Maccsand (Pty) Ltd v city of Cape Town 2012 (4) SA 181 (CC)

The Constitutional Court in Maccsand (Pty) Ltd v City of Cape Town (CCT 103/11) 2012 ZACC 7 decided that the granting of mining rights or mining permits by the Minister of Mineral Resources in terms of the Mineral and Petroleum Resources Development Act 28 of 2002 does not obviate the obligation on an applicant to obtain authorisations in terms of other legislation that deals with functional domains other than minerals, mining and prospecting. This applies to all other legislation, irrespective of whether the responsible administrator of such other legislation is in the national, provincial or local sphere of government. The effect of the decision is that planning and other authorities which derive their statutory mandate and powers from other legislation retain all their powers as regards planning and rezoning, for instance. In addition, the Minister of Mineral Resources cannot make a decision on behalf of, or for, such functionaries. The judgement also clarified the question of whether or not a national Act can supersede provincial legislation dealing with a distinctly different functional domain. In principle, the decision also indicates that the fact that a range of authorisations are required in terms of separate statutory instruments (each with its own functional domain and administered by its own functionary) does not necessarily amount to conflicts between these instruments. An owner of land may now insist that his land may not be used for mining purposes if it is not zoned for such purposes. It is submitted that, in order to provide certainty to land owners, developers and government functionaries, and to promote investor confidence (especially in the mining sector), an intergovernmental system for the consideration of applications by the functionaries responsible for the separate statutory instruments needs to be developed as a high priority

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Mapping Policy Responses to Food Systems Transformation in Malawi

Key Findings -The dominance of traditional food systems may not be able to sustainably address the food and nutrition needs of an increasing Malawian population. -Due to the multifaceted nature of food systems, not only food and nutrition policies and or agricultural policies influence food systems. Other relevant sectoral policies can also have a significant positive or negative influence on food systems. -Although some policies may be considered indirectly linked to FSN or may not have FSN as one of its policy goals, they could inadvertently constitute a driving force to transforming the food system. -Most policies in Malawi addressed food availability but less focus on accessibility and affordability which has implications on achieving FSN. -Policy coherence and multi-sectoral policy approaches to transforming food systems are crucial in achieving sustainable food systems outcomes (FSN, socioeconomic and environmental outcomes)

Interactions Between Oxytocin Receptor Gene Methylation and Callous-Unemotional Traits Impact Socioaffective Brain Systems in Conduct-Disordered Offenders

BACKGROUND: The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., perturbed socioaffective reactivity and empathy, callousness) in youths with conduct disorder (CD). Whereas oxytocin receptor gene methylation (OXTRMeth) and its downstream neuromodulatory effects are deemed relevant to CU traits, nothing is known of how OXTRMeth interacts with CU traits to impact socioaffective brain systems in youngsters with CD. METHODS: Hence, we uniquely probed OXTRMeth × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition and resonance of distressing socioaffective stimuli (angry and fearful faces), in juvenile offenders with CD (n = 39) versus matched healthy control youths (n = 27). RESULTS: Relative to healthy control youths, elevated OXTRMeth and CU levels in youths with CD essentially interacted to predict frontoparietal hyperactivity and amygdalo-frontoparietal disconnection during task performance. Specifically, increasing OXTRMeth and CU levels in youths with CD interactively predicted midcingulate hyperactivity during both emotion conditions, with insular, temporoparietal, and precuneal hyperactivity additionally emerging during emotion recognition. Interactions between high OXTRMeth and CU levels in youths with CD additionally predicted centromedial amygdala decoupling from ventromedial/orbitofrontal regions during emotion recognition, along with basolateral amygdala decoupling from precuneal and temporoparietal cortices during emotion resonance. CONCLUSIONS: These results uniquely suggest that interactions between OXTRMeth and CU traits in youths with CD may affect brain systems critical to decoding and integrating socioaffective information. Developmental models of CU traits and psychopathy could thus possibly advance by further examining OXTR epigenetic effects, which may hold promise for indicated prevention and personalized treatment by targeting oxytocinergic function

Neural processing of socioemotional content in conduct-disordered juvenile offenders with limited prosocial emotions

Background: Reflecting evidence on Callous-Unemotional (CU) traits (e.g., lack of empathy and guilt, shallow affect), the DSM-5 added a categorical CU-based specifier for Conduct Disorder (CD), labeled ‘with Limited Prosocial Emotions’ (LPE). Theory and prior work suggest that CD youths with and without LPE will likely differ in neural processing of negative socioemotional content. This proposition, however, is mainly derived from studies employing related, yet distinct, operationalizations of CU traits (e.g., dimensional measure/median split/top quartile), thus precluding direct examination of LPE-specific neurocognitive deficits. Methods: Employing a DSM-5 informed LPE proxy, neural processing of recognizing and resonating negative socioemotional content (angry and fearful faces) was therefore examined here among CD offenders with LPE (CD/LPE+; N = 19), relative to CD offenders without LPE (CD/LPE-; N = 31) and healthy controls (HC; N = 31). Results: Relative to HC and CD/LPE- youths and according to a linearly increasing trend (CD/LPE- < HC < CD/LPE+), CD/LPE+ youths exhibited hyperactivity within dorsolateral, dorsomedial, and ventromedial prefrontal regions during both emotion recognition and resonance. During emotion resonance, CD/LPE+ youths additionally showed increased activity within the posterior cingulate and precuneal cortices in comparison to HC and CD/LPE- youths, which again followed a linearly increasing trend (CD/LPE- < HC < CD/LPE+). These effects moreover seemed specific to the LPE specifier, when compared to a commonly employed method for CU-based grouping in CD (i.e., median split on CU scores). Conclusions: These data cautiously suggest that CD/LPE+ youths may exhibit an over-reliance on cortical neurocognitive systems when explicitly processing negative socioemotional information, which could have adverse downstream effects on relevant socioemotional functions. The findings thus seem to provide novel, yet preliminary, clues on the neurocognitive profile of CD/LPE+, and additionally highlight the potential scientific utility of the LPE specifier

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N=50, mean age=16.83 +/- 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile

Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT₂/5-HT₃/5-HT₄ ligands

The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT(2C) antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT(2C) agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT(3) antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT(3) agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT(4) antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT(4) agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT(2/3/4) subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT(2) and 5-HT(3) agonists, the 5-HT(4) agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT(4) antagonist RS 39604. We conclude by discussing the implications of these findings

Disorganized Amygdala Networks in Conduct-Disordered Juvenile Offenders With Callous-Unemotional Traits

Background The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., deficient emotional reactivity, callousness) in conduct-disordered (CD) youth. Though subregion-specific anomalies in amygdala function have been suggested in CU pathophysiology among antisocial populations, system-level studies of CU traits have typically examined the amygdala as a unitary structure. Hence, nothing is yet known of how amygdala subregional network function may contribute to callous-unemotionality in severely antisocial people. Methods We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral amygdala (BLA) and centromedial amygdala (CMA) networks across three matched groups of juveniles: CD offenders with CU traits (CD/CU+; n = 25), CD offenders without CU traits (CD/CU−; n = 25), and healthy control subjects (n = 24). We additionally examined whether perturbed amygdala subregional connectivity coincides with altered volume and shape of the amygdaloid complex. Results Relative to CD/CU− and healthy control youths, CD/CU+ youths showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared with CD/CU− and healthy control youths, CD/CU+ youths showed diminished CMA connectivity with ventromedial/orbitofrontal regions. Critically, these connectivity changes coincided with local hypotrophy of BLA and CMA subregions (without being statistically correlated) and were associated to more severe CU symptoms. Conclusions These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+