State of the art: Reproduction and pregnancy in rheumatic diseases

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

Quantification of nanoparticles at the single-cell level: an overview about state-of-the-art techniques and their limitations.

With the increasing production and use of engineered nanoparticles it is crucial that their interaction with biological systems is understood. Due to the small size of nanoparticles, their identification and localization within single cells is extremely challenging. Therefore, various cutting-edge techniques are required to detect and to quantify metals, metal oxides, magnetic, fluorescent, as well as electron-dense nanoparticles. Several techniques will be discussed in detail, such as inductively coupled plasma atomic emission spectroscopy, flow cytometry, laser scanning microscopy combined with digital image restoration, as well as quantitative analysis by means of stereology on transmission electron microscopy images. An overview will be given regarding the advantages of those visualization/quantification systems, including a thorough discussion about limitations and pitfalls.

A history and overview of phenotypic variability in CYP2D6 activity

CYP2D6 is a human cytochrome P450 that is responsible for the metabolism of a large number of drugs and chemicals. Interest in CYP2D6 has largely centered on the wide interindividual variability in its catalytic activity that stems from a common genetic polymorphism in the CYP2D6 gene. Two major phenotypes exist, extensive metabolizer (EM) and poor metabolizer (PM), together with the two less studied phenotypes of ultrarapid metabolizer (UM) and intermediate metabolizer. These phenotypes are the expression of an underlying allelomorphism in CYP2D6 and are also context dependent. Several drugs that are CYP2D6 substrates display polymorphic metabolism, that is, the existence in the population of multiple phenotypes, in particular EM and PM. The most notable drugs in this regard are debrisoquine and sparteine, although there are also data for a few others, in particular, dextromethorphan and metoprolol. Many nongenetic factors can alter the expression of CYP2D6 phenotypes, the most significant of which is the presence of other drugs. In this context, the EM phenotype may not be immutable, with potential conversion into a PM phenocopy, due to significantly impaired CYP2D6 metabolism in the presence of other CYP2D6 substrates and inhibitors. This phenotype interconversion generated great concern and helped drive the movement away from phenotyping based upon drug administration to genotyping of acquired DNA samples. However, ascertaining the presence of CYP2D6 alleles in a DNA sample does not determine the metabolism and pharmacokinetics of CYP2D6 substrates in that subject: it is a forecast, much like the weather forecast and, as we all know regarding the weather, the forecast can be inaccurate at times.

Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.

Post-Empire Imaginaries? Anglophone Literature, History, and the Demise of Empires

Empires as political entities may be a thing of the past, but as a concept, empire is alive and kicking. From heritage tourism and costume dramas to theories of the imperial idea(l): empire sells. Post-Empire Imaginaries? Anglophone Literature, History, and the Demise of Empires presents innovative scholarship on the lives and legacies of empires in diverse media such as literature, film, advertising, and the visual arts. Though rooted in real space and history, the post-empire and its twin, the post-imperial, emerge as ungraspable ideational constructs. The volume convincingly establishes empire as welcoming resistance and affirmation, introducing post-empire imaginaries as figurations that connect the archives and repertoires of colonial nostalgia, postcolonial critique, post-imperial dreaming.

From Connecting Hindus to Uniting Global Hinduism: History and Guiding Principles of Hinduism Today

Hinduism Today is a quarterly magazine that appears in roughly 15.000 copies, shipped to nearly 60 countries worldwide. The majority of readers are Hindus in diverse diaspora countries, mainly Singapur, Malaysia, Mauritius, Trinidad und the USA. Its editors are monks of Kauai Adheenam, belonging to the Śaiva Siddhānta Church, situated in Kauai, Hawai’i, USA. One of the magazine’s declared goals is to foster global Hindu solidarity and educate Hindus worldwide about their religion. In this paper, I want to take a look at the history of this magazine in connection with the Śaiva Siddhānta Church, and at the development of the expressed aims behind its publication. For this, I draw on fieldwork done in Kauai in January, 2014. After a brief introduction to some theoretical and methodological preliminaries of my work, I shall, give an overview of the history of the Śaiva Siddhānta Church, founded by Satguru Sivaya Subramuniyaswami. Following this, I will deal in more detail with the origins and development of the magazine and the websites connected with it. I will focus especially on the role the magazine was intended to play for global Hindu diasporas. A fourth chapter will analyze the modes of definition employed in order to depict Hinduism as a unified global religion. In conclusion, I shall briefly reflect upon the specific agenda of “Global Hinduism” and the strategies of positioning as followed by the publishers of Hinduism Today.

Psychological adaptation to spousal bereavement in old age. The role of trait resilience, marital history, and context of death

This research examined the effect of marital status and gender on various indicators of psychological adaptation, namely depressive symptoms, loneliness, and life satisfaction. It further explores the role of trait resilience, marital history, and context of death for predicting These outcomes in bereaved individuals. Four hundred eighty widowed individuals aged between 60 and 89 were compared with 759 married peers. Main effects were found for marital status and gender for all indicators. The regression analyses illustrate the multifaceted structure of psychological adaptation. Trait resilience is a key factor in adapting to spousal bereavement, whereas marital history and the context are secondary.

Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.