Leadership for health improvement: implementation and evaluation

Purpose The purpose of this paper is to present a co-authored reflection on the health improvement leadership development programme and the key evaluation messages derived from piloting in an English National Health Service region. It highlights the specific attributes of this approach to health improvement leadership development and clarifies health improvement development issues. Design/methodology/approach Appreciative inquiry and soft systems methodology are combined in an evaluation approach designed to capture individual as well as organisation learning and how it impacts on leadership in specific contexts. Findings The evaluation exposes the health improvement leadership needs of a multi-organisation cohort, offers some explanations for successful achievement of learning needs while also exposing of the challenges and paradoxes faced in this endeavour. Originality/value There are limited reported templates of how to develop leadership for health improvement. This paper details a whole systems approach, acknowledging the impact of context on leadership and an approach to evaluating such complex initiatives

Mineral Acquisition from Clay by Budongo Forest Chimpanzees

Chimpanzees of the Sonso community, Budongo Forest, Uganda were observed eating clay and drinking clay-water from waterholes. We show that clay, clay-rich water, and clay obtained with leaf sponges, provide a range of minerals in different concentrations. The presence of aluminium in the clay consumed indicates that it takes the form of kaolinite. We discuss the contribution of clay geophagy to the mineral intake of the Sonso chimpanzees and show that clay eaten using leaf sponges is particularly rich in minerals. We show that termite mound soil, also regularly consumed, is rich in minerals. We discuss the frequency of clay and termite soil geophagy in the context of the disappearance from Budongo Forest of a formerly rich source of minerals, the decaying pith of Raphia farinifera palms

Single-chain Fv phage display propensity exhibits strong positive correlation with overall expression levels

<p>Abstract</p> <p>Background</p> <p>Single chain Fvs (scFvs) are widely applied in research, diagnostics and therapeutic settings. Display and selection from combinatorial libraries is the main route to their discovery and many factors influence the success of this process. They exhibit low thermodynamic stability, resulting in low levels of premature cytosolic folding or aggregation which facilitates <it>sec </it>YEG-mediated translocation and phage in <it>E. coli</it>. However, there is little data analysing how this is related to and influenced by scFv protein expression.</p> <p>Results</p> <p>We characterised the relationship between overall scFv expression and display propensity for a panel of 15 anti-tetanus toxin scFvs and found a strong positive correlation (Rho = 0.88, p < 0.005) between the two parameters. Display propensity, overall expression and soluble localisation to the periplasm and extracellular fractions were clone specific characteristics which varied despite high levels of sequence homology. There was no correlation between display of scFv or its expression in non-fused (free) form with soluble scFv localisation to the periplasm or culture supernatant. This suggests that divergence in the fate of scFv-pIII and non-fused scFv after translocation to the periplasm accounts for the observed disparity. Differential degrees of periplasmic aggregation of non-fused scFv between clones may affect the partitioning of scFv in the periplasm and culture supernatant abrogating any correlation. We suggest that these factors do not apply to the scFv-pIII fusion since it remains anchored to the bacterial inner membrane as part of the innate phage packaging and budding process.</p> <p>Conclusion</p> <p>We conclude that in the absence of premature cytosolic aggregation or folding, the propensity of a scFv to be displayed on phage is directly related to its overall expression level and is thus indirectly influenced by factors such as codon bias, mRNA abundance or putative DNA motifs affecting expression. This suggests that scFvs capable of high overall expression and display levels may not produce high yields of non phage-fused soluble protein in either the periplasmic or extracellular fractions of <it>E. coli</it>. This should be considered when screening clones selected from combinatorial libraries for further study.</p> <p>The nucleotide and amino acid sequences of the anti-tetanus toxin scFvs have been deposited in the EMBL data base: accession numbers-C1: <ext-link ext-link-type="embl" ext-link-id="AM749134">AM749134</ext-link>, C2: <ext-link ext-link-type="embl" ext-link-id="AM749135">AM749135</ext-link>, C3: <ext-link ext-link-type="embl" ext-link-id="AM749136">AM749136</ext-link>, C4: <ext-link ext-link-type="embl" ext-link-id="AM749137">AM749137</ext-link>, C5: <ext-link ext-link-type="embl" ext-link-id="AM749138">AM749138</ext-link>, N1: <ext-link ext-link-type="embl" ext-link-id="AM749139">AM749139</ext-link>, N2: <ext-link ext-link-type="embl" ext-link-id="AM749140">AM749140</ext-link>, N3: <ext-link ext-link-type="embl" ext-link-id="AM749141">AM749141</ext-link>, N4: <ext-link ext-link-type="embl" ext-link-id="AM749142">AM749142</ext-link>, N5: <ext-link ext-link-type="embl" ext-link-id="AM749143">AM749143</ext-link> J1; <ext-link ext-link-type="embl" ext-link-id="AM749144">AM749144</ext-link>, J2: <ext-link ext-link-type="embl" ext-link-id="AM749145">AM749145</ext-link>, J3: <ext-link ext-link-type="embl" ext-link-id="AM749146">AM749146</ext-link>, J4: <ext-link ext-link-type="embl" ext-link-id="AM749147">AM749147</ext-link>, J5: <ext-link ext-link-type="embl" ext-link-id="AM749148">AM749148</ext-link>.</p

Organizational network strengthening effects on antiretroviral therapy initiation and adherence

The WHO recommends antiretroviral therapy (ART) initiation immediately after HIV diagnosis. When HIV services are fragmented and poorly coordinated, initiation of ART can be delayed. MEASURE Evaluation conducted an organizational network intervention in Addis Ababa, Ethiopia, which increased referral network density and client satisfaction in the intervention versus control networks. The objective of our study was to extend the parent study by assessing effects of network density on the speed of ART initiation and adherence to ART. Measures of client-time since HIV diagnosis, use of ART, satisfaction with HIV-related services, and adherence were obtained from cross-sectional interviews with female service recipients with HIV/AIDS at baseline (T1, 402) and at 18-month follow-up (T2, 524) and compared between network sites. We used weighted least squares estimation with probit regression techniques in a structural equation modeling framework for analyses. On average at follow-up, clients in the intervention network were more likely to have quicker ART initiation, and were initiated on ART 15 days faster than clients in the control network. Moreover, quicker ART initiation was associated with higher adherence. A unit increase in speed of ART initiation was associated with 0.5 points increase in latent adherence score in the intervention group (ρ < .05). Satisfaction with care positively predicted adherence to ART. Network density had no direct effect on ART adherence. This quasi-experiment demonstrated that increased referral network density, through improved HIV client referrals, can enhance speed of ART initiation, resulting in improved adherence. © Society of Behavioral Medicine 2018

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Reduced relative volume in motor and attention regions in developmental coordination disorder: a voxel-based morphometry study.

Background and Objectives: Developmental coordination disorder (DCD) is a prevalent childhood movement disorder, impacting the ability to perform movement skills at an age appropriate level. Although differences in grey matter (GM) volumes have been found in related developmental disorders, no such evidence has been linked with DCD to date. This cross-sectional study assessed structural brain differences in children with and without DCD. Methods: High-resolution structural images were acquired from 44 children aged 7.8–12 years, including 22 children with DCD (≤16th percentile on MABC-2; no ADHD/ASD), and 22 typically developing controls (≥20th percentile on MABC-2). Structural voxel-based morphology analysis was performed to determine group differences in focal GM volumes. Results: Children with DCD were found to have significant, large, right lateralised reductions in grey matter volume in the medial and middle frontal, and superior frontal gyri compared to controls. The addition of motor proficiency as a covariate explained the between-group GM volume differences, suggesting that GM volumes in motor regions are reflective of the level of motor proficiency. A positive correlation between motor proficiency and relative GM volume was also identified in the left posterior cingulate and precuneus. Conclusions: GM volume reductions in premotor frontal regions may underlie the motor difficulties characteristic of DCD. It is possible that intervention approaches targeting motor planning, attention, and executive functioning processes associated with the regions of reduced GM volume may result in functional improvements in children with DCD

Selective deforestation and exposure of African wildlife to bat-borne viruses

Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017–2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how “upstream” drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk.Peer reviewe

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI

Mimicking subsecond neurotransmitter dynamics with femtosecond laser stimulated nanosystems

Existing nanoscale chemical delivery systems target diseased cells over long, sustained periods of time, typically through one-time, destructive triggering. Future directions lie in the development of fast and robust techniques capable of reproducing the pulsatile chemical activity of living organisms, thereby allowing us to mimic biofunctionality. Here, we demonstrate that by applying programmed femtosecond laser pulses to robust, nanoscale liposome structures containing dopamine, we achieve sub-second, controlled release of dopamine – a key neurotransmitter of the central nervous system – thereby replicating its release profile in the brain. The fast delivery system provides a powerful new interface with neural circuits and to the larger range of biological functions that operate on this short timescale