Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

International audienceAGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Kakistocracy or the true story of what happened in the post-Soviet area

The article ‘Kakistocracy or The true story of what happened in the post-Soviet area’ argues that the countries, emerged after the collapse of the Soviet Empire, chose three distinct models of development: the Baltic model, when Estonia, Latvia and Lithuania joined the Euro-Atlantic security structures; the Belarusian model, when the country opted for an authoritarian rule with a possible transition from the communist totalitarianism to an open society; and the Russian model, when under the slogans of democracy and market economy a new type of regime was established in Russia and a number of post-Soviet countries. To characterize this new type of regime the definition of ‘kakistocracy’ has been introduced, which means a merger between the state structures and the oligarchic elements as a result of the systematic plunder of national assets and establishment of a rule of lawlessness and illegal usurpation of power under the slogans of democracy and market economy. Furthermore, the split of the CiS and the formation of two groups of countries, respectively the GUAM and the CSTO, have been considered from the viewpoint of their different strategic goals and orientations. A section is devoted to the cardinal differences between the strategic visions of Yeltsin and Putin. The latter’s policy can be formulated as the Putin’s doctrine aimed at restoring Russia’s influence through centralization of power, internally, and demonstration of military force and energetic blackmail, externally. The kakistocratic regimes lead to a political and socio-economic collapse, triggering popular unrest. This exactly was the reason of the ‘orange’ revolutions, which in most of the cases are the only way to topple kakistocratcy. In conclusion, it is suggested that the other way of getting rid of kakistocracy would be a cardinal change in Russia’s policy. While the strategic goal of the country should remain restoring its international influence and authority, the means should shift from heavily relying on military power and energetic resources toward focusing on the Russian spiritual values and potential for facing new threats and challenges to international peace and security

The Obama administration and targeted killings

Diese Masterbeit behandelt das kontroverse und aktuelle Thema von gezielten Tötungen während den aufeinander folgenden US-Regierungen von George W. Bush und Barack Obama. Ersterer begann einen globalen Kampf gegen den Terrorismus und letzterer entwickelte die Doktrin seines Vorgängers durch Diversifizierung von Kriegstechnologien und der Ausdehnung der geographischen Reichweite für die Benutzung moderner Kampfwaffen weiter. Während die Benutzung moderner Waffen, einschließlich Drohnen, als logische Folgerung im Kontext des beispiellosen Fortschrittes von modernen Technologien gesehen werden sollte, wirft sie gleichzeitig eine Anzahl von grundsätzlichen Problemen auf: In der Praxis haben bewaffnete Drohnen, entgegen internationaler Menschenrechtsnormen, zu massiven Verlusten in der Zivilbevölkerung geführt und menschliches Leid gebracht. Die Arbeit beschäftigt sich mit der Problematik von gezielten Tötungen in einer umfassenden Analyse von legalen, militärischen und politischen Aspekten der diesbezüglich adoptierten Strategie der US-Regierung im letzten Jahrzehnt. Sie beginnt mit einer juristischen Analyse, die bestimmte Aspekte der Benutzung von bewaffneten Drohnen aus der Perspektive der Zulässigkeit von bestehenden internationalen Verpflichtungen erörtert. Darüber hinaus wird eine vergleichende Analyse zwischen den Regierungen von George W. Bush und von Barack Obama im Kontext von Anti-Terror Operationen durchgeführt. Basierend auf vorhandenen Tatsachen über die Benutzung von bewaffneten Drohnen werden die Gemeinsamkeiten der strategischen Herangehensweisen zwischen den beiden Regierungen aufgezeigt, mit der Folgerung, dass die Benutzung von Drohnen und gezielten Tötungen unter dem Präsidenten Obama drastisch gestiegen sind. Die zentralen Teile der Arbeit widmen sich den grundsätzlichen Kontroversen über die Strategie und der Umsetzung von gezielten Tötungen. Eine detaillierte Analyse über die Vereinbarkeit von bewaffneten Drohnen mit der Charta der Vereinten Nationen, humanitärem Völkerrecht, Menschenrechtsnormen und den Prinzipien des gerechten Krieges im Kontext von jus ad bellum und jus in bello demonstriert die Vielschichtigkeit des Problems. Die Arbeit argumentiert, dass die unkontrollierte Verbreitung von Drohnen, zu eklatanten Verletzungen des humanitären Völkerrechts und von Menschenrechten führen kann und schlägt vor, dass neue Herangehensweisen auf theoretischer, politischer und diplomatischer Ebene sehr gründlich erörtert werden müssen, um eine Balance zwischen neuen Technologien und dem internationalen Rechtsrahmen zu finden. Abschließend macht die Masterarbeit Vorschlage über mögliche Wege, um die problematischen Aspekte von bewaffneten Drohnen und gezielten Tötungen zu überwinden.The thesis is devoted to the controversial and topical issue of targeted killings under the two consecutive American administrations of George W. Bush and Barack Obama. The first launched a global war on terrorism and the latter developed his predecessor’s doctrine through diversification of war technologies and broadening the geographic scope of the use of modern weapons, first of all, Unmanned Combat Aerial Vehicles (UCAV), largely known as drones. While the use of modern weapons, including drones, should be considered as a logical undertaking in the context of the unprecedented progress of modern technologies, it raises, at the same time, a number of fundamental problems from the viewpoint of international humanitarian law (IHL) and human rights law insofar as in practice the use of drones has brought about massive losses of civilian lives and human suffering, The thesis considers the problematic of targeted killings from different angles through a comprehensive analysis of legal, military and political aspects of the strategy adopted by the American administration over the past decade. It starts with the legal analysis making an attempt to spread light over a number of aspects of the use of drones from the perspective of their admissibility under the existing international commitments. Chapter Two contains a comparative analysis between the administrations of George W. Bush and Barack Obama in the context of antiterrorist operations. Based on abundant facts of the use of drones it clearly demonstrates the similarity of strategic approaches between the two administrations, pointing out, however, that under President Obama the use of drones, i.e., targeted killings, has drastically increased. The central part of the thesis, Chapter Three is devoted to the major controversies triggered by the strategy and practice of targeted killings. A rather detailed analysis of the compatibility of the use of drones with the UN Charter, IHL, human rights law, and the principle of just war doctrine both in the context of jus ad bellum and jus in bello demonstrates the complexity of the problem. The thesis argues that uncontrolled drone proliferation may bring about blatant breaches of IHL and human rights law and suggests that new approaches at theoretical, political and diplomatic level should become subject to in-depth deliberations in order to find a balance between the use of new technologies and the international legal framework. The thesis concludes with suggestions on the possible ways of overcoming the problematic issues linked to targeted killings and the use of combat drones

Bifunctional Agents for MRI, PET and Fluorescence Imaging and Study of Nanoparticles Formed from Water Oxidation Catalysts /

The work is divided into four parts : (1) MRI contrast agents are designed to enhance T₁ relaxivity by coupling them to dendrimers, the precise structure of which can be controlled through synthesis. Cyclen is used as a starting scaffold for the synthesis of bifunctional Gd-DOTA and Gd- DOTMA analogues. One unique side chain on the macrocycle contains an azide moiety that can be clicked to an alkyne- containing core, making a first-generation dendrimer with the potential to improve MRI efficiency. (2) PET tracers are designed to specifically coordinate ⁶⁴Cu, a positron source, while containing clickable side arms. A functionalized cross-bridge tetraazamacrocycle with two identical azide-bearing side arms can be clicked to alkynyl amino acid, which provides several advantages with respect to applications. (3) Using the results of part 1, MRI-fluorescence imaging agents are constructed. Preliminary tests determine their efficiency as bimodal agents. (4) My contributions to a separate project to investigate the fate of water oxidation catalysts under acidic conditions are described. We have synthesized and characterized four novel bifunctional MRI imaging agents to date. Preliminary studies show successful clicking of these complexes to form dendrimers. We are also currently synthesizing and optimizing a unique bifunctional PET tracer. Future work includes, but is not limited to, optimization of syntheses, full characterization of the bifunctional PET tracer, theoretical calculations of expected T₁ relaxivities of bifunctional MRI contrast agents, imaging cells in tissue-like matrices for MRI- fluorescence agents, and designing more robust water oxidation catalyst

Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea in Veterans With Gulf War Illness.

Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p ≤ 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI

Differential Cognitive Impairment in HCV Coinfected Men With Controlled HIV Compared to HCV Monoinfection

BackgroundIndividuals infected with both HIV and hepatitis C virus (HCV) have shown impaired performance on different neuropsychological (NP) tests; however, whether coinfected individuals with controlled HIV and minimal liver damage in the era of antiretroviral therapy have impairment is understudied.MethodsNineteen HCV monoinfected, 17 HIV/HCV coinfected, and 17 control male participants were evaluated for depression, attention, executive function, information processing, fine motor speed, and verbal/visual learning/memory. Eleven controls and 14 HIV monoinfected participants with controlled viral load from a previous study were also included for comparison. At time of testing, participants were not using drugs or alcohol and did not have cirrhosis. A global deficit score (GDS) was calculated from 7 domains of NP tests and alterations in specific domains were determined.ResultsHIV/HCV subjects had a higher depression score (11.1 ± 7.5) than controls (5.4 ± 4.1, P = 0.010) and a higher GDS score (0.77 ± 0.47) than HCV (0.46 ± 0.34, P = 0.036), HIV (0.45 ± 0.36, P = 0.008), and controls (0.30 ± 0.29, P = 0.001). Coinfection was associated with worse scores in attention working memory (P =0.007), executive function (P = 0.01), fine motor function (P = 0.011), verbal learning/memory (P < 0.001), and visual learning/memory (P < 0.001) compared to controls. Within the HCV group, viral load was associated with lower attention, executive function, and information processing speed and positively with GDS.ConclusionsCoinfection significantly increased the risk of cognitive impairment in subjects with controlled HIV viral loads. In HCV monoinfected but not coinfected subjects, HCV viral load correlated with worsening GDS, suggesting different pathways for NP impairment