23 research outputs found
The crucial necessity of designing competency based curriculum for post graduate medical education in Iran
Surveying Birjand faculty members’, paramedical and nursing students\\\' viewpoints on educational evaluation plan
Background and Aim: The aim of educational evaluation is to improve learning and create a suitable situation for academic staff. The present study was performed to assess the viewpoints of BUMS teachers and students regarding the evaluation plan and the effect of it on educational development.
Materials and Methods: The present study was a cross-sectional and descriptive-analytical one. It was performed in the second half of the academic year 2008-9 in Birjand University of Medical Sciences.
The study sample included 79 faculty members and 321 paramedical and nursing students. Their opinions were separately studied using two questionnaires for students and faculty members. Content validity and reliability of the two questionnaires employed were confirmed by respective specialists. The gathered data was analyzed by means of SPSS software (V: 16) and Chi-square at the significant level α≤0.05.
Results: It was found that 76 % of faculty members believed that evaluation had some positive effects leading to the betterment of the process of teaching. But, %74.7 of them believed that some changes in the process should take place. Besides, %69.9 of the faculty members thought that the questionnaires were irresponsibly and carelessly filled out by the students.
On the other hand, %59.5 of the students believed that the results of the evaluation were not considerably taken into account. They believed that evaluation forms were not suitable evaluative means for teaching.
Conclusion: The results of the present study showed that most of faculty members and students are not optimistic about evaluation plan. Therefore, assuring students and teachers of the effectiveness of evaluation regarding the improvement of educational condition will result in more responsibility in students and more motivation in their teachers
Evidence-based health human resources planning and medical professionals’ education in Iran
ORIGINAL ARTICLE Corresponding Author Qualitative and Quantitative Examination of Household Hazardous Waste in Tehran
ABSTRACT Tehran Metropolitan is one of the most crowded cities in the world. A large volume of various kind of solid waste are daily produced in the city which can cause lots of adverse environmental impacts. In the meanwhile, household hazardous waste has more importance than the others whereas it contains enormous toxic materials. Such toxins, by entering food chains and accumulating in humans can lead to a variety of gene mutations, cancer and congenital anomalies. Thus separation and optimal management of these materials is extremely important. The first step for management of this class of materials is identification of compounds and determination of quantities of the components. The current study focuses on determining the hazardous rate of the household wastes in Tehran. Accordingly, the Strict 2 of Tehran Metropolitan was selected as case study. Random sampling and questionnaire were applied to conduct the research. The obtained results indicated that around 10% of entire household wastes were hazardous within 2010-2011. Besides, the findings revealed that the amount of the hazardous material in winter is more than it in summer. The findings derived from the questionnaire suggested that 30% of residents have enough knowledge of household hazardous wastes, most of which possess a bachelor's degree or higher. In the meanwhile, only less than 10% separate the hazardous materials
Spray drying of pharmaceuticals and biopharmaceuticals: experimental optimization of process and formulation
Oral consumption is the most commonly used method of small molecule drug delivery due
to its simple administration, flexible formulation design, cost-effectiveness and established
production technology. The typical pathway for an orally ingested drug involves dissolution in the
gastrointestinal fluid, followed by permeation across the gut membrane and systemic circulation
until it reaches the point of action. The rate of dissolution is therefore of critical importance to
ensure high drug adsorption and maximum efficacy. The Biopharmaceutical Classification System
(BCS) classified active pharmaceutical ingredients (APIs) into 4 categories based on their
solubility and permeability among which BCS class II APIs are defined as being poorly soluble
but highly permeable. The share of BCS class II APIs of newly developed drugs has increased
from 30% to 60% in recent years. Therefore, it is critical for the industry to incorporate effective
formulation approaches for improving solubility and dissolution rates of these APIs. In this regard,
a number of approaches have been investigated. Amorphous solid dispersion (ASD) is a successful
approach for transforming and stabilizing crystalline drugs to amorphous form with higher
solubility/dissolution rates. Spray drying (SD) is a solvent-based drying method that has been used
for formulating ASDs with improved solubility and stability.
Biopharmaceuticals are pharmaceuticals that are inherently biological in nature and
manufactured using biotechnology. This broad definition includes any type of blood product,
vaccines, antibodies, proteins and nucleic acids. Protein-based pharmaceuticals are among the
fastest growing categories of therapeutic agents. Therefore, the development of stable protein based formulations with controlled physicochemical properties is of high interest. Reversible and
irreversible aggregation in liquid protein formulations specifically at high concentrations is a
challenging problem for biopharmaceutical producers. Spray drying is (SD) is a solvent-based
technique in which solutions are atomized and dried using heat in a drying chamber. It is known
for its high throughput and compatibility with continuous manufacturing. SD has previously been
demonstrated as an effective technique for the preparation of ASDs and it has been used as an
alternative method to freeze-drying for drying and stabilizing high concentration formulations of
biopharmaceuticals. To date however, the development of spray drying processes for large
biomolecules has proved challenging primarily due to protein/enzymatic inactivation caused by
high drying temperatures and the shear stress induced by atomization. Overcoming this issue will require a comprehensive understanding of the effect of formulation and process parameters on
spray dried biological formulations.
Chapter 1 reviews the fundamental principles of SD by explaining every individual step
of the process from atomization to the drying chamber set up. It comprehensively covers the
applications of SD in preparing ASDs and formulating stable biopharmaceuticals. The effect of
process and formulation parameters on SD of biopharmaceuticals such as vaccines and proteins
for pulmonary delivery applications are discussed. This follows an attempt to elucidate the
systematic use of the Design of Experiment (DoE) approach for optimizing the SD process for
different applications to conclude this chapter.
Chapter 2 highlights the use of the DoE approach for formulating ternary ASD
compositions of Ibuprofen (IBU) as a model BCS class II API. Based on the DoE approach a range
of 16 formulations of IBU, HPMCP-HP55 and Kollidon VA 64 were spray dried. Statistical
analysis was employed to decipher the interrelation of various SD process and formulation factors,
namely solution feed rate, inlet temperature, API to excipients ratio and dichloromethane (DCM)
/methanol (MeOH) ratio. The significance of composition (IBU:excipient) was shown as the
determining factor in preparing stable ASD formulations. The effect of intermolecular interactions
was investigated by Fourier-Transform Infrared spectroscopy (FTIR) and Carbon-13 Solid-State
Nuclear Magnetic Resonance spectroscopy (ssNMR) analyses indicating that hydrogen bond
formation between the carboxyl groups of IBU within the ASDs is highly likely. Studies show that
the solubility of IBU in ASD formulations is improved relative to pure IBU. This was attributed
to both the amorphous structure of IBU and of the existence of amphiphilic excipient, Kollidon
VA64, in the formulation. This study indicates that ASD is an effective strategy for improving the
dissolution rate of IBU as a BCS class II API.
Chapter 3 investigates the influence of three different solvent-based techniques on the
physicochemical properties and quality of ASDs of IBU. Solvent-based techniques of
electrospinning (ES), spray-drying (SD) and rotary evaporation (RE), were used for formulating
ASDs of IBU as a model BCS class II API with two cellulosic excipients, HPMCAS and HPMCP HP55 in an attempt to determine the effect of processing technique on the critical quality attributes
(CQAs) of ASDs. Principal component analysis (PCA) of Raman spectra of crystalline and
amorphous IBU was used for qualitative analysis of the homogeneity of ASDs as a determining factor for the stability of ASDs during long-term storage. Results show that while ASD formation
is solely dependent on API:excipient ratio, the ASD homogeneity is totally dependent on the
processing technique. Samples produced by ES gave the least homogenous ASD compared with
RE and SD samples potentially influencing long-term storage stability. Moreover, ES samples had
the highest API release rate which was further confirmed to be due to the nanofibrous morphology
and higher specific surface area of these samples. The presence of crystalline IBU in samples and
the ASD forming strengths of each of the polymers was assessed by Differential Scanning
Calorimetry (DSC). The higher melting point depression, higher glass transition temperature (Tg),
and increased abundance of functional groups suitable for hydrogen bonding of HPMCAS proved
it to be a significantly better ASD former relative to HPMCP-HP55. This chapter concludes by
outlining the significance of the three solvent-based processing techniques (ES, SD and RE) on
the physicochemical properties of ASDs such as dissolution rate, specific surface area and
homogeneity, factors that could ultimately affect their stability and downstream processing
capacity.
Chapter 4 develops a rational approach towards the spray drying of biopharmaceuticals
using lysozyme as a model biomolecule. A two-step approach is suggested towards a
comprehensive understanding of the behaviour of large biomolecules during the spray drying
process with a view to developing tailored spray drying protocols for biological molecules. A full
factorial Design of Experiments (DoE) was employed to define the most critical process and
formulation parameters. With respect to parameters such as feeding rate, outlet temperature (Tout)
and feed solid concentration, Tout was determined to be the most statistically significant factor
affecting the enzymatic activity of lysozyme based on screening analysis of the DoE. The second
step of the study involved performing forced deactivation studies to identify critical points of
potential enzymatic deactivation during the drying process. This was performed by investigating
the inactivation of lysozyme both in solution and solid-state at wet-bulb (Twb) and outlet
temperatures respectively. Results show that there is no substantial inactivation of lysozyme in
solution at Twb (35-45 °C). However, lysozyme in solid form experienced a significant degree of
inactivation when heated to temperatures similar to Tout (70-90 °C). This inactivation was fitted by
an Arrhenius equation, where the inactivation energy and Arrhenius constant were estimated. The
approaches and models presented herein provide a roadmap for improved understanding of the critical process and formulation parameters required for the successful spray drying of large
biomolecules.
Chapter 5 summarises the additional contributions the author made during his Ph.D.
period. It consists of a brief introduction to the results of three different projects on which the
author is listed as a co-author:
1. Particle engineering of lignin via spray drying as a potential excipient for the
pharmaceutical industry.
2. Co-crystal polymorphic control by nanodroplet and electrical confinement.
3. A study on the effect of polymeric excipient on the downstream processing of hot-melt
extruded cocrystals of ibuprofen.
Chapter 6 provides a conclusive overview of the whole thesis.
Chapter 7 discusses potential future directions in the field of spray drying of
pharmaceuticals and biopharmaceuticals. If applied correctly spray drying as one of the leading
continuous drying and formulating techniques in small molecule sector possess immense potential
to become a major player in processing large molecule APIs as well.
This thesis follows two main objectives:
Firstly, developing novel ternary amorphous solid dispersions via spray drying for
improving the dissolution and physicochemical properties of BCS class II APIs. In an attempt to
meet this goal, the design of experiment (DoE) approach as part of the quality by design (QbD)
strategy in pharmaceutical and biopharmaceutical industry was used for simultaneous analysis of
interrelations of process and formulation techniques. Chapters three and four are focused on spray
drying novel ternary amorphous solid dispersion of ibuprofen as a small molecule API with low
aqueous solubility.
Secondly, enabling the spray drying of biopharmaceuticals via a systematic understanding
of the effect of process and formulation factors on the bioactivity and physicochemical properties
of the large molecule API. The DoE approach was chosen as an approach with care for elucidating
the critical factors affecting the bioactivity and physicochemical properties of lysozyme as a
biomolecule
Author Correction: The method of lines extension for the analysis of multilayered graphene-loaded structures in cylindrical coordinates
Spray drying of pharmaceuticals and biopharmaceuticals: experimental optimization of process and formulation
Oral consumption is the most commonly used method of small molecule drug delivery due
to its simple administration, flexible formulation design, cost-effectiveness and established
production technology. The typical pathway for an orally ingested drug involves dissolution in the
gastrointestinal fluid, followed by permeation across the gut membrane and systemic circulation
until it reaches the point of action. The rate of dissolution is therefore of critical importance to
ensure high drug adsorption and maximum efficacy. The Biopharmaceutical Classification System
(BCS) classified active pharmaceutical ingredients (APIs) into 4 categories based on their
solubility and permeability among which BCS class II APIs are defined as being poorly soluble
but highly permeable. The share of BCS class II APIs of newly developed drugs has increased
from 30% to 60% in recent years. Therefore, it is critical for the industry to incorporate effective
formulation approaches for improving solubility and dissolution rates of these APIs. In this regard,
a number of approaches have been investigated. Amorphous solid dispersion (ASD) is a successful
approach for transforming and stabilizing crystalline drugs to amorphous form with higher
solubility/dissolution rates. Spray drying (SD) is a solvent-based drying method that has been used
for formulating ASDs with improved solubility and stability.
Biopharmaceuticals are pharmaceuticals that are inherently biological in nature and
manufactured using biotechnology. This broad definition includes any type of blood product,
vaccines, antibodies, proteins and nucleic acids. Protein-based pharmaceuticals are among the
fastest growing categories of therapeutic agents. Therefore, the development of stable protein based formulations with controlled physicochemical properties is of high interest. Reversible and
irreversible aggregation in liquid protein formulations specifically at high concentrations is a
challenging problem for biopharmaceutical producers. Spray drying is (SD) is a solvent-based
technique in which solutions are atomized and dried using heat in a drying chamber. It is known
for its high throughput and compatibility with continuous manufacturing. SD has previously been
demonstrated as an effective technique for the preparation of ASDs and it has been used as an
alternative method to freeze-drying for drying and stabilizing high concentration formulations of
biopharmaceuticals. To date however, the development of spray drying processes for large
biomolecules has proved challenging primarily due to protein/enzymatic inactivation caused by
high drying temperatures and the shear stress induced by atomization. Overcoming this issue will require a comprehensive understanding of the effect of formulation and process parameters on
spray dried biological formulations.
Chapter 1 reviews the fundamental principles of SD by explaining every individual step
of the process from atomization to the drying chamber set up. It comprehensively covers the
applications of SD in preparing ASDs and formulating stable biopharmaceuticals. The effect of
process and formulation parameters on SD of biopharmaceuticals such as vaccines and proteins
for pulmonary delivery applications are discussed. This follows an attempt to elucidate the
systematic use of the Design of Experiment (DoE) approach for optimizing the SD process for
different applications to conclude this chapter.
Chapter 2 highlights the use of the DoE approach for formulating ternary ASD
compositions of Ibuprofen (IBU) as a model BCS class II API. Based on the DoE approach a range
of 16 formulations of IBU, HPMCP-HP55 and Kollidon VA 64 were spray dried. Statistical
analysis was employed to decipher the interrelation of various SD process and formulation factors,
namely solution feed rate, inlet temperature, API to excipients ratio and dichloromethane (DCM)
/methanol (MeOH) ratio. The significance of composition (IBU:excipient) was shown as the
determining factor in preparing stable ASD formulations. The effect of intermolecular interactions
was investigated by Fourier-Transform Infrared spectroscopy (FTIR) and Carbon-13 Solid-State
Nuclear Magnetic Resonance spectroscopy (ssNMR) analyses indicating that hydrogen bond
formation between the carboxyl groups of IBU within the ASDs is highly likely. Studies show that
the solubility of IBU in ASD formulations is improved relative to pure IBU. This was attributed
to both the amorphous structure of IBU and of the existence of amphiphilic excipient, Kollidon
VA64, in the formulation. This study indicates that ASD is an effective strategy for improving the
dissolution rate of IBU as a BCS class II API.
Chapter 3 investigates the influence of three different solvent-based techniques on the
physicochemical properties and quality of ASDs of IBU. Solvent-based techniques of
electrospinning (ES), spray-drying (SD) and rotary evaporation (RE), were used for formulating
ASDs of IBU as a model BCS class II API with two cellulosic excipients, HPMCAS and HPMCP HP55 in an attempt to determine the effect of processing technique on the critical quality attributes
(CQAs) of ASDs. Principal component analysis (PCA) of Raman spectra of crystalline and
amorphous IBU was used for qualitative analysis of the homogeneity of ASDs as a determining factor for the stability of ASDs during long-term storage. Results show that while ASD formation
is solely dependent on API:excipient ratio, the ASD homogeneity is totally dependent on the
processing technique. Samples produced by ES gave the least homogenous ASD compared with
RE and SD samples potentially influencing long-term storage stability. Moreover, ES samples had
the highest API release rate which was further confirmed to be due to the nanofibrous morphology
and higher specific surface area of these samples. The presence of crystalline IBU in samples and
the ASD forming strengths of each of the polymers was assessed by Differential Scanning
Calorimetry (DSC). The higher melting point depression, higher glass transition temperature (Tg),
and increased abundance of functional groups suitable for hydrogen bonding of HPMCAS proved
it to be a significantly better ASD former relative to HPMCP-HP55. This chapter concludes by
outlining the significance of the three solvent-based processing techniques (ES, SD and RE) on
the physicochemical properties of ASDs such as dissolution rate, specific surface area and
homogeneity, factors that could ultimately affect their stability and downstream processing
capacity.
Chapter 4 develops a rational approach towards the spray drying of biopharmaceuticals
using lysozyme as a model biomolecule. A two-step approach is suggested towards a
comprehensive understanding of the behaviour of large biomolecules during the spray drying
process with a view to developing tailored spray drying protocols for biological molecules. A full
factorial Design of Experiments (DoE) was employed to define the most critical process and
formulation parameters. With respect to parameters such as feeding rate, outlet temperature (Tout)
and feed solid concentration, Tout was determined to be the most statistically significant factor
affecting the enzymatic activity of lysozyme based on screening analysis of the DoE. The second
step of the study involved performing forced deactivation studies to identify critical points of
potential enzymatic deactivation during the drying process. This was performed by investigating
the inactivation of lysozyme both in solution and solid-state at wet-bulb (Twb) and outlet
temperatures respectively. Results show that there is no substantial inactivation of lysozyme in
solution at Twb (35-45 °C). However, lysozyme in solid form experienced a significant degree of
inactivation when heated to temperatures similar to Tout (70-90 °C). This inactivation was fitted by
an Arrhenius equation, where the inactivation energy and Arrhenius constant were estimated. The
approaches and models presented herein provide a roadmap for improved understanding of the critical process and formulation parameters required for the successful spray drying of large
biomolecules.
Chapter 5 summarises the additional contributions the author made during his Ph.D.
period. It consists of a brief introduction to the results of three different projects on which the
author is listed as a co-author:
1. Particle engineering of lignin via spray drying as a potential excipient for the
pharmaceutical industry.
2. Co-crystal polymorphic control by nanodroplet and electrical confinement.
3. A study on the effect of polymeric excipient on the downstream processing of hot-melt
extruded cocrystals of ibuprofen.
Chapter 6 provides a conclusive overview of the whole thesis.
Chapter 7 discusses potential future directions in the field of spray drying of
pharmaceuticals and biopharmaceuticals. If applied correctly spray drying as one of the leading
continuous drying and formulating techniques in small molecule sector possess immense potential
to become a major player in processing large molecule APIs as well.
This thesis follows two main objectives:
Firstly, developing novel ternary amorphous solid dispersions via spray drying for
improving the dissolution and physicochemical properties of BCS class II APIs. In an attempt to
meet this goal, the design of experiment (DoE) approach as part of the quality by design (QbD)
strategy in pharmaceutical and biopharmaceutical industry was used for simultaneous analysis of
interrelations of process and formulation techniques. Chapters three and four are focused on spray
drying novel ternary amorphous solid dispersion of ibuprofen as a small molecule API with low
aqueous solubility
(Re)construction of personal identity photography in autobiographies of Annie Ernaux, Anny Duperey, Hervé Guibert and Lydia Flem
L’accident, l’abus sexuel, le viol, le harcèlement moral, la violence, l’humiliation sociale et professionnelle ou encore la guerre sont parmi des causes probables du traumatisme d’un individu pour qui des effets post-traumatiques peuvent être omniprésents durant plusieurs années, et paralyser conséquemment certains aspects ou la totalité de sa vie. La présence du traumatisme dans la littérature, qui n’a pas seulement attiré l’attention de nombreux écrivains, mais aussi des théoriciens, des philosophes ou encore des psychologues, nous a menée à nous demander de quelle manière l’événement traumatisant – qui rend l’individu sidéré et le pousse dans l’ombre et le silence – peut apparaître dans la littérature et être traduit par elle. Notre hypothèse consiste ainsi à tenter de prouver comment l’auteur, après l’expérience d’un événement traumatisant, reconstruit son identité dans un récit de soi et à examiner quel est le rôle de la photographie dans ce processus la reconstruction. Les quatre auteurs de notre corpus – Annie Ernaux, Anny Duperey, Hervé Guibert et Lydia Flem –, ont été choisis selon deux points essentiels qu’ils ont en commun : l’expérience traumatisante, qui est exprimée dans leurs récits de soi, et l’emploi de la photographie pour réaliser ou accomplir leur pratique littéraire. La problématique qui apparaît est que, premièrement, la notion d’identité est assez complexe à définir et qu’elle doit être considérée dans ses rapports, d’un côté, au temps et aux différents composants de l’identité et, de l’autre côté, au soi et à l’autrui ; Deuxièmement dans certains cas, comme la maladie, la souffrance, la honte et les tabous sociaux ou encore la perte des proches, les événements traumatisants ne peuvent pas être racontés et mis en scène à cause des manques langagière, des refoulements et des oublis. Les projets de la narration exigent, par conséquent, l’usage d’un dispositif photographique pour permettre aux auteurs d’exprimer l’indicible et le refoulé. C’est dans cette perspective que la photographie et la littérature se croisent et qu’une étude psychanalytique (particulièrement les notions du traumatisme, de la résilience, ou des actes manqués) permettra d’analyser plus profondément la quête identitaire des auteurs. Ainsi, dans ces recherches, nous nous appuyons sur des axes d’étude divers tels que sociologiques, psychanalytiques ou philosophiques, afin d’analyser certaines questions-clés autour du concept de l’identité, de la photographie et son essence, du récit de soi et de ses fonctions dans la reconstruction de l’identité, du traumatisme et de ses effets sur la vie, ou encore de la photobiographie en tant que genre hybride.An accident, a sexual assault, a rape, a moral harassment, any type of abuse or violence, social and professional humiliation or even war are among the probable causes of an individual's trauma for whom post-traumatic effects can be omnipresent for several years, and consequently paralyze certain aspects or even his whole life. The presence of trauma in literature, which has attracted the attention not only of many writers, but also theorists, philosophers and psychologists, has led us to wonder how the traumatic event - which makes the individual staggered and pushes him into shadow and silence - can appear in the literature, and be interpreted by it. Our hypothesis thus consists in trying to prove how the author, after the experience of a traumatic event, reconstructs his identity in a self-narrative and to examine what is the role of photography in this reconstruction process. The four authors of our corpus - Annie Ernaux, Anny Duperey, Hervé Guibert and Lydia Flem - were chosen according to two essential points they have in common: the traumatic experience, which is expressed in their self-narratives and the use of photography to achieve or accomplish their literary practice. The problem that emerges at first is that the notion of identity is quite complex to define and it must be considered in its relations, on one hand, to time and to the different components of identity and, on the other hand, to oneself and to the others; Secondly, in some cases, such as illness, suffering, shame and social taboos or the loss of loved ones, traumatic events cannot be recounted and staged because of language gaps, repressions and forgetfulness. For these reasons, self-narrative projects require the use of a photographic device to enable authors to express the unspeakable and the repressed. It is in this perspective that photography and literature intersect and that a psychoanalytic study (particularly the notions of trauma, resilience, or faulty acts) will allow a more in-depth analysis of the authors' quest for identity. Therefore, in this research, we rely on various axes of study such as sociological, psychoanalytic or philosophical, in order to analyze certain key questions around the concept of identity, of photography and its essence, of self-narrative and its functions in reconstructing identity, trauma and its effects on life, or photo-biography as a hybrid genre
Application of deep neural networks to automated analysis of hatching lines for artist identification
Automated analysis of art has gained interest in the computer science research community over the past decade, resulting in the onset of computer vision solutions for authentication and attribution of art. Attribution and authentication are two of the most critical tasks in the domain of art. Several studies have approached these tasks with an emphasis on analyzing paintings in the visual spectrum, however, with a limited scope to a specific artist, limited datasets, or without rigorous evaluations of the robustness of such approaches. Contrary to paintings, the application of computer vision methodologies for authentication and attribution of drawings and prints has been only sparsely explored.
In this dissertation, we introduce a novel approach for attribution and authentication of drawings and sketches at the visual spectrum by automated analysis of hatching lines. Hatching is a prevalent technique in drawing and printmaking, often used to introduce toning, shading, or illusion of light and volume. Since artists tend to add hatching lines spontaneously, we hypothesize that these areas of drawings could carry unique physical and unconscious characteristics of the artist, which can be used to identify the artist. We further hypothesize that such unique characteristics can be quantified by a computational model that will enable automatic attribution and authentication.
We investigated the application of deep convolutional neural networks [1] for detecting and localizing hatching lines in drawings, sketches, and prints and identifying artists based on their hatching characteristics. We conducted several experiments on different sets of drawings and prints by different artists from different eras, using different techniques and with various degrees of complexity. We concluded that we can indeed identify artists based solely on their hatchings with an accuracy of 90-100% in most cases. In addition, we extensively evaluated the robustness of our approach in hatching detection.Ph.D.Includes bibliographical reference
