The estimated burden of fungal disease in South Africa

Background. With a population of 56.5 million, over 7 million persons living with HIV, one of the world’s highest rates of tuberculosis (TB) and a large proportion of the population living in poverty, South Africa (SA)’s fungal disease burden is probably substantial and broad in scope.Objectives. To estimate the burden of fungal disease in SA.Methods. Using total and at-risk populations and national, regional and occasionally global data, we estimated the incidence and prevalence of the majority of fungal diseases in SA.Results. Estimates for the annual incidence of HIV-related life-threatening fungal disease include cryptococcal meningitis (8 357 cases), Pneumocystis pneumonia (4 452 cases) and endemic mycoses (emergomycosis, histoplasmosis and blastomycosis, with 100, 60 and 10 cases per year, respectively). We estimate 3 885 cases of invasive aspergillosis annually. The annual burden of candidaemia and Candida peritonitis is estimated at 5 421 and 1 901 cases, respectively. The epidemic of pulmonary TB has probably driven up the prevalence of chronic pulmonary aspergillosis to 99 351 (175.8/100 000), perhaps the highest in the world. Fungal asthma probably affects >100 000 adults. Mucosal candidiasis is common, with an annual prevalence estimated at 828 666 and 135 289 oral and oesophageal cases, respectively, complicating HIV infection alone (estimates in other conditions not made), and over a million women are estimated to be affected by recurrent vulvovaginal candidiasis each year. Tinea capitis in children is common and conservatively estimated at >1 000 000 cases. The inoculation mycoses sporotrichosis, chromoblastomycosis and eumycetoma occur occasionally (with 40, 40 and 10 cases estimated, respectively). Overall, we estimate that over 3.2 million South Africans are afflicted by a fungal disease each year (7.1% of the population).Conclusions. Significant numbers of South Africans are estimated to be affected each year by fungal infections, driven primarily by the syndemics of HIV, TB and poverty. These estimates emphasise the need for better epidemiological data, and for improving the diagnosis and management of these diseases

Spin accumulation induced resistance in mesoscopic ferromagnet/ superconductor junctions

We present a description of spin-polarized transport in mesoscopic ferromagnet-superconductor (F/S) systems, where the transport is diffusive, and the interfaces are transparent. It is shown that the spin reversal associated with Andreev reflection generates an excess spin density close to the F/S interface, which leads to a spin contact resistance. Expressions for the contact resistance are given for two terminal and four terminal geometries. In the latter the sign depends on the relative magnetization of the ferromagnetic electrodes.Comment: RevTeX 10 pages, 4 figures, submitted to Phys.Rev. Let

Comparing the influence of mixed reality, a 3D viewer, and MRI on the spatial understanding of brain tumours

Background: Multiple 3D visualization techniques are available that obviates the need for the surgeon to mentally transform the 2D planes from MRI to the 3D anatomy of the patient. We assessed the spatial understanding of a brain tumour when visualized with MRI, 3D models on a monitor or 3D models in mixed reality.Methods: Medical students, neurosurgical residents and neurosurgeons were divided into three groups based on the imaging modality used for preparation: MRI, 3D viewer and mixed reality. After preparation, the participants needed to position, scale, and rotate a virtual tumour inside a virtual head of the patient in the same orientation as the original tumour would be. Primary outcome was the amount of overlap between the placed tumour and the original tumour to evaluate accuracy. Secondary outcomes were the position, volume and rotation deviation compared to the original tumour.Results: A total of 12 medical students, 12 neurosurgical residents, and 12 neurosurgeons were included. For medical students, the mean amount of overlap for the MRI, 3D viewer and mixed reality group was 0.26 (0.22), 0.38 (0.20) and 0.48 (0.20) respectively. For residents 0.45 (0.23), 0.45 (0.19) and 0.68 (0.11) and for neurosurgeons 0.39 (0.20), 0.50 (0.27) and 0.67 (0.14). The amount of overlap for mixed reality was significantly higher on all expertise levels compared to MRI and on resident and neurosurgeon level also compared to the 3D viewer. Furthermore, mixed reality showed the lowest deviations in position, volume and rotation on all expertise levels.Conclusion: Mixed reality enhances the spatial understanding of brain tumours compared to MRI and 3D models on a monitor. The preoperative use of mixed reality may therefore support the surgeon to improve spatial 3D related surgical tasks such as patient positioning and planning surgical trajectories

New and confirmed records of fishes from the Cabo Verde archipelago based on photographic and genetic data

In recent decades the Cabo Verde ichthyofauna has been studied more extensively, and nowadays photo-recording is employed as a valuable asset under special caution and consideration. Four species reported here are new records for Cabo Verde: Carlarius sp., sea catfish; Serranus cabrilla, comber; Branchiostegus semifasciatus, African tilefish and Lutjanus dentatus, African coastal snapper. The presence in Cabo Verde of Glaucostegus cemiculus, blackchin guitarfish; Elops senegalensis, Senegalese ladyfish; Lophius spp., bathydemersal monkfishes; Rachycentron canadum, cobia; Pagrus auriga, African seabream; Lutjanus dentatus, African coastal snapper and Mugil cephalus, grey mullet, was re-confirmed by photo-records. Squalus megalops, cosmopolitan spurdog, was identified by genetic fingerprinting. The, two littoral species, P. auriga and M. cephalus, are firmly established in the archipelago and additional information on their occurrence is given. The findings reported in the present contribution may well be the result of a wider sharing of information between fishermen and other seafarers and scientists, rather than an indicator of recent faunal changes

Anti-inflammatory therapy with nebulised dornase alfa in patients with severe COVID-19 pneumonia A Randomised Clinical Trial

BACKGROUND: SARS-CoV2 infection causes severe, life-threatening pneumonia. Hyper-inflammation, coagulopathy and lymphopenia are associated with pathology and poor outcomes in these patients. Cell-free (cf) DNA is prominent in COVID-19 patients, amplifies inflammation and promotes coagulopathy and immune dysfunction. We hypothesized that cf-DNA clearance by nebulised dornase alfa may reduce inflammation and improve disease outcomes. Here, we evaluated the efficacy of nebulized dornase alfa in patients hospitalised with severe COVID-19 pneumonia. METHODS: In this randomised controlled single-centre phase 2 proof-of-concept trial, we recruited adult patients admitted to hospital that exhibited stable oxygen saturation (≥94%) on supplementary oxygen and a C-reactive protein (CRP) level ≥30mg/L post dexamethasone treatment. Participants were randomized at a 3:1 ratio to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until hospital discharge. A 2:1 ratio of historical controls to treated individuals (HC, 2:1) were included as the primary endpoint comparators. The primary outcome was a reduction in systemic inflammation measured by blood CRP levels over 7 days post-randomisation, or to discharge if sooner. Secondary and exploratory outcomes included time to discharge, time on oxygen, D-dimer levels, lymphocyte counts and levels of circulating cf-DNA. RESULTS: We screened 75 patients and enrolled 39 participants out of which 30 in dornase alfa arm, and 9 in BAC group. We also matched the recruited patients in the treated group (N=30) to historical controls in the BAC group (N=60). For the the primary outcome, 30 patients in the dornase alfa were compared to 69 patients in the BAC group. Dornase alfa treatment reduced CRP by 33% compared to the BAC group at 7-days (P=0.01). The dornase alfa group least squares mean CRP was 23.23 mg/L (95% CI 17.71 to 30.46) and the BAC group 34.82 mg/L (95% CI 28.55 to 42.47). A significant difference was also observed when only randomised participants were compared. Furthermore, compared to the BAC group, the chance of live discharge was increased by 63% in the dornase alfa group (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), lymphocyte counts were improved (least-square mean: 1.08 vs 0.87, P=0.02) and markers of coagulopathy such as D-dimer were diminished (least-square mean: 570.78 vs 1656.96μg/mL, P=0.004). Moreover, the dornase alfa group exhibited lower circulating cf-DNA levels that correlated with CRP changes over the course of treatment. No differences were recorded in the rates and length of stay in the ICU or the time on oxygen between the groups. Dornase alfa was well-tolerated with no serious adverse events reported. CONCLUSION: In this proof-of-concept study in patients with severe COVID-19 pneumonia, treatment with nebulised dornase alfa resulted in a significant reduction in inflammation, markers of immune pathology and time to discharge. The effectiveness of dornase alfa in patients with acute respiratory infection and inflammation should be investigated further in larger trials

Resting energy expenditure in children at risk of hypothalamic dysfunction

Objective: Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage. Patients and methods: A retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage. Results: In total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE. Conclusion: REE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions

A draft genome sequence of the elusive giant squid, Architeuthis dux

Background: The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea-dwelling species will allow several pending evolutionary questions to be unlocked. Findings: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome. Conclusions: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments