288 research outputs found
Investigation of aerosol indirect effects on monsoon clouds using ground-based measurements over a high-altitude site in Western Ghats
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 0.50āÆgāÆmā3 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 30āÆ%
Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders
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
ŠŃŠµŠ½ŠøŠ²Š°Š½ŠøŠµ ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŠø ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŠ¹ Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃŠµŃŠ°Š±Š°ŃŃŠ²Š°ŃŃŠµŠ¹ Š¾ŃŃŠ°ŃŠ»Šø
The essence of the concept āfinancial 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£ ŃŃŠ°ŃŃŃ ŃŠ¾Š·ŠŗŃŠøŃŠ¾ ŃŃŃŠ½ŃŃŃŃ ŠæŠ¾Š½ŃŃŃŃ ŃŃŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼ŃŃŠ½Š¾Ń Š±ŠµŠ·ŠæŠµŠŗŠø
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Š±ŠµŠ·ŠæŠµŠŗŠø ŠæŃŠ“ŠæŃŠøŃŠ¼ŃŃŠ²Š°, ŃŠ¾ Š“Š¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²ŠøŃŠ²ŠøŃŠø ŠæŃŠ“Ń
ŃŠ“ ŃŠµŠ¹ŃŠøŠ½Š³Š¾Š²Š¾Ń Š¾ŃŃŠ½ŠŗŠø ŠæŠ¾ŠŗŠ°Š·Š½ŠøŠŗŠ°
ŃŃŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼ŃŃŠ½Š¾Ń Š±ŠµŠ·ŠæŠµŠŗŠø ŠæŃŠ“ŠæŃŠøŃŠ¼ŃŃŠ²Š°. ŠŠ¾ŃŠ»ŃŠ“Š¶ŠµŠ½Š¾ Š“ŠøŠ½Š°Š¼ŃŠŗŃ Š²ŠøŃŠ¾Š±Š½ŠøŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° ŃŠ°
Š¼Š¾Š»Š¾ŃŠ½ŠøŃ
ŠæŃŠ¾Š“ŃŠŗŃŃŠ² Š£ŠŗŃŠ°ŃŠ½Šø. ŠŠøŃŠ²ŠøŃŠø Š¾Š±Š»Š°ŃŃŃ Š£ŠŗŃŠ°ŃŠ½Šø, ŃŠŗŃ Ń Š»ŃŠ“ŠµŃŠ°Š¼Šø Š· Š²ŠøŃŠ¾Š±Š½ŠøŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ°
ŃŃŠ“ŠŗŠ¾Š³Š¾ Š¾Š±ŃŠ¾Š±Š»ŠµŠ½Š¾Š³Š¾. ŠŃŠ¾Š°Š½Š°Š»ŃŠ·Š¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼ŃŠŗŃ Š²ŠøŃŠ¾Š±Š½ŠøŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° ŃŠ° Š¼Š¾Š»Š¾ŃŠ½ŠøŃ
ŠæŃŠ¾Š“ŃŠŗŃŃŠ²
Š½Š° Š¾Š“Š½Ń Š¾ŃŠ¾Š±Ń, ŃŠ¾ Š“Š¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²ŃŃŠ°Š½Š¾Š²ŠøŃŠø ŃŠ¾ŃŃŃŠ½Šµ Š·ŃŠ¾ŃŃŠ°Š½Š½Ń ŠæŠ¾ŠæŠøŃŃ Š½Š° Š¾Š“Š½Ń Š¾ŃŠ¾Š±Ń.
ŠŠøŠ·Š½Š°ŃŠµŠ½Š¾ ŠæŃŠ“ŠæŃŠøŃŠ¼ŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃŠµŃŠ¾Š±Š½Š¾Ń Š³Š°Š»ŃŠ·Ń. ŠŃŠ¾Š²ŠµŠ“ŠµŠ½Š¾ Š¾ŃŃŠ½ŠŗŃ ŃŠ½ŃŠµŠ³ŃŠ°Š»ŃŠ½Š¾Š³Š¾
ŠæŠ¾ŠŗŠ°Š·Š½ŠøŠŗŠ° ŃŃŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼ŃŃŠ½Š¾Ń Š±ŠµŠ·ŠæŠµŠŗŠø ŠæŃŠ“ŠæŃŠøŃŠ¼ŃŃŠ² Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃŠµŃŠ¾Š±Š½Š¾Ń Š³Š°Š»ŃŠ·Ń. ŠŠ°
ŃŠµŠ·ŃŠ»ŃŃŠ°ŃŠ°Š¼Šø Š¾ŃŃŠ½ŠŗŠø Š·Š°ŠæŃŠ¾ŠæŠ¾Š½Š¾Š²Š°Š½Š¾ ŃŠ»ŃŃ
Šø ŠæŃŠ“Š²ŠøŃŠµŠ½Š½Ń ŠµŃŠµŠŗŃŠøŠ²Š½Š¾ŃŃŃ ŃŠæŃŠ°Š²Š»ŃŠ½Š½Ń ŃŃŠ½Š°Š½ŃŠ¾Š²Š¾-ŠµŠŗŠ¾Š½Š¾Š¼ŃŃŠ½Š¾Ń Š±ŠµŠ·ŠæŠµŠŗŠø ŃŠ°ŠŗŠøŃ
ŠæŃŠ“ŠæŃŠøŃŠ¼ŃŃŠ², ŃŠŗ: ŠŠŠ¢ Ā«ŠŃŠ±Š½Š¾Š¼Š¾Š»Š¾ŠŗŠ¾Ā», ŠŠŠ¢ Ā«ŠŃŠæāŃŠ½ŃŃŠŗŠøŠ¹
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Š¼Š¾Š»Š¾ŃŠ½Š¾ŠŗŠ¾Š½ŃŠµŃŠ²Š½ŠøŠ¹ ŠŗŠ¾Š¼Š±ŃŠ½Š°ŃĀ».Š ŃŃŠ°ŃŃŠµ ŃŠ°ŃŠŗŃŃŃŠ¾ ŃŃŃŠ½Š¾ŃŃŃ ŠæŠ¾Š½ŃŃŠøŃ ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ°Ń
Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŃ ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŃ. Š Š°ŃŃŠ¼Š¾ŃŃŠµŠ½Š¾ Š¼ŠµŃŠ¾Š“ŠøŃŠµŃŠŗŠøŠµ ŠæŠ¾Š“Ń
Š¾Š“Ń Š¾ŃŠ½Š¾ŃŠøŃŠµŠ»ŃŠ½Š¾ Š¾ŃŠµŠ½ŠøŠ²Š°Š½ŠøŃ
ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŠø ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŃ, ŃŃŠ¾ ŠæŠ¾Š·Š²Š¾Š»ŠøŠ»Š¾ Š²ŃŃŠ²ŠøŃŃ ŠæŠ¾Ń
Š¾Š“
ŃŠµŠ¹ŃŠøŠ½Š³Š¾Š²Š¾Š¹ Š¾ŃŠµŠ½ŠŗŠø ŠæŠ¾ŠŗŠ°Š·Š°ŃŠµŠ»Ń ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŠø ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŃ.
ŠŃŃŠ»ŠµŠ“Š¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼ŠøŠŗŃ ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° Šø Š¼Š¾Š»Š¾ŃŠ½ŃŃ
ŠæŃŠ¾Š“ŃŠŗŃŠ¾Š² Š£ŠŗŃŠ°ŠøŠ½Ń. ŠŃŃŠ²Š»ŠµŠ½Ń
Š¾Š±Š»Š°ŃŃŠø Š£ŠŗŃŠ°ŠøŠ½Ń, ŠŗŠ¾ŃŠ¾ŃŃŠµ ŃŠ²Š»ŃŃŃŃŃ Š»ŠøŠ“ŠµŃŠ°Š¼Šø ŠæŠ¾ ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Ń Š¼Š¾Š»Š¾ŠŗŠ° Š¶ŠøŠ“ŠŗŠ¾Š³Š¾
Š¾Š±ŃŠ°Š±Š¾ŃŠ°Š½Š½Š¾Š³Š¾. ŠŃŠ¾Š°Š½Š°Š»ŠøŠ·ŠøŃŠ¾Š²Š°Š½Š¾ Š“ŠøŠ½Š°Š¼ŠøŠŗŃ ŠæŃŠ¾ŠøŠ·Š²Š¾Š“ŃŃŠ²Š° Š¼Š¾Š»Š¾ŠŗŠ° Šø Š¼Š¾Š»Š¾ŃŠ½ŃŃ
ŠæŃŠ¾Š“ŃŠŗŃŠ¾Š² Š½Š°
Š¾Š“Š½Š¾Š³Š¾ ŃŠµŠ»Š¾Š²ŠµŠŗŠ°, ŃŃŠ¾ ŠæŠ¾Š·Š²Š¾Š»ŠøŠ»Š¾ ŃŃŃŠ°Š½Š¾Š²ŠøŃŃ ŠµŠ¶ŠµŠ³Š¾Š“Š½ŃŠ¹ ŃŠ¾ŃŃ ŃŠæŃŠ¾ŃŠ° Š½Š° Š¾Š“Š½Š¾Š³Š¾ ŃŠµŠ»Š¾Š²ŠµŠŗŠ°.
ŠŠæŃŠµŠ“ŠµŠ»ŠµŠ½Ń ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŃ Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃŠµŃŠ°Š±Š°ŃŃŠ²Š°ŃŃŠµŠ¹ Š¾ŃŃŠ°ŃŠ»Šø. ŠŃŠ¾Š²ŠµŠ“ŠµŠ½Š° Š¾ŃŠµŠ½ŠŗŠ°
ŠøŠ½ŃŠµŠ³ŃŠ°Š»ŃŠ½Š¾Š³Š¾ ŠæŠ¾ŠŗŠ°Š·Š°ŃŠµŠ»Ń ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŠø ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŠ¹
Š¼Š¾Š»Š¾ŠŗŠ¾ŠæŠµŃŠµŃŠ°Š±Š°ŃŃŠ²Š°ŃŃŠµŠ¹ Š¾ŃŃŠ°ŃŠ»Šø. ŠŠ¾ ŃŠµŠ·ŃŠ»ŃŃŠ°ŃŠ°Š¼ Š¾ŃŠµŠ½ŠŗŠø ŠæŃŠµŠ“Š»Š¾Š¶ŠµŠ½Ń ŠæŃŃŠø ŠæŠ¾Š²ŃŃŠµŠ½ŠøŃ
ŃŃŃŠµŠŗŃŠøŠ²Š½Š¾ŃŃŠø ŃŠæŃŠ°Š²Š»ŠµŠ½ŠøŃ ŃŠøŠ½Š°Š½ŃŠ¾Š²Š¾-ŃŠŗŠ¾Š½Š¾Š¼ŠøŃŠµŃŠŗŠ¾Š¹ Š±ŠµŠ·Š¾ŠæŠ°ŃŠ½Š¾ŃŃŠø ŃŠ°ŠŗŠøŃ
ŠæŃŠµŠ“ŠæŃŠøŃŃŠøŠ¹,
ŠŗŠ°Šŗ: ŠŠŠ Ā«ŠŃŠ±Š½Š¾Š¼Š¾Š»Š¾ŠŗŠ¾Ā», ŠŠŠ Ā«ŠŃŠæŃŠ½ŃŠŗŠøŠ¹ Š¼Š¾Š»Š¾ŃŠ½Š¾ŠŗŠ¾Š½ŃŠµŃŠ²Š½ŃŠ¹ ŠŗŠ¾Š¼Š±ŠøŠ½Š°ŃĀ», ŠŠŠ
Ā«ŠÆŠ³Š¾ŃŠøŠ½ŃŠŗŠøŠ¹ Š¼Š°ŃŠ»Š¾Š·Š°Š²Š¾Š“Ā», ŠŠŠ Ā«ŠŠµŃŠ²Š¾Š¼Š°Š¹ŃŠŗŠøŠ¹ Š¼Š¾Š»Š¾ŃŠ½Š¾ŠŗŠ¾Š½ŃŠµŃŠ²Š½ŃŠ¹ ŠŗŠ¾Š¼Š±ŠøŠ½Š°ŃĀ»
Evaluation of Magnetic Micro- and Nanoparticle Toxicity to Ocular Tissues
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 100ā250 mV range and b-waves were in the 500ā600 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
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 Gās approach
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 āwhite 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 Gās 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
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
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
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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