Perceptions of leadership in undergraduate pharmacy students through a mixed methods study

Poster abstract from Conference; Royal Pharmaceutical Society Winter Summit 2017

Development of a neuro-fuzzy technique for automated parameter optimization of inverse treatment planning

<p>Abstract</p> <p>Background</p> <p>Parameter optimization in the process of inverse treatment planning for intensity modulated radiation therapy (IMRT) is mainly conducted by human planners in order to create a plan with the desired dose distribution. To automate this tedious process, an artificial intelligence (AI) guided system was developed and examined.</p> <p>Methods</p> <p>The AI system can automatically accomplish the optimization process based on prior knowledge operated by several fuzzy inference systems (FIS). Prior knowledge, which was collected from human planners during their routine trial-and-error process of inverse planning, has first to be "translated" to a set of "if-then rules" for driving the FISs. To minimize subjective error which could be costly during this knowledge acquisition process, it is necessary to find a quantitative method to automatically accomplish this task. A well-developed machine learning technique, based on an adaptive neuro fuzzy inference system (ANFIS), was introduced in this study. Based on this approach, prior knowledge of a fuzzy inference system can be quickly collected from observation data (clinically used constraints). The learning capability and the accuracy of such a system were analyzed by generating multiple FIS from data collected from an AI system with known settings and rules.</p> <p>Results</p> <p>Multiple analyses showed good agreements of FIS and ANFIS according to rules (error of the output values of ANFIS based on the training data from FIS of 7.77 ± 0.02%) and membership functions (3.9%), thus suggesting that the "behavior" of an FIS can be propagated to another, based on this process. The initial experimental results on a clinical case showed that ANFIS is an effective way to build FIS from practical data, and analysis of ANFIS and FIS with clinical cases showed good planning results provided by ANFIS. OAR volumes encompassed by characteristic percentages of isodoses were reduced by a mean of between 0 and 28%.</p> <p>Conclusion</p> <p>The study demonstrated a feasible way to automatically perform parameter optimization of inverse treatment planning under guidance of prior knowledge without human intervention other than providing a set of constraints that have proven clinically useful in a given setting.</p

Models of in vitro spermatogenesis

Understanding the mechanisms that lead to the differentiation of male germ cells from their spermatogonial stem cells through meiosis to give rise to mature haploid spermatozoa has been a major quest for many decades. Unlike most other cell types this differentiation process is more or less completely dependent upon the cells being located within the strongly structured niche provided by mature Sertoli cells within an intact seminiferous epithelium. While much new information is currently being obtained through the application and description of relevant gene mutations, there is still a considerable need for in vitro models with which to explore the mechanisms involved. Not only are systems of in vitro spermatogenesis important for understanding the basic science, they have marked pragmatic value in offering ex vivo systems for the artificial maturation of immature germ cells from male infertility patients, as well as providing opportunities for the transgenic manipulation of male germ cells. In this review, we have summarized literature relating to simplistic culturing of germ cells, co-cultures of germ cells with other cell types, especially with Sertoli cells, cultures of seminiferous tubule fragments, and briefly mention the opportunities of xenografting larger testicular pieces. The majority of methods are successful in allowing the differentiation of small steps in the progress of spermatogonia to spermatozoa; few tolerate the chromosomal reduction division through meiosis, and even fewer seem able to complete the complex morphogenesis which results in freely swimming spermatozoa. However, recent progress with complex culture environments, such as 3-d matrices, suggest that possibly success is now not too far away

Fracturing ranked surfaces

Discretized landscapes can be mapped onto ranked surfaces, where every element (site or bond) has a unique rank associated with its corresponding relative height. By sequentially allocating these elements according to their ranks and systematically preventing the occupation of bridges, namely elements that, if occupied, would provide global connectivity, we disclose that bridges hide a new tricritical point at an occupation fraction $p=p_{c}$, where $p_{c}$ is the percolation threshold of random percolation. For any value of $p$ in the interval $p_{c}< p \leq 1$, our results show that the set of bridges has a fractal dimension $d_{BB} \approx 1.22$ in two dimensions. In the limit $p \rightarrow 1$, a self-similar fracture is revealed as a singly connected line that divides the system in two domains. We then unveil how several seemingly unrelated physical models tumble into the same universality class and also present results for higher dimensions

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

An intervention program to reduce the number of hospitalizations of elderly patients in a primary care clinic

<p>Abstract</p> <p>Background</p> <p>The elderly population consumes a large share of medical resources in the western world. A significant portion of the expense is related to hospitalizations.</p> <p>Objectives</p> <p>To evaluate an intervention program designed to reduce the number of hospitalization of elderly patients by a more optimal allocation of resources in primary care.</p> <p>Methods</p> <p>A multidimensional intervention program was conducted that included the re-engineering of existing work processes with a focus on the management of patient problems, improving communication with outside agencies, and the establishment of a system to monitor quality of healthcare parameters. Data on the number of hospitalizations and their cost were compared before and after implementation of the intervention program.</p> <p>Results</p> <p>As a result of the intervention the mean expenditure per elderly patient was reduced by 22.5%. The adjusted number of hospitalizations/1,000 declined from 15.1 to 10.7 (29.3%). The number of adjusted hospitalization days dropped from 132 to 82 (37.9%) and the mean hospitalization stay declined from 8.2 to 6.7 days (17.9%). The adjusted hospitalization cost ($/1,000 patients) dropped from$32,574 to $18,624 (42.8%). The overall clinic expense, for all age groups, dropped by 9.9%.</p> <p>Conclusion</p> <p>Implementation of the intervention program in a single primary care clinic led to a reduction in hospitalizations for the elderly patient population and to a more optimal allocation of healthcare resources.</p