HOW CAN THE BALANCED SCORECARD DEVELOP A LEADERSHIP DEVELOPMENT PROGRAM FOR THE FBI?

Superior performance with long-lasting effects is the hallmark of a thriving organization. The success or failure of any organization hinges on its leaders to make the correct decisions at the correct time. As an organization grows in size and diversity, leadership must look both horizontally and vertically to ensure that the mission is completed. The leadership of any successful organization must be able to rely on its executive level management, its subordinates, as well as those in positions of authority who are similar in nature. This research paper examines the use of Kaplan and Norton’s balanced scorecard as a conceptual model to evaluate the Federal Bureau of Investigation’s performance. The paper explores the balanced scorecard’s identified deficits, discusses the potential reasons for the deficiencies, and makes recommendations on potential ways to address these shortcomings.Civilian, Federal Bureau of InvestigationApproved for public release. Distribution is unlimited

Does Nicotine Replacement Therapy Reduce the Withdrawal Symptom of Craving, or Urge to Smoke, in Dependent Adult Smokers During Smoking Cessation?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not nicotine replacement therapy reduces the withdrawal symptom of craving, or urge to smoke, in dependent adult smokers during smoking cessation. STUDY DESIGN: Systematic review of three English language and peer-reviewed randomized-controlled trials published in 2009, 2010, and 2011. DATA SOURCES: One single-blinded randomized-controlled crossover trial, one double-blinded, placebo controlled, randomized-controlled crossover trial, and one single-blinded, placebo controlled, randomized-controlled crossover trial OUTCOMES MEASURED: Withdrawal symptoms of craving, irritability, difficulty concentrating, and restlessness were measured on a 100mm visual analog scale (VAS). Adverse effects (AEs) of mouth and throat irritation, aching jaw, feeling sick, vomiting, flatulence/belching, stomachache, heartburn, diarrhea, hiccups, feeling high, feeling dizzy, headache, palpitations, sweatiness, and cold hands/feet were measured based upon their frequency and strength. One study measured slightly different withdrawal symptoms (depressed mood, irritability, restlessness, hunger, and poor concentration) on a Moods and Physical Symptoms Scale (MPSS) and time spent with urges and strength of urges on a six-point Likert Scale. This study also measured the adverse effects of feeling unwell, nausea, throat irritation, and dizziness on a 10-point scale. Temporary smoking cessation was measured in all three studies. RESULTS: Thornley et al found that the active pouch significantly decreased craving in comparison to placebo. The gum decreased craving; however, the findings were not considered to be statistically significant. In McRobbie et al, all three types of NRT proved to significantly decrease craving in comparison to placebo. Similarly, Shahab et al found that both innovative and older types of NRT decreased craving. The Nicotine Cannon was more tolerable than older types of NRT. Overall, the NRT products caused more adverse reactions than placebo, but also led to more cases of temporary smoking cessation. CONCLUSION: The results of all three studies show that nicotine replacement therapy decreases the withdrawal symptom of craving, allowing smokers to be more successful in their attempts to quit in the short term. No one NRT product is significantly better than another in decreasing craving

Optimization of path based sensor spacing on a freeway segment for travel time prediction during incidents

Congestion on freeways is increasing and a key source of it is non-recurring incidents. Accurate vehicle travel time predictions are needed during these incidents in order for roadway users to make informed trip decisions. Path based sensors are becoming a leading technology in gathering real-time travel time data. The data is used to make travel time predictions that are then provided through various means, such as dynamic message signs, to roadway users. These types of sensor are located at stationary points along a roadway and collect individual vehicle travel time data from vehicles as they drive pass the sensors. The accuracy of the predictions, in terms of representing future travel times, is dependent on many factors including the sensor spacing along the roadway, the duration and location of a traffic incident, and the uncongested and congested traffic speeds and traffic flows. Understanding the relationship between the travel time prediction accuracy and the different variables is necessary to optimize sensor spacing. In addition, because incidents occur at different times of the day, have varying durations, occur at different locations, and cause different capacity reductions depending on the severity of the incident, the sensor spacing cannot be based on one incident scenario. Instead, multiple incident scenarios, along with the probability of each occurring, needs to be taken into account. Path based sensor spacing during incidents on a freeway segment is optimized in this dissertation. In addition, the marginal benefit of additional sensors is calculated. A mathematical model and a solution methodology are developed. The mathematical model applies macroscopic traffic principles and shock wave theory. It calculates the travel time prediction error by sensor spacing during an incident on a freeway segment. The solution algorithm consists of four main steps. First, historical incident data for the roadway are gathered. Second, the mathematical model is applied to determine the average travel time prediction error by sensor spacing for each of the historical incidents. Third, the weighted average travel time prediction error by sensor spacing is calculated, which considers all the possible incidents and the frequency of each occurring. Fourth, the optimal spacing is chosen which minimizes the weighted average error. The applicability of the model and solution methodology is demonstrated through a case study of a ten mile freeway segment in Northern New Jersey

What is a Partition?

Buildings from the nineteenth century are rich with history and tradition in their materials,design and construction. Over the past few years in Richmond, many of the formerly vacant buildings have been converted into residential “lofts”. These spaces have the potential to teach and serve us in a way we could never duplicate today. The space we live in has the power to determine how well we function. I believe this is one of the keys to happiness. I like to think of these buildings holistically in terms of past, present, and future . I will supplement the space with partitions to optimize its functionality today while respecting its history and not hindering its future. The use and placement of the partitions resulted in a functionally defined yet open space

An approach to analyse the specific impact of rapamycin on mRNA-ribosome association

<p>Abstract</p> <p>Background</p> <p>Recent work, using both cell culture model systems and tumour derived cell lines, suggests that the differential recruitment into polysomes of mRNA populations may be sufficient to initiate and maintain tumour formation. Consequently, a major effort is underway to use high density microarray profiles to establish molecular fingerprints for cells exposed to defined drug regimes. The aim of these pharmacogenomic approaches is to provide new information on how drugs can impact on the translational read-out within a defined cellular background.</p> <p>Methods</p> <p>We describe an approach that permits the analysis of de-novo mRNA-ribosome association in-vivo during short drug exposures. It combines hypertonic shock, polysome fractionation and high-throughput analysis to provide a molecular phenotype of translationally responsive transcripts. Compared to previous translational profiling studies, the procedure offers increased specificity due to the elimination of the drugs secondary effects (e.g. on the transcriptional read-out). For this pilot "proof-of-principle" assay we selected the drug rapamycin because of its extensively studied impact on translation initiation.</p> <p>Results</p> <p>High throughput analysis on both the light and heavy polysomal fractions has identified mRNAs whose re-recruitment onto free ribosomes responded to short exposure to the drug rapamycin. The results of the microarray have been confirmed using real-time RT-PCR. The selective down-regulation of TOP transcripts is also consistent with previous translational profiling studies using this drug.</p> <p>Conclusion</p> <p>The technical advance outlined in this manuscript offers the possibility of new insights into mRNA features that impact on translation initiation and provides a molecular fingerprint for transcript-ribosome association in any cell type and in the presence of a range of drugs of interest. Such molecular phenotypes defined pre-clinically may ultimately impact on the evaluation of a particular drug in a living cell.</p

Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: Inherent potential for biosynthetic versus live recombinant microbicides

<p>Abstract</p> <p>Background</p> <p>Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.</p> <p>Methods and Results</p> <p>Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6%) had potential to cleave the HSV-2 genome in > 100 but < 400 sites; 69(23.9%) in > 400 but < 700 sites; and the 9(3.1%) enzymes: BmyI, Bsp1286I, Bst2UI, BstNI, BstOI, EcoRII, HgaI, MvaI, and SduI cleaved in more than 700 sites. But for the 4: PacI, PmeI, SmiI, SwaI that had no sign of activity on HSV-2 genomic DNA, all 130(45%) other enzymes cleaved < 100 times. In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.</p> <p>Conclusion</p> <p>Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.</p

Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components

Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates’ therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers