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Career education has been supported by legislation and by American educators. Career education has expanded from extensive research, and public and academic dissatisfaction with educational institutions has precipitated demands for increased relevance and accountability of educational programs. (Author/JB)

Author recommends team teaching because of its good effect on the attitudes of students. (GB)

We report research and development conducted to enable the safe implementation of a highly enantioselective palladium-catalyzed desymmetrization of a meso–bis-ester using trimethylsilylazide (TMSN3) as the nucleophile. This work is used as a case example to discuss safe practices when considering the use of azide reagents or intermediates, with a focus on the thermodynamic and quantitative analysis of the hazards associated with hydrazoic acid (HN3).

Background Metropolitan versus nonmetropolitan status and area median income may independently affect care for and outcomes of acute coronary syndromes. We sought to determine whether location of care modifies the association among area income, receipt of cardiac catheterization, and mortality following an acute coronary syndrome in a universal health care system. Methods and Results We studied a cohort of 14 012 acute coronary syndrome patients admitted to cardiology services between April 18, 2004, and December 31, 2011, in southern Alberta, Canada. We used multivariable logistic regression to determine the odds of cardiac catheterization within 1 day and 7 days of admission and the odds of 30‐day and 1‐year mortality according to area median household income quintile for patients presenting at metropolitan and nonmetropolitan hospitals. In models adjusting for area income, patients who presented at nonmetropolitan facilities had lower adjusted odds of receiving cardiac catheterization within 1 day of admission (odds ratio 0.22, 95% CI 0.11–0.46, P P P =0.008) but no significant difference for 1‐year mortality ( P =0.12). There were no differences in adjusted mortality among metropolitan patients. Conclusion Within a universal health care system, the association among area income and receipt of cardiac catheterization and 30‐day mortality differed depending on the location of initial medical care for acute coronary syndromes. Care protocols are required to improve access to care and outcomes in patients from low‐income nonmetropolitan communities.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

People can be forgiven for growing weary of the headline "Hurricane Katrina, the Costliest Natural Disaster in U.S. History." Compassion fatigue has set in among caring people who are desperate for a headline that announces a return to "normal." And then there are the inevitable questions about what the new normal may be, why people would live in such an environmentally endangered place in the first place, and what insanity would cause them to want to rebuild in the same location. The purpose of this brief essay is to comment on what happened to the New Orleans Metropolitan Area, to look at why such a tragedy was hardly unexpected, and to speculate on some of the geographical possibilities of a post-Katrina New Orleans. These comments are by necessity preliminary and incomplete, based on early reports from journalists and researchers and on personal experience. WHAT HAPPENED? By the morning of Friday, 26 August, Hurricane Katrina was heading northward into the Gulf of Mexico, with a predicted landfall on the Florida Panhandle. Throughout the day, the projected course of the storm shifted to the west, so that by Friday evening the target zone was approaching the New Orleans area. This was far from the first time that New Orleans had been in the bull's-eye, but earlier storms had veered away from the city at the last minute or turned out to be only a nuisance. This time felt different. Given the category 5 status of the storm--meaning that winds of more than 155 miles per hour and a storm surge generally of at least 18 feet could be expected--and the steering currents guiding it, a growing sense of dread descended on New Orleans that Katrina might be the "Big One." New Orleans has every reason to fear the Big One. Much of the city lies below sea level and is surrounded by hurricane-protection levees. The only areas above sea level within the city itself are on the natural levees along the Mississippi River, on old river distributaries such as the Gentilly and Metairie Ridges, and on the shores of Lake Pontchartrain, much of which is artificially created land. In most of these locations "high ground" is defined as anything above sea level; the truly "alpine" parts of the city rise to about 15 feet next to the river (Figures 1 and 2). The remainder of the city was built by draining wetlands and clearing land for development, which led to soil subsidence and life below sea level for many neighborhoods. Rainstorms are a constant threat; rainwater is removed from below-sea-level areas using 180 miles of canals, 22 pumping stations, and a water-removal capability of 30 billion gallons a day (Campanella 2002; Lewis 2003; Colten 2005; Pittman 2005,12). It has long been feared that the Big One would not only exceed pumping capacities but disable the pumps altogether. [FIGURE 1 OMITTED] By Saturday, 27 August, New Orleans was implementing its evacuation plans. All interstate-highway lanes were converted to outbound only to help the hundreds of thousands of motorists who were fleeing the metropolitan area. For those without vehicles, evacuation was much more problematic. Public transportation was extremely limited, if it existed at all. Perhaps 150,000 people either could not evacuate or simply refused to leave (Kent 2005, 3; Renne 2006). Evacuation exacted hardships not only on evacuees but also on the surrounding communities to which evacuees relocated. The city of Baton Rouge swelled to nearly double its population (Dyer 2006); virtually every motel room in southern Mississippi, southern Alabama, eastern Texas, and inland Louisiana was taken; and highway rest stops became makeshift evacuation areas. On 29 August Katrina made a direct strike on the coast of Mississippi, which experienced massive devastation even though what was initially a category 5 storm had weakened to a strong category 3 by landfall--with winds of 111-130 miles per hour and a storm surge generally of 9-12 feet for a category 3 storm. …

Historians of the smaller of the United States naval services have tended to dismiss or denigrate the career of the fifteenth Commandant of the Marine Corps, usually describing him as an avuncular and uninspiring sinecure holder. An examination of Fuller's tenure at the helm of the Corps at the time of the retrenchment imposed during the Herbert C. Hoover administration and the stimulus for naval growth that followed under the Franklin D. Roosevelt administration reveals an officer far more adroit than usually depicted.

Tuberculosis remains a global health problem, and programs dedicated to discovery of novel compounds against Mycobacterium tuberculosis require robust assays for high-throughput screening of chemical and natural product libraries. Enzymes involved in the biosynthesis of mycolic acids, vital components of the mycobacterial cell wall, have received much attention as potential drug targets. KasA and KasB, examples of the beta-ketoacyl-acyl carrier protein synthase I/II (KASI/II) class of condensing enzymes of the M. tuberculosis fatty acid synthase II system have been the focus of several studies designed to biochemically characterize these enzymes. Whilst robust methods have been developed for FabH-like proteins, fast and sensitive assays for high-throughput screening of KASI/II enzymes have not been available. Here we report the development of a direct scintillation proximity assay (SPA) for the KASI/II enzymes, KasA and KasB. The SPA was more sensitive than existing assays, as shown by its ability to measure activity using less enzyme than other assay formats, and the SPA was validated using the known KAS inhibitor thiolactomycin. In addition, the KasA and KasB SPA was adapted for use with Staphylococcus aureus FabF to show the versatility of this assay format to KAS enzymes from other pathogenic organisms.

Analogues of the natural antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis β-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-[3-(4-acetyl-phenyl)-prop-2-ynyl]-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency, compared to thiolactomycin, against this key condensing enzyme, involved in M. tuberculosis mycolic acid biosynthesis. Analogues of the antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded activity against cloned mtFabH condensing enzyme.

Mycolic acids are vital components of the Mycobacterium tuberculosis cell wall, and enzymes involved in their formation represent attractive targets for the discovery of novel anti-tuberculosis agents. Biosynthesis of the fatty acyl chains of mycolic acids involves two fatty acid synthetic systems, the multifunctional polypeptide fatty acid synthase I (FASI), which performs de novo fatty acid synthesis, and the dissociated FASII system, which consists of monofunctional enzymes, and acyl carrier protein (ACP) and elongates FASI products to long chain mycolic acid precursors. In this study, we present the initial characterization of purified KasA and KasB, two beta-ketoacyl-ACP synthase (KAS) enzymes of the M. tuberculosis FASII system. KasA and KasB were expressed in E. coli and purified by affinity chromatography. Both enzymes showed activity typical of bacterial KASs, condensing an acyl-ACP with malonyl-ACP. Consistent with the proposed role of FASII in mycolic acid synthesis, analysis of various acyl-ACP substrates indicated KasA and KasB had higher specificity for long chain acyl-ACPs containing at least 16 carbons. Activity of KasA and KasB increased with use of M. tuberculosis AcpM, suggesting that structural differences between AcpM and E. coli ACP may affect their recognition by the enzymes. Both enzymes were sensitive to KAS inhibitors cerulenin and thiolactomycin. These results represent important steps in characterizing KasA and KasB as targets for antimycobacterial drug discovery.

Background — Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. Methods and Results — Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. Conclusions — Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.

Mycolic acids are generated in Mycobacterium tuberculosis as a result of the interaction of two fatty acid biosynthetic systems: the multifunctional polypeptide, FASI, in which the acyl carrier protein (ACP) domain forms an integral part of the polypeptide, and the dissociated FASII system, which is composed of monofunctional enzymes and a discrete ACP (AcpM). In order to characterize enzymes of the FASII system, large amounts of AcpM are required to generate substrates such as holo-AcpM, malonyl-AcpM and acyl-AcpM. The M. tuberculosis acpM gene was overexpressed in Escherichia coli and AcpM purified, yielding approximately 15-20 mg/l of culture. Analysis of AcpM by mass spectrometry, N-terminal sequencing, amino acid analysis, and gas chromatography indicated the presence of three species, apo-, holo-, and acyl-AcpM, the former comprising up to 65% of the total pool. The apo-AcpM was purified away from the in vivo generated holo- and acyl-forms, which were inseparable and heterogeneous with respect to acyl chain lengths. Once purified, we were able to convert apo-AcpM into holo- and acyl-forms. These procedures provide the means for the preparation of the large quantities of AcpM and derivatives needed for characterization of the purified enzymes of the mycobacterial FASII system.

The purpose of the present study was to determine whether that which clinically appeared to be spasmus nutans could actually represent retinal sensory deficits diagnosable by electroretinography. Eight patients clinically thought to have spasmus nutans underwent electroretinography according to international standards. Five had normal electroretinograms and represented cases of true spasmus nutans. Three patients had abnormal electroretinograms, indicating that they did not have spasmus nutans. The clinical findings used to diagnose spasmus nutans can be simulated by retinal dystrophies. A normal electroretinogram is needed to confirm the diagnosis of spasmus nutans.

This paper argues that there has been a major change since the mid-1980s in the extent to which other workers involved in child protection recognize the value of the contribution of school nurses. Evidence for this is drawn from a longitudinal study in an English shire county using a vignette approach to explore workers' perceptions of the handling of child protection issues. While in part the greater recognition of the role of the school nurse can be attributed to the adoption of child protection procedures, this provides only a partial explanation. School nurses in the 1990s were better qualified and more experienced, while other workers such as school heads and social workers recognized the need to work with others, such as the school nurse, in order to meet their own objectives. The paper concludes that there is a case for more formal recognition of school nurses in child protection because, like health visitors, with whom they have a follow-on colleague relationship, they are often the most significant health workers for children who may be neglected or abused. Copyright © 2000 John Wiley & Sons, Ltd.

The biosynthesis of lipoarabinomannan (LAM), a key mycobacterial lipoglycan that has been implicated in numerous immunoregulatory functions, was examined utilizing D-mannosamine (ManN) as a tool to identify mannosyltransferase genes involved in LAM synthesis. Cell-free reactions utilizing cellular membranes of mycobacteria as the enzyme source indicated that ManN inhibited the synthesis of phosphatidylinositol mannosides, early precursors to LAM. A selection strategy was devised to screen a Mycobacterium tuberculosis genomic library in Mycobacterium smegmatis for clones conferring conditional resistance to ManN, with the rationale that overexpression of the gene(s) encoding a target of ManN would impart a ManN-resistant phenotype under these conditions. This strategy led to the identification of pimB, whose deduced amino acid sequence shows similarity to mannosyltransferases and other glycosyltransferases. Partially purified recombinant PimB protein from Escherichia coli or membranes from M. smegmatis overexpressing the pimB gene were used in cell-free assays to show that PimB catalyzes the formation of triacylphosphatidylinositol dimannoside from GDP-mannose and triacylphosphatidylinositol monomannoside.

Several definitions of career exploration are discussed in the article, and an interpretation is offered for the middle/junior high school level: student exploratory behaviors in regard to self and occupational concepts are best denoted by their inclusion of problem-solving or hypothesis testing. (Author/AJ)

5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1H-indole dihydrochloride (1) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatography-free preparation of this compound is described. The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.