On the importance of returning emigrants for the transformation process in Iraqi Kurdistan

Das irakische Kurdistan befindet sich seit dem Ende des Ersten Golfkriegs 1991 in einem tief greifenden und immer noch unabgeschlossenen Transformationsprozess. Dieser Prozess wurde durch grenzübergreifende Migration und Remigration stark beeinflusst. Die Entstehung von transnationalen Räumen, d. h. der kurdischen Diaspora, ermöglichte es Remigranten im Allgemeinen und hochqualifizierten Remigranten im Besonderen, durch grenzübergreifende Beziehungen die sozialpolitische sowie die kulturelle Entwicklung in der kurdischen Region nach 1991 nachhaltig zu beeinflussten. Theoretischen Überlegungen zufolge sind Migranten bzw. Remigranten als bedeutende Akteure in wirtschaftlichen, sozialpolitischen sowie kulturellen Entwicklungsprozessen in den Herkunftsländern zu sehen. Sie beeinflussen durch finanzielle Transferleistungen sowie durch temporäre oder auch dauerhafte Rückkehr und damit einhergehende Investitionen indirekt den Transfer von Wissen sowie den Transfer von sozialpolitischem bzw. kulturellem Kapital und Unternehmertum in ihre Herkunftsländer. Bisherige Studien zur Rolle der Remigranten im Entwicklungs- bzw. Transformationsprozess betonen vorrangig die ökonomischen Effekte. Sie sind aber darüber einig, dass Remigranten Wissen und sozialkulturelle Werte aus dem Ausland mitbringen und an regionale Akteure weitergeben. Die Frage, auf welchen Wegen Remigranten ihr Wissen und ihre Erfahrungen an regionale Akteure weitergeben, bleibt meistens offen und ist größtenteils noch unterforscht. Am Beispiel von hochqualifizierten kurdischen Remigranten wird in dieser Arbeit dargelegt, wie Remigranten als eine neue Elitengruppe innerhalb der kurdischen Gesellschaft durch sozialkulturellen Transfer sowie Wissenstransfer den Transformationsprozess beeinflussen und wie die kurdische Gesellschaft von ihrem Wissen profitieren. Darüber hinaus hat die Arbeit das Ziel, die Verzahnung des Migrationsprozesses mit Transformationsprozessen und daraus resultierende bzw. damit verbundene sozialkulturelle und politische Kulturtransfers aufzuzeigen.Since the end of the Gulf war in 1991, the Iraqi Kurdistan has been in a dramatic and still ongoing transformation process. This process has been deeply influenced by cross-border migration and remigration. Due to the development of transnational areas (the so called Kurdish Diaspora) the highly skilled returning migrants were able to influence the socio-political and the cultural development of the Kurdish area after 1991. According to theoretical considerations, migrants and returning migrants are major stakeholders in economical, socio-political and cultural development processes in their countries of origin. Through transfer payments and temporary or even permanent returns, thus resulting in investments, returning migrants indirectly effect the transfer of knowledge and socio-political, cultural and entrepreneurship in their countries of origin. So far, surveys on the role of returning migrants in the development and transformation process shows prior emphasis on their economic effects. What they all show though, is that returning migrants pass on knowledge and socio-cultural values from abroad to their regional stakeholders. However, the question of how the returning migrants pass on their knowledge and experience stays unsought. Using the example of highly skilled Kurdish returning migrants, this paper is going to show how this new elite group amongst the Kurdish society influences the transformation process through socio-cultural and knowledge transfer and how the Kurdish society profits from them. Furthermore, this paper aims to illustrate the correlation between migration and the transformation process which results in socio-cultural and political transfers

Analysis of Hypertension Control Rates Among Participants in the Georgia Hypertension Management and Outreach Program

Background: This study utilized health department electronic medical records retrospectively to evaluate hypertension control rates achieved by the Georgia Hypertension Management and Outreach Program (HMOP), an education, screening, and treatment control program that provides services, including blood pressure screening and assessment, referral to physicians, counseling, educational material, disease case management, and treatment. Methods: Hypertension control rates after at least 6 months of study participation were determined for patients participating in the program for at least 6 months between 2010 and 2014, and for African American and uninsured subgroups. Results: The overall hypertension control rate was 61.1%, above the 2012 national average of 51.8%. The control rates for African Americans and the uninsured were 58.9% and 62%, respectively, compared to 41.7% and 28.7% nationally. Conclusions: Although potential bias sources in the use of retrospectively obtained electronic medical records should be considered, this analysis suggests that the Georgia HMOP provides substantial improvements in hypertension control for a population of patients with otherwise poor control. Key words: hypertension, blood pressure, cardiovascular diseases, African Americans, medically uninsure

Reduction in albuminuria with dapagliflozin cannot be predicted by baseline clinical characteristics or changes in most other risk markers

The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was -71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined

The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet

Introduction: Proximal tubule sodium uptake is diminished following sodium glucose cotransporter 2 (SGLT2) inhibition. We previously showed that during SGLT2 inhibition, the kidneys adapt by increasing sodium uptake at distal tubular segments, thereby maintaining body sodium balance. Despite continuous glycosuria, we detected no increased urine volumes. We therefore assessed the adaptive renal responses to prevent excessive fluid loss. Methods: We conducted a mechanistic open-label study in people with type 2 diabetes mellitus with preserved kidney function, who received a standardized sodium intake (150 mmol/d) to evaluate the effects of dapagliflozin on renin-angiotensin-aldosterone system (RAAS) hormones, volume-related biomarkers, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), at start of treatment (day 4), end of treatment (day 14), and follow-up (day 18). Results: A total of 14 people were enrolled. Plasma renin and angiotensin II and urinary aldosterone and angiotensinogen were acutely and persistently increased during treatment with dapagliflozin. Plasma copeptin level was numerically increased after 4 days (21%). Similarly, fractional urea excretion was significantly decreased at start of treatment (−17%). Free water clearance was significantly decreased after 4 days (−74%) and 14 days (−41%). All changes reversed after dapagliflozin discontinuation. Conclusion: Dapagliflozin-induced osmotic diuresis triggers kidney adaptive mechanisms to maintain volume and sodium balance in people with type 2 diabetes and preserved kidney function. ClinicalTrials.gov (identification: NCT03152084)

Ultrasound-Enhanced Drug Transport and Distribution in the Brain

Drug delivery in the brain is limited by slow drug diffusion in the brain tissue. This study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. In vitro exposure to ultrasound at various frequencies (85 kHz, 174 kHz, and 1 MHz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kDa across porcine brain tissue. A maximum enhancement of 24-fold was observed at 85 kHz and 1,200 J/cm2. In vivo exposure to 1-MHz ultrasound further demonstrated the ability of ultrasound to facilitate molecule distribution in the brain of a non-human primate. Finally, ultrasound under conditions similar to those used in vivo was shown to cause no damage to plasmid DNA, siRNA, adeno-associated virus, and fetal rat cortical neurons over a range of conditions. Altogether, these studies demonstrate that ultrasound can increase drug permeation in the brain in vitro and in vivo under conditions that did not cause detectable damage

Measurement and Correlation of Acoustic Cavitation with Cellular and Tissue Bioeffects

Targeted intracellular delivery is a goal of many novel drug delivery systems to treat site-specific diseases thereby increasing the effectiveness of drugs and reducing side effects associated with current drug administration. The development of ultrasound-enhanced delivery is aimed at providing a targeted means to deliver drugs and genes intracellularly by utilizing ultrasound s ability to non-invasively focus energy into the body and generate cavitation, which has been found to cause transient poration of cells. To address some of the current issues in this field, the goals of this study were (i) to develop a measurement of cavitation to correlate with cellular bioeffects and (ii) to evaluate the ability of ultrasound to target delivery into cells in viable tissue. In addition, this study sought to exploit the shear-based mechanism of cavitation by (iii) developing a simplified device to expose cells to shear stress and cause intracellular uptake of molecules. This study has shown that broadband noise levels of frequency spectra processed from cavitation sound emissions can be used to quantify the kinetic activity of cavitation and provide a unifying parameter to correlate with the cellular bioeffects. We further demonstrated that ultrasound can target delivery of molecules into endothelial and smooth muscle cells in viable arterial tissue and determined approximate acoustic energies relevant to drug delivery applications. Lastly, we developed a novel device to expose cells to high-magnitude shear stress for short durations by using microfluidics and demonstrated the ability of this method to cause delivery of small and macromolecules into cells. In conclusion, this work has advanced the field of ultrasound-enhanced delivery in two major areas: (i) developing a real-time non-invasive measurement to correlate with intracellular uptake and viability that can be used as means to predict and control bioeffects in the lab and potentially the clinic and (ii) quantitatively evaluating the intracellular uptake into viable cells in tissue due to ultrasound that suggest applications to treat cardiovascular diseases and dysfunctions. Finally, by using shear forces generated in microchannels, we have fabricated a simple and inexpensive device to cause intracellular uptake of small and large molecules, which may have applications in biotechnology.Ph.D.Committee Chair: Mark Prausnitz; Committee Member: Athanassios Sambanis; Committee Member: Carson Meredith; Committee Member: Levent Degertekin; Committee Member: W. Robert Taylo

Relationships between Mechanical Stress and Markers of Inflammation in Diseased Human Coronary Arteries

Rupture of atherosclerotic plaque is one of the primary causes of death due to cardiovascular disease. The factors directing plaque progression to instability are poorly understood. It is well-known that arteries respond to changes in mechanical stress by remodeling, and that remodeling is mediated by the inflammatory response. Studies have shown that both mechanical stress and markers of inflammation are increased in the fibrous cap and shoulder regions of plaque, where rupture most often occurs. In this study we hypothesized that there are spatial relationships between the local mechanical environment and expression of markers of inflammation in atherosclerosis, and that these relationships are plaque-progression dependent. To test these hypotheses, we analyzed cross-sections at intervals along the length of human coronary atherosclerotic arteries. For each cross-section, a heterogeneous finite element model was developed to determine the spatial distribution of stress. In addition, novel techniques for quantifying inflammatory markers at high spatial resolution were used to determine the distributions of inflammatory markers. The distributions of stress and five markers of inflammation activated NF-kB, macrophages, MMP-1, nitrotyrosine, and microvessels - were then compared to determine whether spatial relationships exists. We demonstrated that the probability of activated NF-kB expression increases monotonically with increasing stress in all stages of plaque progression. This indicates that the relationship between mechanical stress and NF-kB activation is a player throughout the disease process. We found that the relationship between mechanical stress and macrophages is highly dependent on the state of plaque progression. In intermediate stages of progression macrophages increase with moderate stress but drop off again at very high stresses, while in the advanced stage macrophages continue to increase monotonically with stress. We found that MMP1 increases with stress in stages of progression where active remodeling is occurring, but decreases with stress in mature stable plaque. We found no relationship between mechanical stress and nitrotyrosine expression or microvessels. Taken together, these results support the role of mechanical stress in instigating and maintaining the inflammatory response, and help explain how mechanical input is able to direct the complex biological changes involved in remodeling.Ph.D.Committee Chair: Raymond P. Vito; Committee Member: Alexander Rachev; Committee Member: Hamid Garmestani; Committee Member: Robert Guldberg; Committee Member: Rudolph Gleason; Committee Member: W. Robert Taylo