12 research outputs found
The persistent signature of tropical cyclones in ambient seismic noise
No full textThe spectrum of ambient seismic noise shows strong signals associated with tropical cyclones, yet a detailed understanding of these signals and the relationship between them and the storms is currently lacking. Through the analysis of more than a decade of seismic data recorded at several stations located in and adjacent to the northwest Pacific Ocean, here we show that there is a persistent and frequency-dependent signature of tropical cyclones in ambient seismic noise that depends on characteristics of the storm and on the detailed location of the station relative to the storm. An adaptive statistical model shows that the spectral amplitude of ambient seismic noise, and notably of the short-period secondary microseisms, has a strong relationship with tropical cyclone intensity and can be employed to extract information on the tropical cyclones
The persistent signature of tropical cyclones in ambient seismic noise
No full textThe spectrum of ambient seismic noise shows strong signals associated with tropical cyclones, yet a detailed understanding of these signals and the relationship between them and the storms is currently lacking. Through the analysis of more than a decade of seismic data recorded at several stations located in and adjacent to the northwest Pacific Ocean, here we show that there is a persistent and frequency-dependent signature of tropical cyclones in ambient seismic noise that depends on characteristics of the storm and on the detailed location of the station relative to the storm. An adaptive statistical model shows that the spectral amplitude of ambient seismic noise, and notably of the short-period secondary microseisms, has a strong relationship with tropical cyclone intensity and can be employed to extract information on the tropical cyclones.We thank the US Geological Survey (USGS) and the Incorporated Research Institutions for Seismology (IRIS) for providing openly available seismic data. L.G. acknowledges support from a Lamont–Doherty Earth Observatory Postdoctoral Fellowship. L.G. also acknowledges partial support for this work from Princeton University and King Abdullah University of Science and Technology. S.J.C. acknowledges support from NOAA grants NA15OAR4310095 and NA16OAR4310079. S.P. was supported by the NOAA CICS grant NA14OAR4320106. We would like to thank John Knaff (NOAA) for making the tropical cyclone size data available for this study. We also wish to acknowledge the editor Peter Shearer and the two anonymous reviewers, whose comments helped us to improve the manuscript. This is the Lamont–Doherty Contribution Number 8172
Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations
No full textIn the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects of mitochondrial DNA-related respiratory-chain complexes constitute a frequent biochemical signature. In order to identify responsible genes, we used exome-next-generation sequencing in a selected cohort of patients with this biochemical signature. In an isolated patient, we found two mutant alleles for EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase. The brain magnetic resonance imaging of this patient was hallmarked by extensive symmetrical cerebral white matter abnormalities sparing the periventricular rim and symmetrical signal abnormalities of the thalami, midbrain, pons, medulla oblongata and cerebellar white matter. Proton magnetic resonance spectroscopy showed increased lactate. We matched this magnetic resonance imaging pattern with that of a cohort of 11 previously selected unrelated cases. We found mutations in the EARS2 gene in all. Subsequent detailed clinical and magnetic resonance imaging based phenotyping revealed two distinct groups: mild and severe. All 12 patients shared an infantile onset and rapidly progressive disease with severe magnetic resonance imaging abnormalities and increased lactate in body fluids and proton magnetic resonance spectroscopy. Patients in the 'mild' group partially recovered and regained milestones in the following years with striking magnetic resonance imaging improvement and declining lactate levels, whereas those of the 'severe' group were characterized by clinical stagnation, brain atrophy on magnetic resonance imaging and persistent lactate increases. This new neurological disease, early-onset leukoencephalopathy with thalamus and brainstem involvement and high lactate, is hallmarked by unique magnetic resonance imaging features, defined by a peculiar biphasic clinical course and caused by mutations in a single gene, EARS2, expanding the list of medically relevant defects of mitochondrial DNA translation. © 2012 The Author
Magnetic resonance imaging pattern recognition in hypomyelinating disorders
No full textHypomyelination is observed in the context of a growing number of genetic disorders that share clinical characteristics. The aim of this study was to determine the possible role of magnetic resonance imaging pattern recognition in distinguishing different hypomyelinating disorders, which would facilitate the diagnostic process. Only patients with hypomyelination of known cause were included in this retrospective study. A total of 112 patients with Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis, Salla disease and fucosidosis were included. The brain scans were rated using a standard scoring list; the raters were blinded to the diagnoses. Grouping of the patients was based on cluster analysis. Ten clusters of patients with similar magnetic resonance imaging abnormalities were identified. The most important discriminating items were early cerebellar atrophy, homogeneity of the white matter signal on T2-weighted images, abnormal signal intensity of the basal ganglia, signal abnormalities in the pons and additional T2 lesions in the deep white matter. Eight clusters each represented mainly a single disorder (i.e. Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, infantile GM1 and GM2 gangliosidosis, Pelizaeus-Merzbacher-like disease and fucosidosis); only two clusters contained multiple diseases. Pelizaeus-Merzbacher-like disease was divided between two clusters and Salla disease did not cluster at all. This study shows that it is possible to separate patients with hypomyelination disorders of known cause in clusters based on magnetic resonance imaging abnormalities alone. In most cases of Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis and fucosidosis, the imaging pattern gives clues for the diagnosis. © 2010 The Author
CLIPPERS. Обзор литературы и собственные наблюдения
No full textCLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a rare inflammatory disease of the central nervous system, during which the pons of the brain is damaged. This disease was described for the first time in 2010 by S.J. Pittock et.al. At present, there have been around 50 described cases of the disease. Up to the present moment, there are difficulties diagnosing this disease. In the article, a literature review and three clinical cases are presented. Furthermore, the necessity of further research is shown for improving the accuracy and specificity of the diagnostic criteria, as well as for defining biomarkers and developing algorithms of effective therapy.CLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive tosteroids) – хроническое лимфоцитарное воспаление с поражением моста, контрастным усилениемпериваскулярных пространств, отвечающее на терапию глюкокортикостероидными препаратами,представляет собой редкое воспалительное заболевание центральной нервной системы, вовлекающеепреимущественно мост головного мозга. Впервые заболевание было описано в 2010 г. S.J. Pittock исоавт. В настоящее время в литературе описано около 50 случаев. Заболевание до настоящего временивызывает диагностические проблемы. В статье приведен краткий обзор литературы и собственныенаблюдения трех клинических случаев. Показана необходимость дальнейших исследований дляповышения точности и специфичности диагностических критериев, определения биомаркеров иразработки алгоритмов эффективной терапии
Micellar chromatographic partition coefficients and their application in predicting skin permeability
No full textThe major goal for physicochemical screening of pharmaceuticals is to predict human drug absorption, distribution, elimination, excretion and toxicity. These are all dependent on the lipophilicity of the drug, which is expressed as a partition coefficient i.e. a measure of a drug’s preference for the lipophilic or hydrophilic phases. The most common method of determining a partition coefficient is the shake flask method using octanol and water as partitioning media. However, this system has many limitations when modeling the interaction of ionised compounds with membranes, therefore, unreliable partitioning data for many solutes has been reported. In addition to these concerns, the procedure is tedious and time consuming and requires a high level of solute and solvent purity. Micellar liquid chromatography (MLC) has been proposed as an alternative technique for measuring partition coefficients utilising surfactant aggregates, known as micelles.
This thesis investigates the application of MLC in determining micelle-water partition coefficients (logPMW) of pharmaceutical compounds of varying physicochemical properties. The effect of mobile phase pH and column temperature on the partitioning of compounds was evaluated. Results revealed that partitioning of drugs solely into the micellar core was influenced by the interaction of charged and neutral species with the surface of the micelle. Furthermore, the pH of the mobile phase significantly influenced the partitioning behaviour and a good correlation of logPMW was observed with calculated distribution coefficient (logD) values. More interestingly, a significant change in partitioning was observed near the dissociation constant of each drug indicating an influence of ionised species on the association with the micelle and retention on the stationary phase. Elevated column temperatures confirmed partitioning of drugs considered in this study was enthalpically driven with a small change in the entropy of the system because of the change in the nature of hydrogen bonding. Finally, a quantitative structure property relationship was developed to evaluate biological relevance in terms of predicting skin permeability of the newly developed partition coefficient values. This study provides a better surrogate for predicting skin permeability based on an easy, fast and cheap experimental methodology, and the method holds the predictive capability for a wider population of drugs.
In summary, it can be concluded that MLC has the ability to generate partition
coefficient values in a shorter time with higher accuracy, and has the potential to replace the octanol-water system for pharmaceutical compounds
First-generation student transition to university: an exploratory study into the first-year experience of students attending University Kebangsaan Malaysia
No full textTransition is the movement, the passage of change from one role to another. This research offers an in-depth understanding of how the transition to university is experienced by first-generation students. To explore and understand the process of change underlying the transition process, this research uses qualitative research methods, semi-structured interviews and journal writing. Drawing from the data, a longitudinal case study followed the 16 students’ transition experiences for nine months, from the first semester to the end of the second semester of the first year. The research focused on three fundamental issues: higher education aspirations and decisions, the challenges encountered in the initial week of first year and the adjustment process, arguing that an understanding of these three aspects is necessary for a better understanding of the formation of learner identity. The research findings demonstrate that in the early weeks of university students experienced disjuncture between expectations held prior to commencing university and the reality they encounter. These phases are characterized as experiencing conflict with their new role and anxieties with their ability to manage the academic demands and expectations. Based on the evidence gathered, this is caused by inaccurate information they receive from third parties and during their prior educational experience. Early experience, whether positive or negative, is an important phase within this movement. Students become more active agents by being engaged and identifying difficulties and finding solutions. Student engagement both in class and out-of-class provides them with more accurate information on the knowledge and skills for their learning identity. Academic and non-academic support received both on and off campus comes from a range of sources including lecturers, peers and seniors, parents and family members, all of whom are identified as important contributors to the adjustment process of these first-generation students
Mothering from the inside: narratives of motherhood and imprisonment
No full textTwo thirds of the 4,000 women who are in prison in England and Wales are mothers of dependent children. Imprisonment can severely alter, disrupt or even terminate mothering. However, there is a relative absence of empirical research within this area. Therefore, we know little of the meaning of mothering and motherhood for women in prison. The main aim of this research was to explore the way in which women in prison make sense of motherhood and construct their mothering identity.
To achieve this, the analytical framework of biographical disruption was adopted and adapted; replacing chronic illness as the critical event with imprisonment. The study was underpinned by a narrative methodology to focus upon the ways in which the narratives of mothers in prison are constructed/ reconstructed and presented.
In depth narrative interviews were conducted with 16 women. The interviews lasted between forty five minutes and three hours. The interviews were recorded, transcribed and then analysed using the Listening Guide. On the basis of those interviews, three different narratives were constructed, the Wounded Mother, the Unbecoming Mother and the Suspended Mother.
The findings of this research illustrate that the relationship between imprisonment and biographical disruption is multi-faceted. Mothering identities can be fundamentally threatened, yet can also be reinforced. This research has also highlighted that it is often the compounding impact of repeated disruptions, culminating in prison that represents the most profound disruption to the mothering identities of women in prison. The implications of the research for policy and practice are also considered
Cannabinoids for the control of experimental multiple sclerosis
No full textPhDThere have been numerous studies reporting that cannabinoids, both exogenous
and endogenous, have a potential beneficial function during incidences of
neurological damage. Using gene knockout mice and cannabinoid-selective agents,
this study demonstrates the diverse actions of cannabinoids with a particular focus
on experimental autoimmune encephalomyelitis, an animal model of multiple
sclerosis. The results presented here report on the action of stimulators of
cannabinoid receptors in the nervous system (CNS) on; immune function, as a
mechanism of suppressing autoimmune attack of the central nervous system, as
agents to suppress neurodegenerative events leading to disease progression and as
agents that can control signs of disease that occur as the consequences of
autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the
psychoactive component in cannabis and the CB1 cannabinoid receptor appears to
be central to many of the therapeutic actions of cannabis but also to the side-effect
potential of cannabinoid drugs. This study reports on methods to avoid
psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists
whilst exploiting the therapeutic potential of the cannabinoid system in order to
control spasticity. This was achieved by targeting mechanisms of endocannabinoid
degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore,
this study also reports the development of novel cannabinoid compounds that are
excluded from the brain and inhibit spasticity and also demonstrates the
mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This
study provides further evidence for the efficacy of cannabinoid compounds during
an ongoing CNS disease and also their efficacy for treating the consequences of
CNS autoimmune disease, which hopefully, will give additional impetus for further
clinical investigations of cannabinoid agents in not only multiple sclerosis but also
other neurodegenerative diseases of the CNS
Analysis of the effects of a Constructivist-Based Mathematics Problem Solving Instructional Program on the achievement of Grade Five Students in Belize, Central America.
No full textThis thesis examined whether social constructivist activities can improve the mathematical competency of grade five students in Belize, Central America. The sample included 342 students and eight teachers from two rural and urban schools. A switching replication design was employed enabling students in the experimental groups to be taught using social constructivist activities for 12 weeks and the controls exposed to similar instructional practices from weeks 7 to 12. Students‘ performance was assessed using Pre-test, Post test 1 and 2 with an internal consistency of 0.89, 0.90 and 0.93 respectively. As revealed by the repeated measures ANOVA within subject analysis, there were significant differences among the pre-test and post test 1 and 2 results. That is, students in the control groups, who were instructed using a procedural approach from weeks 1 to 6, demonstrated higher gains than the experimental groups who were immersed in social constructivist activities. Furthermore, when the control groups became immersed in similar activities from weeks 7 to 12, they continued to outperform the experimental groups who were exposed to social constructivist activities alone. Hence, due to this unexpected result, the aim of this thesis became to explain why these results came about and what implications for teaching were highlighted by the consideration.
Besides the quantitative results highlighted above, qualitative data was also obtained as part of the study. For example, students were videoed within constructivist math groups and their performance analyzed using Pirie and Kieren‘s (1994) Model of Growth for Mathematical Understanding. The data from the video recording revealed that use of one step math problems did not enabled students to restructure their thinking to solve innovative problems. Data from semi-structured interviews also revealed that some students lacked basic math skills and were not exposed or guided to solve complex problems. Besides the need for careful examination of social constructivist activities on performance, this thesis underscores the importance of relevant teaching and learning activities, the important role of teachers during social constructivist activities and the need to identify suitable forms of assessment to measure performance
