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n L conformation suggest that the structural picture of L during infection might be more complex than previously appreciated.Adeno-associated viruses (AAV) have attracted significant attention in the field of gene and cell therapy due to highly effective delivery of therapeutic genes into human cells. The ability to generate recombinant AAV vectors compromised of unique or substituted protein sequences has led to the development of capsid variants with improved therapeutic properties. Seeking novel AAV vectors capable of enhanced transduction for therapeutic applications, we have developed a series of unique capsid variants termed AAV X-Vivo (AAV-XV) derived from chimeras of AAV12 VP1/2 sequences and the VP3 sequence of AAV6. These AAV variants showed enhanced infection of human primary T cells, hematopoietic stem cells, and neuronal cell lines over wildtype parental viruses, and superiority over AAV6 for genomic integration of DNA sequences by AAV alone or in combination with CRISPR gene editing. AAV-XV variants demonstrate transduction efficiency equivalent to AAV6 at multiplicities of infection 2 logs lower, enabling T cell engihigh, which has resulted in unfortunate recent safety concerns and deaths in patients given higher-dose AAV gene therapy. We have generated new AAV variants possessing unique combinations of capsid proteins for gene and cell therapy applications termed AAV-XV, which have high levels of cell transduction and gene delivery at lower MOI. Furthermore, we demonstrate a novel finding, and an important consideration for recombinant AAV design, that a region of the AAV genome encoding the capsid viral protein and AAP is critical for both virus yield and the enhancement of infection/transduction.

Ghana's shift from low-income to middle-income status will make it ineligible to receive concessional aid in the future. While transition may be a reflection of positive changes in a country, such as economic development or health progress, a loss of support from donor agencies could have negative impacts on health system performance and population health. We aimed to identify key challenges and opportunities that Ghana will face in dealing with aid transition, specifically from the point of view of country-level stakeholders.

We conducted key informant interviews with 18 stakeholders from the government, civil society organisations and donor agencies in Ghana using a semistructured interview guide. We performed directed content analysis of the interview transcripts to identify key themes related to anticipated challenges and opportunities that might result from donor transitions.

Overall, stakeholders identified challenges more frequently than opportunities. All stakeholders interviewed believe that Ghtment to health. The loss of aid could be turned into an opportunity to integrate vertical programmes into a more comprehensive health system.

Stakeholders in Ghana believe transitioning away from aid for health presents both challenges and opportunities. The challenges could be addressed by conducting a transition readiness assessment, identifying health sector priorities, developing a transition plan with a budget to continue critical health programmes and mobilising greater political commitment to health. The loss of aid could be turned into an opportunity to integrate vertical programmes into a more comprehensive health system.

Indigenous communities worldwide are leading calls for all research involving Indigenous people to be underpinned by values and principles articulated by them. Many researchers are explicitly adopting these principles to guide what, where, how and when research is undertaken with Indigenous people. With critical reflection to support the implementation of such principles largely absent from published literature, this paper explores both the implementation of, and the outcomes from a set of guiding principles used in a large-scale Australian research collaboration to improve Indigenous health.

In this inductive qualitative study, we adopted a principles-focused evaluation approach. Based on interviews with 35 actors in the collaboration and a review of project documents, we generated themes that were then iteratively discussed, refined and categorised into (1) 'strategies'-activities by which implementation of our guiding principles were recognised; (2) 'outcomes'-results seen from implementing the principion platform' approach.

Our findings show that principles guiding collaborations are valuable in providing a focus, direction and a way of working together when they are collaboratively developed, hold genuine meaning for all members and are implemented within a culture of continuous critical reflection, learning and adaptation, with ongoing reinterpretation of the principles over time.

Our findings show that principles guiding collaborations are valuable in providing a focus, direction and a way of working together when they are collaboratively developed, hold genuine meaning for all members and are implemented within a culture of continuous critical reflection, learning and adaptation, with ongoing reinterpretation of the principles over time.

To determine if subpopulations of students benefit equally from school-based physical activity interventions in terms of cardiorespiratory fitness and physical activity. To examine if physical activity intensity mediates improvements in cardiorespiratory fitness.

Pooled analysis of individual participant data from controlled trials that assessed the impact of school-based physical activity interventions on cardiorespiratory fitness and device-measured physical activity.

Data for 6621 children and adolescents aged 4-18 years from 20 trials were included.

Peak oxygen consumption (VO

mL/kg/min) and minutes of moderate and vigorous physical activity.

Interventions modestly improved students' cardiorespiratory fitness by 0.47 mL/kg/min (95% CI 0.33 to 0.61), but the effects were not distributed equally across subpopulations. Girls and older students benefited less than boys and younger students, respectively. Students with lower levels of initial fitness, and those with higher levels of baseline physicvity. Interventions could mitigate declining youth cardiorespiratory fitness, increase physical activity and promote cardiovascular health if they can be delivered equitably and their effects sustained at the population level.Cell division, differentiation and function are largely dependent on accurate proteome composition and regulated gene expression. To control this, protein synthesis is an intricate process governed by upstream signalling pathways. Eukaryotic translation is a multistep process and can be separated into four distinct phases initiation, elongation, termination and recycling of ribosomal subunits. Translation initiation, the focus of this article, is highly regulated to control the activity and/or function of eukaryotic initiation factors (eIFs) and permit recruitment of mRNAs to the ribosomes. In this Cell Science at a Glance and accompanying poster, we outline the mechanisms by which tumour cells alter the process of translation initiation and discuss how this benefits tumour formation, proliferation and metastasis.

The first step in bundle design or implementation is to identify the problem being addressed. Several validated approaches are recommended to facilitate this. These include using systematic reviews, adverse event triggers and risk assessment tools. However, these methods do not fully take the local context into account, which will limit the effectiveness of the bundle.

This study explores the potential benefit of using a comprehensive audit to identify an organisation's local context prior to designing and implementing a care bundle.

A comprehensive audit comprising observations of four patient journeys, interviews with 21 staff and clinical data was carried out at one large National Health Service trust in England. A patient warming care bundle was used as the exemplar.

Each of the three data collection methods identified specific local practices which would be addressed within the planning and implementation stages of a care bundle. These practices would not have been identified through other recommended methods.

A comprehensive audit, comprising observations, interviews and clinical data is a successful method to identify local contextual issues prior to care bundle implementation.

A comprehensive audit, comprising observations, interviews and clinical data is a successful method to identify local contextual issues prior to care bundle implementation.

The primary objective is to quantify the lens nuclear opacity using swept-source anterior segment optical coherence tomography (SS-ASOCT) and to evaluate its correlations with Lens Opacities Classification System III (LOCS-III) system and surgical parameters. The secondary objective is to assess the diagnostic performance for hard nuclear cataract.

This cross-sectional study included 1222 patients eligible for cataract surgery (1222 eyes). The latest SS-ASOCT (CASIA-2) was used to obtain high-resolution lens images, and the average nuclear density (AND) and maximum nuclear density (MND) were measured by a custom ImageJ software. Spearman's correlations analysis was used to assess associations of AND/MND with LOCS-III nuclear scores, visual acuity and surgical parameters. The subjects were then split randomly (91) into the training dataset and validating dataset. Receiver operating characteristic curves and calibration curves were constructed for the classification on hard nuclear cataract.

The AND and MND from SS-ASOCT images were significantly correlated with nuclear colour scores (AND r=0.716; MND r=0.660; p<0.001) and nuclear opalescence scores (AND r=0.712; MND r=0.655; p<0.001). The AND by SS-ASOCT images had the highest values of Spearman's r for preoperative corrected distance visual acuity (r=0.3131), total ultrasonic time (r=0.3481) and cumulative dissipated energy (r=0.4265). The nuclear density had good performance in classifying hard nuclear cataract, with area under the curves of 0.859 (0.831-0.886) for AND and 0.796 (0.768-0.823) for MND.

Objective and quantitative evaluation of the lens nuclear density using SS-ASOCT images enable accurate diagnosis of hard nuclear cataract.

Objective and quantitative evaluation of the lens nuclear density using SS-ASOCT images enable accurate diagnosis of hard nuclear cataract.

We previously reported that the visual field (VF) prediction model using the variational Bayes linear regression (VBLR) is useful for accurately predicting VF progression in glaucoma (Invest Ophthalmol Vis Sci. 2014, 2018). We constructed a VF measurement algorithm using VBLR, and the purpose of this study was to investigate its usefulness.

122 eyes of 73 patients with open-angle glaucoma were included in the current study. VF measurement was performed using the currently proposed VBLR programme with AP-7700 perimetry (KOWA). Tebipenem Pivoxil chemical VF measurements were also conducted using the Swedish interactive thresholding algorithm (SITA) standard programme with Humphrey field analyser. VF measurements were performed using the 24-2 test grid. Visual sensitivities, test-retest reproducibility and measurement duration were compared between the two algorithms.

Mean mean deviation (MD) values with SITA standard were -7.9 and -8.7 dB (first and second measurements), whereas those with VBLR-VF were -8.2 and -8.0 dB, respectively.