198,932 research outputs found
Design, Synthesis, and Evaluation of Novel Antimycobacterial Agents With Enhanced Pharmacokinetic Profiles
No full textTuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is one of the leading causes of death worldwide. The present short-course therapy is six months long for drug-susceptible M. tb strains, and up to two years for multi-drug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) due to a lack of effective treatment. Non-tuberculous mycobacteria (NTM) such as the M. avium and M. abscessus complexes (MAC and MABSC, respectively) are opportunistic pathogens found ubiquitously in the environment. NTM infections have increasing prevalence in patients with structural lung diseases, including chronic obstructive pulmonary disease and cystic fibrosis. Current treatment recommendations for MAC and MABSC infections last for at least 12 months and include multidrug therapy with combinations of intravenous and oral antibiotics. The long-combined therapy is accompanied with many adverse effects and is routinely ineffective. Therefore, novel anti-TB and -NTM agents with greater efficacy and shorter treatment times are the need of the hour.
One of the common drug targets for antibiotic intervention is the inhibition of bacterial cell wall biosynthesis. Mycolic acids, which are α-alkylated β-hydroxylated fatty acids, are the primary lipid constituents of the mycobacterial cell wall and are synthesized intracellularly in the cytoplasm. Mycobacterial membrane protein large 3 (MmpL3) is an essential transporter protein that translocates mycolic acids as trehalose monomycolates (TMM), an ester comprising trehalose sugar and a mycolic acid, across the plasma membrane. The inhibition of this novel target obstructs the TMM transport, disrupting the cell wall assembly, leading to the inhibition of cell growth. Our group has previously developed urea- and indole-based compounds that are putative MmpL3 inhibitors with high activity at concentrations of sub-µg/mL against a panel of mycobacteria. However, they have poor aqueous solubility limiting their translational potential. Our efforts to improve the aqueous solubility of the indole-based compounds has yielded the acetamide series. The design is based on the hypothesis that ‘Medicinal chemistry ligand-based optimization of the indole series to generate the acetamide series maintains the pharmacophore while decreasing the percentage of lipophilic carbon atoms, thus retaining potent antimycobacterial activity and increasing aqueous solubility.’ Minimum inhibitory concentration values against a panel of mycobacteria, including M. abscessus and M. tuberculosis were assessed along with in vitro cytotoxicity profiles, pharmacokinetic and physicochemical parameters, including aqueous solubility, permeability, and human plasma protein binding. Based on the preliminary data, of the 39 compounds tested, compounds 192 and 200 were identified as the best leads, with potent activity against both M. tb and M. abscessus strains and 20- to 30-fold improvement in aqueous solubility compared to indoles, while maintaining optimal ADME-Tox.ProQuest Traditional Publishing Optio
Introduction
Get PDFThis Chapter introduces the volume that contains 13 Chapters on different thematic topics of MGNREGA, one of the most celebrated flagship social protection programmes of Government of India in recent years. This programme is being implemented in India since 2006. First, this Chapter provides an overview of important interventions made by the central and state governments of India to reduce poverty through Employment generation related programmes, including a historical perspective on evolution of right-based employment guarantee schemes like MGNREGA. It then describes selected features and makes a critical assessments on specific aspects of implementation of the MGNREGA programme, its implementation status, the major activities covered under MGNREGA programme, its performance and relevance. Then, we discuss growing policy concerns and uncertainties surrounding implementation of the MGNREGA programmes, the delays in payments of wage to labor force participating in the programme, fluctuation of budget allocations over the years. The Chapter then provides a synoptic view of the selected empirical studies on MGNREGA, its implementation, and outcomes across the states in India. Following this overview on MGNREGA, the Chapter presents an overview of the Chapters contained in this volume for the benefit of the readers. The Chapter concludes by highlighting the imperative for recasting the MGNREGA from the future perspective in terms of responding to the emerging challenges in rural India: (a) increasing drought induced distress conditions prevail across the states; (b) the need for making MGNREGA a broad-based programme through incorporating skill based activities and imparting technical skills to the rural workforce through the MGNREGA to ensure ling-term livelihood benefits to the programme participants, and (c) the efficacy of the programme towards sustaining the rural livelihoods
Attitude of intensive care specialists toward deceased organ donation in Germany. Results of a questionnaire at the 12th Congress of the German Interdisciplinary Association for Intensive and Emergency Medicine
No full textBackground. Organ transplantation is the only treatment option for many patients with end-organ failure. Due to lack of transplantable organs, patients already on the waiting list die every day. The number of organ donors in Germany fell in 2012 by 12.8%, reaching its lowest level since 2002. The medical and nursing personnel in intensive care units have a key role in the recruitment of potential organ donors; therefore, a survey was conducted on this subject. Materials and methods. At the 12th Congress of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI) in December 2012, a point prevalence study using a paper-pencil survey was performed. Results. A total of 1045 questionnaires were analyzed. Of respondents, 81% favor organ donation in the event of their own brain death. The approval rate in the medical profession was 84% and 75% of the nursing profession. Only 45.3% of the participants (47% physicians, nursing 44%) had an organ donor card and nearly half (45%) had already confided their opinion towards organ donation to their family or friends. The main reasons for a lack of acceptance of organ donation was the concept of brain death (40%), fear of abuse by organ trade (29%), and the lack of integrity of the body after death (11%). The particularly intense discussion about organ donation and transplantation in 2012 resulted in a predominantly negative change of attitude in 45% of respondents. Conclusion. The vast majority of the intensive care personnel supports organ donation, but less than half of the respondents have an organ donor card. The reports of irregularities in the organ allocation were scrutinized, but had apparently no significant impact on the individual and collective fundamental donor decision
Economic and Institutional Determinants of Mergers & Acquisitions in BRICS, G7 and G20 Economies
Get PDFFactors contributing towards increasing the number of mergers and acquisitions (M &A) among firms and the volume of business and sales of these firms are assessed empiricallybased on results of the static and dynamic panel data models for BRICS, G7 and G20 countries in this investigation. While the higher rates of economic growth and foreign direct investment (FDI) contribute positively to the occurrence of M &A activities, these effects are even more prominent with greater efficiency in government institution, qualities of regulation, voice accountability and control of corruption. In the meantime, higher inflation and corporation tax rates reduce not only the numbers but the volumes of the M & A activities. Size of the business matters, medium or large corporations merge to exploit scale economies, to benefit from larger markets and to retain market power by operating across the globe.
Has Profitability of Foodgrain Production Declined After Implementation of MGNREGS in India?
Get PDFWhether national rural employment guarantee scheme (MGNREGS) introduced during 2006 has increased the farm wage rate substantially to the point that has reduced farm profitability due to the programme. This is still an unsettled issue in the literature. Hence, in this paper, an attempt has been made to analyse these issues utilising cost of cultivation survey data published by the Commission for Agricultural Costs and Prices. With the data of different states from 2000–01 to 2010–11, the study has covered five different foodgrain crops namely paddy, wheat, jowar, bengal gram (channa) and pigeon peas (red gram) for the analysis. The study does not seem to support the argument that the profitability of foodgrain crops has declined after the introduction of MGNREGS. This is not only true with high area with high productivity (HAHP) states but also with high area with low productivity (HALP) states. However, this study shows that the real cost incurred on account of human labour has increased considerably in all five crops in both High and low productivity states during the MGNREGS period (2006–07 to 2010–11) as compared to preceding years. In fact, real profitability even after subtracting the cost of imputed value of family labour cost used in the cultivation of the crops (cost C2) has either increased or the losses incurred reduced in all five crops in both HAHP and HALP states. The number of years profit realised by the farmers has also increased in most crops during post-MGNREGS period as compared to pre-MGNREGS period (2000–01 to 2005–06). Increased productivity of most of these crops also might have helped to increase the profitability of farmers across the country, even taking account increase in human labour cost during the same period
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
One and a half ventricle repair: clinical and animal study
Get PDFSUMMARY
Since the first description of the so called “one and a half ventricle repair”, published by Billingsly et al. in 1989 1, this type of correction has been applied to several complex congenital cardiac anomalies. The rationale underlying this repair is twofold. On one hand the aim is to reduce the blood flow to, and therefore to downsize the pre-load of, a dysfunctional or hypoplastic right ventricle (RV), considered to be unable to sustain a biventricular correction. On the other hand the one and a half ventricle repair (1.5 VR) permits to maintain a complete and physiological separation of pulmonary and systemic circulations, avoiding blood mixing and desaturation. Furthermore it represents a valid alternative to the Fontan circulation in the setting of a less but still functioning RV, with the advantage to provide a pulsatile pulmonary blood flow and to prevent systemic venous hypertension 2,3. One and a half ventricle repair consists of bidirectional cavo-pulmonary shunt (BCPS) in addition to complete closure of intracardiac communications, associated or not with repair of other congenital heart defects. It can be appropriate for a wide spectrum of congenital anomalies, provided that the RV is large enough to manage the blood supply from the inferior vena cava. However, feasibility in adult population is being explored 1,4.
This study has divided in two parts:
1. Clinical study 2. Experimental study in animals.
In clinical study we have reviewed our institutional experience with 1.5 VR to evaluate early and long term results and explore the impact of associated cardiac malformations on outcomes of the one and a half ventricle repair. Animal study in rabbits was conducted to evaluate the effect of a pulsatile venous flow pattern in superior vena cava and to understand an immediate & after pharmacologically induced stress test the hemodynamic changes in superior vena cava, right atrium, right ventricle, pulmonary artery and inferior vena cava district.
A. Clinical study
Methods
All patients who underwent one and a half ventricle repair between March 1994 and January 2012 were included. All available clinical and operative data were reviewed. Patients were divided in: Group A - patients with right ventricle hypoplasia/dysfunction and malformations of tricuspid or pulmonary valves; Group B - patients with associated complex malformations involving other cardiac structures.
Results
This is an 18 years retrospective clinical review of 24 consecutive patients who underwent one and a half ventricle repair at our Institution. Mean age at repair was 11.9 years (range 4 months – 66.8 years). Mean TV annulus Z-score was -3.2 (range -6.2 to 3.6). Mean pulmonary vascular resistance was 1.75 U/m2 (range 1.0 to 3.0). Three patients had heterotaxy syndrome. Sixteen patients underwent previous cardiac operation, one of these had a Fontan operation.
There was no death at operation. Postoperative complications occurred in 19 patients (79 %), and were: chylothorax/chylopericardium (n=7), BAV III (n=2), arrhythmias (n=7), renal failure (n=4), heart failure (n=4), cardiac/pleural effusion (n=11), SVC syndrome (n=2), pulmonary infection (n=3), hemi diaphragm paralysis that required diaphragm plasty (n=1), SVC thrombosis with PE (n=1). Five patients required definitive PM implantation. All patients were discharged home alive and well, after a mean hospital stay of 32 ± 29 days. At a mean follow up of 8.3 years (range 1 month – 17.9 years, FU completeness: 96 %), there were 2 late deaths (1 non cardiac related). Among survivors, functional status was NYHA class I in 19 patients (90.4%). Late adverse events occurred in 10 patients (43 %) including: late reoperation (n=3), one of these was a biventricular conversion; haemodynamic procedures (n=6); arrhythmias (n=2); neurological event (n=1); other complications (n=5).
Overall freedom from adverse events, surgery and interventional procedures was 56.5 %, 87 % and 73,9 % respectively. Freedom from adverse event in Group A (n=12) was 83.3 % while in Group B (n=11) was 27.3 %. Statistical analysis demonstrated that Group B had a significantly lower freedom from adverse events than Group A (p = 0.015).
B. Animal Study
Methods
Experiment was performed in experimental Rabbits. Animal care has taken according to established standard for experiment in animals.
Experimental model: RABBIT
Strain: NEW ZEALAND
Total animal number: 30
Weigh of animals:4. 5-5.5 kg
Results
1. After cavapulmonary anastomosis- SVC and PA pressure has increased but RA pressure has decreased, which proves the decrease of the pressure in inferior vena cava district.
2. After pharmacologically induced stress test: increased the pressure in superior vena cava and also increased heart rate but right ventricular, right atrial & pulmonary artery pressures were remained as same as after cavopolmonary anastomosis, as it is in resting condition.
3. That means superior vena cava pressure is always higher after cavapulmonary anastomosis but venous pressure in inferior vena cava district is constant and even lower in comparison with preoperative pressure.
4. We found no any changes of right atrial pressure, after 1.5 ventricular repair and even after pharmacologically induced stress test which proves that the inferior vena cava return is ok and no hypertension in inferior vena cava district even after stress test(good exercise tolerance), which is a very positive finding in favour of one and a half ventricle repair in comparison to Fontan type procedure.
Conclusion
After having the result of both clinical study and experiment in animals we have concluded that the 1.5 VR is a safe and valid option for surgical repair of hypoplasic, borderline or failing right ventricles as an alternative to Fontan procedure. Most patients show good functional status at follow up. This repair provides a low pressure in the inferior vena cava district and allows good early and mid-term outcomes
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Inter-sectoral Linkages and Multipliers of MGNREGA in a Rainfed Village in Karnataka: Applications of Social Accounting Matrix (SAM)
Get PDFThis chapter examines inter-sectoral linkages of Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) interventions in a village economy of Karnataka state. This is done using framework of social analysis matrix (SAM) in Markabbinahalli village, a predominantly a rainfed village, of Bijapur District in northern Karnataka. An in-depth survey was done in 2013, SAM of 82 × 82 column and rows (activities) was constructed to analyze direct, indirect and inter-sectoral linkages of village level activities for year of 2012–13, in relation to MGNREGA interventions. The SAM analysis suggests that additional investment of Rs. 1 million by MGNREGA in the studied village increased 1.1% of total income of the village, provided a full employment to 18 households at the rate of 340 days of work per person per household annually at a wage rate of Rs. 300 per day. Major share of the MGNREGA investment went to indirect impact (84%), also known as multiplier effects of the investment. The net impact of MGNREGA on labour income in the studied village was weak due to expenditure to several activities that were produced outside of villages such as machinery uses in construction, skilled labour uses, etc. We suggest that making the programme more demand driven, taking more labour intensive work activities under MGNREGA would also ensure more circulation of MGNREGA expenditures within the local economy, which would produces more employment and income locally due to increased feedback and inter-sectoral linkage (or multiplier) effects
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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