One health: a concept led by Africa, with global benefits

Titus Mlengeya Kamani and others argue that Africa is well positioned and equipped to conduct and benefit from an integrated approac

Stresses in cement mantles of hip replacements: effect of femoral implant sizes, body mass index and bone quality

The effects of femoral prosthetic heads of diameters 22 and 28 mm were investigated on the stability of reconstructed hemi-pelves with cement mantles of thicknesses 1-4 mm and different bone qualities. Materialise medical imaging package and I-Deas finite element (FE) software were used to create accurate geometry of a hemi-pelvis from CT-scan images. Our FE results show an increase in cement mantle stresses associated with the larger femoral head. When a 22 mm femoral head is used on acetabulae of diameters 56 mm and above, the probability of survivorship can be increased by creating a cement mantle of at least 1 mm thick. However, when a 28 mm femoral head is used, a cement mantle thickness of at least 4 mm is needed. Poor bone quality resulted in an average 45% increase in the tensile stresses of the cement mantles, indicating resulting poor survivorship rate

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-γ

Drug Delivery Technolog

Hematopoietic Stem Cell Transplantation for Primary Immunodeficiencies

The field of primary immunodeficiencies has pioneered many of the advances in haematopoietic stem cell transplantation and cellular therapies over the last 50 years. The first patients to demonstrate sustained benefit and prolonged cure from the primary genetic defect following allogeneic haematopoietic stem cell transplantation were patients with primary immunodeficiencies. Although primary immunodeficiency patients began the modern era of haematopoietic stem cell transplantation, the history is nevertheless short-in answer to the question "what is the long term outcome of patients transplanted for primary immunodeficiencies?" we often have to say that we do not know. We believe that most patients who undergo haematopoietic stem cell transplantation for primary immunodeficiencies should live a normal lifespan with a fully corrected immune system. We are now beginning to understanding long term outcomes, the relationship to the underlying genetic defect, age, and pre-morbid condition of the patient at time of transplantation, stem cell source and donor, and effect of pre-transplant cytoreductive chemotherapy conditioning. The long term consequences of post-transplant complications such as graft vs. host disease, veno-occlusive disease, or immune dysregulation are also being recognized. Additionally, some genetic defects have a systemic distribution, and we are learning the natural history of these defects once the immunodeficiency has been removed

Farmers’ perceptions of climate change : identifying types

Ambitious targets to reduce greenhouse gas (GHG) emissions from agriculture have been set by both national governments and their respective livestock sectors. We hypothesize that farmer self-identity influences their assessment of climate change and their willingness to im- plement measures which address the issue. Perceptions of climate change were determined from 286 beef/sheep farmers and evaluated using principal component analysis (PCA). The analysis elicits two components which evaluate identity (productivism and environmental responsibility), and two components which evaluate behavioral capacity to adopt mitigation and adaptation measures (awareness and risk perception). Subsequent Cluster Analyses reveal four farmer types based on the PCA scores. ‘The Productivist’ and ‘The Countryside Steward’ portray low levels of awareness of climate change, but differ in their motivation to adopt pro-environmental behavior. Conversely, both ‘The Environmentalist’ and ‘The Dejected’ score higher in their awareness of the issue. In addition, ‘The Dejected’ holds a high sense of perceived risk; however, their awareness is not conflated with an explicit understanding of agricultural GHG sources. With the exception of ‘The Environmentalist’, there is an evident disconnect between perceptions of agricultural emission sources and their contribution towards GHG emissions amongst all types. If such linkages are not con- ceptualized, it is unlikely that behavioral capacities will be realized. Effective communication channels which encour- age action should target farmers based on the groupings depicted. Therefore, understanding farmer types through the constructs used in this study can facilitate effective and tai- lored policy development and implementation

Effects of salt water on the ballistic protective performance of bullet-resistant body armour

Bullet-resistant body armour is used by law enforcement agencies and military personnel worldwide, often in inclement weather. Some fibre types used in body armour perform poorly when wet, resulting in a reduced level of protection; this is why most body armour protective elements are water-repellent treated and/or protected by a water-resistant cover. Some of the users operate in the maritime environment. The effect of salt water on body armour performance has not been previously reported. In this work the effect of soaking body armour in salt water and exposing body armour for up to 10 soaking and drying cycles in salt water was investigated. The effectiveness of the water-resistant cover was investigated by considering three cover conditions: (i) intact, (ii) cut and (iii) removed. Wet armour was heavier and provided significantly less protection from 9 mm Luger FMJ ammunition when compared to not-exposed armour irrespective of cover condition. A degradation in performance of armours exposed to soaking and drying cycles was noted, but this was similar across all regimes considered (one, three, five and ten cycles) and not as great as for wet armours

The functional head of the Cambrian radiodontan (stem-group Euarthropoda) Amplectobelua symbrachiata

© The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation

Aims: Treosulfan is an alkylating agent increasingly used prior to haematopoietic stem cell transplantation. The aim of this study was to develop a population pharmacokinetic (PK) model of treosulfan in paediatric haematopoietic stem cell transplantation recipients and to explore the effect of potential covariates on treosulfan PK. Also, a limited sampling model (LSM) will be developed to accurately predict treosulfan exposure suitable for a therapeutic drug monitoring setting. Methods: In this multicentre study, 91 patients, receiving a total dose of 30, 36 or 42 g/m2 treosulfan, administered over 3 consecutive days, were enrolled. A population PK model was developed and demographic factors, as well as laboratory parameters, were included as potential covariates. In addition, a LSM was developed using data from 28 patients. Results: A 2-compartment model with first order elimination best described the data. Bodyweight with allometric scaling and maturation function were identified as significant predictors of treosulfan clearance. Treosulfan clearance reaches 90% of adult values at 4 postnatal years. A model-based dosing table is presented to target an exposure of 1650 mg*h/L (population median) for different weight and age groups. Samples taken at 1.5, 4 and 7 hours after start of infusion resulted in the best limited sampling strategy. Conclusions: This study provides a treosulfan population PK model in children and captures the developmental changes in clearance. A 3-point LSM allows for accurate and precise estimation of treosulfan exposure

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice