Competitive integration of time and reward explains value-sensitive foraging decisions and frontal cortex ramping dynamics.

Patch foraging presents a ubiquitous decision-making process in which animals decide when to abandon a resource patch of diminishing value to pursue an alternative. We developed a virtual foraging task in which mouse behavior varied systematically with patch value. Mouse behavior could be explained by a model integrating time and rewards antagonistically, scaled by a latent patience state.

Neural control of affiliative touch in prosocial interaction.

The ability to help and care for others fosters social cohesiveness and is vital to the physical and emotional well-being of social species, including humans. Affiliative social touch, such as allogrooming (grooming behaviour directed towards another individual), is a major type of prosocial behaviour that provides comfort to others. Affiliative touch serves to establish and strengthen social bonds between animals and can help to console distressed conspecifics.

A Multi-Brain Framework for Social Interaction.

Social interaction can be seen as a dynamic feedback loop that couples action, reaction, and internal cognitive processes across individual agents. A fuller understanding of the social brain requires a description of how the neural dynamics across coupled brains are linked and how they coevolve over time. We elaborate a multi-brain framework that considers social interaction as an integrated network of neural systems that dynamically shape behavior, shared cognitive states, and social relationships.

Cortical Representations of Conspecific Sex Shape Social Behavior.

A central question related to virtually all social decisions is how animals integrate sex-specific cues from conspecifics. Using microendoscopic calcium imaging in mice, we find that sex information is represented in the dorsal medial prefrontal cortex (dmPFC) across excitatory and inhibitory neurons. These cells form a distributed code that differentiates the sex of conspecifics and is strengthened with social experience.

Reciprocal Copy Number Variations at 22q11.2 Produce Distinct and Convergent Neurobehavioral Impairments Relevant for Schizophrenia and Autism Spectrum Disorder.

Background: 22q11.2 deletions and duplications are copy number variations (CNVs) that predispose to developmental neuropsychiatric disorders. Both CNVs are associated with autism spectrum disorder (ASD), while the deletion confers disproportionate risk for schizophrenia.

Correlated Neural Activity and Encoding of Behavior across Brains of Socially Interacting Animals.

Social interactions involve complex decision-making tasks that are shaped by dynamic, mutual feedback between participants. An open question is whether and how emergent properties may arise across brains of socially interacting individuals to influence social decisions. By simultaneously performing microendoscopic calcium imaging in pairs of socially interacting mice, we find that animals exhibit interbrain correlations of neural activity in the prefrontal cortex that are dependent on ongoing social interaction.

US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.

This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100.

Myelinating glia differentiation is regulated by extracellular matrix elasticity.

The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM.

Phase I study evaluating the combination of lapatinib (a Her2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528.

Purpose: Everolimus, an oral inhibitor of mammalian target of rapamycin, can augment the efficacy of HER inhibitors in preclinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus and to describe its anti-tumor activity in the Phase I setting.

Methods: In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed.

Modafinil for excessive sleepiness associated with shift-work sleep disorder.

Background: Patients with shift-work sleep disorder chronically have excessive sleepiness during night work and insomnia when attempting to sleep during the day. We evaluated the use of modafinil for treating sleepiness in patients with this disorder.

Methods: In a three-month, double-blind trial, we randomly assigned 209 patients with shift-work sleep disorder to receive either 200 mg of modafinil or placebo before the start of each shift.

CJD decontamination of surgical instruments.

Following the CJD protocol and decontamination processes (Table 1) as recommended in the Health Canada CJD Guideline will serve to prevent transmission of CJD via surgical instruments, "Preparation of the work area" and "safe handling of strong chemicals used for decontamination" are other topics that must be addressed by staff in the OR and SPD. The appendix offers a quick reference that summarizes many of the important points which staff in the OR caring for patients, and staff in SPD caring for instruments, need to be aware of.

Induction of somatic intrachromosomal recombination inversion events by cyclophosphamide in a transgenic mouse model.

Somatic intrachromosomal recombination (SICR) can result in chromosomal inversion and deletion, mechanisms which are important in carcinogenesis. We have utilised a transgenic mouse model to study SICR inversion events in spleen cells. The transgenic construct is designed so that expression of an Escherichia coli lacZ transgene only occurs in a cell when an SICR inversion event occurs in the region of the transgene.

Teniposide (VM-26) as a single drug treatment for patients with extensive small cell lung carcinoma: a Phase II study of the Southwest Oncology Group.

Background: Teniposide (VM-26) was reported to have activity in small cell lung carcinoma (SCLC). The authors performed a Phase II study of teniposide as a treatment for patients with previously untreated extensive SCLC.

Methods: The study was open to patients with a histologic or cytologic diagnosis of extensive SCLC who had not received prior radiation or chemotherapy.

A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study.

Interest in high-dose cytarabine (HDAC) for both induction and postremission therapy for acute myeloid leukemia (AML) prompted the Southwest Oncology Group (SWOG) to initiate a randomized trial comparing HDAC with standard-dose cytarabine (SDAC) for remission induction of previously untreated AML and to compare high-dose treatment versus conventional doses for consolidation therapy. Patients less than 65 years of age with de novo or secondary AML were randomized for induction between SDAC 200 mg/ m2/d for 7 days by continuous infusion or HDAC at 2 g/ m2 intravenously every 12 hours for 12 doses; both groups received daunorubicin (DNR) at 45 mg/m2/d intravenously for 3 days. Complete responders to SDAC were randomized to receive either two additional courses of SDAC plus DNR or one course of HDAC plus DNR.

The 3' enhancer region determines the B/T specificity and pro-B/pre-B specificity of immunoglobulin V kappa-J kappa joining.

Using transgenic substrates, we found that the immunoglobulin kappa gene 3' enhancer (E3') acts as a negative regulator in V kappa-J kappa joining. Although the E3' was originally identified as a transcriptional enhancer, it acts in a suppressive manner for recombinational regulation. Base substitution analysis has shown that the PU.

A prospective evaluation of the roles of allogeneic marrow transplantation and low-dose monthly maintenance chemotherapy in the treatment of adult acute myelogenous leukemia (AML): a Southwest Oncology Group study.

Between February 1982 and December 1986, the Southwest Oncology Group conducted a prospective study in patients with newly diagnosed acute myeloid leukemia (AML) with two objectives: to evaluate the role of allogeneic marrow transplantation for patients in first remission, and to evaluate the role of low-dose monthly maintenance therapy in those patients not transplanted in first remission. Among 522 evaluable patients, 295 (57%) achieved complete remission (CR), including 70% of patients age 49 or less. Twenty-four patients (15%) age 49 or less in CR were not HLA-typed, mostly because of financial constraints.

Building coalitions: a community wide approach for promoting farming health and safety.

1. The context of agriculture in the Midwest, given many smaller, family run operations, presents multiple and complex challenges; occupational health intervention strategies used in other industries are not immediately applicable. 2.

Detection of somatic DNA recombination in the transgenic mouse brain.

A DNA construct containing the bacterial beta-galactosidase gene (lacZ) was used to study somatic DNA recombination in the transgenic mouse brain. Recombination-positive areas of the adult brain were stained blue with X-gal, a substrate of beta-galactosidase. Blue-colored cells appeared soon after birth, and continued to emerge in postnatal tissue.

Circular DNA resulting from recombination between V-(D)-J joining signals and switch repetitive sequences in mouse thymocytes.

During the course of analyzing circular DNA in mouse thymocytes, novel recombinants were identified with immunoglobulin heavy chain joining gene and switch region probes. These circles represent excision products of recombination between the heptamer-nonamer motif for V-(D)-J joining and a repetitive sequence for class switching. The molecular mechanisms that generate "hybrid circles" are discussed.