Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

A Binaural Cochlear Implant Sound Coding Strategy Inspired by the Contralateral Medial Olivocochlear Reflex.

OBJECTIVES: In natural hearing, cochlear mechanical compression is dynamically adjusted via the efferent medial olivocochlear reflex (MOCR). These adjustments probably help understanding speech in noisy environments and are not available to the users of current cochlear implants (CIs). The aims of the present study are to: (1) present a binaural CI sound processing strategy inspired by the control of cochlear compression provided by the contralateral MOCR in natural hearing; and (2) assess the benefits of the new strategy for understanding speech presented in competition with steady noise with a speech-like spectrum in various spatial configurations of the speech and noise sources. DESIGN: Pairs of CI sound processors (one per ear) were constructed to mimic or not mimic the effects of the contralateral MOCR on compression. For the nonmimicking condition (standard strategy or STD), the two processors in a pair functioned similarly to standard clinical processors (i.e., with fixed back-end compression and independently of each other). When configured to mimic the effects of the MOCR (MOC strategy), the two processors communicated with each other and the amount of back-end compression in a given frequency channel of each processor in the pair decreased/increased dynamically (so that output levels dropped/increased) with increases/decreases in the output energy from the corresponding frequency channel in the contralateral processor. Speech reception thresholds in speech-shaped noise were measured for 3 bilateral CI users and 2 single-sided deaf unilateral CI users. Thresholds were compared for the STD and MOC strategies in unilateral and bilateral listening conditions and for three spatial configurations of the speech and noise sources in simulated free-field conditions: speech and noise sources colocated in front of the listener, speech on the left ear with noise in front of the listener, and speech on the left ear with noise on the right ear. In both bilateral and unilateral listening, the electrical stimulus delivered to the test ear(s) was always calculated as if the listeners were wearing bilateral processors. RESULTS: In both unilateral and bilateral listening conditions, mean speech reception thresholds were comparable with the two strategies for colocated speech and noise sources, but were at least 2 dB lower (better) with the MOC than with the STD strategy for spatially separated speech and noise sources. In unilateral listening conditions, mean thresholds improved with increasing the spatial separation between the speech and noise sources regardless of the strategy but the improvement was significantly greater with the MOC strategy. In bilateral listening conditions, thresholds improved significantly with increasing the speech-noise spatial separation only with the MOC strategy. CONCLUSIONS: The MOC strategy (1) significantly improved the intelligibility of speech presented in competition with a spatially separated noise source, both in unilateral and bilateral listening conditions; (2) produced significant spatial release from masking in bilateral listening conditions, something that did not occur with fixed compression; and (3) enhanced spatial release from masking in unilateral listening conditions. The MOC strategy as implemented here, or a modified version of it, may be usefully applied in CIs and in hearing aids.

Using Coding to Improve Localization and Backscatter Communication Performance in Low-Power Sensor Networks

Backscatter communication is an emerging wireless technology that recently has gained an increase in attention from both academic and industry circles. The key innovation of the technology is the ability of ultra-low power devices to utilize nearby existing radio signals to communicate. As there is no need to generate their own energetic radio signal, the devices can benefit from a simple design, are very inexpensive and are extremely energy efficient compared with traditional wireless communication. These benefits have made backscatter communication a desirable candidate for distributed wireless sensor network applications with energy constraints.

The backscatter channel presents a unique set of challenges. Unlike a conventional one-way communication (in which the information source is also the energy source), the backscatter channel experiences strong self-interference and spread Doppler clutter that mask the information-bearing (modulated) signal scattered from the device. Both of these sources of interference arise from the scattering of the transmitted signal off of objects, both stationary and moving, in the environment. Additionally, the measurement of the location of the backscatter device is negatively affected by both the clutter and the modulation of the signal return.

This work proposes a channel coding framework for the backscatter channel consisting of a bi-static transmitter/receiver pair and a quasi-cooperative transponder. It proposes to use run-length limited coding to mitigate the background self-interference and spread-Doppler clutter with only a small decrease in communication rate. The proposed method applies to both binary phase-shift keying (BPSK) and quadrature-amplitude modulation (QAM) scheme and provides an increase in rate by up to a factor of two compared with previous methods.

Additionally, this work analyzes the use of frequency modulation and bi-phase waveform coding for the transmitted (interrogating) waveform for high precision range estimation of the transponder location. Compared to previous methods, optimal lower range sidelobes are achieved. Moreover, since both the transmitted (interrogating) waveform coding and transponder communication coding result in instantaneous phase modulation of the signal, cross-interference between localization and communication tasks exists. Phase discriminating algorithm is proposed to make it possible to separate the waveform coding from the communication coding, upon reception, and achieve localization with increased signal energy by up to 3 dB compared with previous reported results.

The joint communication-localization framework also enables a low-complexity receiver design because the same radio is used both for localization and communication.

Simulations comparing the performance of different codes corroborate the theoretical results and offer possible trade-off between information rate and clutter mitigation as well as a trade-off between choice of waveform-channel coding pairs. Experimental results from a brass-board microwave system in an indoor environment are also presented and discussed.

Coding Strategies for X-ray Tomography

This work focuses on the construction and application of coded apertures to compressive X-ray tomography. Coded apertures can be made in a number of ways, each method having an impact on system background and signal contrast. Methods of constructing coded apertures for structuring X-ray illumination and scatter are compared and analyzed. Apertures can create structured X-ray bundles that investigate specific sets of object voxels. The tailored bundles of rays form a code (or pattern) and are later estimated through computational inversion. Structured illumination can be used to subsample object voxels and make inversion feasible for low dose computed tomography (CT) systems, or it can be used to reduce background in limited angle CT systems.

On the detection side, coded apertures modulate X-ray scatter signals to determine the position and radiance of scatter points. By forming object dependent projections in measurement space, coded apertures multiplex modulated scatter signals onto a detector. The multiplexed signals can be inverted with knowledge of the code pattern and system geometry. This work shows two systems capable of determining object position and type in a 2D plane, by illuminating objects with an X-ray `fan beam,' using coded apertures and compressive measurements. Scatter tomography can help identify materials in security and medicine that may be ambiguous with transmission tomography alone.

(Table 2, page 50) Toolik lake sediment chemistry (0-1 cm interval)

The sediments within Toolik Lake in arctic Alaska are characterized by extremely low rates of organic matter sedimentation and unusually high concentrations of iron and manganese. Pore water and solid phase measurements of iron, manganese, trace metals, carbon, nitrogen, phosphorus, and sulfur are consistent with the hypothesis that the reduction of organic matter by iron and manganese is the most important biogeochemical reaction within the sediment. Very low rates of dissolved oxygen consumption by the sediments result in an oxidizing environment at the sediment-water interface. This results in high retention of upwardly-diffusing iron and manganese and the formation of metal-enriched sediment. Phosphate in sediment pore waters is strongly adsorbed by the metal-enriched phases. Consequently, fluxes of phosphorus from the sediments to overlying waters are very small and contribute to the oligotrophic nature of the Toolik Lake aquatic system. Toolik Lake contains an unusual type of lacustrine sediment, and in many ways the sediments are similar to those found in oligotrophic oceanic environments.

A Group-Enhanced Sprint Interval Training Program for Amateur Athletes

Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s “all-out” efforts with 4 min active recovery, repeated 4–6 times per session), and were assigned to “true group”, aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants— regardless of condition — significant main effects for time were identified for maximal oxygen uptake (2.5–2.8 mL·kg−1·min−1, p < 0.001, η2 = 0.03), time-trial performance (14–32 s, p < 0.001, η2 = 0.37), and anaerobic power (1.1–1.7 k·h−1, p < 0.001, η2 = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η2 = 0.13), task self-efficacy (p = 0.018, η2 = 0.15), and scheduling self-efficacy (p = 0.003, η2 = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements

Coding Manuals

The VRAG-R is designed to assess the likelihood of violent or sexual reoffending among male offenders. The data set comprises demographic, criminal history, psychological assessment, and psychiatric information about the offenders gathered from institutional files together with post-release recidivism information. The VRAG-R is a twelve-item actuarial instrument and the scores on these items form part of the data set. Because one of the goals of the VRAG-R development project was to compare the VRAG-R to the VRAG, subjects' VRAG scores are included in this data set. Access to the VRAG-R dataset is restricted. Contact Data Services, Queen's University Library (academic.services@queensu.ca) for access.

Individual Variation in VO2peak Response Following Sprint Interval Training: The Role of Peripheral Adaptation

There is a large degree of heterogeneity in response to regular physical activity at the individual level, with some exhibiting no or very small improvements in VO2peak following highly controlled exercise training. The purpose of this thesis was to examine individual variation in VO2peak response to sprint interval training (SIT) in relation to individual responses to multiple measures of peripheral physiological adaptation. Specifically, VO2peak, capillary density, fibre-specific SDH content, and type I fibre % were measured in 23 young, healthy, recreationally active males before and after 4 weeks SIT (Tabata protocol 4 x per week). The key findings of this experiment included that, when separated into tertiles of VO2peak response, the high (HI) and low (LO) groups differed significantly in VO2peak change after training. Secondly, there was no difference between HI and LO groups for response in any of capillary density, fibre-specific SDH content, or fibre type %, with no correlation found between individual VO2peak response and changes in any measured peripheral variable. Together, these results confirm that individuals respond heterogeneously to SIT and suggest that this heterogeneity does not result from differences in individual changes in capillary density, fibre-specific SDH content or type I fibre %. It is speculated that some other combination of peripheral physiological adaptation must explain variability in VO2peak response to 4 weeks of SIT.

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.

PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.

RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.

CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1, 2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassifi cation. Findings Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1–3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5–2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6–40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7–1·9 million) in 2005, to 1·2 million deaths (1·1–1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued eff orts from governments and international agencies in the next 15 years to end AIDS by 2030.

Constructing strongly-MDS convolutional codes with maximum distance profile

This paper revisits strongly-MDS convolutional codes with maximum distance profile (MDP). These are (non-binary) convolutional codes that have an optimum sequence of column distances and attains the generalized Singleton bound at the earliest possible time frame. These properties make these convolutional codes applicable over the erasure channel, since they are able to correct a large number of erasures per time interval. The existence of these codes have been shown only for some specific cases. This paper shows by construction the existence of convolutional codes that are both strongly-MDS and MDP for all choices of parameters.

ICTM: an interval tessellation-based model for reliable topographic segmentation

This work introduces a tessellation-based model for the declivity analysis of geographic regions. The analysis of the relief declivity, which is embedded in the rules of the model, categorizes each tessellation cell, with respect to the whole considered region, according to the (positive, negative, null) sign of the declivity of the cell. Such information is represented in the states assumed by the cells of the model. The overall configuration of such cells allows the division of the region into subregions of cells belonging to a same category, that is, presenting the same declivity sign. In order to control the errors coming from the discretization of the region into tessellation cells, or resulting from numerical computations, interval techniques are used. The implementation of the model is naturally parallel since the analysis is performed on the basis of local rules. An immediate application is in geophysics, where an adequate subdivision of geographic areas into segments presenting similar topographic characteristics is often convenient.

Cardiorespiratory fitness and aerobic performance adaptations to a 4-week sprint interval training in young healthy untrained females

Purpose The aim of this study was to test the effects of sprint interval training (SIT) on cardiorespiratory fitness and aerobic performance measures in young females. Methods Eight healthy, untrained females (age 21 ± 1 years; height 165 ± 5 cm; body mass 63 ± 6 kg) completed cycling peak oxygen uptake ( V˙O2V˙O2 peak), 10-km cycling time trial (TT) and critical power (CP) tests pre- and post-SIT. SIT protocol included 4 × 30-s “all-out” cycling efforts against 7 % body mass interspersed with 4 min of active recovery performed twice per week for 4 weeks (eight sessions in total). Results There was no significant difference in V˙O2V˙O2 peak following SIT compared to the control period (control period: 31.7 ± 3.0 ml kg−1 min−1; post-SIT: 30.9 ± 4.5 ml kg−1 min−1; p > 0.05), but SIT significantly improved time to exhaustion (TTE) (control period: 710 ± 101 s; post-SIT: 798 ± 127 s; p = 0.00), 10-km cycling TT (control period: 1055 ± 129 s; post-SIT: 997 ± 110 s; p = 0.004) and CP (control period: 1.8 ± 0.3 W kg−1; post-SIT: 2.3 ± 0.6 W kg−1; p = 0.01). Conclusions These results demonstrate that young untrained females are responsive to SIT as measured by TTE, 10-km cycling TT and CP tests. However, eight sessions of SIT over 4 weeks are not enough to provide sufficient training stimulus to increase V˙O2V˙O2 peak.