Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and the lateral frontal cortices are involved in such control processes, putatively in close interplay with the BG. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra [SN] and the ventral tegmental area) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial RT prolongations that are thought to reflect cognitive control in a stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and in the absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the BG and the associated subthalamic nucleus

Stochastic Models on a Ring and Quadratic Algebras. The Three Species Diffusion Problem

The stationary state of a stochastic process on a ring can be expressed using traces of monomials of an associative algebra defined by quadratic relations. If one considers only exclusion processes one can restrict the type of algebras and obtain recurrence relations for the traces. This is possible only if the rates satisfy certain compatibility conditions. These conditions are derived and the recurrence relations solved giving representations of the algebras.Comment: 12 pages, LaTeX, Sec. 3 extended, submitted to J.Phys.

Conference Discussion of the Nuclear Force

Discussion of the nuclear force, lead by a round table consisting of T. Cohen, E. Epelbaum, R. Machleidt, and F. Gross (chair). After an invited talk by Machleidt, published elsewhere in these proceedings, brief remarks are made by Epelbaum, Cohen, and Gross, followed by discussion from the floor moderated by the chair. The chair asked the round table and the participants to focus on the following issues: (i) What does each approach (chiral effective field theory, large Nc, and relativistic phenomenology) contribute to our knowledge of the nuclear force? Do we need them all? Is any one transcendent? (ii) How important for applications (few body, nuclear structure, EMC effect, for example) are precise fits to the NN data below 350 MeV? How precise do these fits have to be? (iii) Can we learn anything about nonperturbative QCD from these studies of the nuclear force? The discussion presented here is based on a video recording made at the conference and transcribed afterward.Comment: Discussion at the 21st European Conference on Few Body Problems (EFP21) held at Salamanca, Spain, 30 Aug - 3 Sept 201

The Pennsylvania Dutchman Vol. 8, No. 4

● Such Fancy Boxes, Yet ● Dried Corn ● Pennsylvania Dutch Cooking is Corny ● The Amish at Play ● Colonial Button Mold ● Illness and Cure of Domestic Animals Among the Pennsylvania Dutch ● Pennsylvania Dutch Pioneershttps://digitalcommons.ursinus.edu/dutchmanmag/1011/thumbnail.jp

Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population

Abstract Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare oncogenic drivers in solid tumours. This study aimed to interrogate a large real-world database of comprehensive genomic profiling data to describe the genomic landscape and prevalence of NTRK gene fusions. NTRK fusion-positive tumours were identified from the FoundationCORE® database of >295,000 cancer patients. We investigated the prevalence and concomitant genomic landscape of NTRK fusions, predicted patient ancestry and compared the FoundationCORE cohort with entrectinib clinical trial cohorts (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]). Overall NTRK fusion-positive tumour prevalence was 0.30% among 45 cancers with 88 unique fusion partner pairs, of which 66% were previously unreported. Across all cases, prevalence was 0.28% and 1.34% in patients aged ≥18 and <18 years, respectively; prevalence was highest in patients <5 years (2.28%). The highest prevalence of NTRK fusions was observed in salivary gland tumours (2.62%). Presence of NTRK gene fusions did not correlate with other clinically actionable biomarkers; there was no co-occurrence with known oncogenic drivers in breast, or colorectal cancer (CRC). However, in CRC, NTRK fusion-positivity was associated with spontaneous microsatellite instability (MSI); in this MSI CRC subset, mutual exclusivity with BRAF mutations was observed. NTRK fusion-positive tumour types had similar frequencies in FoundationCORE and entrectinib clinical trials. NTRK gene fusion prevalence varied greatly by age, cancer type and histology. Interrogating large datasets drives better understanding of the characteristics of very rare molecular subgroups of cancer and allows identification of genomic patterns and previously unreported fusion partners not evident in smaller datasets

A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial.

Background: Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited. Objectives: This study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3). Methods: Women First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was(DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtainedDRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA). Results: A total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P \u3c 0.001, respectively). Rates of preterm birth did not differ among arms. Conclusions: In low-resource populations, benefits on fetal growth-related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester. This trial was registered at clinicaltrials.gov as NCT01883193

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network´s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health.Fil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Stolka, Kristen B.. Research Triangle Institute International; Estados UnidosFil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados UnidosFil: Honnungar, Narayan V.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Mastiholi, Shivanand C.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Ramadurg, Umesh Y.. S. Nijalingappa Medical College; IndiaFil: Dhaded, Sangappa M.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Pasha, Omrana. Aga Khan University; PakistánFil: Patel, Archana. Indira Gandhi Government Medical College and Lata Medical Research Foundation; IndiaFil: Esamai, Fabian. University School of Medicine; KeniaFil: Chomba, Elwyn. University of Zambia; ZambiaFil: Garces, Ana. Universidad de San Carlos; GuatemalaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados UnidosFil: Goldenberg, Robert L.. Columbia University; Estados UnidosFil: Hibberd, Patricia L.. Massachusetts General Hospital for Children; Estados UnidosFil: Liechty, Edward A.. Indiana University; Estados UnidosFil: Krebs, Nancy F.. University of Colorado School of Medicine; Estados UnidosFil: Hambidge, Michael K.. University of Colorado School of Medicine; Estados UnidosFil: Moore, Janet L.. Research Triangle Institute International; Estados UnidosFil: Wallace, Dennis D.. Research Triangle Institute International; Estados UnidosFil: Derman, Richard J. Christiana Care Health Services; Estados UnidosFil: Bhalachandra, Kodkany S.. KLE University. Jawaharlal Nehru Medical College; IndiaFil: Bose, Carl L.. University of North Carolina; Estados Unido

Comparative study: the effect of annealing conditions on the properties of P3HT:PCBM blends

This paper presents a detailed study on the role of various annealing treatments on organic poly(3-hexylthiophene) and [6]-phenyl-C61-butyric acid methyl ester blends under different experimental conditions. A combination of analytical tools is used to study the alteration of the phase separation, structure and photovoltaic properties of the P3HT:PCBM blend during the annealing process. Results showed that the thermal annealing yields PCBM ‘‘needle-like’’ crystals and that prolonged heat treatment leads to extensive phase separation, as demonstrated by the growth in the size and quantity of PCBM crystals. The substrate annealing method demonstrated an optimal morphology by eradicating and suppressing the formation of fullerene clusters across the film, resulting in longer P3HT fibrils with smaller diameter. Improved optical constants, PL quenching and a decrease in the P3HT optical bad-gap were demonstrated for the substrate annealed films due to the limited diffusion of the PCBM molecules. An effective strategy for determining an optimized morphology through substrate annealing treatment is therefore revealed for improved device efficiency.Web of Scienc