288 research outputs found

    Investigation of aerosol indirect effects on monsoon clouds using ground-based measurements over a high-altitude site in Western Ghats

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    The effect of aerosols on cloud droplet number concentration and droplet effective radius is investigated from ground-based measurements over a high-altitude site where clouds pass over the surface. First aerosol indirect effect (AIE) estimates were made using (i) relative changes in cloud droplet number concentration (AIEn) and (ii) relative changes in droplet effective radius (AIEs) with relative changes in aerosol for different cloud liquid water contents (LWCs). AIE estimates from two different methods reveal that there is systematic overestimation in AIEn as compared to that of AIEs. Aerosol indirect effects (AIEn and AIEs) and dispersion effect (DE) at different LWC regimes ranging from 0.05 to 0.50ā€Ægā€Æmāˆ’3 were estimated. The analysis demonstrates that there is overestimation of AIEn as compared to AIEs, which is mainly due to DE. Aerosol effects on spectral dispersion in droplet size distribution play an important role in altering Twomey's cooling effect and thereby changes in climate. This study shows that the higher DE in the medium LWC regime offsets the AIE by 30ā€Æ%

    Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

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    Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

    ŠžŃ†ŠµŠ½ŠøŠ²Š°Š½ŠøŠµ фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚Šø ŠæрŠµŠ“ŠæрŠøятŠøŠ¹ Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃ€ŠµŃ€Š°Š±Š°Ń‚Ń‹Š²Š°ŃŽŃ‰ŠµŠ¹ Š¾Ń‚Ń€Š°ŃŠ»Šø

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    The essence of the concept ā€œfinancial and economic security of the enterpriseā€ is covered. Methodological approaches to the enterprise financial and economic security evaluation are considered, enabling the method of index numberrating score of the enterprise financial and economic security to be found. Dynamics of milk anddairy production in Ukraine has been studied. Ukrainian regions leading in liquid processed milk production have been identified. Dynamics of milk and dairy production per man has been analyzed which allowed to find out the annual increase in demand per man. Integrated index of the dairy enterprise financial and economic security has been evaluated. As a result, the ways to increase the managerial efficiency of financial and economic security of the following enterprises:PJSC "Dubnomoloko", PJSC "Kupyans'ki milk canning plant", PJSC the "Yagotyns'ki creamery", PJSC the "Pervomais'ki milk canning plant" are offered.Š£ стŠ°Ń‚Ń‚Ń– рŠ¾Š·ŠŗрŠøтŠ¾ сутŠ½Ń–ŃŃ‚ŃŒ ŠæŠ¾Š½ŃŃ‚Ń‚Ń фіŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼Ń–чŠ½Š¾Ń— Š±ŠµŠ·ŠæŠµŠŗŠø ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š²Š°. Š Š¾Š·Š³Š»ŃŠ½ŃƒŃ‚Š¾ Š¼ŠµŃ‚Š¾Š“ŠøчŠ½Ń– ŠæіŠ“хŠ¾Š“Šø щŠ¾Š“Š¾ Š¾Ń†Ń–Š½ŃŽŠ²Š°Š½Š½Ń фіŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼Ń–чŠ½Š¾Ń— Š±ŠµŠ·ŠæŠµŠŗŠø ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š²Š°, щŠ¾ Š“Š¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²ŠøяŠ²ŠøтŠø ŠæіŠ“хіŠ“ рŠµŠ¹Ń‚ŠøŠ½Š³Š¾Š²Š¾Ń— Š¾Ń†Ń–Š½ŠŗŠø ŠæŠ¾ŠŗŠ°Š·Š½ŠøŠŗŠ° фіŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼Ń–чŠ½Š¾Ń— Š±ŠµŠ·ŠæŠµŠŗŠø ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š²Š°. Š”Š¾ŃŠ»Ń–Š“Š¶ŠµŠ½Š¾ Š“ŠøŠ½Š°Š¼Ń–Šŗу Š²ŠøрŠ¾Š±Š½ŠøцтŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° тŠ° Š¼Š¾Š»Š¾Ń‡Š½Šøх ŠæрŠ¾Š“уŠŗтіŠ² Š£ŠŗрŠ°Ń—Š½Šø. Š’ŠøяŠ²ŠøтŠø Š¾Š±Š»Š°ŃŃ‚Ń– Š£ŠŗрŠ°Ń—Š½Šø, яŠŗі є Š»Ń–Š“ŠµŃ€Š°Š¼Šø Š· Š²ŠøрŠ¾Š±Š½ŠøцтŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° ріŠ“ŠŗŠ¾Š³Š¾ Š¾Š±Ń€Š¾Š±Š»ŠµŠ½Š¾Š³Š¾. ŠŸŃ€Š¾Š°Š½Š°Š»Ń–Š·Š¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼Ń–Šŗу Š²ŠøрŠ¾Š±Š½ŠøцтŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° тŠ° Š¼Š¾Š»Š¾Ń‡Š½Šøх ŠæрŠ¾Š“уŠŗтіŠ² Š½Š° Š¾Š“Š½Ńƒ Š¾ŃŠ¾Š±Ńƒ, щŠ¾ Š“Š¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²ŃŃ‚Š°Š½Š¾Š²ŠøтŠø щŠ¾Ń€Ń–чŠ½Šµ Š·Ń€Š¾ŃŃ‚Š°Š½Š½Ń ŠæŠ¾ŠæŠøту Š½Š° Š¾Š“Š½Ńƒ Š¾ŃŠ¾Š±Ńƒ. Š’ŠøŠ·Š½Š°Ń‡ŠµŠ½Š¾ ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š²Š° Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃ€ŠµŃ€Š¾Š±Š½Š¾Ń— Š³Š°Š»ŃƒŠ·Ń–. ŠŸŃ€Š¾Š²ŠµŠ“ŠµŠ½Š¾ Š¾Ń†Ń–Š½Šŗу іŠ½Ń‚ŠµŠ³Ń€Š°Š»ŃŒŠ½Š¾Š³Š¾ ŠæŠ¾ŠŗŠ°Š·Š½ŠøŠŗŠ° фіŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼Ń–чŠ½Š¾Ń— Š±ŠµŠ·ŠæŠµŠŗŠø ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š² Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃ€ŠµŃ€Š¾Š±Š½Š¾Ń— Š³Š°Š»ŃƒŠ·Ń–. Š—Š° рŠµŠ·ŃƒŠ»ŃŒŃ‚Š°Ń‚Š°Š¼Šø Š¾Ń†Ń–Š½ŠŗŠø Š·Š°ŠæрŠ¾ŠæŠ¾Š½Š¾Š²Š°Š½Š¾ шŠ»ŃŃ…Šø ŠæіŠ“Š²ŠøщŠµŠ½Š½Ń ŠµŃ„ŠµŠŗтŠøŠ²Š½Š¾ŃŃ‚Ń– уŠæрŠ°Š²Š»Ń–Š½Š½Ń фіŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼Ń–чŠ½Š¾Ń— Š±ŠµŠ·ŠæŠµŠŗŠø тŠ°ŠŗŠøх ŠæіŠ“ŠæрŠøєŠ¼ŃŃ‚Š², яŠŗ: ŠŸŠŠ¢ Ā«Š”ŃƒŠ±Š½Š¾Š¼Š¾Š»Š¾ŠŗŠ¾Ā», ŠŸŠŠ¢ Ā«ŠšŃƒŠæā€™ŃŠ½ŃŃŒŠŗŠøŠ¹ Š¼Š¾Š»Š¾Ń‡Š½Š¾ŠŗŠ¾Š½ŃŠµŃ€Š²Š½ŠøŠ¹ ŠŗŠ¾Š¼Š±Ń–Š½Š°Ń‚Ā», ŠŸŠŠ¢ Ā«ŠÆŠ³Š¾Ń‚ŠøŠ½ŃŃŒŠŗŠøŠ¹ Š¼Š°ŃŠ»Š¾Š·Š°Š²Š¾Š“Ā», ŠŸŠŠ¢ Ā«ŠŸŠµŃ€Š²Š¾Š¼Š°Š¹ŃŃŒŠŗŠøŠ¹ Š¼Š¾Š»Š¾Ń‡Š½Š¾ŠŗŠ¾Š½ŃŠµŃ€Š²Š½ŠøŠ¹ ŠŗŠ¾Š¼Š±Ń–Š½Š°Ń‚Ā».Š’ стŠ°Ń‚ŃŒŠµ рŠ°ŃŠŗрытŠ¾ сущŠ½Š¾ŃŃ‚ŃŒ ŠæŠ¾Š½ŃŃ‚Šøя фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ°Ń Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚ŃŒ ŠæрŠµŠ“ŠæрŠøятŠøя. Š Š°ŃŃŠ¼Š¾Ń‚Ń€ŠµŠ½Š¾ Š¼ŠµŃ‚Š¾Š“ŠøчŠµŃŠŗŠøŠµ ŠæŠ¾Š“хŠ¾Š“ы Š¾Ń‚Š½Š¾ŃŠøтŠµŠ»ŃŒŠ½Š¾ Š¾Ń†ŠµŠ½ŠøŠ²Š°Š½Šøя фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚Šø ŠæрŠµŠ“ŠæрŠøятŠøя, чтŠ¾ ŠæŠ¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²Ń‹ŃŠ²Šøть ŠæŠ¾Ń…Š¾Š“ рŠµŠ¹Ń‚ŠøŠ½Š³Š¾Š²Š¾Š¹ Š¾Ń†ŠµŠ½ŠŗŠø ŠæŠ¾ŠŗŠ°Š·Š°Ń‚ŠµŠ»Ń фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚Šø ŠæрŠµŠ“ŠæрŠøятŠøя. Š˜ŃŃŠ»ŠµŠ“Š¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼ŠøŠŗу ŠæрŠ¾ŠøŠ·Š²Š¾Š“стŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° Šø Š¼Š¾Š»Š¾Ń‡Š½Ń‹Ń… ŠæрŠ¾Š“уŠŗтŠ¾Š² Š£ŠŗрŠ°ŠøŠ½Ń‹. Š’Ń‹ŃŠ²Š»ŠµŠ½Ń‹ Š¾Š±Š»Š°ŃŃ‚Šø Š£ŠŗрŠ°ŠøŠ½Ń‹, ŠŗŠ¾Ń‚Š¾Ń€Ń‹Šµ яŠ²Š»ŃŃŽŃ‚ся Š»ŠøŠ“ŠµŃ€Š°Š¼Šø ŠæŠ¾ ŠæрŠ¾ŠøŠ·Š²Š¾Š“стŠ²Ńƒ Š¼Š¾Š»Š¾ŠŗŠ° Š¶ŠøŠ“ŠŗŠ¾Š³Š¾ Š¾Š±Ń€Š°Š±Š¾Ń‚Š°Š½Š½Š¾Š³Š¾. ŠŸŃ€Š¾Š°Š½Š°Š»ŠøŠ·ŠøрŠ¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼ŠøŠŗу ŠæрŠ¾ŠøŠ·Š²Š¾Š“стŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° Šø Š¼Š¾Š»Š¾Ń‡Š½Ń‹Ń… ŠæрŠ¾Š“уŠŗтŠ¾Š² Š½Š° Š¾Š“Š½Š¾Š³Š¾ чŠµŠ»Š¾Š²ŠµŠŗŠ°, чтŠ¾ ŠæŠ¾Š·Š²Š¾Š»ŠøŠ»Š¾ устŠ°Š½Š¾Š²Šøть ŠµŠ¶ŠµŠ³Š¾Š“Š½Ń‹Š¹ рŠ¾ŃŃ‚ сŠæрŠ¾ŃŠ° Š½Š° Š¾Š“Š½Š¾Š³Š¾ чŠµŠ»Š¾Š²ŠµŠŗŠ°. ŠžŠæрŠµŠ“ŠµŠ»ŠµŠ½Ń‹ ŠæрŠµŠ“ŠæрŠøятŠøя Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃ€ŠµŃ€Š°Š±Š°Ń‚Ń‹Š²Š°ŃŽŃ‰ŠµŠ¹ Š¾Ń‚Ń€Š°ŃŠ»Šø. ŠŸŃ€Š¾Š²ŠµŠ“ŠµŠ½Š° Š¾Ń†ŠµŠ½ŠŗŠ° ŠøŠ½Ń‚ŠµŠ³Ń€Š°Š»ŃŒŠ½Š¾Š³Š¾ ŠæŠ¾ŠŗŠ°Š·Š°Ń‚ŠµŠ»Ń фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚Šø ŠæрŠµŠ“ŠæрŠøятŠøŠ¹ Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃ€ŠµŃ€Š°Š±Š°Ń‚Ń‹Š²Š°ŃŽŃ‰ŠµŠ¹ Š¾Ń‚Ń€Š°ŃŠ»Šø. ŠŸŠ¾ рŠµŠ·ŃƒŠ»ŃŒŃ‚Š°Ń‚Š°Š¼ Š¾Ń†ŠµŠ½ŠŗŠø ŠæрŠµŠ“Š»Š¾Š¶ŠµŠ½Ń‹ ŠæутŠø ŠæŠ¾Š²Ń‹ŃˆŠµŠ½Šøя эффŠµŠŗтŠøŠ²Š½Š¾ŃŃ‚Šø уŠæрŠ°Š²Š»ŠµŠ½Šøя фŠøŠ½Š°Š½ŃŠ¾Š²Š¾-эŠŗŠ¾Š½Š¾Š¼ŠøчŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃ‚Šø тŠ°ŠŗŠøх ŠæрŠµŠ“ŠæрŠøятŠøŠ¹, ŠŗŠ°Šŗ: ŠŸŠŠž Ā«Š”ŃƒŠ±Š½Š¾Š¼Š¾Š»Š¾ŠŗŠ¾Ā», ŠŸŠŠž Ā«ŠšŃƒŠæяŠ½ŃŠŗŠøŠ¹ Š¼Š¾Š»Š¾Ń‡Š½Š¾ŠŗŠ¾Š½ŃŠµŃ€Š²Š½Ń‹Š¹ ŠŗŠ¾Š¼Š±ŠøŠ½Š°Ń‚Ā», ŠŸŠŠž Ā«ŠÆŠ³Š¾Ń‚ŠøŠ½ŃŠŗŠøŠ¹ Š¼Š°ŃŠ»Š¾Š·Š°Š²Š¾Š“Ā», ŠŸŠŠž Ā«ŠŸŠµŃ€Š²Š¾Š¼Š°Š¹ŃŠŗŠøŠ¹ Š¼Š¾Š»Š¾Ń‡Š½Š¾ŠŗŠ¾Š½ŃŠµŃ€Š²Š½Ń‹Š¹ ŠŗŠ¾Š¼Š±ŠøŠ½Š°Ń‚Ā»

    Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues

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    Purpose: Magnetic nanoparticles (MNPs) may be used for focal delivery of plasmids, drugs, cells, and other applications. Here we ask whether such particles are toxic to ocular structures. Methods: To evaluate the ocular toxicity of MNPs, we asked if either 50 nm or 4 mm magnetic particles affect intraocular pressure, corneal endothelial cell count, retinal morphology including both cell counts and glial activation, or photoreceptor function at different time points after injection. Sprague-Dawley rats (n = 44) were injected in the left eye with either 50 nm (3 ml, 1.65 mg) or 4 mm(3ml, 1.69 mg) magnetic particles, and an equal volume of PBS into the right eye. Electroretinograms (ERG) were used to determine if MNPs induce functional changes to the photoreceptor layers. Enucleated eyes were sectioned for histology and immunofluorescence. Results: Compared to control-injected eyes, MNPs did not alter IOP measurements. ERG amplitudes for a-waves were in the 100ā€“250 mV range and b-waves were in the 500ā€“600 mV range, with no significant differences between injected and noninjected eyes. Histological sectioning and immunofluorescence staining showed little difference in MNP-injected animals compared to control eyes. In contrast, at 1 week, corneal endothelial cell numbers were significantly lower in the 4 mm magnetic particle-injected eyes compared to either 50 nm MNP- or PBS-injected eyes. Furthermore, iron deposition was detected after 4 mm magnetic particle but not 50 nm MNP injection

    Support Vector Machine Implementations for Classification & Clustering

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    BACKGROUND: We describe Support Vector Machine (SVM) applications to classification and clustering of channel current data. SVMs are variational-calculus based methods that are constrained to have structural risk minimization (SRM), i.e., they provide noise tolerant solutions for pattern recognition. The SVM approach encapsulates a significant amount of model-fitting information in the choice of its kernel. In work thus far, novel, information-theoretic, kernels have been successfully employed for notably better performance over standard kernels. Currently there are two approaches for implementing multiclass SVMs. One is called external multi-class that arranges several binary classifiers as a decision tree such that they perform a single-class decision making function, with each leaf corresponding to a unique class. The second approach, namely internal-multiclass, involves solving a single optimization problem corresponding to the entire data set (with multiple hyperplanes). RESULTS: Each SVM approach encapsulates a significant amount of model-fitting information in its choice of kernel. In work thus far, novel, information-theoretic, kernels were successfully employed for notably better performance over standard kernels. Two SVM approaches to multiclass discrimination are described: (1) internal multiclass (with a single optimization), and (2) external multiclass (using an optimized decision tree). We describe benefits of the internal-SVM approach, along with further refinements to the internal-multiclass SVM algorithms that offer significant improvement in training time without sacrificing accuracy. In situations where the data isn't clearly separable, making for poor discrimination, signal clustering is used to provide robust and useful information ā€“ to this end, novel, SVM-based clustering methods are also described. As with the classification, there are Internal and External SVM Clustering algorithms, both of which are briefly described

    Improving prevention, monitoring and management of diabetes among ethnic minorities: contextualizing the six Gā€™s approach

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    Objective: People from Black, Asian and Minority Ethnic (BAME) groups are known to have an increased risk of devel-oping diabetes and face greater barriers to accessing healthcare resources compared to their ā€˜white Britishā€™ counter-parts. The extent of these barriers varies by demographics and different socioeconomic circumstances that people find themselves in. The purpose of this paper is to present and discuss a new framework to understand, disentangle and tackle these barriers so that improvements in the effectiveness of diabetes interventions for BAME communities can be achieved. Results: The main mediators of lifestyle behavioural change are gender, generation, geography, genes, God/religion, and gaps in knowledge and economic resources. Dietary and cultural practices of these individuals significantly vary according to gender, generation, geographical origin and religion. Recognition of these factors is essential in increas-ing knowledge of healthy eating, engagement in physical activity and utilisation of healthcare services. Use of the six Gā€™s framework alongside a community centred approach is crucial in developing and implementing culturally sensi-tive interventions for diabetes prevention and management in BAME communities. This could improve their health outcomes and overall wellbeing

    Cancer risk in persons with HIV/AIDS in India: a review and future directions for research

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    Background India has a large and evolving HIV epidemic. Little is known about cancer risk in Indian persons with HIV/AIDS (PHA) but risk is thought to be low. Methods To describe the state of knowledge about cancer patterns in Indian PHA, we reviewed reports from the international and Indian literature. Results As elsewhere, non-Hodgkin lymphomas dominate the profile of recognized cancers, with immunoblastic/large cell diffuse lymphoma being the most common type. Hodgkin lymphoma is proportionally increased, perhaps because survival with AIDS is truncated by fatal infections. In contrast, Kaposi sarcoma is rare, in association with an apparently low prevalence of Kaposi sarcoma-associated herpesvirus. If confirmed, the reasons for the low prevalence need to be understood. Cervical, anal, vulva/vaginal and penile cancers all appear to be increased in PHA, based on limited data. The association may be confounded by sexual behaviors that transmit both HIV and human papillomavirus. Head and neck tumor incidence may also be increased, an important concern since these tumors are among the most common in India. Based on limited evidence, the increase is at buccal/palatal sites, which are associated with tobacco and betel nut chewing rather than human papillomavirus. Conclusion With improving care of HIV and better management of infections, especially tuberculosis, the longer survival of PHA in India will likely increase the importance of cancer as a clinical problem in India. With the population's geographic and social diversity, India presents unique research opportunities that can be embedded in programs targeting HIV/AIDS and other public health priorities

    An Integrated Approach to the Prediction of Chemotherapeutic Response in Patients with Breast Cancer

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    BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities

    Chronic Delivery of Antibody Fragments Using Immunoisolated Cell Implants as a Passive Vaccination Tool

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    BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the AĪ² peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the AĪ² peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration
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