Off Premises Sunday Sales in Georgia Localities: Will it Affect Traffic Accidents?

Discussions about public policy relating to alcohol cause a polarizing reaction to many people in this country, particularly in the South. The state of Georgia, for example, has a long history of policies regulating alcohol which reflects its membership as part of the “Bible Belt” where Sunday is regarded as a holy day and therefore alcohol cannot and should not be purchased on this day. Given that the impetus of alcohol control policy has generally widened the availability of alcohol since the Prohibition, the moral concerns of voters regarding alcohol regulation have been superseded in the public debate with safety and health concern

Satisfaction With Local Conditions and the Intention To Move

The recent economic downturn has presented many challenges to local communities and policy- makers. Foreclosed properties, job losses, and other challenges that local residents face can threaten the economic viability of local communities. Another consequence of the economic downturn is decreased government budgets, forcing policymakers to make decisions about how to allocate scarce resources effectively. When making decisions about local and regional policy, it would be useful to know how local characteristics contribute to the decisions residents make about whether to remain in a local community or to relocate. Exhibits 1 through 4 present maps created to investigate the relationship between residents’ perceptions of local conditions and the intentions of residents to move. The maps are of the ZIP Codes in the five core counties in the Atlanta metropolitan area (Clayton, Cobb, DeKalb, Fulton, and Gwinnett), combined with data from a public opinion survey conduced by the A.L. Burruss Institute of Public Service at Kennesaw State University

A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors

<div><p>The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4–18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4). The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%), with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection) occurring in one patient each. Pharmacokinetics was dose-saturable at doses above 50 mg/m²/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5) and 4 of 5 patients with high-grade glioma (dose levels 2 and 3) experienced stable disease for two months. Five subjects with neuroblastoma (dose levels 1 through 4) achieved stable disease which was prolonged (≥11 months) in three. No objective responses were noted. In conclusion, the use of perifosine was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated. Our RP2D is 50 mg/m2/day.</p></div

Genomewide Expression Profile Analysis of the Candida glabrata Pdr1 Regulon▿†

The ABC transporters Candida glabrata Cdr1 (CgCdr1), CgPdh1, and CgSnq2 are known to mediate azole resistance in the pathogenic fungus C. glabrata. Activating mutations in CgPDR1, a zinc cluster transcription factor, result in constitutive upregulation of these ABC transporter genes but to various degrees. We examined the genomewide gene expression profiles of two matched azole-susceptible and -resistant C. glabrata clinical isolate pairs. Of the differentially expressed genes identified in the gene expression profiles for these two matched pairs, there were 28 genes commonly upregulated with CgCDR1 in both isolate sets including YOR1, LCB5, RTA1, POG1, HFD1, and several members of the FLO gene family of flocculation genes. We then sequenced CgPDR1 from each susceptible and resistant isolate and found two novel activating mutations that conferred increased resistance when they were expressed in a common background strain in which CgPDR1 had been disrupted. Microarray analysis comparing these reengineered strains to their respective parent strains identified a set of commonly differentially expressed genes, including CgCDR1, YOR1, and YIM1, as well as genes uniquely regulated by specific mutations. Our results demonstrate that while CgPdr1 activates a broad repertoire of genes, specific activating mutations result in the activation of discrete subsets of this repertoire

Patient characteristics and responses.

<p>Patient characteristics and responses.</p

Perifosine dose level 2 (~50 mg/m²/day).

<p>Perifosine dose level 2 (~50 mg/m²/day).</p