancer (CRC) survivors. Using data from a large, multi-regional, population-based cohort, we describe the rate of surveillance colonoscopy and its association with geographic, sociodemographic, clinical, and health services characteristics. METHODS: We studied CRC survivors enrolled in the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Eligible survivors were diagnosed between 2003 and 2005, had curative surgery for CRC, and were alive without recurrences 14 months after surgery with curative intent. Data came from patient interviews and medical record abstraction. We used a multivariate logit model to identify predictors of colonoscopy use. RESULTS: Despite guidelines recommending surveillance, only 49% of the 1423 eligible survivors received a colonoscopy within 14 months after surgery. We observed large regional differences (38% to 57%) across regions. Survivors who received screening colonoscopy were more likely to: have colon cancer than rectal cancer (OR = 1.41, 95% CI: 1.05-1.90); have visited a primary care physician (OR = 1.44, 95% CI: 1.14-1.82); and received adjuvant chemotherapy (OR = 1.75, 95% CI: 1.27-2.41). Compared to survivors with no comorbidities, survivors with moderate or severe comorbidities were less likely to receive surveillance colonoscopy (OR = 0.69, 95% CI: 0.49-0.98 and OR = 0.44, 95% CI: 0.29-0.66, respectively). CONCLUSIONS: Despite guidelines, more than half of CRC survivors did not receive surveillance colonoscopy within 14 months of surgery, with substantial variation by site of care. The association of primary care visits and adjuvant chemotherapy use suggests that access to care following surgery affects cancer surveillance.