Pharmacological manipulation of NMDA receptor activation and synaptic norepinephrine levels: Effects on sustained attention in male rats

Impaired attention is common in many neurological disorders. Normal attention promotes the selective processing of important sensory information. This selective processing relies on neurotransmitters, like glutamate, and neuromodulators, like norepinephrine, acting in frontal, parietal, and visual cortices. We tested treatments targeting the glutamatergic and noradrenergic systems using a rat model of attentional lapses.Rats were trained to respond quickly to stimuli in a two-choice reaction time task (2CRTT). Response times were split into initiation time (IT) and movement time (MT). Performance measures were derived from IT and MT distributions. IT mode represents sensorimotor processing speed when rats are attentive. IT deviation from mode (devmode) measures distribution skew which is thought to reflect attentional lapses. Altered MT mode or trials completed could reflect drug-induced side-effects. We tested the NMDA receptor co-agonist, D-serine, in a group of rats. We then tested a combination treatment of D-serine and the norepinephrine reuptake inhibitor, atomoxetine (ATX). New rats were used in a follow-up test. Data were analyzed using linear mixed models or repeated measures ANOVA. We did not find an effect of D-serine on IT mode; however, the highest dose (300 mg/kg) reduced IT devmode. The initial test of the combination treatment (100 mg/kg D-serine with 0.5 mg/kg ATX) did not reveal an effect on IT mode; however, the combination treatment reduced IT devmode with no effect following either drug alone. The follow-up test (125 mg/kg D-serine with 0.3 mg/kg ATX) did not reveal an effect on IT mode; however, IT devmode was reduced following ATX or the combination treatment. Importantly, the combination treatment reduced IT devmode more than either drug alone. Furthermore, the combination treatment did not increase MT mode or trials completed compared to ATX alone. Activating NMDA receptors with D-serine appears to reduce attentional lapses without affecting sensorimotor processing speed. The present findings also support the efficacy of a combination treatment comprising D-serine and ATX. This combination treatment does not appear to increase unwanted side-effects associated with ATX. Taken together, these findings suggest that simultaneously targeting glutamate and NE systems could be a safe and effective strategy for treating impaired attention

Klinefelter’s Syndrome: A fortuitously diagnosed by non-invasive prenatal testing

Case Report: A male infant born at 37 weeks gestation. His mother was a 29-year-old, gravida 4 para 3 woman. During her pregnancy she was curious as to the gender of the fetus and requested a non-invasive prenatal test (NIPT) rather than fetal ultrasound. The NIPT returned with a karyotype of XXY. The male infant was born vaginally with a birth weight of 2670 grams. Apgar scores were 8 and 9 at one and five minutes respectively. He was admitted to the newborn intensive care unit secondary to respiratory distress. He had no obvious dysmorphic features. He had normal appearing male genitalia with testes descended bilaterally. Fluorescent in situ hybridization and blood chromosomes confirmed an XXY karyotype. He was discharged from the newborn intensive care unit with follow up by genetic counselors and close monitoring for developmental delays Background: Klinefelter Syndrome (KS), a genetic disorder caused by the presence of supernumerary sex chromosomes. An additional X chromosome(s) and hypogonadism are the two defining features of KS. The excess of genes from the additional X chromosome drives the pathogenesis of the disease and distinguishing features of the affected individuals. The increase in the prevalence of prenatal testing has led to the earlier recognition of fetal chromosomal abnormalities. Early detection of KS through NIPT has given the family much needed information and allowing for early diagnosis and intervention, to promote the best outcome for the child. This case shows a patient that will benefit from the early diagnosis of a KS to implement early and timely interventions upon delivery and then later in the developing years. The neonate presented with no distinct, characteristic signs of KS, common in many individuals. Two findings, other than the NIPT results, weakly suggest any possible abnormality. Klinefelter neonates report mildly higher incidences of respiratory distress and low birth weight necessitating need for NICU admission. The underwhelming clinical presentation of the neonate shows that if NIPT wasn’t conducted, neither our patient nor his family would have known he was 47,XXY, until much later in life. IMPLICATIONS: Timely hormonal intervention is possible for our patient because of NIPT. This demonstrates a need of a standard KS screen. With the technology of NIPT advancing and improving in its ability to detect a variety of other conditions outside of the traditional autosomal aneuploidy, it should be considered a technique for screening for clinically silent conditions, such as mild KS phonotypes.https://digitalcommons.unmc.edu/chri_forum/1021/thumbnail.jp

The Epsilon Calculus and Herbrand Complexity

Hilbert's epsilon-calculus is based on an extension of the language of predicate logic by a term-forming operator $\epsilon_{x}$. Two fundamental results about the epsilon-calculus, the first and second epsilon theorem, play a role similar to that which the cut-elimination theorem plays in sequent calculus. In particular, Herbrand's Theorem is a consequence of the epsilon theorems. The paper investigates the epsilon theorems and the complexity of the elimination procedure underlying their proof, as well as the length of Herbrand disjunctions of existential theorems obtained by this elimination procedure.Comment: 23 p

Putting Families First: How the Opioid Epidemic is Affecting Children and Families, and the Child Welfare Policy Options to Address It

Abstract: Opioids and Child Welfare Across the country, placements in foster care are rising. In 2016, the U.S. Department of Health and Human Services reported that 273,539 children in the U.S. entered foster care. In 34 percent of those cases, parental drug abuse was one of the factors leading to the child’s removal from their family. Additionally, the U.S. Substance Abuse and Mental Health Services Administration estimates that 400,000 births nationally are affected by prenatal exposure to alcohol and illicit drugs, which represents 10 percent of all live births. As the opioid epidemic continues, increasing numbers of children are at high risk for developmental and behavioral disorders because of their prenatal substance and alcohol exposure. In addition, children who remain at home may endure the challenges and trauma resulting from impaired caregiving due to parental substance use disorders (SUDs). This article explores the intersection of the opioid epidemic and child welfare, examining current research and publicly available data to discuss policy opportunities for better serving families affected by parental SUDs, including: ensuring health and safety for infants prenatally exposed to substances; appropriate identification, diagnosis, and treatment of developmental and behavioral needs; ensuring parents have access to outpatient treatment and services that can allow families to stay together when safe and appropriate; and ensuring sufficient access to inpatient treatment options that can serve parents and children together

Graph Distillation for Action Detection with Privileged Modalities

We propose a technique that tackles action detection in multimodal videos under a realistic and challenging condition in which only limited training data and partially observed modalities are available. Common methods in transfer learning do not take advantage of the extra modalities potentially available in the source domain. On the other hand, previous work on multimodal learning only focuses on a single domain or task and does not handle the modality discrepancy between training and testing. In this work, we propose a method termed graph distillation that incorporates rich privileged information from a large-scale multimodal dataset in the source domain, and improves the learning in the target domain where training data and modalities are scarce. We evaluate our approach on action classification and detection tasks in multimodal videos, and show that our model outperforms the state-of-the-art by a large margin on the NTU RGB+D and PKU-MMD benchmarks. The code is released at http://alan.vision/eccv18_graph/.Comment: ECCV 201