Effects of acute and chronic hypohydration on tolerance to plus Gz acceleration in man. I - Physiological results

Effects of acute and chronic hypohydration on human physiological tolerance to gravity acceleratio

Application of neural networks to South African GPS TEC modelling

The propagation of radio signals in the Earth’s atmosphere is dominantly affected by the ionosphere due to its dispersive nature. Global Positioning System (GPS) data provides relevant information that leads to the derivation of total electron content (TEC) which can be considered as the ionosphere’s measure of ionisation. This paper presents part of a feasibility study for the development of a Neural Network (NN) based model for the prediction of South African GPS derived TEC. The South African GPS receiver network is operated and maintained by the Chief Directorate Surveys and Mapping (CDSM) in Cape Town, South Africa. Vertical total electron content (VTEC) was calculated for four GPS receiver stations using the Adjusted Spherical Harmonic (ASHA) model. Factors that influence TEC were then identified and used to derive input parameters for the NN. The well established factors used are seasonal variation, diurnal variation, solar activity and magnetic activity. Comparison of diurnal predicted TEC values from both the NN model and the International Reference Ionosphere (IRI-2001) with GPS TEC revealed that the IRI provides more accurate predictions than the NN model during the spring equinoxes. However, on average the NN model predicts GPS TEC more accurately than the IRI model over the GPS locations considered within South Africa

Risk Factors of Microbial Keratitis in Uganda: A Case Control Study.

Purpose: Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda.Methods: Using a nested case control, we recruited healthy community controls for patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018. Controls were individually matched for age, gender and village of the cases on a 1:1 ratio. We collected information on demographics, occupation, HIV and Diabetes Mellitus status. In STATA version 14.1, multivariable conditional logistic regression was used to generate odds ratios for risk factors of MK and a likelihood ratio test used to assess statistical significance of associations.Results: Two hundred and fifteen case-control pairs were enrolled. The HIV positive patients among the cases was 9% versus 1% among the controls, p = .0003. Diabetes 7% among the cases versus 1.4% among the controls, p = .012. Eye trauma was 29% versus 0% among the cases and controls. In the multivariable model adjusted for age, sex and village, HIV (OR 83.5, 95%CI 2.01-3456, p = .020), Diabetes (OR 9.38, 95% CI 1.48-59.3, p = .017) and a farming occupation (OR 2.60, 95%CI 1.21-5.57, p = .014) were associated with MK. Compared to a low socio-economic status, a middle status was less likely to be associated with MK (OR 0.29, 95%CI 0.09-0.89, p < .0001).Conclusion: MK was associated with HIV, Diabetes, being poor and farming as the main occupation. More studies are needed to explore how these factors predispose to MK

Epidemiology of Microbial Keratitis in Uganda: A Cohort Study.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda.Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60).Results: 313 individuals were enrolled. Median age was 47 years (range 18-96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8-32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04-2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12-4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03-1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70-26.6], p < .0001).Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions

Multi-instrument observations of large-scale atmospheric gravity waves/traveling ionospheric disturbances associated with enhanced auroral activity over Svalbard

This study reports on observations of large-scale atmospheric gravity waves/traveling ionospheric disturbances (AGWs/TIDs) using Global Positioning System (GPS) total electron content (TEC) and Fabry–Perot Interferometer’s (FPI’s) intensity of oxygen red line emission at 630 nm measurements over Svalbard on the night of 6 January 2014. TEC large-scale TIDs have primary periods ranging between 29 and 65 min and propagate at a mean horizontal velocity of ~749–761 m/s with azimuth of ~345–347° (which corresponds to poleward propagation direction). On the other hand, FPI large-scale AGWs have larger periods of ~42–142 min. These large-scale AGWs/TIDs were linked to enhanced auroral activity identified from co-located all-sky camera and IMAGE magnetometers. Similar periods, speed and poleward propagation were found for the all-sky camera (~60–97 min and ~823 m/s) and the IMAGE magnetometers (~32–53 min and ~708 m/s) observations. Joule heating or/and particle precipitation as a result of auroral energy injection were identified as likely generation mechanisms for these disturbances. © 2018 COSPAR. Published by Elsevier Ltd. All rights reserved

Multi-instrument observations of large-scale atmospheric gravity waves/traveling ionospheric disturbances associated with enhanced auroral activity over Svalbard

This study reports on observations of large-scale atmospheric gravity waves/traveling ionospheric disturbances (AGWs/TIDs) using Global Positioning System (GPS) total electron content (TEC) and Fabry-Perot Interferometer’s (FPI’s) intensity of oxygen red line emission at 630 nm measurements over Svalbard on the night of 6 January 2014. TEC large-scale TIDs have primary periods ranging between 29 and 65 minutes and propagate at a mean horizontal velocity of ∼749–761 m/s with azimuth of ∼345°–347° (which corresponds to poleward propagation direction). On the other hand, FPI large-scale AGWs have larger periods of ∼42–142 minutes. These large-scale AGWs/TIDs were linked to enhanced auroral activity identified from co-located all-sky camera and IMAGE magnetometers. Similar periods, speed and poleward propagation were found for the all-sky camera (∼60–97 minutes and ∼823 m/s) and the IMAGE magnetometers (∼32–53 minutes and ∼708 m/s) observations. Joule heating or/and particle precipitation as a result of auroral energy injection were identified as likely generation mechanisms for these disturbances

Simultaneous Occurrence of Traveling Ionospheric Disturbances, Farley Buneman and Gradient Drift Instabilities Observed by the Zhongshan SuperDARN HF Radar

We show that Traveling Ionospheric Disturbances (TIDs) may affect the Farley Buneman Instability (FBI) and Gradient Drift Instability (GDI) echoes referred to as the Near Range Echoes (NREs) in the SuperDARN radar backscatter from the lower part of the E‐region. TIDs and NREs are observed concomitantly by the Zhongshan SuperDARN radar (69.38°S, 76.38°E) in the far and near ranges, respectively. At the moment, there is no study about the effects of TIDs on the NREs caused by the FBI using the SuperDARN radars. The GDI are more likely to occur at a lower altitude while FBI occurs at a slightly higher altitude in the lower part of the ionospheric E‐region. We use the Spearman Correlation Coefficient (SCC) to show that a part of the NREs backscatter power could be statistically explained by the MSTIDs backscatter power received by the same radar. We also investigate the simultaneous occurrence rate of the NREs and MSTIDs during the 24th solar cycle. Seasonal variability shows that MSTIDs‐NREs events over Zhongshan mostly occur in summer and equinoxes during local night and morning. The majority of these events lasted between ∼4 and ∼8 hr. Most events disappeared early in the morning. Statistics of the Spearman correlation coefficient values show that ∼9% of NRE amplitude modulation could be due to the MSTIDs. There are almost equal numbers of negative and positive Spearman correlation coefficient values. The relative velocity between the E‐region NREs and the F‐region MSTIDs switching the electric field polarities between the crests and troughs could be the cause of those equal number of the Spearman correlation coefficient values. The orientation of the ionospheric current relative to the MSTID polarization electric field may also play a significant role in the reported Spearman correlation coefficient values. We argue that in some cases, the TIDs might have been close enough to the NREs altitude to modulate them directly by transporting the plasma up and down through shear or compression

HRP2 and pLDH-Based Rapid Diagnostic Tests, Expert Microscopy, and PCR for Detection of Malaria Infection during Pregnancy and at Delivery in Areas of Varied Transmission: A Prospective Cohort Study in Burkina Faso and Uganda.

BACKGROUND: Intermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings. CONCLUSIONS/SIGNIFICANCE: The study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined

Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease

Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda

OBJECTIVES: To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda. DESIGN: Randomized single-blind controlled trial. SETTING: Tororo, Uganda, an area of high-level malaria transmission. PARTICIPANTS: Children aged one to ten years with confirmed uncomplicated P. falciparum malaria. INTERVENTIONS: Amodiaquine + artesunate or artemether–lumefantrine. OUTCOME MEASURES: Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS: Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether–lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether–lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%–24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether–lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%–25.2%). Amodiaquine + artesunate and artemether–lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens. CONCLUSIONS: Amodiaquine + artesunate and artemether–lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether–lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated