Difficulties in proving medical errors: Where do we stand?

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Application of support vector machine learning for orodispersible films disintegration time prediction

1. INTRODUCTION Orodispersible films (ODF) have emerged as innovative dosage forms that provide wide variety of advantages for patients and manufacturers over conventional dosage forms. The prominent characteristic of ODFs is fast disintegration followed by good patients acceptability [1]. Therefore, relevant disintegration time (DT) is usually considered as ODF critical quality attribute. Extensive research on ODFs is generating a lot of data, but lack of standardization is the main obstacle that limits their comparative evaluation. The following work aims to explore literature data on ODFs characteristics using the predictive data-classification algorithm Support vector machine (SVM) and assess its applicability in pharmaceutical development based on the set of experimentally obtained data. 2. MATERIALS AND METHODS 2.1. Materials Hydroxypropyl cellulose (Klucel GF, Ashland, USA), ethanol (≥99.8%, Honeywell, Charlotte, NC, USA) and glycerol, 85% (w/w) (Ph. Eur.) were used for preparation of printing and casting dispersion. 2.2. Data pre-processing Comprehensive data exploration has been conducted in the PubMed database using most common synonyms for ODFs with fifteen synonyms in singular and plural. Built database had following attributes: manufacturing approach, polymer selection, polymer molecular weight (KDa), polymer load (%), mechanical properties (tensile strength (MPa), Young's modulus (MPa), elongation at break (%)), disintegration method and disintegration time (DT) (s). 2.3. ODF preparation and characterisation Polymer dispersions for solvent casting and semi-solid extrusion 3D printing were prepared by dispersing HPC in ethanol:glicerol solution followed by continuous stirring on the magnetic stirrer. Prepared dispersions were: (i) casted on a unit-dose plexiglas plates, or (ii) printed using Ultimaker 2+ (Ultimaker, , Netherlands). ODFs were characterized in terms of mechanical properties using Z-LX Table-Top Testing Machine (Shimadzu, Japan) and DT using adapted compendial tester (Erweka ZT52, Germany) with a weight. 3. RESULTS AND DISCUSSION 3.1. Data pre-processing 274 papers (without reviews) were identified via search, of which 112 were included in the database. Nominal data from literature was transformed into numerical, using coding operator so that each nominal data had corresponding numerical value. Critical attributes for films fast disintegration were derived. 18 polymers were included as categorical data and were further differentiated on the basis of molecular weight. Values for most commonly evaluated mechanical properties were included as numerical data. Different DT methods were classified in seven classes (Table 1), while the manufacturing methods were classified in five classes. RapidMiner Studio 9.10 (RapidMiner, Dortmund, Germany) was used to transform data and employ SMV algorithm. 3.2. SVM model prediction Attributes with the highest weight were polymer load and DT method employed (Figure 1). The polymer type and characteristic did have conclusive effects on DT as their weight varied during data mining. This can be attributed to inconclusive data provided in papers and lot of missing values for those attributes. Mechanical properties had low weight, which can be explained with the broad value range for those attributes. Different research groups had different approach to disintegration testing, which lowered model precision as it was reported that SVM does not have high accuracy when data is imbalanced [3]. Relative error value was 20%, which can be considered as high, but, having in mind great diversity in presented data and methodology, obtained value is still acceptable for the pilot study. 3.3. Experimental validation HPC-based films prepared by 3D printing had tensile strength, elongation at break and Young’s modulus of 3.5 MPa, 137% and 5 MPa, respectively. Average DT was 69 s. For casted films, relevant values were 3.4 MPa, 105% and 3 MPa, and DT was 27 s. Experimentally obtained results were entered into model simulator (Figure 2) to simulate situation reflecting the experimental set up in which HPC-based films were prepared by 3D printing and solvent casting, and relevant attribute values obtained by samples characterization. In the case were manufacturing method was set to be 3D printing (coded as 1) predicted DT value was close to experimentally obtained value, i.e. 71.7 and 69 s, respectively. When solvent casting method was considered, predicted DT value was remarkedly higher than the experimentally obtained one, indicating bad predictability. It might be assumed that good predictability obtained in the case of 3D printed films is associated with lower data variability due to more simple sample composition and robust preparation method. In the case of casted films, data was much more complex due to a higher number of research papers and approaches to characterisation. 4. CONCLUSION The obtained results indicate that SVM algorithm can be employed to predict ODF DT value based on the dataset created using literature data. However, in order to obtain meaningful predictions, larger dataset, with fewer inconsistences and less missing values would be advantageous.9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow,Ljubljana, Slovenia, 15 th -17 th September, 202

The painted lady in soybean production - soybean pest scouting

The painted lady (Vanessa cardui L.) is a pest of soybean in Serbia and many countries in south-eastern Europe (Croatia, Bosnia, Hungary, Romania, Bulgaria). It occurs also in central, western and northern Europe (Austria, France, Germany). This pest appears occasionally, typically once in four to five years, when it can be of economic importance. It can cause severe damage in high infestation years with more than one third of the leaf canopy eaten. However, spraying with insecticide is only rarely required or economically justified.Legumes Translated Practice Note 1

The Impact of Water Deficit on The Soybean (Glycine max L.) Reproductive Stage of Development

Experiment was conducted in 2014, 2015 and 2016 at the Institute of Field and Vegetable Crops, Novi Sad, Serbia, to study the effects of water deficit treatments during a soybean reproductive stage. Two water deficit treatments were conducted T-1 (from beginning of blossom to seed maturation) and T-2 (from beginning of seed filling to seed maturation period) and control (no water deficit). The results showed that water deficit during seed formation has a significant effect on germination energy, germination precentage and abnormal seedling. Obtained results are of great importance for farmers, because under favorable conditions, a large number of abnormal seedling has the ability to sprout, reach the reproductive stage and participate in yield formation

Improved Oxygen Reduction on GC-Supported Large-Sized Pt Nanoparticles by the Addition of Pd

PdPt bimetallic nanoparticles on carbon-based supports functioning as advanced electrode materials have attracted attention due to their low content of noble metals and high catalytic activity for fuel cell reactions. Glassy carbon (GC)-supported Pt and PdPt nanoparticles, as promising catalysts for the oxygen reduction reaction (ORR), were prepared by the electrochemical deposition of Pt and the subsequent spontaneous deposition of Pd. The obtained electrodes were examined using X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM), and electroanalytical techniques. An XPS analysis of the PdPt/GC with the highest ORR performance revealed that the stoichiometric ratio of Pd: Pt was 1:2, and that both Pt and Pd were partially oxidized. AFM images of PdPt2/GC showed the full coverage of GC with PdPt nanoparticles with sizes from 100–300 nm. The ORR activity of PdPt2/GC in an acid solution approached that of polycrystalline Pt (E1/2 = 0.825 V vs. RHE), while exceeding it in an alkaline solution (E1/2 = 0.841 V vs. RHE). The origin of the improved ORR on PdPt2/GC in an alkaline solution is ascribed to the presence of a higher amount of adsorbed OH species originating from both PtOH and PdOH that facilitated the 4e-reaction pathway

Harvesting soybean

High soybean yields and quality require the harmony of all production factors. Timely and efficient soybean harvest is one of the key challenges. Inappropriate harvesting can lead to harvest losses of up to 30%. The main factors that impact harvest losses are pre-harvest activities (seedbed preparation, crop canopy), harvest time and combine harvester settings. Successful soybean harvesting is about recovering the highest proportion of the grain with the best possible quality and purity at the optimal time.Legumes Translated Practice Note 2

Microwave synthesis of N-CQDs : effect of wavelength on degradation of organic pollution in water

Industries today realis high amounts of different hazards into the environment without any pre– treatment, which is why the remediation from organic pollution still represents one of the most important issues in waste water treatment. Organic dyes from textile industry are one of the extremely geno‒toxic and cyto‒toxic pollutants. Thus, finding the appropriate photocatalyst for the treatment of contaminated water under sunlight is still a challenging work from economical and green chemistry approach. Here we present a microwave assisted synthesis of nitrogen doped carbon quantum dots with high efficiency in degradation of Rose Bengal organic dye from water under visible, blue, green and red light irradiation in batch system. The effect of microwave irradiation power and time on size and photocatalytic activity of synthesized dots were also investigated

Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

Poor solubility is one of the key reasons for the poor bioavailability of carbamazepine drugs. This study considers formulation of solid surfactant systems with carbamazepine, in order to increase its dissolution rate. Solid-state surfactant systems were formed by application of fractional experimental design. Poloxamer 237 and Poloxamer 338 were used as the surfactants and Brij (R) 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite) and a synthetic adsorbent carrier (Neusilin (R) UFL2) on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influences of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR and PXRD). It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions

Possibility of improving organic agriculture by introducing biodynamic preparations

Povećanje površina pod organskom proizvodnjom, a i tražnja za organskim proizvodima pokrenuli su i intenzivirali istraživanja koja će imati za cilj unapređenje i definisanje agronomskih praksi za dalji razvoj ovog sistema proizvodnje. Cilj ovog rada, je predstavljanje praktičnih metoda koje mogu da unaprede postojeći proizvodni proces u organskoj proizvodnji. Strateško opredeljenje ka održivom razvoju i uvođenju održivih sistema gajenja je proces koji podrazumeva usklađivanje različitih sfera proizvodnje ali i celokupnog lanca proizvodnje hrane. Organska proizvodnja i biodimanička poljoprivreda su se pokazali kao najefikasniji sistemi održive poljoprivrede. Fokus oba sistema gajenja je u održavanju biološke ravnoteže, jer u lancu ishrane sve mora da bude pod strogom kontrolom i to u svim segmentima. Biodinamička poljoprivreda je dobar primer održivog sistema poljoprivredne proizvodnje sa karakterističnim metodama i preparatima koji se primenjuju i čine je prepoznatljivom. Razlikujemo devet biodinamičkih preparata koji se koriste za prskanje zemljišta, biljaka i za pripremu komposta. U savremenim istraživanjima često su u upotrebi biljni ekstrakti, koji su po načinu pripreme vrlo slični biodinamičkim preparatima i primenjuju se u organskoj proizvodnji. Najčešće su u upotrebi tečno đubrivo od koprive (504), vodeni ekstrakt rastavića (preparat 508). Upoznavanje sa biodinamičkim preparatima i načinima njihove primene jedan je od koraka ka njihovom potencijalnom uvođenju u praksu u organskoj proizvodnji.The increase of areas under organic production, as well as the demand for organic products have started and intensified the research that aim to improve and define agricultural practices for the further development of this production system. The aim of this paper is to present practical methods that can improve the existing production process in organic production. Strategic commitment to sustainable development and introduction of sustainable cultivation systems is a process that involves the harmonization of different spheres of production, but also the entire food production chain. Organic production and biodynamic agriculture have proven to be the most efficient systems of sustainable agriculture.The focus of both cultivation systems is on maintaining biological balance, where everything in the food chain must be under strict control in all segments. Biodynamic agriculture is a good example of a sustainable system of agricultural production with characteristic methods and applications of preparations that makes it recognizable. We differentiate nine biodynamic preparations that are used for spraying of soil and plants and for compost. In modern research, plant extracts are often in use, which in terms of preparation are very similar to biodynamic preparations and it can be used in organic production. The most commonly used liquid fertilizer is from nettle (504) and water extract of horsetail (preparation 508). Introduction of biodynamic preparations and methods for application are the one of the steps towards their potential use in practice in organic production