A framework for interpreting functional networks in schizophrenia

Some promising genetic correlates of schizophrenia have emerged in recent years but none explain more than a small fraction of cases. The challenge of our time is to characterize the neuronal networks underlying schizophrenia and other neuropsychiatric illnesses. Early models of schizophrenia have been limited by the ability to readily evaluate large-scale networks in living patients. With the development of resting state and advanced structural magnetic resonance imaging, it has become possible to do this. While we are at an early stage, a number of models of intrinsic brain networks have been developed to account for schizophrenia and other neuropsychiatric disorders. This paper reviews the recent voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and resting functional magnetic resonance imaging literature in light of the proposed networks underlying these disorders. It is suggested that there is support for recently proposed models that suggest a pivotal role for the salience network. However, the interactions of this network with the default mode network and executive control networks are not sufficient to explain schizophrenic symptoms or distinguish them from other neuropsychiatric disorders. Alternatively, it is proposed that schizophrenia arises from a uniquely human brain network associated with directed effort including the dorsal anterior and posterior cingulate cortex (PCC), auditory cortex, and hippocampus while mood disorders arise from a different brain network associated with emotional encoding including the ventral anterior cingulate cortex (ACC), orbital frontal cortex, and amygdala. Both interact with the dorsolateral prefrontal cortex and a representation network including the frontal and temporal poles and the fronto-insular cortex, allowing the representation of the thoughts, feelings, and actions of self and others across time

DNET: A communications facility for distributed heterogeneous computing

This document describes DNET, a heterogeneous data communications networking facility. DNET allows programs operating on hosts on dissimilar networks to communicate with one another without concern for computer hardware, network protocol, or operating system differences. The overall DNET network is defined as the collection of host machines/networks on which the DNET software is operating. Each underlying network is considered a DNET 'domain'. Data communications service is provided between any two processes on any two hosts on any of the networks (domains) that may be reached via DNET. DNET provides protocol transparent, reliable, streaming data transmission between hosts (restricted, initially to DECnet and TCP/IP networks). DNET also provides variable length datagram service with optional return receipts

Philanthropic Fundraising of Higher Education Institutions: A Review of the Malaysian and Australian Perspectives

Currently, higher education institutions are facing rapidly rising costs and limitations in governmental funding. Accordingly, higher education institutions need sustainable forms of funding to operate effectively and remain competitive. In their attempts to identify causes and initiatives, world universities have paid more attention to philanthropic support. In their effort to raise funds, many institutions have grappled with questions of why donors give and what motivates donors to give. To address these questions, scholars must consider the influence of demographic and socio-economic characteristics, as well as internal and external motivational parameters on successful giving behaviour. However, much more attention has been paid to universities in Western countries and the United States. This study aims to review the factors influencing organizational philanthropic fundraising success and to gain an understanding of factors affecting donors’ giving decisions and perceptions of giving. This work focuses on donors’ giving to Malaysian and Australian public universities

Are We Over-Lawyering International Affairs

This panel will discuss the role of lawyers — particularly government lawyers — in addressing questions of legal policy. We will discuss fundamental questions such as: Should lawyers decide legal policy? Or, is that best left to the policymakers? Should lawyers give advice as to legal policy, or should they stick to providing answers as to what the law is? How should lawyers respond to what a policymaker thinks is the legal question, but is really a question of legal policy? If lawyers find the law vague or lacking, should they fill in the gaps, advising as to what the law should be? Was Secretary of State Rice right when she warned the American Society of International Law that lawyers should not stretch laws, such as the Geneva Conventions, to apply to circumstances they were not designed for? Did the Office of the Justice Department’s opinions on interrogation techniques stretch in the other direction when they held that laws did not restrict the President’s authority? Should lawyers indicate the quality of the response to a question? For example, should they say how a court would, or should, decide, or is it just enough to say that this is a reasonable answer and others may differ? What should a government lawyer do after losing an intra-governmental policy argument on a legal issue? Is the answer different if the argument was over a legal policy issue

Extension Assistance for Integrated Pest Management Programs in K-12 Schools

We developed a training and education program in integrated pest management (IPM) for K-12 school building and grounds managers. The purpose of the program was to reduce exposure of children to pesticides at schools. Web-based and hard copy resource materials were developed in a cooperative effort between University of Wisconsin-Extension and the state\u27s Department of Agriculture. Since 1999, personnel at 46% of Wisconsin\u27s public schools have received training, education, and assistance in developing IPM programs. This high degree of voluntary participation is expected to affect pending legislation aimed at mandating IPM in schools

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

The first year counts: cancer survival among Indigenous and non-Indigenous Queenslanders, 1997–2006

Objective: To examine the differential in cancer survival between Indigenous and non-Indigenous people in Queensland in relation to time after diagnosis, remoteness and area-socioeconomic disadvantage. Design, setting and participants: Descriptive study of population-based data on all 150 059 Queensland residents of known Indigenous status aged 15 years and over who were diagnosed with a primary invasive cancer during 1997–2006. Main outcome measures: Hazard ratios for the categories of area- socioeconomic disadvantage, remoteness and Indigenous status, as well as conditional 5-year survival estimates. Results: Five-year survival was lower for Indigenous people diagnosed with cancer (50.3%; 95% CI, 47.8%–52.8%) compared with non-Indigenous people (61.9%; 95% CI, 61.7%–62.2%). There was no evidence that this differential varied by remoteness (P = 0.780) or area-socioeconomic disadvantage (P = 0.845). However, it did vary by time after diagnosis. In a time-varying survival model stratified by age, sex and cancer type, the 50% excess mortality in the first year (adjusted HR, 1.50; 95% CI, 1.38–1.63) reduced to near unity at 2 years after diagnosis (HR, 1.03; 95% CI, 0.78–1.35). Conclusions: After a wide disparity in cancer survival in the first 2 years after diagnosis, Indigenous patients with cancer who survive these 2 years have a similar outlook to non-Indigenous patients. Access to services and socioeconomic factors are unlikely to be the main causes of the early lower Indigenous survival, as patterns were similar across remoteness and area- socioeconomic disadvantage. There is an urgent need to identify the factors leading to poor outcomes early after diagnosis among Indigenous people with cancer

In vitro Studies on Metabolism of Salvinorin A

Microbial transformation of natural products is a well established model for mammalian metabolism. Salvinorin A, a diterpenoid isolated from the hallucinogenic mint Salvia divinorum Epling & Játiva-M (Lamiaceae), is a potent non-nitrogenous κ-opioid receptor agonist. The metabolism of salvinorin A has still not yet been well established. Thirty fungal species were screened for the ability to metabolize salvinorin A. We observed that salvinorin A undergoes fast hydrolysis of the acetate group at carbon atom C2, resulting in formation of the pharmacologically inactive product, salvinorin B. Ex vivo experiments were also performed using organelle fractions isolated from rat liver and brain. Crude tissue homogenate and individual organelles show that the primary route of salvinorin A metabolism is hydrolysis to salvinorin B. No metabolic transformation of salvinorin B was observed in these studies