Screening for primary aldosteronism- normal ranges for aldosterone and renin in three South African population groups

Objective. To establish normal ranges for plasma aldosterone, renin and aldosterone / renin (A/ R) ratio in South African normotensives under typical ou tpatient conditions, and to estimate the prevalence of primary aldosteronism (PA) among hypertensives in primary care settings.Design and methods. One hundred and thirty-six normotensive subjects and 154 sex- and age-matched hypertensives at three primary care clinics had measurements of blood pressure, plasma creatinine, K+, aldosterone, plasma renin activity, and spot urine for urinary Na+/ creatinine ratio. Medication was not withdrawn before testing.Results. Mean plasma renin activity in black normotensive subjects (0.95 ± 1.25 ng/ ml/ h, mean± standard deviation (SD)) was significantly lower than in white (2.09 ± 1.12 ng/ ml/ h; P < 0.0001) and coloured (1.81 ± 1.86 ng/ ml/ h, P = 0.013) normotensives. Mean plasma aldosterone in black normotensives (306 ± 147 pmol/ 1) was also significantly lower than in white (506 ± 324 pmol/1, P = 0.0002) and coloured (418 ± 304 pmol/1, P = 0.0148) normotensives. In hypertensives, there were no significant differences in renin or aldosterone levels between the three population groups. Urinary Na+ /creatinine ratios, an index of Na+ intake, were not significantly different in the three population groups. None of the normotensives had an A/R ratio ≥ 1 000 plus aldosterone ≥ 750, while 7.1% of hypertensives exceeded these levels, suggesting that they are appropriate criteria for screening for PA.Conclusions. A large fraction of black normotensive subjects had low renin and aldosterone levels compared with whites, suggesting a salt-retaining tendency in black subjects. These results have important implications for the interpretation of plasma renin and aldosterone levels in hypertensive patients. In primary care settings, 7.1% of hypertensives had biochemical results indicating the need for investigation of PA

Successful nesting by 2 endangered Hawaiian waterbird species in a restored Indigenous wetland agroecosystem

The Hawaiian Stilt (Himantopus mexicanus knudseni) and Hawaiian Gallinule (Gallinula galeata sandvicensis) are federally endangered waterbirds endemic to the Hawaiian Islands. Both species are conservation-reliant; their population persistence is dependent on invasive predator control and removal of invasive plants that degrade habitat. We present observations of successful nesting by one Hawaiian Stilt pair and one Hawaiian Gallinule pair at a site managed within an adaptive Indigenous agroecological framework on the island of O‘ahu, Hawai‘i. The Hawaiian Stilt nest, found in February 2019, contained 4 eggs and produced 3 hatchlings, 2 of which were banded and monitored after hatching. The Hawaiian Gallinule nest, found in February 2020, contained 6 eggs and produced 5 hatchlings. Although no individuals were banded from this nest, 2 adults and 2 hatchlings were continuously observed in the nesting area after the eggs hatched. Lo‘i kalo Hawaiian wetland agroecosystems centered around the cultivation of kalo (taro; Colocasia esculenta), have the potential to expand Hawaiian waterbird habitat beyond state and federal protected areas. We are aware of unpublished accounts of Hawaiian waterbirds nesting in commercially farmed lo‘i kalo, but until now, there have been no previously published accounts of native waterbirds breeding in lo‘i kalo managed as Indigenous agroecosystems

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS. MethodsSamples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression. ResultsThere were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 x 10(-12)), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0x10(-7)). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0x10(-4)). DiscussionAlthough telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS

Safety evaluation of the single-dose Ad26. COV2.S vaccine among healthcare workers in the Sisonke study in South Africa : a phase 3b implementation trial

Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data.Funding for the Sisonke Study was provided by: The National Department of Health through baseline funding to the South African Medical Research Council; the Solidarity Response Fund NPC; The Michael & Susan Dell Foundation; the ELMA Vaccines and Immunization Foundation; the ELMA Vaccines and Immunization Foundation; and the Bill & Melinda Gates Foundation.https://journals.plos.org/plosmedicinedm2022Paediatrics and Child HealthSchool of Health Systems and Public Health (SHSPH

The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration

Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability

Consciousness: A Connectionist Perspective

Cognitive scientists seeking a computational account of consciousness almost universally opt for a process theory of some kind: a theory that explains phenomenal experience in terms of the computational processes defined over the brain's representational vehicles. But until recently cognitive science has been dominated by the classical computational theory of mind. Today there is a new player on the scene, connectionism, which takes its inspiration from a computational framework known as parallel distributed processing (PDP). It is therefore appropriate to ask whether connectionism has anything distinctive to say about consciousness, and in particular, whether it might challenge the dominance of process theories. I argue that connectionism has the resources to hazard a vehicle theory of consciousness. A vehicle theory places consciousness right at the focus of cognition by identifying it with the explicit representation of information in the brain. Classicism can't support such a theory because it is committed to the existence of explicit representations whose contents are not phenomenally conscious. The connectionist vehicle theory of consciousness aligns phenomenal experience with stable patterns of activation in neurally realised PDP networks. It suggests that consciousness is an amalgam of phenomenal elements, both sensory and non-sensory, and the product of a multitude of consciousness-making mechanisms scattered throughout the brain. This somewhat unorthodox picture is supported, I claim, by careful analysis of experience, and by the evidence of the neurosciences. One obstacle facing this account is the apparent evidence, both direct and indirect, for the activity of unconscious explicit representations in human cognition. I establish that much of the direct evidence for this thesis is open to doubt on methodological grounds. And studies that support the dissociation thesis indirectly, by way of an inference to the best explanation, are vulnerable to alternative connectionist explanations of the relevant phenomena. What is most significant about the connectionist vehicle theory of consciousness is not the fact that it's a connectionist theory of consciousness, but that it's a vehicle theory - an account which takes cognitive science into largely unexplored territory, but in so doing brings into clearer focus the issues with which any theory of consciousness must contend.Thesis (Ph.D.)--Department of Philosophy, 1998

Dynamic currency hedging for international stock portfolios

The paper studies dynamic currency risk hedging of international stock portfolios using a currency overlay. A dynamic conditional correlation (DCC) multivariate GARCH model is employed to estimate time-varying covariance among stock market returns and currency returns. The conditional covariance is then used in the estimation of risk-minimizing conditional hedge ratios. The study considers seven developed economies over the period January 2002 to April 2010 and estimates daily conditional hedge ratios for portfolios of various stock market combinations. Conditional hedging is shown to dominate traditional static hedging and unconditional hedging in terms of risk reduction both in-sample and out-of-sample, especially during the recent global financial crisis. Conditional hedging also proves to consistently reduce portfolio risk for various levels of foreign investments