A leatherback turtle stranding at danger point, Gansbaai, South Africa

A dead, mature male leatherback turtle was sighted at Danger Point, Gansbaai on South Africa’s southwest coast. Leatherback turtle sightings are rare along this coastline although the site lies between two areas of known aggregation; a tropical breeding area to the east and the highly productive Benguela upwelling ecosystem foraging area to the west.VW South Africa and Marine Dynamicshttp://www.sawma.co.za/am201

An albino Cape cormorant Phalacrocorax capensis

Albinism has been recorded in many vertebrate taxa (Halls 2004). It is a genetic anomaly in which an autosomal recessive gene causes an absence of the enzyme tyrosinase, resulting in a total lack of melanin pigment in the skin, scales, hairs, feathers and eyes (van Grouw 2006). The skin and eye colour of albinos is pink because the blood can be seen through the transparent, unpigmented tissues. In birds, it is the most frequently reported colour aberration, although it is the least frequent in occurrence. This is because it is commonly mistaken for the most frequently inheritable aberration in birds, leucism, which is a partial or total lack of melanin in the plumage (sometimes also in the skin)—but not in the eye—due to an inherited disorder of the deposition of these pigments (van Grouw 2006). There are at least 10 other types of inheritable colour aberrations in birds.We thank M. Nowers for contacting the Dyer Island Conservation Trust (DICT) in regard to the sighting, H. Adams for transporting the bird to the Southern African Foundation for the Conservation of Coastal Birds (SANCCOB) rehabilitation facility, N. Parsons for performing the autopsy and D. Hamerton for granting access to the collections of the Iziko South African Museum of Cape Town.http://www.marineornithology.org/am2013ab201

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Global seascape ecology of the white shark

The movements of predators are inherently connected to their prey and environment. Yet, quantifying the movements of predators in inaccessible areas, such as the marine environment, has traditionally been challenging. In recent years, technical advancements in the development and miniaturisation of biologgers and their attachment and retrieval devices have seen an unprecedented increase in our ability to answer questions addressing the movement ecology of highly mobile marine animals. White sharks Carcharodon carcharias are long-lived, top marine predators that feed on a variety of prey in a range of environments. Despite being globally distributed, rare and threatened, they are found to seasonally aggregate in areas of high and predictable prey abundance. These aggregations offer a unique setting to answer questions on the movement ecology of a large marine predator, as many individuals, often varying in size and sex, are found in comparatively small areas that often serve as foraging grounds. In this thesis, I assess the seascape ecology of white sharks at local, regional and global scales using novel biologging tools and exploring their interactions with prey and the environment. At a local scale, I used animal-borne video and environmental data collection devices (AVEDs) to determine how white sharks interact with their preferred prey in a complex marine seascape in South Africa. Previous studies identified white sharks forage diurnally in this seascape, and in response, Cape fur seals Arctocephalus pusillus pusillus refuge in kelp forest. The use of AVEDs revealed white sharks make repeated movements into kelp forest throughout the day while raising their activity and turning rates. Cape fur seals were seen in footage grouping in numbers, hunkering to the seafloor, and blowing bubbles as white sharks approached. Though no predation events were captured in the footage, the results combined with the previous studies revealed white sharks are capable of foraging in kelp forests. At a regional scale, in the Northeast Pacific, I used biologging data from white sharks of three size-classes in four contrasting habitats in a multivariate statistical framework to elucidate both the internal and external determinants of movement and behaviour. I reveal distinct hierarchical similarity in movement characteristics, primarily driven by habitat, bathymetry in particular, and secondarily driven by size. Sharks in all habitats revealed distinct movement and behaviour between day and night, characteristic of a diurnal activity rhythm irrespective of circumstance. The availability of prey and access to deep water between these habitats are likely drivers of these differences. The two island habitats provide more elephant seal Mirounga angustirostris prey and are situated closer to the continental shelf edge. The other areas are either far from it and contain more harbour seals Phoca vitulina, or only host juvenile, piscivorous white sharks. Finally, I tested if the diurnal activity rhythm detected in the Northeast Pacific white shark population was characteristic of the species globally. I used scale-free estimates of activity derived from accelerometers deployed on 104 white sharks of four populations and eight aggregation areas to test for local adaptations in activity rhythms. Overall, linear modelling revealed consistent diurnal activity rhythms, irrespective of size or population, suggesting strong conservation of activity rhythms in this species. Despite the overall conservation of diurnal activity, generalised additive mixed models revealed some degree of site-specific plasticity, with peak activity differing between sites. I suggest that strong conservation in the diurnality of white sharks is driven by sensory specialisation for foraging in well-lit environments. In contrast, behavioural plasticity in the peak of activity is driven by the availability of prey at a given location. Together, my thesis reveals the major external and internal factors driving the movements and routines of white sharks. While white sharks display moderate plasticity in their movements and behaviours between different habitats, they also appear to be constrained to diurnal foraging, possibly due to the evolution of their sensory system making them diurnal specialists. As a threatened species that require protection yet can be potentially dangerous to water users, balanced management strategies involving multiple stakeholders are required in areas the species frequents. These strategies should consider the internal and external factors found influential on the movements and behaviours of white sharks. Given the results of this thesis, white sharks have a conserved diurnal circadian rhythm; potential challenges remain, as the time white sharks are more likely to be active reflects the time when people are more likely to be using coastal waters

Foraging ecology of white sharks Carcharodon carcharias at Dyer Island, South Africa

Dyer Island is thought to host one of the most abundant populations of white sharks on the planet; this is often credited to the large (55 – 60,000) Cape fur seal colony at Geyser Rock. Yet relatively little work has ever been produced from the area. This may be attributed to the harshness in its location as a study site, exposed to wind and swell from west to east which limits research periods. This study accounts for over 220 hrs of manual tracking at Dyer Island with a further 68 added from the inshore shallow areas of the bay. Sharks focused their movements and habitat use to reefs or channels that allowed access to Cape fur seals. Movement- Based Kernel Estimates (MKDE) were used to compute home range estimates for shark movements through and around the heterogeneous structures of Dyer Island and Geyser Rock. Inshore two core areas were revealed, one being the major reef system at Joubertsdam and the other at a kelp reef where the tracked shark had fed on a Cape fur seal. At Dyer Island one core area was identified in a narrow channel, ‘Shark Alley’, here a second tracked shark foraged for entire days within meters of rafting Cape fur seals. Rate of Movement (ROM) and Linearity (LI) of tracks were low during daytime and movements were focused around areas such as Shark Alley or other areas close to the seal colony before moving into deeper water or distant reefs with higher rates of ROM and LI at night. If moonlight was strong foraging would take place to the south of Geyser Rock but with higher ROM and LI than observed during the day. Foraging patterns in this study contrast studies from other sites in South Africa and home range and activity areas were comparatively much smaller than observed in Mossel Bay. It has been established that several known white sharks forage at Dyer Island and the other studied aggregation sites, such differences in foraging would suggest that they are able to adapt their foraging behaviour to suit the environment they are in; making them site specific in their foraging ecology. Both satellite and acoustic telemetry are revealing aggregation hotspots of white sharks in South Africa. It is important that such information is used to assist the recovery of the species which has been protected since 1991, yet is rarely considered in planning of coastal developments.Dissertation (MSc)--University of Pretoria, 2012.Zoology and EntomologyMScUnrestricte

Fine scale movements and activity areas of white sharks (Carcharodon carcharias) in Mossel Bay, South Africa

Previous work on white sharks indicate the species show seasonally limited movement patters, at certain aggregation sites small areas may play vital roles in the life history of a large amount of the population. Acoustic telemetry was used to estimate habitat use of white sharks, Carcharodon carcharias, while aggregating at Mossel Bay, South Africa. Total range of all shark tracks combined accumulated 782 hrs and covered an area of 93.5 km2 however, within this range, sharks were found to highly utilise a core habitat (50% Kernel, K50) of just 1.05 km2 over a reef system adjacent to a river mouth. Individual tracks revealed additional core habitats, some of which were previously undocumented and one adjacent to a commercial harbor. Much was found to be dependent on the size of the shark, with larger sharks (>400cm) occupying smaller activity areas than sub-adult (300-399 cm) and juvenile (<300 cm) conspecifics, while Index of Reuse (IOR) and Index of Shared Space (IOSS) were both found to increase with shark size. Such results provide evidence that larger white sharks are more selective in habitat use, which indicates they have greater experience within aggregation sites. Furthermore, the focused nature of foraging means spatially restricted management strategies would offer a powerful tool to aid enforcement of current protective legislation for the white shark in similar environments of limited resources and capacity.Tracking equipment was supplied by World Wildlife Fund - South Africa (WWF-SA) and National Geographic Channel, Talking Pictures and Off the Fence productions. Transmitters were supplied by Marine and Coastal Management and PADI Aware. Fuel was provided, in part, by Marine and Coastal Management (now Oceans and Coasts).http://www.springerlink.com/content/102877/hb201

Core habitat use of an apex predator in a complex marine landscape

Manual acoustic telemetry was used to describe core habitat use of white sharks in the complex marine landscape of the Dyer Island and Geyser Rock system near Gansbaai, South Africa. We compared home range estimates and swimming pattern analyses to those established at Mossel Bay, another white shark aggregation area roughly 300 km to the east. Traditional home range estimates used in Mossel Bay did not account for movement or barriers, and were thus biased towards areas with very little shark movement (i.e. potential resting areas). We found that adapting a Movement-based Kernel Density Estimate (MKDE) could account for movement and barriers, resolving these issues. At Dyer Island and Geyser Rock, daytime shark habitat use was adjacent to the seal colony, with low rates of movement, non-linear swimming patterns and small activity areas. At night, rates of movement and linearity increased as sharks travelled further from the islands into deeper waters. MKDEs revealed 4 focal areas of habitat use: a channel between the 2 islands, an area to the south of the seal colony, another area near a kelp feature to the southwest of the seal colony and a reef system to the northwest. These results differed significantly from the habitat use at Mossel Bay, where focal areas occurred adjacent to the seal colony during the hours of dawn and dusk. We discuss possible explanations for these differences. This study is the first to make use of MKDEs in a complex marine landscape and highlights important differences in habitat use of a threatened species between 2 separate aggregation areas.Dyer Island Conservation Trust, Marine Dynamics Shark Tours and Dyer Island Cruises, VW South Africa and the National Lotteryhttp://www.int-res.comhb201