Changes in the characteristics of new drug applications for the treatment and prevention of diabetes mellitus

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program, 2007.Includes bibliographical references (p. 99-102).Efforts in managing diabetes, including the medical advances in novel therapies and public health policies of disease control and prevention, have not reduced the disease prevalence since 1990s. I analyze this phenomenon from the technology and policy viewpoints underlying diabetes treatment and prevention, in order to control and manage the disease in a cost-benefit balanced manner. The innovative performance of the antidiabetic drug therapy is investigated by analyzing the fifteen New Drug Applications (NDAs) of the antidiabetics approved by the US Food and Drug Administration since the early 1990s. I examine the characteristics of the clinical trials supporting NDAs and observe how the complexity of clinical trials has changed over time. Nine out of the twenty-five selected indicators are found to exhibit an increasing trend of complexity. The trend is more pronounced in the oral antiglycemics group (seven indicators) than the subcutaneous group (two indicators). Interestingly, this trend in increasing complexity in clinical trials is generally consistent with that of the increasing R&D costs in the pharmaceutical industry, possibly account for the declining innovative performance of the industry over the time period under investigation. A system dynamics approach is applied to assess current public health policies in diabetes control and prevention.(cont.) The benefit of system thinking is to avoid potential policy resistance by identifying the problematic characteristics of the system, such as time-delays, feedback, and structure of stocks and flows. For diabetes management, the public health system can be considered a "dynamic-complex" system in terms of current policy made by the National Diabetes Control and Prevention Program. Despite providing earlier and expanded screening as well as improved availability and accessibility of treatment for diabetes, the policy results in the increase of prevalence. More undiagnosed people are diagnosed, thus increasing the incidence, whereas people already diagnosed prolong their lifespan due to the better and more accessible medical care. A future successful chronic disease management program should systematically integrate the efforts from both the treatment and prevention perspectives.by Hsiao-Lan Sharon Lin.S.M

The Changes of Cerebral Morphology Related to Aging in Taiwanese Population

<div><p>A cross-sectional study with the 3-dimensional (3D) MRI reconstruction technique was conducted to investigate cerebral complexity changes related to age differences in native Taiwanese population. In our sample of 85 participants aged between 25 and 81, age was associated with gradual ventricular expansion. A nonlinear quadratic relationship between white matter volume and age was found overall in the brain. Widespread age-related reduction in white matter was detected from late adulthood onwards. However, no significant age-related changes in the cortex and whole brain volume were determined throughout adulthood. These findings provided information in describing brain structural complexity, which might in the future serve as an objective diagnostic index or as a predictive parameter for neurological diseases. Our method then may be used for cross-cultural longitudinal studies to evaluate the effect of disease, environment and aging on the brain.</p> </div

Regression models.

a.<p>ref.: reference group.</p>b.<p>LRT: likelihood ratio test, for testing the non-linear the association between age and dependent variables.</p

The relationship between age and average ventricle volume.

<p>The volume of ventricle  = 0.013× age²−0.74× age+7.23× sex+31.4; male  = 1, female  = 0.</p

Three-dimensional reconstruction neuroimages of brain at different structures (vertical view).

<p>Three-dimensional reconstruction neuroimages of brain at different structures (vertical view).</p

The relationship between age and average white matter volume.

<p>The volume of white matter  = −0.09× age²+9.85× age+41.76× sex+152.56; male  = 1, female  = 0.</p

The relationship between age and average whole brain volume.

<p>The whole brain volume  = 1008.13+146.08× sex; male  = 1, female  = 0.</p

A selection of Slovenian literary heroes for the preschool period

V vrtcih slovenske literarne junake vse bolj spodrivajo tuji fantazijski junaki, za katere se otroci navdušijo prek risank, revij in video igric. Slovenski junaki so pomemben del naše kulture in so lahko nekakšni spremljevalci v domovinski vzgoji pri najmlajših. To delo naj služi kot promocija slovenskih literarnih junakov pri otrocih vseh starosti, z začetkom v predšolskem obdobju. V delu je opredeljeno merilo izbire likovpredstavljene so njihove zgodbe, posebne lastnosti in upodobitevjunaki so po izvoru opredeljeni kot ljudski ali umetninavedeni so avtorji in zgodovinske okoliščine nastankaraziskane so njihova prepoznavnost in zastopanost v različnih medijih (slikanice, avdio- in video mediji, oglasi) ter dostopnost teh medijev.In preschools, Slovenian literary heroes are being displaced by foreign fantastic heroes that impress children via cartoons, magazines and video games. Slovenian heroes are an important part of our culture and can act as companions of sorts within citizenship education of youngsters. This thesis should serve as a promotion of Slovenian literary heroes for children of all ages, beginning with the preschool period. The thesis defines the selection criterion of charactersit introduces their stories, special characteristics and depictionsit defines heroes by origin as folk or artificialit lists the authors and historical circumstances of productionit investigates their recognisability and representation in various media (picture books, audio- and video media, advertisements) and the accessibility of these media

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and P-Conditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and P-Conditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and P-Conditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10 215 and P-Conditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene(Region 2: rs451360; P = 1.90 x 10(-18) and P-Conditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci