Novel in vitro method to study the structured solubility of bioequivalent fasted intestinal media with other biopharmaceutical applications

Drug solubility is a key parameter controlling oral absorption, but intestinal solubility is difficult to assess in vitro. Human intestinal fluid (HIF) aspirates can be applied but they are variable, difficult to obtain and expensive. Simulated intestinal fluids (SIF) are a useful surrogate but multiple recipes are available, and the optimum is unknown. This situation creates difficulties during drug discovery and development research. A recent study characterized fasted HIF (FaHIF) aspirates using a multidimensional approach and determined 9 fasted simulated intestinal fluid (Fa9SIF) media recipes that represented over ninety percent of HIF compositional variability. These Fa9SIF recipes have been applied to determine the equilibrium solubility of twenty-one drugs. The solubility measurements enclose literature solubility values in both FaHIF and SIF, and are statistically equivalent to the previous design of experiment (DoE) studies. However, they have a narrower solubility range, suggesting an improved equivalence to in vivo solubility. This also highlights that intestinal solubility is a range and not a single value. The Fa9SIF media was examined and provided in the majority of cases a structured solubility behaviour, that is consistent with physicochemical properties and previous solubility studies. The study also indicates that the use of two appropriate bioequivalent fasted intestinal media from the nine will identify in vitro the maximum and minimum fasted solubility boundaries for drugs and due to the media derivation, this is probably applicable in vivo. Statistical comparisons were further carried out, of the Fa9SIF media system against FaHIF, and do not detect a difference, and individual drug analysis produces an 85% correlation. An innovative in vitro vs FaHIF correlation window was determined, which enclosed 94% of solubility values from an additional data set, further validating equivalence. The Fa9SIF media system represents a new methodology for in vitro in vivo solubility correlation, this radically transforms predictive ability which will benefit drug discovery, development and formulation studies. The equilibrium solubility of the twenty-one drugs were also used for further biopharmaceutical applications including the developability classification system, supersaturation techniques, and physiology based pharmacokinetic (PBPK) modelling.Drug solubility is a key parameter controlling oral absorption, but intestinal solubility is difficult to assess in vitro. Human intestinal fluid (HIF) aspirates can be applied but they are variable, difficult to obtain and expensive. Simulated intestinal fluids (SIF) are a useful surrogate but multiple recipes are available, and the optimum is unknown. This situation creates difficulties during drug discovery and development research. A recent study characterized fasted HIF (FaHIF) aspirates using a multidimensional approach and determined 9 fasted simulated intestinal fluid (Fa9SIF) media recipes that represented over ninety percent of HIF compositional variability. These Fa9SIF recipes have been applied to determine the equilibrium solubility of twenty-one drugs. The solubility measurements enclose literature solubility values in both FaHIF and SIF, and are statistically equivalent to the previous design of experiment (DoE) studies. However, they have a narrower solubility range, suggesting an improved equivalence to in vivo solubility. This also highlights that intestinal solubility is a range and not a single value. The Fa9SIF media was examined and provided in the majority of cases a structured solubility behaviour, that is consistent with physicochemical properties and previous solubility studies. The study also indicates that the use of two appropriate bioequivalent fasted intestinal media from the nine will identify in vitro the maximum and minimum fasted solubility boundaries for drugs and due to the media derivation, this is probably applicable in vivo. Statistical comparisons were further carried out, of the Fa9SIF media system against FaHIF, and do not detect a difference, and individual drug analysis produces an 85% correlation. An innovative in vitro vs FaHIF correlation window was determined, which enclosed 94% of solubility values from an additional data set, further validating equivalence. The Fa9SIF media system represents a new methodology for in vitro in vivo solubility correlation, this radically transforms predictive ability which will benefit drug discovery, development and formulation studies. The equilibrium solubility of the twenty-one drugs were also used for further biopharmaceutical applications including the developability classification system, supersaturation techniques, and physiology based pharmacokinetic (PBPK) modelling

Subperiosteal resection of mid-clavicle in Sprengel’s deformity correction

We report the results of fifteen cases of Sprengel’s deformity treated surgically by initial subperiosteal resection of the middle third of the clavicle in conjunction with surgical release of all attachments of the scapula to the spine, excision of any omovertebral bone and resection of prominent supraspinous process of scapula. The patients included ten female and three male patients (age range at the time of operation, 3.3–10 years; mean: 6.11 years). The deformity involved the left shoulder in eight patients, the right shoulder in three and two were bilateral. All patients were followed for an average of 5.9 years (range 4–11 years). Preoperatively, the arc of total abduction (glenohumeral and scapulothoracic) ranged from 80 to 140°, and the average was 110°. The shoulders were level, and the range of motion was dramatically improved with an average range of abduction of 166.5° (range 140–180°). The age of the patients and the presence of an omovertebral bone did not influence the results. All patients and their parents expressed satisfaction with the operative results. We feel that our procedure is a simple one, which helps to improve the degree of correction, avoid neurovascular complications and has the advantage of complete regeneration of the clavicle. The technique provides an easy, safe method of repositioning the scapula at its normal level

Non-vascularized fibular graft reconstruction after resection of giant aneurysmal bone cyst (ABC)

The aim of this study was to present the results of non-vascularized fibular graft for reconstruction of bone defects after en block resection of giant aneurysmal bone cyst (ABC) of the extremities. Between 1998 and 2006, three patients, aged 6, 8 and 23 years, with giant aneurysmal bone cysts were treated. The cysts were located in the humerus, proximal femur and metatarsal. All patients were given en bloc resection of the cyst followed by non-vascularized fibular bone graft, with the graft length ranging from 6 to 18 cm. All patients needed supplementary fixation with a single Kirschner wire or plate and screws. At the final follow-up, bony union was achieved in each case, and there was no recurrence, limitation of range of motion or disability. In addition, complete regeneration of the fibula at the donor site was seen in the two children. We propose a criterion for giant ABC, when the transverse diameter of the cyst is up to three times or more of the transverse diameter of the nearby bone, it is then called a giant ABC. Non-vascularized fibular graft is an optimal and valuable method for the reconstruction of bone defects after resection of giant ABC in the extremities

PSYCHOSOCIAL DEVELOPMENT PORTRAYED IN JANE AUSTEN’S EMMA

This paper investigates the bildungsroman phenomenon as depicted in Jane Austen’s Emma (1817) by consulting Erik Erikson’s theory of psychosocial development as a framework of analysis. The most two conflicting readings in this regard could be best seen in Buckley’s (1974) claim which excluded Emma from the bildungsroman, for the genre has always been associated with the protagonist’s physical quest seeking maturity and social integration. However, Kohn (1995) read Emma as a domestic bildungsroman when he argued that Emma did not have to travel physical distances to achieve her maturity. For Kohn, Emma matured within her social sphere. This paper particularly traced Emma’s psychological and social development since this type of development is the basic ingredient of any bildungsroman novel. This paper argued that Emma cannot be read as bildungsroman not because the protagonist did set on a quest, as Buckley claimed, but mainly because Emma did not develop a sense of psychological or social maturation. After placing Emma in Erikson’s developmental stages, the study revealed that she did not really mature neither she realized her own identity. This paper proposed that Emma should not be classified as bildungsroman because the heroine distorted the real meaning of maturity and social integrity.

Pandora Operation and Analysis Software

Pandora Operation and Analysis Software controls the Pandora Sun- and sky-pointing optical head and built-in filter wheels (neutral density, UV bandpass, polarization filters, and opaque). The software also controls the attached spectrometer exposure time and thermoelectric cooler to maintain the spectrometer temperature to within 1 C. All functions are available through a GUI so as to be easily accessible by the user. The data are automatically stored on a miniature computer (netbook) for automatic download to a designated server at user defined intervals (once per day, once per week, etc.), or to a USB external device. An additional software component reduces the raw data (spectrometer counts) to preliminary scientific products for quick-view purposes. The Pandora systems are built from off-the-shelf commercial parts and from mechanical parts machined using electronic machine shop drawings. The Pandora spectrometer system is designed to look at the Sun (tracking to within 0.1 ), or to look at the sky at any zenith or azimuth angle, to gather information about the amount of trace gases or aerosols that are present

Screen architecture: A phenomenology of dread atmospheres in thriller films.

By looking at thriller films, and establishing their relationship to suspense, my thesis examines the construction of dread atmosphere and how it enables the viewer to become part of that atmosphere. The aim of the thesis is to develop a comprehensive reading of the atmosphere of dread by adopting the approach of phenomenology, and through an investigation and analysis of its definition of the process of embodiment, in order to identify some of the atmospheric corporeal situations in dread spaces that are used to increase the corporeality of the viewer, so as to ultimately reveal the experience of suspense. By doing that, this thesis elaborates on Hanich’s analysis and description of cinematic dread’s atmosphere. The thesis builds a structure of embodiment based on Merleau-Ponty’s Phenomenology of Perception and on the work of other phenomenologists from different fields including film, architecture and video games, to create a framework whereby the viewer’s embodiment with the screen is understood. In addition, it adopts Shīrāzī’s approach of Phenomenal Phenomenology to read a dread scene from the Silence of the Lambs phenomenologically. This reading identified new atmospheric corporeal situations, named as quasi-things in Griffero’s terms, which have not previously been discussed in the context of film under the framework of the phenomenology of text, of transparency and of surveillance. The research found that any situation that is linked with the senses, such as through ‘sensorimotor verbs’ and ‘sensorial transparency’, is experienced more corporeally, consciously, affectively, and eventually increases the sense of embodiment. The researcher extends the conception of these phenomena by means of a horizontal reading of other films to make the observations more objective and generalizable to thrillers in general and the dread atmosphere in specific. The significance of my research lies in making a contribution to the understanding of the kinesthetic experience of cinematic space and to promoting its potential in theorising related arts such as architecture, Virtual Reality, and video games

High Precision, Absolute Total Column Ozone Measurements from the Pandora Spectrometer System: Comparisons with Data from a Brewer Double Monochromator and Aura OMI

We present new, high precision, high temporal resolution measurements of total column ozone (TCO) amounts derived from ground-based direct-sun irradiance measurements using our recently deployed Pandora single-grating spectrometers. Pandora's small size and portability allow deployment at multiple sites within an urban air-shed and development of a ground-based monitoring network for studying small-scale atmospheric dynamics, spatial heterogeneities in trace gas distribution, local pollution conditions, photochemical processes and interdependencies of ozone and its major precursors. Results are shown for four mid- to high-latitude sites where different Pandora instruments were used. Comparisons with a well calibrated double-grating Brewer spectrometer over a period of more than a year in Greenbelt MD showed excellent agreement and a small bias of approximately 2 DU (or, 0.6%). This was constant with slant column ozone amount over the full range of observed solar zenith angles (15-80), indicating adequate Pandora stray light correction. A small (1-2%) seasonal difference was found, consistent with sensitivity studies showing that the Pandora spectral fitting TCO retrieval has a temperature dependence of 1% per 3K, with an underestimation in temperature (e.g., during summer) resulting in an underestimation of TCO. Pandora agreed well with Aura-OMI (Ozone Measuring Instrument) satellite data, with average residuals of <1% at the different sites when the OMI view was within 50 km from the Pandora location and OMI-measured cloud fraction was <0.2. The frequent and continuous measurements by Pandora revealed significant short-term (hourly) temporal changes in TCO, not possible to capture by sun-synchronous satellites, such as OMI, alone

Automatic diagnosis of tuberculosis disease based on Plasmonic ELISA and color-based image classification

Tuberculosis (TB) remains one of the most devastating infectious diseases and its treatment efficiency is majorly influenced by the stage at which infection with the TB bacterium is diagnosed. The available methods for TB diagnosis are either time consuming, costly or not efficient. This study employs a signal generation mechanism for biosensing, known as Plasmonic ELISA, and computational intelligence to facilitate automatic diagnosis of TB. Plasmonic ELISA enables the detection of a few molecules of analyte by the incorporation of smart nanomaterials for better sensitivity of the developed detection system. The computational system uses k-means clustering and thresholding for image segmentation. This paper presents the results of the classification performance of the Plasmonic ELISA imaging data by using various types of classifiers. The five-fold cross-validation results show high accuracy rate (>97%) in classifying TB images using the entire data set. Future work will focus on developing an intelligent mobile-enabled expert system to diagnose TB in real-time. The intelligent system will be clinically validated and tested in collaboration with healthcare providers in Malaysia