Authoritarian constitutionalism: The South African experience

Over the past century, law was a central mechanism in the governance of the authoritarian regimes that preceded democratic South Africa. At the same time, the dialectical quality of law created a space for litigation strategies, which, at the very least, tempered the excesses of racist rule. Hence, an ambiguous legal history preceded the introduction of the 1996 Constitution,3 which, in turn, influenced the democratic model that was opted for by the constitutional negotiators at the Convention for a Democratic South Africa (CODESA) in the early 1990s

Escaping death: how cancer cells and infected cells resist cell-mediated cytotoxicity

Cytotoxic lymphocytes are critical in our immune defence against cancer and infection. Cytotoxic T lymphocytes and Natural Killer cells can directly lyse malignant or infected cells in at least two ways: granule-mediated cytotoxicity, involving perforin and granzyme B, or death receptor-mediated cytotoxicity, involving the death receptor ligands, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL). In either case, a multi-step pathway is triggered to facilitate lysis, relying on active pro-death processes and signalling within the target cell. Because of this reliance on an active response from the target cell, each mechanism of cell-mediated killing can be manipulated by malignant and infected cells to evade cytolytic death. Here, we review the mechanisms of cell-mediated cytotoxicity and examine how cells may evade these cytolytic processes. This includes resistance to perforin through degradation or reduced pore formation, resistance to granzyme B through inhibition or autophagy, and resistance to death receptors through inhibition of downstream signalling or changes in protein expression. We also consider the importance of tumour necrosis factor (TNF)-induced cytotoxicity and resistance mechanisms against this pathway. Altogether, it is clear that target cells are not passive bystanders to cell-mediated cytotoxicity and resistance mechanisms can significantly constrain immune cell-mediated killing. Understanding these processes of immune evasion may lead to novel ideas for medical intervention

‘It’s too late’. Is it really? Considerations for amblyopia treatment in older children

In recent years, media coverage has demonstrated instances in which families of children aged 7 and older, newly diagnosed with strabismic and/or anisometropic amblyopia through community eyecare services, were told it was ‘too late’ for their child to effectively respond to conventional amblyopia treatment (occlusion or atropine penalisation). Formal guidance pertaining to binocular vision anomalies from eyecare professional bodies does not specifically make reference to a child’s age, beyond stating the importance of early diagnosis and treatment of strabismus/amblyopia. However, there have been many changes in the way we view the recovery period for amblyopia, and it is well demonstrated both within literature and clinical practice that conventional treatment can improve amblyopic eye visual acuity in children beyond the age of 7 years. The occurrence of these media described cases within the community eyecare sphere would suggest it is worthwhile revisiting the literature on the subject of amblyopia treatment in older children (aged 7+ years), to address misconceptions and place in the spotlight current considerations facing clinicians when treating newly diagnosed amblyopia within this age group. This perspective review provides an evidence-based update covering the various considerations associated with treatment of amblyopia in older children, along with recent amblyopia treatment advances that could have an impact on treatment prospects for this patient group. Considerations include the risks, benefits and efficacy of treating newly diagnosed amblyopia in older children, monitoring density of suppression to mitigate intractable diplopia risk, and recent findings regarding binocular treatments for amblyopia

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Neural regions associated with gain-loss frequency and average reward in older and younger adults

Research on the biological basis of reinforcement-learning has focused on how brain regions track expected value based on average reward. However, recent work suggests that humans are more attuned to reward frequency. Furthermore, older adults are less likely to use expected values to guide choice than younger adults. This raises the question of whether brain regions assumed to be sensitive to average reward, like the medial and lateral PFC, also track reward frequency, and whether there are age-based differences. Older (60-81 years) and younger (18-30 years) adults performed the Soochow Gambling task, which separates reward frequency from average reward, while undergoing fMRI. Overall, participants preferred options that provided negative net payoffs, but frequent gains. Older adults improved less over time, were more reactive to recent negative outcomes, and showed greater frequency-related activation in several regions, including DLPFC. We also found broader recruitment of prefrontal and parietal regions associated with frequency value and reward prediction errors in older adults, which may indicate compensation. The results suggest greater reliance on average reward for younger adults than older adults

Maintenance Requirements of Implant Supported Fixed Prostheses Opposed by Either Implant Supported Fixed Prostheses or Natural Teeth: 5 Years Results

AIM: To compare the maintenance requirements of implant supported fixed prostheses opposed by implant supported fixed prostheses natural teeth or complete dentures. METHOD: The maintenance requirements were obtained by examining the dental records of 15 people, of whom 6 were edentulous in both arches and 9 edentulous in one arch. The results were compared to those obtained from 22 edentulous people in whom implants had been used in the mandible (control group). All the patients were treated with Nobel Biocare implants using standard implant and prosthetic protocols. RESULTS: The main maintenance requirement was the need to repair part of the superstructure. The artificial teeth and the acrylic resin had to be repaired on 44 occasions in the group with implants in both jaws and 14 occasions in the group with implants opposed by natural teeth. This compared with 2 occasions in the control group. Similarly the group with implants in both jaws were more likely to fracture the gold alloy framework, an event which occurred on 6 occasions. The Kruskal- Wallis one way analysis of variance on ranks was used to identify significant differences and Dunn’s method of All Pairwise Multiple Comparison Procedures was used to distinguish which group differed from the other. The group with implants in both jaws was significantly different to the other two groups in relation to the higher incidence of fracture of the teeth and acrylic resin superstructure (p<0.0001) and fracture of the gold alloy framework (p = 0.0002). CONCLUSION: The maintenance requirements of implant supported fixed prostheses opposed by implant supported fixed prostheses are much greater than when opposed by natural teeth or complete dentures

Should Medical Schools Incorporate Formal Training in Informatics?

Are we preparing future generations of physicians with the skills to practice in the information age? Has the health care IT industry matured to the stage that we can standardize training physicians in how to search and synthesize massive databases of clinical information and tease out complex diagnoses based upon scant information? Will literacy in information technology become a differentiator between physicians’ abilities? For the proposition of changing existing curriculum in medical schools to incorporate formal informatics training is Michael Chen, a second year medical student at the University of Maryland School of Medicine. Taking the opposing position is Nabile Safdar, M.D., assistant professor of radiology at the University of Maryland School of Medicines

Flexible production and entry: institutional, technological, and organizational determinants

Academics, the media, and policymakers have all raised concerns about the implications of human workers being replaced by machines or software. Few have discussed the implications of the reverse: firms’ ability to replace capital with workers. We show that this flexibility can help new firms overcome uncertainty and increase entrepreneurial entry. We develop a simple real options model where permissive labor regulations allow firms to take advantage of capital-labor substitutability by replacing ‘rigid’ capital with ‘flexible’ labor. The model highlights institutional, technological, and organizational preconditions to using this flexibility. Using a large and comprehensive dataset on entry by standalone firms and group affiliates, we provide evidence in support of the model