METHODS FOR QUANTITATIVE ANALYSIS OF IN-VIVO BONE MICROSTRUCTURE USING COMPUTED TOMOGRAPHY

Bone health can be assessed by observing alterations in trabecular microarchitecture. These alterations are an early indicator for a range of musculoskeletal diseases ranging from osteoporosis to osteoarthritis. Fractures due to loss of bone are also seen in patients undergoing radiation therapy. Early detection of changes in the trabecular microstructure can be used to help design protocols and therapies targeting the factors affecting bone health. In-vivo evaluation if bone microarchitecture is still a challenge due to the limited spatial resolution provided by conventional computed tomography (CT). In this thesis, we investigate different high-resolution modalities to perform quantitative analysis of trabecular bone. New diagnostic imaging modalities with enhanced spatial resolution include Cone Beam CT (CBCT) systems with flat-panel detectors (FPD) and CMOS detectors. The FPD and CMOS detectors offer higher spatial resolution than the detectors in Conventional CT. Another example of a new modality with potential application in the imaging of trabecular microstructures is a recently introduces ultra–high resolution (UHR) multi-detector CT which has ~2x better spatial resolution than Conventional CT (Aquilion Precision CT, Canon Medical). We also investigate the performance of this novel Precision CT for trabecular microstructure imaging. The modalities are evaluated using bone morphometry parameters extracted from the scanned volumes. Bone metrics (including BV/TV, Tb.Th, Tb.Sp, and Tb.N, each defined below) are computed from the images obtained from CMOS-CBCT, FPD-CBCT, Conventional CT and Precision CT. These values are compared with the bone metrics obtained from analysis performed on Micro-CT (which is taken as a ‘gold standard’ reference and basis of comparison). Those studies involved imaging of cadaveric bone samples. A patient study is also performed to assess the feasibility of imaging trabecular structures in realistic clinical scenarios as opposed to a controlled experimental environment while imaging cadaveric samples. In cadaveric samples, imaging using CBCT achieves improved performance in quantification of bone microstructure. The methods and results offer motivation and a platform for ongoing development of quantitative imaging and evaluation of bone health in osteoporosis, osteoarthritis and bone loss due to radiation therapy

Metformin: Pros and Cons

Metformin was approved for the treatment of Type 2 Diabetes Mellitus in 1958 for UK, in 1972 for Canada and in 1995 by FDA in USA. Metformin is the drug of choice for patients who are obese and have type 2 diabetes mellitus. Though metformin was at first proven to treat hyperglycemia, many other uses of metformin are proven to be effective. It is also used for gestational diabetes mellitus, obesity, hyper secretion of ovarian androgen, poly-cystic ovary syndrome (PCOS), anti-psychotic therapy induced weight gain, cancer treatment and anti-aging. Metformin causes a decrease in appetite thus known to act on obesity. The other action of metformin is reduction of circulating levels of insulin and insulin like growth factor 1 (IGF-1) which is associated with anticancer action. There are ongoing researches about the effect of metformin on anti-aging properties and proved that metformin is linked with anti-aging factors. Three main factors that are related with aging are oxidation, glaciation and methylation. Metformin as all drugs, have unwanted effects as well. Many side effects of metformin are considered mild where lactic acidosis and vitamin B12 deficiency happens to be the major

C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factor

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two late onset neurodegenerative diseases, have been shown to share overlapping cellular pathologies and genetic origins. Studies suggest that a hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common cause of familial FTD and ALS pathology. The C9orf72 protein is predicted to be a differentially expressed in normal and neoplastic cells domain protein implying that C9orf72 functions as a guanine nucleotide exchange factor (GEF) to regulate specific Rab GTPases. Reported studies thus far point to a putative role for C9orf72 in lysosome biogenesis, vesicular trafficking, autophagy and mechanistic target of rapamycin complex1 (mTORC1) signaling. Here we report the expression, purification and biochemical characterization of C9orf72 protein. We conclusively show that C9orf72 is a GEF. The distinctive presence of both Rab- and Rho-GTPase GEF activities suggests that C9orf72 may function as a dual exchange factor coupling physiological functions such as cytoskeleton modulation and autophagy with endocytosis

A Survey on Deep Learning in Medical Image Registration: New Technologies, Uncertainty, Evaluation Metrics, and Beyond

Over the past decade, deep learning technologies have greatly advanced the field of medical image registration. The initial developments, such as ResNet-based and U-Net-based networks, laid the groundwork for deep learning-driven image registration. Subsequent progress has been made in various aspects of deep learning-based registration, including similarity measures, deformation regularizations, and uncertainty estimation. These advancements have not only enriched the field of deformable image registration but have also facilitated its application in a wide range of tasks, including atlas construction, multi-atlas segmentation, motion estimation, and 2D-3D registration. In this paper, we present a comprehensive overview of the most recent advancements in deep learning-based image registration. We begin with a concise introduction to the core concepts of deep learning-based image registration. Then, we delve into innovative network architectures, loss functions specific to registration, and methods for estimating registration uncertainty. Additionally, this paper explores appropriate evaluation metrics for assessing the performance of deep learning models in registration tasks. Finally, we highlight the practical applications of these novel techniques in medical imaging and discuss the future prospects of deep learning-based image registration

Neighborhood Influences on Perceived Social Support Among Parents: Findings from the Project on Human Development in Chicago Neighborhoods

Background: Social support is frequently linked to positive parenting behavior. Similarly, studies increasingly show a link between neighborhood residential environment and positive parenting behavior. However, less is known about how the residential environment influences parental social support. To address this gap, we examine the relationship between neighborhood concentrated disadvantage and collective efficacy and the level and change in parental caregiver perceptions of non-familial social support. Methodology/Principal Findings: The data for this study came from three data sources, the Project on Human Development in Chicago Neighborhoods (PHDCN) Study's Longitudinal Cohort Survey of caregivers and their offspring, a Community Survey of adult residents in these same neighborhoods and the 1990 Census. Social support is measured at Wave 1 and Wave 3 and neighborhood characteristics are measured at Wave 1. Multilevel linear regression models are fit. The results show that neighborhood collective efficacy is a significant ($\beta$ = .04; SE = .02; p = .03), predictor of the positive change in perceived social support over a 7 year period, however, not of the level of social support, adjusting for key compositional variables and neighborhood concentrated disadvantage. In contrast concentrated neighborhood disadvantage is not a significant predictor of either the level or change in social support. Conclusion: Our finding suggests that neighborhood collective efficacy may be important for inducing the perception of support from friends in parental caregivers over time

Somatic mutations affect key pathways in lung adenocarcinoma

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd

Sorption studies of semi-crystalline polyamides

Sorption is the penetration and dispersion of a gas or liquid molecule through a solid surface such as a polymer. Sorption studies were undertaken to analyse the effect of the sorbent on polymers. In this experiment, the weight gained by polymers and the diffusion coefficient of acetone was studied on polyamide 6, polyamide 66, polyamide 11 and polyamide 12. Ten polymer beads of each material were immersed in 10 and 15 ml of dried acetone. The polymers were weighed at regular intervals over a period of time till the weight reached steady state. The moles of acetone in the container was also measured at those intervals using gas chromatography. Polyamide 6 and polyamide 66 did not absorb any acetone. Polyamide 11 and polyamide 12 absorbed considerable amounts of acetone. Polyamide 12 absorbed slightly more acetone than polyamide 11. Consequently, the diffusion coefficient of polyamide 12 was higher than polyamide 11. However, both the weight of polyamide 11 and polyamide 12 did not reach steady state during the course of the experiment.Bachelor of Engineering (Chemical and Biomolecular Engineering

When place and time matter: How to conduct safe inter-hospital transfer of patients

Inter-hospital transfer (IHT) of patients is often needed for diagnostic or therapeutic interventions. However, the transfer process carries its own risks as a poorly and hastily conducted transfer could lead to adverse events. In this article, we have reviewed literature on the key elements of IHT process including pre-transfer patient stabilization. We have also discussed various modes of transfer, physiological effects of transfer, possible adverse events and how to avoid or mitigate these. Even critically ill-patients can be transported safely by experienced and trained personnel using appropriate equipment. The patient must be maximally stabilized prior to transfer though complete optimization may be possible only at the receiving hospital. Ground or air transport may be employed depending on the urgency, feasibility and availability. Meticulous pre-transfer check and adherence to standard protocols during the transfer will help keep the entire process smooth and event free. The transport team should be trained to anticipate and manage any possible adverse events, medical or technical, during the transfer. Coordination between the referring and receiving hospitals would facilitate prompt transfer to the definitive destination avoiding delay at the emergency or casualty. Documentation of the transfer process and transfer of medical record and investigation reports are important for maintaining continuity of medical care and for medico-legal purposes

Terminal treatment: an analysis of palliative care in India

The realm of palliative care is a relatively new specialty of care in Indian medical facilities, emerging only about 30 years ago. Major religious and culture aspects within the region have shaped how Indian physicians, healthcare workers, and patients respond to the concept of palliative care. Through a detailed literature search and analysis, the limitations and benefits of the current palliative care system in India will be discussed with approaches to pain management, psychosocial wellbeing, and the connotations presented with end-of-life care. The inextricable ties with religious practices and cultural norms in Indian medicine have further emphasized ideas of natural death and suffering in current lives to avoid condemnation in next. Based on the principles of karma and natural healing practice in India, it is possible that palliative care in India relies on familial support rather than medical intervention as found more commonly in Western practices