Outcomes of antiretroviral treatment program in Ethiopia: Retention of patients in care is a major challenge and varies across health facilities

BACKGROUND: Many resource-limited countries are scaling up antiretroviral treatment (ART) towards universal access. However, there are few studies which evaluated outcomes of ART programs in these countries. In addition, these studies generally include a limited number of facilities and patients creating a clear need for studies with a wide range of facilities and large numbers of patients. In this study, we intended to evaluate the outcomes of the ART services in 55 health facilities in Ethiopia. METHODS: A retrospective longitudinal study was conducted to determine levels of patient retention in care, CD4 count and shift to second-line ART regimen in 30 hospitals and 25 health centers selected as sentinel sites for monitoring the outcomes of ART program in the country. The outcomes were determined at baseline, after 6, 12 and 24 months on ART. Data was collected from routine patient registers and charts, and entered and analyzed using EPI-Info statistical software. RESULTS: Health facilities were able to retain 29,893 (80%), 20,079 (74%) and 5,069 (68%) of their patients after 6, 12 and 24 months on ART, respectively. Retention rates vary across health facilities, ranging from 51% to 85% after 24 months on ART. Mortality was 5%, 6% and 8% after 6, 12 and 24 months on ART. More than 79% of patients with available CD4-cell counts had a baseline CD4-cell counts less than 200 cells per micro-liter of blood. The median CD4-cell counts (based on patients who were retained after 24 months on ART) increased from 125 (inter-quartile (IQ), 68-189) at baseline to 242 (IQ, 161-343), 269 (IQ, 185-380) and 316 (IQ, 226-445) cells per micro-liter after 6, 12, and 24 months on ART, respectively. The transition to second-line ART remained very low, 0.33%, 0.58% and 2.13% after 6, 12 and 24 months on ART. Discussion and conclusion: The outcomes of the ART services in the 55 health facilities in Ethiopia are similar to those in other countries. Retention of patients in care is a major challenge and varies across health facilities with high, medium and low retention rates. We therefore recommend further studies to understand the organization of care in health facilities with high, medium and low retention rates. It is also imperative that early initiation of patients on ART is taken seriously as more than 79% of the patients had baseline CD4-cell counts less than 200 cells per micro-liter of blood. Finally, we recommend that the shift to second-line ART might be too low and warrants close monitoring

Early Embryonic Vascular Patterning by Matrix-Mediated Paracrine Signalling: A Mathematical Model Study

During embryonic vasculogenesis, endothelial precursor cells of mesodermal origin known as angioblasts assemble into a characteristic network pattern. Although a considerable amount of markers and signals involved in this process have been identified, the mechanisms underlying the coalescence of angioblasts into this reticular pattern remain unclear. Various recent studies hypothesize that autocrine regulation of the chemoattractant vascular endothelial growth factor (VEGF) is responsible for the formation of vascular networks in vitro. However, the autocrine regulation hypothesis does not fit well with reported data on in vivo early vascular development. In this study, we propose a mathematical model based on the alternative assumption that endodermal VEGF signalling activity, having a paracrine effect on adjacent angioblasts, is mediated by its binding to the extracellular matrix (ECM). Detailed morphometric analysis of simulated networks and images obtained from in vivo quail embryos reveals the model mimics the vascular patterns with high accuracy. These results show that paracrine signalling can result in the formation of fine-grained cellular networks when mediated by angioblast-produced ECM. This lends additional support to the theory that patterning during early vascular development in the vertebrate embryo is regulated by paracrine signalling

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Self-organizing continuous attractor network models of hippocampal spatial view cells.

Single neuron recording studies have demonstrated the existence of hippocampal spatial view neurons which encode information about the spatial location at which a primate is looking in the environment. These neurons are able to maintain their firing even in the absence of visual input. The standard neuronal network approach to model networks with memory that represent continuous spaces is that of continuous attractor networks. It has recently been shown how idiothetic (self-motion) inputs could update the activity packet of neuronal firing for a one-dimensional case (head direction cells), and for a two-dimensional case (place cells which represent the place where a rat is located). In this paper, we describe three models of primate hippocampal spatial view cells, which not only maintain their spatial firing in the absence of visual input, but can also be updated in the dark by idiothetic input. The three models presented in this paper represent different ways in which a continuous attractor network could integrate a number of different kinds of velocity signal (e.g., head rotation and eye movement) simultaneously. The first two models use velocity information from head angular velocity and from eye velocity cells, and make use of a continuous attractor network to integrate this information. A fundamental feature of the first two models is their use of a 'memory trace' learning rule which incorporates a form of temporal average of recent cell activity. Rules of this type are able to build associations between different patterns of neural activities that tend to occur in temporal proximity, and are incorporated in the model to enable the recent change in the continuous attractor to be associated with the contemporaneous idiothetic input. The third model uses positional information from head direction cells and eye position cells to update the representation of where the agent is looking in the dark. In this case the integration of idiothetic velocity signals is performed in the earlier layer of head direction cells

Self-organizing continuous attractor networks and motor function.

Motor skill learning may involve training a neural system to automatically perform sequences of movements, with the training signals provided by a different system, used mainly during training to perform the movements, that operates under visual sensory guidance. We use a dynamical systems perspective to show how complex motor sequences could be learned by the automatic system. The network uses a continuous attractor network architecture to perform path integration on an efference copy of the motor signal to keep track of the current state, and selection of which motor cells to activate by a movement selector input where the selection depends on the current state being represented in the continuous attractor network. After training, the correct motor sequence may be selected automatically by a single movement selection signal. A feature of the model presented is the use of 'trace' learning rules which incorporate a form of temporal average of recent cell activity. This form of temporal learning underlies the ability of the networks to learn temporal sequences of behaviour. We show that the continuous attractor network models developed here are able to demonstrate the key features of motor function. That is, (i) the movement can occur at arbitrary speeds; (ii) the movement can occur with arbitrary force; (iii) the agent spends the same relative proportions of its time in each part of the motor sequence; (iv) the agent applies the same relative force in each part of the motor sequence; and (v) the actions always occur in the same sequence

Self-organizing continuous attractor networks and path integration: two-dimensional models of place cells.

Single-neuron recording studies have demonstrated the existence of neurons in the hippocampus which appear to encode information about the place where a rat is located, and about the place at which a macaque is looking. We describe 'continuous attractor' neural network models of place cells with Gaussian spatial fields in which the recurrent collateral synaptic connections between the neurons reflect the distance between two places. The networks maintain a localized packet of neuronal activity that represents the place where the animal is located. We show for two related models how the representation of the two-dimensional space in the continuous attractor network of place cells could self-organize by modifying the synaptic connections between the neurons, and also how the place being represented can be updated by idiothetic (self-motion) signals in a neural implementation of path integration

Alignment between nationally determined contributions and the sustainable development goals for West Africa

The UN Sustainable Development Goals (SDGs) and the 2015 Paris Agreement are two of the most important policy frameworks of the twenty-first century. However, the alignment of national commitments linked to them has not yet been analysed for West African states. Such analyses are vital to avoid perverse outcomes if states assess targets and develop SDG implementation plans, and Nationally Determined Contributions (NDC) under the Paris Agreement, without integrated planning and cross-sectoral alignment. This article provides a situation analysis guided by the following questions: (a) Which priority sectors are mentioned in relation to adaptation and mitigation in West African NDCs? (b) Are the NDCs of West African states well aligned with the SDGs? (c) What are the co-benefits of NDCs in contributing towards the SDGs? and (d) How are West African states planning to finance actions in their NDCs? The study uses iterative content analysis to explore key themes for adaptation and mitigation within NDCs of 11 West African states and their alignment to selected SDGs. A national multi-stakeholder workshop was held in Ghana to examine the co-benefits of the NDCs in contributing towards the SDGs and their implementation challenges. Results show that agriculture and energy are priority sectors where NDCs have pledged significant commitments. The analysis displays good alignment between mitigation and adaptation actions proposed in NDCs and the SDGs. These represent opportunities that can be harnessed through integration into national sectoral policies. However, cross-sectoral discussions in Ghana identify significant challenges relating to institutional capacity, a lack of coordination among institutions and agencies, and insufficient resources in moving towards integrated implementation of national planning priorities to address successfully both NDC priorities and the SDGs. Key policy insights • Positive alignments between West African NDCs and SDGs present opportunities for mutual benefits that can advance national development via a more climate resilient pathway. • NDCs of West African states can provide mutual benefits across the water–energy–food nexus, such as through climate-smart agriculture and low carbon energy technologies. • Ghanaian multi-sectoral insights show the need to empower national coordinating bodies to overcome misalignments across different sectors

Self-organizing continuous attractor networks and path integration: one-dimensional models of head direction cells.

Some neurons encode information about the orientation or position of an animal, and can maintain their response properties in the absence of visual input. Examples include head direction cells in rats and primates, place cells in rats and spatial view cells in primates. 'Continuous attractor' neural networks model these continuous physical spaces by using recurrent collateral connections between the neurons which reflect the distance between the neurons in the state space (e.g. head direction space) of the animal. These networks maintain a localized packet of neuronal activity representing the current state of the animal. We show how the synaptic connections in a one-dimensional continuous attractor network (of for example head direction cells) could be self-organized by associative learning. We also show how the activity packet could be moved from one location to another by idiothetic (self-motion) inputs, for example vestibular or proprioceptive, and how the synaptic connections could self-organize to implement this. The models described use 'trace' associative synaptic learning rules that utilize a form of temporal average of recent cell activity to associate the firing of rotation cells with the recent change in the representation of the head direction in the continuous attractor. We also show how a nonlinear neuronal activation function that could be implemented by NMDA receptors could contribute to the stability of the activity packet that represents the current state of the animal