Valerie M. Hudson

Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation.

Though the cause of cystic fibrosis (CF) pathology is understood to be the mutation of the CFTR protein, it has been difficult to trace the exact mechanisms by which the pathology arises and progresses from the mutation. Recent research findings have noted that the CFTR channel is not only permeant to chloride anions, but other, larger organic anions, including reduced glutathione (GSH). This explains the longstanding finding of extracellular GSH deficit and dramatically reduced extracellular GSH:GSSG (glutathione disulfide) ratio found to be chronic and progressive in CF patients. Given the vital role of GSH as an antioxidant, a mucolytic, and a regulator of inflammation, immune response, and cell viability via its redox status in the human body, it is reasonable to hypothesize that this condition plays some role in the pathogenesis of CF. This hypothesis is advanced by comparing the literature on pathological phenomena associated with GSH deficiency to the literature documenting CF pathology, with striking similarities noted. Several puzzling hallmarks of CF pathology, including reduced exhaled NO, exaggerated inflammation with decreased immunocompetence, increased mucus viscoelasticity, and lack of appropriate apoptosis by infected epithelial cells, are better understood when abnormal GSH transport from epithelia (those without anion channels redundant to the CFTR at the apical surface) is added as an additional explanatory factor. Such epithelia should have normal levels of total glutathione (though perhaps with diminished GSH:GSSG ratio in the cytosol), but impaired GSH transport due to CFTR mutation should lead to progressive extracellular deficit of both total glutathione and GSH, and, hypothetically, GSH:GSSG ratio alteration or even total glutathione deficit in cells with redundant anion channels, such as leukocytes, lymphocytes, erythrocytes, and hepatocytes. Therapeutic implications, including alternative methods of GSH augmentation, are discussed.

A Surplus of Men, A Deficit of Peace: Security and Sex Ratios in Asia's Largest States

and stability rest in large measure on the internal security of nations. Analysts have long examined factors such as arms transfers and ethnic violence in this regard, but the list now includes variables that were not traditionally viewed as related to national security. Unemployment rates, water tables and river oows, infant mortality, migration patterns, infectious disease epidemiology, and a whole host of other variables that tap into the general stability of a society are now understood to affect security. To understand the long-term security dynamics of a region, one must inquire into what Thomas Homer-Dixon and others have termed the “environmental security” of the nations therein. Our own research is surely located in that aeld of inquiry, yet we contemplate a variable that has been by and large neglected even by scholars of environmental security. One overlooked wellspring of insecurity, we argue, is exaggerated gender inequality. Security scholarship is theoretically and empirically impoverished to the extent that it fails to inquire into the relationship between violence against women and violence within and between societies. We believe that our research demonstrates that the long-term security trajectory of a region is affected by this relationship. A Surplus of Men, A Deacit of Peace

Foreign Policy Analysis Yesterday, Today, and Tomorrow

The catalytic shock of the end of the Cold War and the apparent inability of international relations (IR) theory to predict this profound change have raised questions about how we should go about understanding the world of today. Our inherited tools and ways of describing the international arena seem not to work as well as they once did. To explain and predict the behavior of the human collectivities comprising nation-states, IR theory requires a theory of human political choice. Within the study of IR, foreign policy analysis (FPA) has begun to develop such a theoretical perspective. From its inception, FPA has involved the examination of how foreign policy decisions are made and has assumed that human beings, acting individually or in collectivities, are the source of much behavior and most change in international politics. This article reviews the field of foreign policy analysis, examining its research core and its evolution to date. The overview also looks forward, pointing to the future, not only of FPA itself, but to the implications that future developments in FPA may have for the study of international relations.

The Heart of the Matter: The Security of Women and the Security of States

Does the security of women influence the security and behavior of states? Existing evidence linking the situation of women to state-level variables such as economic prosperity and growth, health, and corruption is fairly conclusive. Questions remain, however, concerning the degree to which state security and state security-related behavior is linked to the security of women. The women and peace thesis draws upon evolutionary biology/psychology for ultimate causes of this linkage, and sociological theories of social diffusion and psychological theories of social learning for more proximate causal mechanisms. Together, a new data resourcethe WomanStats Databaseand conventional methodology find a robust, positive relationship between the physical security of women and three measures of state security and peacefulness. In addition, a comparison of this proposition to alternative explanations involving level of democracy, level of economic development, and civilizational identity shows that the physical security of women is a better predictor of state security and peacefulness. Although these results are preliminary, it is still possible to conclude that the security of women must not be overlooked in the study of state security, especially given that the research questions to be raised and the policy initiatives to be considered in the promotion of security will differ markedly if the security of women is seriously considered as a significant influence on state security.

New Insights Into the Pathogenesis of Cystic Fibrosis Pivotal Role of Glutathione System Dysfunction and Implications for Therapy

The cystic fibrosis transmembrane regulator (CFTR) should no longer be viewed primarily as a ‘chloride channel’ but recognized as a channel that also controls the efflux of other physiologically important anions, such as glutathione (GSH) and bicarbonate. More effective approaches to cystic fibrosis treatment may result from this reconceptualization of the CFTR by researchers and clinicians. For example, oxidant damage in cystic fibrosis has been assumed to be a significant part of the pathophysiology of the disease. Generally speaking, antioxidant status in cystic fibrosis is compromised. However, until recently this was seen as secondary to the excessive chemoattraction of neutrophils in this disease caused by mutation of the CFTR protein, leading to a high oxidant burden. New findings suggest that the cystic fibrosis mutations in fact cause a primary dysfunction in the system of one of the body’s most important antioxidant and immune-signaling substances: the reduced GSH system. Cystic fibrosis mutations significantly decrease GSH efflux from cells without redundant channels to the CFTR; this leads to deficiency of GSH in the epithelial lining fluid of the lung, as well as in other compartments, including immune system cells and the gastrointestinal tract. This deficiency is exaggerated over time as the higher-than-normal oxidant burden of cystic fibrosis leads to successively larger decrements in GSH without the normal opportunity to fully recover physiologic levels. This GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction.This overview provides a review of the most pertinent recent research findings in this area. Exogenous augmentation of GSH in the lung epithelial lining fluid is possible, and therapeutic approaches include administration of aerosolized buffered GSH, intravenous GSH, and oral GSH. However, it is important to remember that the pathophysiology of cystic fibrosis is multifactorial, and rectification of GSH system dysfunction in patients with cystic fibrosis will not eliminate all harmful effects of the disease. The promising results of two clinical trials of aerosolized buffered GSH in cystic fibrosis patients have been published or accepted for publication at the time of this writing. GSH depletion in lung epithelial lining fluid has also been noted in other respiratory diseases such as COPD, idiopathic pulmonary fibrosis, and adult respiratory distress syndrome, and therapies to augment GSH may also be contemplated in these diseases.

Artificial intelligence and international politics

For over a decade researchers in international relations have sought ways to combine the rigor of quantitative techniques with the richness of qualitative data. Many have discovered that artificial intelligence computer models allow them to do just that. This is an overview of their research.

Improvement in clinical markers in CF patients using a reduced glutathione regimen: An uncontrolled, observational study

CFTR mutation, which causes cystic fibrosis (CF), has also recently been identified as causing glutathione system dysfunction and systemic deficiency of reduced glutathione (GSH). Such dysfunction and deficiency regarding GSH may contribute to the pathophysiology of CF. We followed 13 patients (age range 1-27 years) with cystic fibrosis who were using a regimen of reduced glutathione (GSH), including oral glutathione and inhaled buffered glutathione in an uncontrolled, observational study. Dosage ranged from 66-148 mg/kg/day in divided doses, and the term examined was the initial 5.5 months of GSH use (45 days of incrementally adjusted dose, plus 4 months of use at full dosage). Baseline and post-measurements of FEV1 percent predicted, BMI percentile, and weight percentile were noted, in addition to bacterial status and pulmonary exacerbations. Significant improvement in the following clinical parameters was observed: average improvement in FEV1 percent predicted (N=10) was 5.8 percentage points (p<0.0001), average weight percentile (N=13) increased 8.6 points (p<0.001), BMI percentile (N=11) improved on average 1.22 points (p<0.001). All patients improved in FEV1 and BMI, if measured in their case; 12 of 13 patients improved in weight percentile. Positive sputum cultures of bacteria in 11 patients declined from 13 to 5 (p<0.03) with sputum cultures of Pseudomonas aeruginosa becoming negative in 4 of 5 patients previously culturing PA, including two of three patients chronically infected with PA as determined by antibody status. Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies.

The WomanStats Project Database: Advancing an Empirical Research Agenda

This article describes the WomanStats Project Database — a multidisciplinary creation of a central repository for cross-national data and information on women available for use by academics, policy-makers, journalists, and all others. WomanStats is freely accessible online, thus facilitating worldwide scholarship on issues with gendered aspects. WomanStats contains over 260 variables for 174 countries and their attendant subnational divisions (where such information is available) and currently contains over 68,000 individual data points. WomanStats provides nuanced data on the situation and status of women internationally and in so doing facilitates the current trend to disaggregate analyses. This article introduces the dataset, which is now publicly available, describes its creation, discusses its utility, and uses measures of association and mapping to draw attention to theoretically interesting patterns concerning the various dimensions of women’s inequality that are worthy of further exploration. Two of nine variables clusters are introduced — women’s physical security and son preference/sex ratio. The authors confirm the multidimensionality of women’s status and show that the impact of democracy and state wealth vary based on the type of violence against women. Overall, the authors find a high level of violence against women worldwide.

Sex and the Shaheed: Insights from the Life Sciences on Islamic Suicide Terrorism

Theoretical insights from evolutionary psychology and biology can help academics and policymakers better understand both deep and proximate causes of Islamic suicide terrorism. The life sciences can contribute explanations that probe the influence of the following forces on the phenomenon of Islamic suicide terrorism: high levels of gender differentiation, the prevalence of polygyny, and the obstruction of marriage markets delaying marriage for young adult men in the modern Middle East. The influence of these forces has been left virtually unexplored in the social sciences, despite their presumptive application in this case. Life science explanations should be integrated with more conventional social science explanations, which include international anarchy, U.S. hegemony and presence in the Middle East, and culturally molded discourse sanctioning suicide terrorism in the Islamic context. Such a consilient approach, melding the explanatory power of the social and life sciences, offers greater insight into the causal context of Islamic fundamentalist suicide terrorism, the motivation of suicide terrorists, and effective approaches to subvert this form of terrorism.

What Is the Relationship between Inequity in Family Law and Violence against Women? Approaching the Issue of Legal Enclaves

“Family law” is the term applied to the legal regulation of marriage and parenthood within a society, and may serve to express a societys accepted ideals concerning male–female relations. Adopting a feminist evolutionary analytic (FEA) approach, we hypothesize that nation-states with higher degrees of inequity in family law favoring men, codifying an evolutionary legacy of male dominance and control over female reproduction, will experience higher rates of violence against women. This hypothesis is borne out in conventional statistical analysis, both bivariate and multivariate, suggesting that policy attention to family law so as to make it more concordant with norms of the Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW) may have salutatory effects on womens physical security over time. These results may also have policy implications for societies with, or contemplating, enclaves of inequitable family law. Where, after all, do universal human rights begin? In small places, close to home. —Eleanor Roosevelt