The psychosis-inducing effect of ketamine is important evidence supporting the glutamate hypothesis of schizophrenia. However, the symptoms the drug produces have not been described systematically.
...To examine the effects of ketamine in healthy people using a structured psychiatric interview.
Ketamine (200 ng/ml) or placebo was administered by continuous infusion to 15 healthy volunteers. Symptoms were rated using the Present State Examination, the Thought, Language and Communication Scale and the Scale for Assessment of Negative Symptoms.
Ketamine induced a range of perceptual distortions, but not hallucinations. Referential ideas were seen in nearly half the sample. There were only mild and infrequent ratings on the thought disorder scale. Affective flattening and alogia were seen in some volunteers.
Ketamine does not reproduce the full picture of schizophrenia. The main point of similarity concerns referential thinking. Phenomena resembling negative symptoms are also seen, but the distinction of these from the drug's sedative effects requires further elucidation.
Background. The proportion of HIV-exposed infants and young children infected with HIV in South Africa (SA) has declined markedly over the past decade as a result of the country’s comprehensive ...prevention of mother-to-child transmission programme. This decrease has in turn reduced the positive predictive value (PPV) of diagnostic assays, necessitating review of early infant diagnosis (EID) algorithms to ensure improved accuracy.Objectives. To evaluate the performance of the GeneXpert HIV-1 qualitative assay (Xpert EID) as a consecutive test for infants with an ‘HIV-detected’ polymerase chain reaction screening test at birth.Methods. We retrospectively analysed a longitudinal cohort of HIV-exposed infants on whom birth testing was performed, using whole-blood ethylenediaminetetra-acetic acid samples, from four tertiary sites in Gauteng Province between June 2014 and December 2019. Birth samples from all infants with a Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test v2.0 (CAP/CTM v2.0) HIV-detected screening test, a concurrent Xpert EID test and a subsequent confirmatory CAP/CTM v2.0 test on a separate specimen were included. Performance of the Xpert EID in predicting final HIV status was determined as proportions with 95% confidence intervals (CIs). A comparison of indeterminate CAP/CTM v2.0 results, as per National Health Laboratory Service resulting practice, with discordant CAP/CTM v2.0 v. Xpert EID results was performed.Results. Of 150 infants who met the inclusion criteria, 6 (3.9%) had an Xpert EID result discordant with final HIV status: 5 (3.3%) were false negatives and 1 (0.7%) was false positive. As a consecutive test, the Xpert EID yielded a sensitivity of 96.5% (95% CI 92 - 98.9), specificity of 85.7% (95% CI 42.1 - 99.6), PPV of 99.3% (95% CI 95.7 - 99.9), negative predictive value of 54.5% (95% CI 32.5 - 74.9) and overall accuracy of 96.1% (95% CI 91.5 - 98.5). Using discordant CAP/CTM v2.0/Xpert EID results as criteria to verify indeterminate results instead of current practice would have reduced the number of indeterminate screening results by 42.1%, from 18 (12.6%) to 11 (7.2%), without increasing the false-positive rate.Conclusions. Addition of the Xpert EID as a consecutive test for specimens with an HIV-detected PCR screening result has the potential to improve the PPV and reduce the indeterminate rate, thereby reducing diagnostic challenges and time to final status, in SA’s EID programme.
Background: Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities. Methods: We studied simple ...discrimination (SD) learning and reversal learning in a sample of 119 first-episode psychosis patients from the Cambridge early psychosis service (CAMEO) and 107 control participants. We used data on reinforcement learning and reversal learning extracted from the Cambridge Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift task, which measures cognitive flexibility but also involves simple reinforcement learning (SD learning) and reversal learning stages. We also gathered diagnostic information to examine whether there were any differences between patients ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed with affective psychosis. Results: Psychosis patients demonstrated deficits in simple reinforcement learning (SD learning) and in reversal learning, with no differences between affective psychosis and schizophrenia-spectrum psychosis. There was a significant modest correlation between reversal errors and negative symptoms (Spearman ρ = 0.3, P = .02). Conclusions: There are reinforcement learning abnormalities in first-episode psychosis, which correlate with negative symptoms, suggesting a possible role for orbitofrontal cortex and ventral striatal pathology in the pathogenesis of motivational deficits in psychosis.
IntroductionFamilies living in extreme poverty require interventions to support early-childhood development (ECD) due to broad risks. This longitudinal cluster randomised trial examines the ...effectiveness of Sugira Muryango (SM), a home-visiting intervention linked to Rwanda’s social protection system to promote ECD and reduce violence compared with usual care (UC).MethodsFamilies with children aged 6–36 months were recruited in 284 geographical clusters across three districts. Cluster-level randomisation (allocated 1:1 SM:UC) was used to prevent diffusion. SM was hypothesised to improve child development, reduce violence and increase father engagement. Developmental outcomes were assessed using the Ages and Stages Questionnaire (ASQ-3) and the Malawi Development Assessment Tool (MDAT) and anthropometric assessments of growth. Violence was assessed using questions from UNICEF Multiple Indicators Cluster Survey (MICS) and Rwanda Demographic and Health Surveys (DHS). Father engagement was assessed using the Home Observation for Measurement of the Environment. Blinded enumerators conducted interviews and developmental assessments.ResultsA total of 541 SM families and 508 UC families were enrolled and included in the analyses. Study attrition (2.0% children; 9.6% caregivers) was addressed by hot deck imputation. Children in SM families improved more on gross motor (d=0.162, 95% CI 0.065 to 0.260), communication (d=0.081, 95% CI 0.005 to 0.156), problem solving (d=0.101, 95% CI 0.002 to 0.179) and personal-social development (d=0.096, 95% CI −0.015 to 0.177) on the ASQ-3. SM families showed increased father engagement (OR=1.592, 95% CI 1.069 to 2.368), decreased harsh discipline (incidence rate ratio, IRR=0.741, 95% CI 0.657 to 0.835) and intimate partner violence (IRR=0.616, 95% CI:0.458 to 0.828). There were no intervention-related improvements on MDAT or child growth.ConclusionSocial protection programmes provide a means to deliver ECD intervention.Trial registration numberNCT02510313.
Autotaxin catalyzes the formation of lysophosphatidic acid, which stimulates tumor growth and metastasis and decreases the effectiveness of cancer therapies. In breast cancer, autotaxin is secreted ...mainly by breast adipocytes, especially when stimulated by inflammatory cytokines produced by tumors. In this work, we studied the effects of an ATX inhibitor, GLPG1690, which is in phase III clinical trials for idiopathic pulmonary fibrosis, on responses to radiotherapy and chemotherapy in a syngeneic orthotopic mouse model of breast cancer. Tumors were treated with fractionated external beam irradiation, which was optimized to decrease tumor weight by approximately 80%. Mice were also dosed twice daily with GLPG1690 or vehicle beginning at 1 day before the radiation until 4 days after radiation was completed. GLPG1690 combined with irradiation did not decrease tumor growth further compared with radiation alone. However, GLPG1690 decreased the uptake of 3'-deoxy-3'-
F-fluorothymidine by tumors and the percentage of Ki67-positive cells. This was also associated with increased cleaved caspase-3 and decreased Bcl-2 levels in these tumors. GLPG1690 decreased irradiation-induced C-C motif chemokine ligand-11 in tumors and levels of IL9, IL12p40, macrophage colony-stimulating factor, and IFNγ in adipose tissue adjacent to the tumor. In other experiments, mice were treated with doxorubicin every 2 days after the tumors developed. GLPG1690 acted synergistically with doxorubicin to decrease tumor growth and the percentage of Ki67-positive cells. GLPG1690 also increased 4-hydroxynonenal-protein adducts in these tumors. These results indicate that inhibiting ATX provides a promising adjuvant to improve the outcomes of radiotherapy and chemotherapy for breast cancer.
We report the discovery by the TESS mission of a super-Earth on a 4.8-days orbit around an inactive M4.5 dwarf (TOI-1680), validated by ground-based facilities. The host star is located 37.14 pc ...away, with a radius of 0.2100 ± 0.0064
R
⊙
, mass of 0.1800 ± 0.0044
M
⊙
, and an effective temperature of 3211 ±100 K. We validated and characterized the planet using TESS data, ground-based multi-wavelength photometry from TRAPPIST, SPECULOOS, and LCO, as well as high-resolution AO observations from Keck/NIRC2 and
Shane.
Our analyses have determined the following parameters for the planet: a radius of 1.466
−0.049
+0.063
R
⊕
and an equilibrium temperature of 404 ± 14 K, assuming no albedo and perfect heat redistribution. Assuming a mass based on mass-radius relations, this planet is a promising target for atmospheric characterization with the
James Webb
Space Telescope (JWST).
In the majority of salmon farming countries, production occurs in zones where practices are coordinated to manage disease agents such as Lepeophtheirus salmonis. To inform the structure of zones in ...specific systems, models have been developed accounting for parasite biology and system hydrodynamics. These models provide individual system farm relationships, and as such, it may be beneficial to produce more generalized principles for informing structures. Here, we use six different forcing scenarios to provide simulations from a previously described model of the Loch Linnhe system, Scotland, to assess the maximum dispersal distance of lice particles released from 12 sites transported over 19 day. Results indicate that the median distance travelled is 6.1 km from release site with <2.5% transported beyond 15 km, which occurs from particles originating from half of the release sites, with an absolute simulated distance of 36 km observed. This provides information suggesting that the disease management areas developed for infectious salmon anaemia control may also have properties appropriate for salmon lice management in Scottish coastal waters. Additionally, general numerical descriptors of the simulated relative lice abundance reduction with increased distance from release location are proposed.
Early childhood development (ECD) programmes are heralded as a way to improve children’s health and educational outcomes. However, few studies in developing countries calculate the effectiveness of ...quality early childhood interventions. This study estimates the cost and cost-effectiveness of the Sugira Muryango (SM) trial, a home-visiting intervention to improve ECD outcomes through positive parent-child relationships. Cost-effectiveness analysis of ECD interventions is challenging given their potential to have multiple benefits. We propose a cost-effectiveness method using a single outcome, in this case the improvement in cognitive development per home-visit session, as an indication of efficiency comparable across similar interventions. The trial intervention cost US$456 per family. This cost will likely fall below US$200 if the intervention is scaled through government systems. The cost-effectiveness analysis suggests that while SM generated a relatively small impact on markers of early development, it did so efficiently. The observed improvements in cognitive development per home-visit are similar to other home-visiting interventions of longer duration. SM by focusing on the family had benefits beyond ECD, including reductions in violence against children and intermate partner violence, further analysis is needed to include these returns in the economic evaluation.
Low‐power localisation systems are crucial for machine‐to‐machine communication technologies. This article investigates LoRa technology for localisation using multiple features of the received ...signal, such as Received Signal Strength Indicator (RSSI), Spreading Factors (SF), and Signal to Noise Ratio (SNR). A novel range‐based technique to estimate the distance of a target node from a LoRa gateway using machine‐learning models that incorporates SF, SNR, and RSSI to train the models is proposed. A modified trilateration approach is then used to localise the target node from three gateways. Our experiment used three LoRaWAN gateways and two sensor nodes, on a sports oval with an approximate area coverage of 30,000 square metres. The authors also used a public LoRaWAN dataset to build a model test the proposed method and compare both range‐based distance mapping with trilateration and fingerprint‐based direct location estimation techniques. Our method achieved an average distance error of 43.97 m on our experimental dataset. The results show that the combination of RSSI, SNR, and SF‐based distance mapping provides ∼10% improvement on ranging accuracy and 26.58% higher accuracy for trilateration‐based localisation when compared with just using RSSI. Our method also achieved 50% superior localisation accuracy with fingerprint‐based direct location estimation approaches.
Collection of a Global Positioning System‐independent low‐cost LoRa‐based localisation dataset. Machine learning‐based estimation of distance from multiple received signal features. Thorough performance analysis of LoRa localisation approaches.
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