Motivation and incentives of rural maternal and neonatal health care providers: a comparison of qualitative findings from Burkina Faso, Ghana and Tanzania.

In Burkina Faso, Ghana and Tanzania strong efforts are being made to improve the quality of maternal and neonatal health (MNH) care. However, progress is impeded by challenges, especially in the area of human resources. All three countries are striving not only to scale up the number of available health staff, but also to improve performance by raising skill levels and enhancing provider motivation. In-depth interviews were used to explore MNH provider views about motivation and incentives at primary care level in rural Burkina Faso, Ghana and Tanzania. Interviews were held with 25 MNH providers, 8 facility and district managers, and 2 policy-makers in each country. Across the three countries some differences were found in the reasons why people became health workers. Commitment to remaining a health worker was generally high. The readiness to remain at a rural facility was far less, although in all settings there were some providers that were willing to stay. In Burkina Faso it appeared to be particularly difficult to recruit female MNH providers to rural areas. There were indications that MNH providers in all the settings sometimes failed to treat their patients well. This was shown to be interlinked with differences in how the term 'motivation' was understood, and in the views held about remuneration and the status of rural health work. Job satisfaction was shown to be quite high, and was particularly linked to community appreciation. With some important exceptions, there was a strong level of agreement regarding the financial and non-financial incentives that were suggested by these providers, but there were clear country preferences as to whether incentives should be for individuals or teams. Understandings of the terms and concepts pertaining to motivation differed between the three countries. The findings from Burkina Faso underline the importance of gender-sensitive health workforce planning. The training that all levels of MNH providers receive in professional ethics, and the way this is reinforced in practice require closer attention. The differences in the findings across the three settings underscore the importance of in-depth country-level research to tailor the development of incentives schemes

Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy

The CCP4 suite: integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.Jon Agirre is a Royal Society University Research Fellow (UF160039 and URF\R\221006). Mihaela Atanasova is funded by the UK Engineering and Physical Sciences Research Council (EPSRC; EP/R513386/1). Haroldas Bagdonas is funded by The Royal Society (RGF/R1/181006). Jose´ Javier Burgos-Ma´rmol and Daniel J. Rigden are supported by the BBSRC (BB/S007105/1). Robbie P. Joosten is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 871037 (iNEXTDiscovery) and by CCP4. This work was supported by the Medical Research Council as part of United Kingdom Research and Innovation, also known as UK Research and Innovation: MRC file reference No. MC_UP_A025_1012 to Garib N. Murshudov, which also funded Keitaro Yamashita, Paul Emsley and Fei Long. Robert A. Nicholls is funded by the BBSRC (BB/S007083/1). Soon Wen Hoh is funded by the BBSRC (BB/T012935/1). Kevin D. Cowtan and Paul S. Bond are funded in part by the BBSRC (BB/S005099/1). John Berrisford and Sameer Velankar thank the European Molecular Biology Laboratory–European Bioinformatics Institute, who supported this work. Andrea Thorn was supported in the development of AUSPEX by the German Federal Ministry of Education and Research (05K19WWA and 05K22GU5) and by Deutsche Forschungsgemeinschaft (TH2135/2-1). Petr Kolenko and Martin Maly´ are funded by the MEYS CR (CZ.02.1.01/0.0/0.0/16_019/0000778). Martin Maly´ is funded by the Czech Academy of Sciences (86652036) and CCP4/STFC (521862101). Anastassis Perrakis acknowledges funding from iNEXT (grant No. 653706), iNEXT-Discovery (grant No. 871037), West-Life (grant No. 675858) and EOSC-Life (grant No. 824087) funded by the Horizon 2020 program of the European Commission. Robbie P. Joosten has been the recipient of a Veni grant (722.011.011) and a Vidi grant (723.013.003) from the Netherlands Organization for Scientific Research (NWO). Maarten L. Hekkelman, Robbie P. Joosten and Anastassis Perrakis thank the Research High Performance Computing facility of the Netherlands Cancer Institute for providing and maintaining computation resources and acknowledge the institutional grant from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Tarik R. Drevon is funded by the BBSRC (BB/S007040/1). Randy J. Read is supported by a Principal Research Fellowship from the Wellcome Trust (grant 209407/Z/17/Z). Atlanta G. Cook is supported by a Wellcome Trust SRF (200898) and a Wellcome Centre for Cell Biology core grant (203149). Isabel Uso´n acknowledges support from STFC-UK/CCP4: ‘Agreement for the integration of methods into the CCP4 software distribution, ARCIMBOLDO_LOW’ and Spanish MICINN/AEI/FEDER/UE (PID2021-128751NB-I00). Pavol Skubak and Navraj Pannu were funded by the NWO Applied Sciences and Engineering Domain and CCP4 (grant Nos. 13337 and 16219). Bernhard Lohkamp was supported by the Ro¨ntgen A˚ ngstro¨m Cluster (grant 349-2013-597). Nicholas Pearce is currently funded by the SciLifeLab and Wallenberg Data Driven Life Science Program (grant KAW 2020.0239) and has previously been funded by a Veni Fellowship (VI.Veni.192.143) from the Dutch Research Council (NWO), a Long-term EMBO fellowship (ALTF 609-2017) and EPSRC grant EP/G037280/1. David M. Lawson received funding from BBSRC Institute Strategic Programme Grants (BB/P012523/1 and BB/P012574/1). Lucrezia Catapano is the recipient of an STFC/CCP4-funded PhD studentship (Agreement No: 7920 S2 2020 007).Peer reviewe

The CCP4 suite : integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world