A ligation-independent sequencing method reveals tRNA-derived RNAs with blocked 3' termini.

Despite the numerous sequencing methods available, the diversity in RNA size and chemical modification makes it difficult to capture all RNAs in a cell. We developed a method that combines quasi-random priming with template switching to construct sequencing libraries from RNA molecules of any length and with any type of 3' modifications, allowing for the sequencing of virtually all RNA species. Our ligation-independent detection of all types of RNA (LIDAR) is a simple, effective tool to identify and quantify all classes of coding and non-coding RNAs. With LIDAR, we comprehensively characterized the transcriptomes of mouse embryonic stem cells, neural progenitor cells, mouse tissues, and sperm. LIDAR detected a much larger variety of tRNA-derived RNAs (tDRs) compared with traditional ligation-dependent sequencing methods and uncovered tDRs with blocked 3' ends that had previously escaped detection. Therefore, LIDAR can capture all RNAs in a sample and uncover RNA species with potential regulatory functions.

Genotypic Analysis of Transmitted and Acquired HIV Drug Resistance in People Living with HIV/AIDS in Surabaya, Indonesia, from 2018 to 2019.

BACKGROUND: Despite the availability of various effective antiretroviral (ARV) drugs, human immunodeficiency virus (HIV) infection has come with HIV drug resistance (HIVDR), which compromises its effectiveness in reducing HIV-related morbidity, mortality, and transmission. The emergence of transmitted (TDR) and acquired HIVDR (ADR) among antiretroviral therapy (ART)-naïve and experienced individuals have been reported in several Indonesian regions. Therefore, continuous HIVDR surveillance is needed in Indonesia, especially in Surabaya, which is identified as having the highest prevalence of HIV infection in East Java; thus, this study aimed to identify the emergence of TDR and ADR among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLWHA). METHODS: Fifty-eight PLWHA infected with HIV type 1 (HIV-1), comprising 21 and 37 ART-naïve and experienced individuals were enrolled in this study, respectively. Blood samples collected from study participants were subjected to genotypic analysis, mainly towards the pol gene encoding protease (PR gene) and reverse transcriptase (RT gene) of HIV-1. RESULTS: Seventeen PR and 21 RT genes were successfully amplified and sequenced from 29 samples. HIV-1 subtyping revealed CRF01_AE as the most dominant subtype (24/29; 82.76%), followed by subtype B (3/29; 10.34%). Uncommon subtypes, including subtype D and a recombinant containing subtypes B and G genomic fragments, were also identified. TDR for PR inhibitors was not detected; however, TDR and ADR for RT inhibitors were identified in 11.11% and 41.67% of samples, respectively. Two amino acid insertions at position 69 of the RT gene (69ins), a previously never-reported mutation in Indonesia, were identified in this study. CONCLUSION: Both TDR and ADR have emerged among PLWHA residing in Surabaya, East Java, Indonesia. Uncommon drug-resistance mutations and subtypes were identified in this study. These situations might hamper ART efficacy and treatment success. Continuous surveillance of HIVDR is necessary to monitor both TDR and ADR in Indonesia.

Temporal Diffusion Ratio (TDR) for imaging restricted diffusion: Optimisation and pre-clinical demonstration.

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for informing on pore sizes, in particular the presence of large axon diameters or other cellular structures. TDR employs the signal from two dMRI acquisitions obtained with the same, large, b-value but with different diffusion gradient waveforms. TDR is advantageous as it employs standard acquisition sequences, does not make any assumptions on the underlying tissue structure and does not require any model fitting, avoiding issues related to model degeneracy. This work for the first time introduces and optimises the TDR method in simulation for a range of different tissues and scanner constraints and validates it in a pre-clinical demonstration. We consider both substrates containing cylinders and spherical structures, representing cell soma in tissue. Our results show that contrasting an acquisition with short gradient duration, short diffusion time and high gradient strength with an acquisition with long gradient duration, long diffusion time and low gradient strength, maximises the TDR contrast for a wide range of pore configurations. Additionally, in the presence of Rician noise, computing TDR from a subset (50% or fewer) of the acquired diffusion gradients rather than the entire shell as proposed originally further improves the contrast. In the last part of the work the results are demonstrated experimentally on rat spinal cord. In line with simulations, the experimental data shows that optimised TDR improves the contrast compared to non-optimised TDR. Furthermore, we find a strong correlation between TDR and histology measurements of axon diameter. In conclusion, we find that TDR has great potential and is a very promising alternative (or potentially complement) to model-based approaches for informing on pore sizes and restricted diffusion in general.

Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019-2021.

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.

Contribution of the World Health Organization/ the special program for research and training in tropical disease (WHO/TDR's) in institution building: lessons from Ethiopia.

BACKGROUND: World Health Organization/Tropical Disease Research (WHO/TDR) has enduring investment in transfers of skills critical to sustaining resilient health research systems through postgraduate training, clinical research and development fellowship (CRDF), bioethics, and grants to neglected tropical disease research. TDR has a long history of partnership with Armauer Hansen Research Institute (AHRI) in Ethiopia. The collaboration started with individuals and lead to institution survival and success. Therefore, the purpose of this study was to explore the impact and lessons learned of TDR initiatives in Ethiopia. METHOD: This study was guided by the 'TDR Impact Pathways'. A total of thirteen in-depth, and five key informant interviews were conducted with individuals who are currently working in Addis Ababa, Gondar, Jimma Universities and AHRI. In addition to the interviews, reports, written communications and publications were reviewed. Interviews were audio recorded, transcribed verbatim, inductively coded, and analyzed thematically. The results were presented following the themes with supportive verbatim quotes. CONCLUSION: TDR's seed grants, training opportunities and technical support catalyzed individual, institutional and national research capacity in Ethiopia. This is a useful indication of how long-term collaboration between individuals could have broader institutional implication as evidenced from the TDR-AHRI complementary partnership.

Accurate Detection and Localization of Water Pipe Leaks through Model-Based TDR Inversion.

The problem of water scarcity affects many areas of the world due to water mismanagement and overconsumption and, more recently, to climate change. Monitoring the integrity of distribution systems is, therefore, increasingly important to avoid the waste of clean water. This paper presents a new signal processing technique for enhancing the performance of the methodology of leak detection in water distribution pipes based on time domain reflectometry (TDR). The new technique is based on a particular kind of TDR inversion (spatial TDR) based on a "gray-box" lumped parameter model of the system. The model does not include, e.g., radiative phenomena, non-TEM (transverse electromagnetic) modes etc. but is capable of reproducing accurately the complicated reflectograms obtained by a TDR leak detection system assuming a proper profile of capacitance per unit length along the sensing element. Even more importantly, the model is identified using only the reflectograms taken by the system with very little prior information about the system components. The developed technique is able to estimate with good accuracy, from reflectograms with unclear or ambiguous interpretation, the position and the extension of a region where water is located. The measurement is obtained without prior electromagnetic characterization of the TDR system components and without the need of modeling or quantifying a number of electromagnetic effects typical of on-site measurements.

Demonstrating the Potential of a Low-Cost Soil Moisture Sensor Network.

Soil moisture is a key parameter of the climate system as it relates to plant transpiration and photosynthesis and impacts land-atmosphere interactions. Recent developments have seen an increasing number of electromagnetic sensors available commercially (EM) for soil volumetric water content (θ). Their use is constantly expanding, and they are becoming increasingly used for agricultural, ecological, and geotechnical applications and climate research, providing decision support and high-resolution data for models and machine-learning algorithms. In this study, a soil moisture sensor network consisting of 10 Sense Cap capacitance-based sensors is evaluated. Analytical performance of the sensors was determined based on laboratory and field measurements with dielectric permittivity (ε) standards and soil media substrates. Sensor response normalisation to standards of known ε was found to reduce intersensor variability and provide robust estimates of θ in soil samples with known θ. Cross-comparison with a time-domain reflectometry (TDR) instrument carried out in two soil media demonstrates good agreement between the two probes throughout the tested range. The data communication performance of the network was evaluated in terms of packet drop rate at different ranges and sampling frequencies. It was noticed that the drop rate increased with distance from the gateway, while sampling frequency had no effect. Sources of errors associated with probe installation were identified and recommendations are provided for sensor deployment. The off-the-shelf all-in-one solution provided by Sense Cap is low cost, user friendly and suitable for implementation at temporal and spatial scales once the identified shortcomings are addressed. The evaluation presented aims to aid stakeholders and users involved in soil and land management practices including crop production, soil conservation, carbon sequestration and pollutants transport.

The Technical Challenges for Applying Unsaturated Soil Sensors to Conduct Laboratory-Scale Seepage Experiments.

Although many unsaturated soil experiments have successfully delivered positive outcomes, most studies just concisely illustrated sensor techniques, because their main objectives focused on bridging research gaps. Inexperienced research fellows might rarely follow up those techniques, so they could encounter very trivial and skill-demanding difficulties, undermining the quality of experimental outcomes. With a motivation to avoid those, this work introduces technical challenges in applying three sensor techniques: high precision tensiometer, spatial time-domain reflectometry (spatial TDR) and digital bench scales, which were utilized to measure three fundamental variables: soil suction, moisture content and accumulative outflow. The technical challenges are comprehensively elaborated from five aspects: the functional mechanism, assembling/manufacturing approaches, installation procedure, simultaneous data-logging configurations and post data/signal processing. The conclusions drawn in this work provide sufficient technical details of three sensors in terms of the aforementioned five aspects. This work aims to facilitate any new research fellows who carry out laboratory-scale soil column tests using the three sensors mentioned above. It is also expected that this work will salvage any experimenters having troubleshooting issues with those sensors and help researchers bypass those issues to focus more on their primary research interests.

Low-Error Soil Moisture Sensor Employing Spatial Frequency Domain Transmissometry.

A new type of soil moisture sensor using spatial frequency domain transmissometry (SFDT) was evaluated. This sensor transmits and receives ultrawideband (1 to 6 GHz) radio waves between two separated antennas and measures the propagation delay time in the soil related to the dielectric constant. This method is expected to be less affected by air gaps between the probes and the soil, as well as being less affected by soil electrical conductivity (EC), than typical commercial sensors. The relationship between output and volumetric water content (θ), and the effects of air gaps and EC were evaluated through experiments using sand samples and the prototype SFDT sensor. The output of the SFDT sensor increased linearly with θ and was not affected by even a high salt concentration for irrigation water, such that the EC of the pore water was 9.2 dS·m-1. The SFDT sensor was almost unaffected by polyethylene tapes wrapped around the sensor to simulate air gaps, whereas a commercially available capacitance sensor significantly underestimated θ. Theoretical models of the SFDT sensor were also developed for the calibration equation and the air gaps. The calculation results agreed well with the experimental results, indicating that analytical approaches are possible for the evaluation of the SFDT sensor.

Rice transcription factor GAMYB modulates bHLH142 and is homeostatically regulated by TDR during anther tapetal and pollen development.

GIBBERELLIN MYB GENE (GAMYB), UNDEVELOPED TAPETUM1 (UDT1), TDR INTERACTING PROTEIN2 (TIP2/bHLH142), TAPETUM DEGENERATION RETARDATION (TDR), and ETERNAL TAPETUM 1/DELAYED TAPETUM DEGENERATION (EAT1/DTD) are important transcription factors that play a crucial role during pollen development in rice. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a 'hub' in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of the bHLH142 promoter during the early stage of pollen development, while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. Altered expression of these transcription factors highlights that a tight, precise, and coordinated regulation among them is essential for normal pollen development. Most notably, we show that the regulatory pathways of GAMYB and UDT1 rely on bHLH142 in a direct and indirect manner, respectively, and function in different tissues with distinct biological roles during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

A SSTDR Methodology, Implementations, and Challenges.

Sequence time-domain reflectometry (STDR) and spread spectrum time-domain reflectometry (SSTDR) detect, locate, and diagnose faults in live (energized) electrical systems. In this paper, we survey the present SSTDR literature for discussions on theory, algorithms used in its analysis, and its more prominent implementations and applications. Our review includes both scientific litera-ture and selected patents. We also discuss future applications of SSTDR.

Neural cell responses to wear debris from metal-on-metal total disc replacements.

PURPOSE: Total disc replacements, comprising all-metal articulations, are compromised by wear and particle production. Metallic wear debris and ions trigger a range of biological responses including inflammation, genotoxicity, cytotoxicity, hypersensitivity and pseudotumour formation, therefore we hypothesise that, due to proximity to the spinal cord, glial cells may be adversely affected. METHODS: Clinically relevant cobalt chrome (CoCr) and stainless steel (SS) wear particles were generated using a six-station pin-on-plate wear simulator. The effects of metallic particles (0.5-50 µm3 debris per cell) and metal ions on glial cell viability, cellular activity (glial fibrillary acidic protein (GFAP) expression) and DNA integrity were investigated in 2D and 3D culture using live/dead, immunocytochemistry and a comet assay, respectively. RESULTS: CoCr wear particles and ions caused significant reductions in glial cell viability in both 2D and 3D culture systems. Stainless steel particles did not affect glial cell viability or astrocyte activation. In contrast, ions released from SS caused significant reductions in glial cell viability, an effect that was especially noticeable when astrocytes were cultured in isolation without microglia. DNA damage was observed in both cell types and with both biomaterials tested. CoCr wear particles had a dose-dependent effect on astrocyte activation, measured through expression of GFAP. CONCLUSIONS: The results from this study suggest that microglia influence the effects that metal particles have on astrocytes, that SS ions and particles play a role in the adverse effects observed and that SS is a less toxic biomaterial than CoCr alloy for use in spinal devices. These slides can be retrieved under Electronic Supplementary Material.

tsRNA signatures in cancer.

Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that ts-101 and ts-53 can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knocked-out cell model for ts-101 and ts-46 in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressed ts-46 and ts-47 in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival.

A New TDR-Based Sensing Cable for Improving Performance of Bridge Scour Monitoring.

The use of time domain reflectometry (TDR) for real-time monitoring of bridge scour process has gone through several stages of development. The recently-proposed concept of bundled TDR sensing cable, in which two sets of insulated steel strands are twisted around and connected to a central coaxial cable to form a compact sensing cable, is a major change that has several advantages including the bottom-up sensing mechanism. Nevertheless, there is big room for improving its measurement sensitivity and signal to noise ratio (SNR). Changes in waveguide configuration also need to be made to avoid the adverse effect of insulation abrasion observed in field implementation. This study evaluated three new conductor and insulator configurations for constructing the sensing waveguide, including a balanced two-conductor waveguide (Type I), an unbalanced three-conductor waveguide with insulation coating on the middle conductor (Type II) and an unbalanced three-conductor with insulation coating on the two outer conductors (Type III). In all cases, the spacing between the two sets of steel strands (i.e., the waveguide conductors) was especially enlarged by replacing some steel strands with non-conductor wires to increases measurement sensitivity and avoid shorted conditions due to insulation abrasion. Experimental results show that Type III has the best performance on all counts. A new improved TDR sensing cable was hence proposed based on Type III configuration. Its performance was further evaluated by a full-scale experiment to take into consideration the long range of measurement in most field conditions. Detailed discussions on improvements of measurement sensitivity and SNR, limitation of sensing range, and mitigating the adverse effect of insulation abrasion are presented.

Variations in Velocity and Sensitivity of Electromagnetic Waves in Transmission Lines Configured in Model Piles with Necking Defects Containing Soils.

This study investigates variations in the velocity and sensitivity of electromagnetic waves in transmission lines configured in defective model piles for the detection of necking defects containing soil. Experiments are performed with model piles containing defects filled with different materials, such as air, sands, and clay. Five different types of transmission lines are configured in model piles. The electromagnetic waves are generated and detected using a time domain reflectometer. The velocity of electromagnetic waves is highest when the defect is filled with air, and it decreases with an increase in the water content. The velocity is lowest when the defect is filled with clay. The sensitivity of transmission lines for detecting defects decreases with an increase in soil water contents. The transmission line with a single electrical wire and epoxy-coated rebar exhibits the highest sensitivity, followed by that with three and two parallel electrical wires. Transmission lines with a single electrical wire and uncoated rebar and those with two parallel electrical wires wrapped with a sheath exhibit poor sensitivity when the defect is filled with clay. This study demonstrates that electromagnetic waves can be effective tools for detecting necking defects with wet and conductive soils in bored piles.

Application of a Monopole Antenna Probe with an Optimized Flange Diameter for Tdr Soil Moisture Measurement.

Soil volumetric water content (θ) is a parameter describing one of the most important factors conditioning proper plant growth. Monitoring soil moisture is of particular importance in the rational use of water resources for irrigation, especially during periods of water scarcity. This paper presents a method of measuring soil moisture in the vicinity of the plant root system by means of a probe designed to be mounted on a mobile device used for precise plant irrigation. Due to the specific field conditions of the measurement, the design of the probe was proposed as a monopole antenna. Electromagnetic simulations of the probe were carried out with Ansys HFSS software to optimise its dimensions. Then a prototype of the probe was manufactured to conduct laboratory measurements with the use of a vector network analyser (VNA) working in the 20 kHz to 8 GHz frequency range. The VNA analyser was configured to work in the time-domain reflectometry (TDR) mode. From measurements of the time distance between reflections from the probe's elements it is possible to calculate the bulk dielectric permittivity of the soil surrounding the probe. Next, based on commonly used soil moisture dielectric calibrations one can determine θ of the soil sample. The paper presents simulation results and laboratory tests of an antenna probe. Due to its tough and durable design, this type of probe gives the possibility of easy application in field conditions, which makes it especially suitable for mechanically demanding measurement systems. As the sensitivity zone is comparatively large, this probe is well-suited to measuring soil moisture in the vicinity of the plant root system.

Review of Novel and Emerging Proximal Soil Moisture Sensors for Use in Agriculture.

The measurement of soil moisture in agriculture is currently dominated by a small number of sensors, the use of which is greatly limited by their small sampling volume, high cost, need for close soil-sensor contact, and poor performance in saline, vertic and stony soils. This review was undertaken to explore the plethora of novel and emerging soil moisture sensors, and evaluate their potential use in agriculture. The review found that improvements to existing techniques over the last two decades are limited, and largely restricted to frequency domain reflectometry approaches. However, a broad range of new, novel and emerging means of measuring soil moisture were identified including, actively heated fiber optics (AHFO), high capacity tensiometers, paired acoustic / radio / seismic transceiver approaches, microwave-based approaches, radio frequency identification (RFID), hydrogels and seismoelectric approaches. Excitement over this range of potential new technologies is however tempered by the observation that most of these technologies are at early stages of development, and that few of these techniques have been adequately evaluated in situ agricultural soils.

Consequences of restricting antimalarial drugs to rapid diagnostic test-positive febrile children in south-west Nigeria.

OBJECTIVES: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission. METHODS: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment. RESULTS: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001). CONCLUSION: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections.

CONSÉQUENCES DE LA RESTRICTION DES ANTIPALUDIQUES AUX ENFANTS FÉBRILES POSITIFS AU TEST DE DIAGNOSTIC RAPIDE DANS LE SUD-OUEST DU NIGÉRIA: OBJECTIFS: Investiguer la conséquence de restreindre le traitement antipaludéen uniquement à des enfants fébriles avec un résultat positif à un test de diagnostic rapide (TDR) du paludisme dans une zone de forte transmission du paludisme. MÉTHODES: Les enfants fébriles âgés de 3 à 59 mois ont été dépistés avec un TDR du paludisme dans des établissements de santé du sud-ouest du Nigéria. Les enfants avec un TDR positif ont reçu de l'artésunate-amodiaquine (ASAQ), tandis que ceux avec un TDR négatif ont été traités sur la base du diagnostic clinique de maladie fébrile non liée au paludisme. Le critère d'évaluation principal était le risque de développer un paludisme positif au microscope dans les 28 jours suivant le traitement. RÉSULTATS: 309 (60,5%) des 511 enfants étaient positifs au TDR du paludisme tandis que 202 (39,5%) étaient négatifs au moment de leur inscription. 18,5% (50/275) des enfants TDR-positifs et 7,6% (14/184) des enfants TDR-négatifs ont développé un paludisme positif au microscope endéans le jour 28 après le traitement (ρ = 0,001). Le risque de développer un paludisme clinique endéans le 28è jour après le traitement était plus élevé dans le groupe TDR-positif que dans le groupe TDR-négatif (OR ajusté = 2,74; IC95%: 1,4 - 5,4). Une proportion plus élevée d'enfants TDR-positifs au moment de l'inscription étaient anémiques au 28è jour par rapport au groupe TDR-négatif (12,6% contre 3,1%; ρ = 0,001). Les enfants du groupe TDR-négatif ont effectué plus de visites non planifiées en raison d'une maladie fébrile que ceux du groupe TDR-positif (23,2% contre 12,0%; ρ = 0,001). CONCLUSION: Le fait de limiter le traitement de combinaison à l'artémisinine (TCA) aux seuls enfants fébriles présentant un résultat positif au TDR n'a pas eu d'effet indésirable significatif. Cependant, le risque de réinfection dans les 28 jours était significativement plus élevé chez les enfants TDR-positifs malgré le traitement par ASAQ. Un TCA à action prolongée pourrait être nécessaire en tant que médicament de choix en première ligne pour traiter le paludisme sans complications dans les régions à forte transmission afin de prévenir les réinfections fréquentes.

Sexual and urinary function following anterior lumbar surgery in females.

AIMS: Anterior lumbar interbody fusion procedures (ALIF) and total disc replacement (TDR) with anterior exposure of the lumbar spine entail a risk of a vascular injury and dysfunction of the sympathetic and parasympathetic nerves due to disturbance of the inferior and superior hypogastric plexus. While retrograde ejaculation is a known complication of the anterior spinal approach in males, post-operative sexual as well as urinary function in females has not yet been thoroughly investigated and was hence the aim of this study. METHODS: Fifteen female patients documented their sexual and urinary function preoperatively, 3 months and 6 months postoperatively, using the validated questionnaires FSFI (Female Sexual Function Index) and ICIQ (International Consultation of Incontinence Questionnaire). Randomization tests were used to statistically analyze expectation values over time (two-sided, P < 0.05). RESULTS: While no statistically significant change in the total FSFI score occurred over time, a significant increase in FSFI desire score was noted between preoperative (2.95 ± 0.8) and 6 months follow-up (3.51 ± 0.6, P = 0.02). Urinary continence remained unchanged over time. CONCLUSION: In summary, ALIF and lumbar TDR do not seem to negatively influence sexual and urinary function in females. In contrast, increased sexual desire was noted, likely secondary to post-surgical pain relief.

Analysis of the Health Product Profile Directory - a new tool to inform priority-setting in global public health.

BACKGROUND: The Health Product Profile Directory (HPPD) is an online database describing 8-10 key characteristics (such as target population, measures of efficacy and dosage) of product profiles for medicines, vaccines, diagnostics and other products that are intended to be accessed by populations in low- and middle-income countries. The HPPD was developed by TDR on behalf of WHO and launched on 15 May 2019. METHODS: The contents of the HPPD were downloaded into an Excel™ spreadsheet via the open access interface and analysed to identify the number of health product profiles by type, disease, year of publication, status, author organization and safety information. RESULTS: The HPPD contains summaries of 215 health product profiles published between 2008 and May 2019, 117 (54%) of which provide a hyperlink to the detailed publication from which the summary was extracted, and the remaining 98 provide an email contact for further information. A total of 55 target disease or health conditions are covered, with 210 profiles describing a product with an infectious disease as the target. Only 5 product profiles in the HPPD describe a product for a non-communicable disease. Four diseases account for 40% of product profiles in the HPPD; these are tuberculosis (33 profiles, 15%), malaria (31 profiles, 14%), HIV (13 profiles, 6%) and Chagas (10 profiles, 5%). CONCLUSION: The HPPD provides a new tool to inform priority-setting in global health - it includes all product profiles authored by WHO (n = 51). There is a need to standardise nomenclature to more clearly distinguish between strategic publications (describing research and development (R&D) priorities or preferred characteristics) compared to target product profiles to guide a specific candidate product undergoing R&D. It is recommended that all profiles published in the HPPD define more clearly what affordability means in the context where the product is intended to be used and all profiles should include a statement of safety. Combining the analysis from HPPD to a mapping of funds available for R&D and those products in the R&D pipeline would create a better overview of global health priorities and how they are supported. Such analysis and increased transparency should take us a step closer to measuring and improving coordination of efforts in global health R&D.