Safe Water Systems: An Evaluation of the Zambia Clorin Program

Clorin is a household water treatment product (a sodium hypochlorite disinfectant) that Society for Family Health launched in Zambia in 1998. This report provides a external assessment of Clorin use in light of the Centers for Disease Control and Pan American Health Organization's overall Safe Water Systems initiative. The intervention took a social marketing approach, targeting low-income households with Clorin at a subsidized price, and sales steadily increased from 1998 to 2004. This involved training for health center staff , neighborhood volunteers, and pharmacists; and promotions through radio, television, newspapers, and posters. The study found that active marketing through community-level personal was very important, while the role of mass media messages was unclear. Collaboration with the government health sector, retailers, and community agents was advised, as was strengthening the water management side of the program

An Investigation of Enantiomer Resolution by Gas Chromatography: Application in Drug Metabolism Studies

The use of gas chromatography for the analytical resolution of optical enantiomers provides a means of assigning configurations, on a correlative basis, to small, and often impure, samples of biological origin. This problem has previously been approached in ;two ways, viz: direct resolution of optical enantiomers on chiral stationary phases, or the employment of chiral reagents to form diastereomeric derivatives which have been separated on conventional columns. In the present work, the latter approach was employed. It was considered that conferment of sufficiently distinctive chromatographic properties would depend on the enhancement of conformational differences between diastereomers. Accordingly, it seemed likely that reagents in which the chirality and the functional group were embodied in a rigid molecular skeleton would be useful as chromatographic resolving agents. On the basis of this hypothesis, a study of the suitability of terpenoid acids for the resolution of enantiomeric alcohols and amines was initiated. The two acids examined were the sesquiterpenoid drimanoic acid and the monoterpenoid chrysanthemic acid. Many good separations were in fact observed for a wide range of enantiomeric alcohols, amines and amino acid methyl esters. The results achieved with these derivatives on columns packed with a non-selective stationary phase (SE-30) are comparable with, or in many cases superior to, those reported with other chiral reagents on capillary columns. An observation that the alpha-phenylbutyryl derivatives of (R)-alpha-phenylethylamine were well separated on conventional packed columns prompted an investigation into the use of alpha-substituted phenylacetic acids as gas chromatographic resolving agents for amines and amino acid methyl esters. Within the series studied, a resolution was achieved for every enantiomeric pair as their amides derived from at least one, and in many cases all of the chiral phenylacetic acids. The mechanisms involved in the resolution are still open to speculation, but examination of the separations obtained within a series of related diastereomeric amides indicated some trends. In general, the degree of resolution achieved increased with the size of the substituent on the chiral acid centre (i. e. R = Me < Et < iPr). Introduction of a more polar substituent (as in alpha-methoxy-phenylacetic acid) produced resolutions comparable to those obtained with the isopropylphenylacetic acid but some effects which could be attributed to the increased polarity of the substituent were noted. The derivatives of alpha-chlorophenylacetic acid showed satisfactory resolutions, but this reagent was judged unsuitable because of racemisation during acylation. All the derivatives were easily prepared, in good yield, without racemisation (except for the alpha-chlorophenyl-acetamides). The diastereomers were thermally and chromatographically stable, as shown by analysis using combined gas chromatography-mass spectrometry (GC-MS). The considerable degree of regularity observed in the elution order of these derivatives rendered the correlative assignment of configuration a feasible proposition. The techniques developed during the examination of enantiomer resolution were subsequently applied to a study of the in vivo metabolism of the oral anti-rheumatic drug (RS)-2-(4-isobutylphenyl) propionic acid ("ibuprofen") in humans. Pour metabolites, resulting from oxidation of the isobutyl side chain, were identified by GLC and GC-MS. Gas chromatographic resolution of diastereomeric amides formed with (R)-(+)-alpha-phenylethylamine showed that the excreted drug was enriched in the (S)-(+)-enantiomer. Similarly, two of the hydroxylated metabolites were shown to be enriched in the (S)-form. Synthesis of one of the minor hydroxylated metabolites, 2,4'-(1-hydroxy-2-methylpropyl) phenylpropionic acid, allowed complete characterisation of the metabolite. Separation of the enantiomeric alcohols as esters of (R)-(-)-alpha-phenylbutyric acid indicated some stereoselectivity in the metabolic hydroxylation. A brief examination of the metabolism of the aldosterone antagonist, spironolactone was also undertaken

Modeling of flexible drug-like molecules : qsar of GBR 12909 analog dat/sert selectivity

The dopamine reuptake inhibitor GBR 12909 and related dialkyl piperazine and piperidine analogs have been studied as agonist substitution therapies acting on the dopamine transporter (DAT) to treat cocaine addiction. Undesirable binding to the serotonin transporter (SERT) can vary greatly depending on the specific substituents on the molecule. This study uses Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices (CoMSIA) techniques to determine a stable and predictive model for DAT/SERT selectivity for a set of flexible GBR 12909 analogs. Families of analogs were constructed from six pairs of naphthyl-substituted piperazine and piperidine templates identified by hierarchical clustering as representative conformers. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies led to focused models that were stable to y-value scrambling. Test set correlation validation led to one acceptable model (q2=0.508, two components, r2=0.685, average residual = 0.00 for the training set, 0.22 for the extended test set). DAT/SERT selectivities higher than that of the most active compound in the QSAR series were predicted for nine novel compounds. This is the first CoMFA/CoMSIA study of the highly flexible GBR 12909 class of dopamine reuptake inhibitors. Previously, molecular modeling was based on more rigid dopamine reuptake inhibitors, and often only on global energy minimum (GEM) structures. Flexible molecules like GBR 12909 have multiple possible binding conformations, distributed across the potential energy surface in key torsional angle space, which can vary from the GEM by as much as 20 kcal/mol or more. The significance of this study lies in the combining of a clustering technique for identifying representative conformers from a set of low-energy (less than 20 kcal/mol from the GEM) conformers with an extensive 3D-QSAR analysis based on each representative conformer and analogs in a similar potential bioactive conformation

The Power of the Jewel: Discovering Historical Meaning Through the Study of Jewelry Made in Britain During the Reign of Queen Victoria, 1837-1901

The thesis: British Victorian jewelry has the power to function as both subject matter and a point of departure for the lively, interdisciplinary study of nineteenth-century Britain. The study begins with an object, a jewel in the hand, understood as an artifact. The beauty, wearability, intrigue, and history of antique jewelry gives it the power to launch historical inquiry and to provide concrete access to the past. Visual, oral, and print resources, along with other period objects from the arts and social sciences are then used to help reveal, enrich, and expand the historical meanings embedded in the jewels. This paper demonstrates numerous ways to examine a jewel to discover what it reveals about its own history, and the historical information that it points to about Victorian Britain. From the style, construction techniques, materials, and the design intentions of the jeweler, the research expands to consider social, cultural, economic and political issues that shaped nineteenth-century Britain and the jewelry that Victorian Britain produced. This method uses visual, photographic, and advertising images, the material culture resources found in museums, universities, special exhibitions, and retail collections, monographs on local, national, and international issues, literature of the era, along with biography, economic, industrial, class, social, artistic and cultural histories to develop and inform the discoveries made from handling the jewelry. Using information from a variety of perspectives, the jewelry can then help the historian create social, economic, political, cultural, and ideological commentary on the era and the society that produced it. Like the jewelry it studies, this interdisciplinary analysis reveals a diversity and variety in nineteenth-century Britain that reflects the sweeping, economic, and technological change brought about by industrialization, investment, imperialist expansion and trade, and the new social and political forces that growth and development unleashed. The interconnected actions among these forces shaped the life, thought, and the jewelry created during the nineteenth-century in Britain. Now, that legacy of connections facilitates the hands-on, interdisciplinary study of British Victorian jewelry, a study that develops historical competence about this exceptional jewelry, while tangibly enriching the historical understanding and appreciation of nineteenth-century Britain

Multiconfigurational electronic wavefunctions in the Full Optimized Reaction Space: the isomerization of nitrosyl hydride to nitrogen hydroxide in the lowest singlet and triplet states

Energy curves are determined for the lowest singlet and triplet states of the HNO molecule. The geometry is varied in that the hydrogen moves through 13 positions around the NO core to describe the isomerization reaction HNO yields HON. Quantitatively determined are the stable and metastable equilibrium positions in both states, the energy differences between these two equilibrium positions and between the two states, and the barriers with respect to isomerization. The calculations are carried out using a novel configuration interaction approach called the Full Optimized Reaction Space method, which involves multiconfigurational self-consistent field calculations as an integral part. In order to interpret the bonding changes occurring during the reaction, a novel type of orbital is developed and calculated. These are called Directed Localized Reaction Orbitals. With their help it proves possible to give an interpretation of the isomerization in terms of concepts which fit chemical intuition

Comparative molecular field analysis (CoMFA) of protonated methylphenidate phenyl-substituted analogs

Protonated methylphenidate (pMP) and several phenyl-substituted pMP analogs were analyzed using Comparative Molecular Field Analysis (CoMFA) to develop a pharmacophore for dopamine transporter (DAT) binding. This research is a part of an interdisciplinary study on using methylphenidate (MP) analogs to block the binding of cocaine to the DAT as a treatment for addiction. A random search conformational analysis using key pMP torsional angles was performed to create conformer families representing possible bioactive conformations. The lowest energy pMP conformer of each family was used as a template to create phenyl-substituted pMP analogs. Partial least squares analysis was used to determine the combination of electrostatic and steric cutoffs that yielded the highest predictability (q 2) . q 2 values above 0.5 were achieved for all conformer families. The best model was used to propose a pharmacophore to predict DAT binding affinity. The results were compared to a previous CoMFA study on neutral MP

Money, Money, Money—Or Not! Budget Realities and Transparency in Collection Development Decision‐Making

Each library’s budget is unique; however, the importance of providing information about the budget is common across all libraries and is a critical factor in how the library is perceived by its constituents. The cost of e‐resources, balancing the collection, and optimizing a flat budget in an era of escalating costs are issues often misinterpreted by the campus community, leading to both misunderstandings and misinformation. Limited budgets, escalating prices, and new acquisitions strategies necessitate clear communication with librarians and faculty about the financial realities and complex decisions surrounding collection development. One academic library used a two‐day workshop format to inform librarians about budget realities in order to provide financial transparency and minimize concerns about budget decisions. Library administrators at a large public university met with librarians to review and clarify funding sources, allocations, expenditures, deficits, high‐cost e‐resources, collection decision factors, and strategies for acquiring content. With a fuller understanding of the complexities of budget guidelines and limitations, librarians brainstormed solutions to real life collection development scenarios. Both an information‐sharing forum and professional development event, the workshop served to update, educate, and generate discussions for both veteran and new librarians. Strategies described in this paper reflect a comprehensive public university perspective and are scalable and adaptable to other types of institutions

A Systematic Literature Review of the Contribution of Past Climate Information Services Pilot Projects in Climate Risk Management

Many pilot-based initiatives have been developed to promote awareness and use of climate information services among vulnerable smallholder farmers in Africa through million-dollar investments. However, despite their experimental nature, these pilot projects have been successful in raising participating farmers’ awareness and use of climate information services and they can inform transferrable good practices. Through a systematic literature review approach, this review sought to understand ways in which these past pilot projects have contributed to climate risk management in the context of smallholder farming and the factors that led to their success. Results showed that climate information services main contribution to climate risk management has been through facilitating farm level decision making. Factors that led to success of the pilots include: use of downscaled information; building institutional partnerships to add value to climate information; involving farmers through the co-designing and co-developing process; face-to-face way of communication; embedding pre-seasonal workshops in the activities of local institutions for sustainability; using diversity of communication channels to enhance reach among others. These factors can be borrowed as good practices to inform future efforts focused on increasing adoption of climate information services among a wider population beyond pilot project reach