Mandela: the road to freedom

Months were spent researching and preparing this four-part series on the dramatic events surrounding NELSON MANDELA, the life-term prisoner who has cast a larger than life shadow on South African politics. Staff writer DENNIS CRUYWAGEN travelled extensively to interview at first hand — or by other means, where necessary — those stalwart ANC veterans who were convicted in the Rivonia Treason Trial and jailed with Mandela. He talked, too, to members of the Mandela family, politicians, lawyers and many others who were close to or knowledgeable about the ANC leader. Official records and other sources on the life and times of Nelson Mandela were also consulted. Compiling the vast amount of information sometimes led to unusual situations. For instance, Mrs Winnie Mandela, always pressed for time, was interviewed — not in her home in Diepkloof, Soweto, as arranged but in a hired car in a Johannesburg traffic jam while following a vehicle driven by her driver. She was late for another appointment. Drawn from various sources this series sets out to reconstruct an overview of 25 years and more of political and personal drama, passion and poignancy.Supplement to The Argus, Tuesday February 6 1990Exclusive Part

Epidemiology and Immune Pathogenesis of Viral Sepsis

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment

A CubeSat for Calibrating Ground-Based and Sub-Orbital Millimeter-Wave Polarimeters (CalSat)

We describe a low-cost, open-access, CubeSat-based calibration instrument that is designed to support ground-based and sub-orbital experiments searching for various polarization signals in the cosmic microwave background (CMB). All modern CMB polarization experiments require a robust calibration program that will allow the effects of instrument-induced signals to be mitigated during data analysis. A bright, compact, and linearly polarized astrophysical source with polarization properties known to adequate precision does not exist. Therefore, we designed a space-based millimeter-wave calibration instrument, called CalSat, to serve as an open-access calibrator, and this paper describes the results of our design study. The calibration source on board CalSat is composed of five "tones" with one each at 47.1, 80.0, 140, 249 and 309 GHz. The five tones we chose are well matched to (i) the observation windows in the atmospheric transmittance spectra, (ii) the spectral bands commonly used in polarimeters by the CMB community, and (iii) The Amateur Satellite Service bands in the Table of Frequency Allocations used by the Federal Communications Commission. CalSat would be placed in a polar orbit allowing visibility from observatories in the Northern Hemisphere, such as Mauna Kea in Hawaii and Summit Station in Greenland, and the Southern Hemisphere, such as the Atacama Desert in Chile and the South Pole. CalSat also would be observable by balloon-borne instruments launched from a range of locations around the world. This global visibility makes CalSat the only source that can be observed by all terrestrial and sub-orbital observatories, thereby providing a universal standard that permits comparison between experiments using appreciably different measurement approaches

Speleothem growth intervals reflect New Zealand montane vegetation response to temperature change over the last glacial cycle

Flowstone speleothem growth beneath Mount Arthur, New Zealand shows a clear relationship to vegetation density and soil development on the surface above. Flowstone does not currently form beneath sub-alpine Nothofagus forest above ca. 1000–1100 m altitude but U-Th dating shows it has formed there during past intervals of warmer-than-present conditions including an early–mid Holocene optimum and the last interglacial from ca. 131–119 ka. Some flowstones growing beneath ca. 600 m surface altitude, currently mantled with dense broadleaf-podocarp forest, grew during full glacial conditions, indicating that local tree line was never below this altitude. This implies that Last Glacial Maximum annual temperature was no more than ca. 4 °C cooler than today. Flowstone growth appears to be a robust indicator of dense surface vegetation and well-developed soil cover in this setting, and indicates that past interglacial climates of MIS 7e, 5e, the early–mid Holocene and possibly MIS 5a were more conducive to growth of trees than was the late Holocene, reflecting regional temperature changes similar in timing to Antarctic temperature changes. Here, flowstone speleothem growth is a sensitive indicator of vegetation density at high altitude, but may respond to other factors at lower altitudes

Opinion piece: non-traditional practical work for traditional campuses

Traditional practical work for higher education in STEM subjects is under pressure from rising student numbers and adesired increase in active learning. Investing in more buildings and staff is financially challenging, while stretching existing resources affects outcomes, health, and participation. A more pragmatic approach is to embrace a less instrumentalist view of practical work in physical spaces and instead adopt a critical post-humanist approach which mixes both humanity and technology to achieve a sum greater than the parts, not bound by the limits of either. We share the experiences of leading UK exponents of non-traditional laboratories in the four main categories of simulation, virtual laboratories, real-asynchronous, and real- synchronous activities, as well as experts in scaling digital education initiatives for university-wide adoption. We foreshadow opportunities, challenges and potential solutions to increasing the opportunity for active learning by students studying at traditional campuses, via the complementary addition of non-traditional practical work

Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.

Background Tetrahydrobiopterin is a cofactor of endothelial NO synthase ( eNOS ), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects ( CHD s) induced by pregestational diabetes mellitus in mice. Methods and Results Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHD s were identified by histological analysis. Cell proliferation, eNOS dimerization, and reactive oxygen species production were assessed in the fetal heart. Pregestational diabetes mellitus results in a spectrum of CHD s in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHD s from 59% to 27%, and major abnormalities, such as atrioventricular septal defect and double-outlet right ventricle, were absent in the sapropterin-treated group. Lineage tracing reveals that pregestational diabetes mellitus results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes mellitus were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered reactive oxygen species levels in the fetal heart. Conclusions Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation, and prevents the development of CHD s in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHD s in pregestational diabetes mellitus

Simulated diabetic ketoacidosis therapy in vitro elicits brain cell swelling via sodium-hydrogen exchange and anion transport.

A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. Our experiments showed that cell swelling was elicited with isolated DKA treatment components, including alkalinization, insulin/alkalinization, and rapid reductions in osmolality. Methyl-isobutyl-amiloride, a nonselective inhibitor of sodium-hydrogen exchangers (NHEs), reduced cell swelling in brain slices elicited with simulated DKA therapy (in vitro) and decreased brain water content in juvenile DKA mice administered insulin and rehydration therapy (in vivo). Specific pharmacological inhibition of the NHE1 isoform with cariporide also inhibited cell swelling, but only in the presence of the anion transport (AT) inhibitor 4,4\u27-diisothiocyanatostilbene-2,2\u27-disulphonic acid. DKA did not alter brain NHE1 isoform expression, suggesting that the cell swelling attributed to the NHE1 was activity dependent. In conclusion, our data raise the possibility that brain cell swelling can be elicited by DKA treatment factors and that it is mediated by NHEs and/or coactivation of NHE1 and AT

Neural evidence for a distinction between short-term memory and the focus of attention

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay period activity may, in fact, reflect the focus of attention, rather than STM. We unconfounded attention and memory by causing external and internal shifts of attention away from items that were being actively retained. Multivariate pattern analysis of fMRI indicated that only items within the focus of attention elicited an active neural trace. Activity corresponding to representations of items outside the focus quickly dropped to baseline. Nevertheless, this information was remembered after a brief delay. Our data also show that refocusing attention toward a previously unattended memory item can reactivate its neural signature. The loss of sustained activity has long been thought to indicate a disruption of STM, but our results suggest that, even for small memory loads not exceeding the capacity limits of STM, the active maintenance of a stimulus representation may not be necessary for its short-term retention