The cuttlefish Sepia officinalis (Sepiidae, Cephalopoda) constructs cuttlebone from a liquid-crystal precursor

Cuttlebone, the sophisticated buoyancy device of cuttlefish, is made of extensive superposed chambers that have a complex internal arrangement of calcified pillars and organic membranes. It has not been clear how this structure is assembled. We find that the membranes result from a myriad of minor membranes initially filling the whole chamber, made of nanofibres evenly oriented within each membrane and slightly rotated with respect to those of adjacent membranes, producing a helical arrangement. We propose that the organism secretes a chitin-protein complex, which self-organizes layer-by-layer as a cholesteric liquid crystal, whereas the pillars are made by viscous fingering. The liquid crystallization mechanism permits us to homologize the elements of the cuttlebone with those of other coleoids and with the nacreous septa and the shells of nautiloids. These results challenge our view of this ultra-light natural material possessing desirable mechanical, structural and biological properties, suggesting that two self-organizing physical principles suffice to understand its formation.Spanish Ministerio de Ciencia e Innovacion [CGL2010-20748-CO2-01, CGL2013-48247-P, FIS2013-48444-C2-2-P]; Andalusian Consejeria de Innovacion Ciencia y Tecnologia [RNM6433]; (Sepiatech, PROMAR program) of the Portuguese Ministerio da Agricultura e do Mar, Portugal [31.03.05.FEP.002]; Junta de Andalucia [RNM363]; FP7 COST Action of the European Community. [TD0903]info:eu-repo/semantics/publishedVersio

Importance of the Public Service in Achieving the UN SDGs

Public service is the engine of effective governance delivery in the world economy; governments across the world cannot function well without the enabling structures of public administration to deliver on their mandate as set out mostly in (political) manifestos, while also making sure the core mandate for meeting citizens’ basic welfare needs are made available through an efficient market system. The operation of such a market system must enable entities or agents to act in the best interest of delivering high services, which would have already been set as dictated through regulation of the legal system – this should also facilitate the presence of information symmetry for agents to operate (Jackson and Jabbie, 2019; Winston, 2006; Weiner and Vining, 2004)

Understanding market failure in the developing country context.

Market failure makes it difficult to achieve the condition of economic efficiency by distorting price mechanisms and normal distribution of goods and services thereby, leading to welfare loss. They are entrenched in the socio-economic fabrics of most developing countries, underpinned by the lack of well-functioning market structures and economic systems – which are supposed to make the market economy resilient to such economic shortcomings

The training and professional expectations of medical students in Angola, Guinea-Bissau and Mozambique

<p>Abstract</p> <p>Background</p> <p>The purpose of this paper is to describe and analyze the professional expectations of medical students during the 2007-2008 academic year at the public medical schools of Angola, Guinea-Bissau and Mozambique, and to identify their social and geographical origins, their professional expectations and difficulties relating to their education and professional future.</p> <p>Methods</p> <p>Data were collected through a standardised questionnaire applied to all medical students registered during the 2007-2008 academic year.</p> <p>Results</p> <p>Students decide to study medicine at an early age. Relatives and friends seem to have an especially important influence in encouraging, reinforcing and promoting the desire to be a doctor.</p> <p>The degree of feminization of the student population differs among the different countries.</p> <p>Although most medical students are from outside the capital cities, expectations of getting into medical school are already associated with migration from the periphery to the capital city, even before entering medical education.</p> <p>Academic performance is poor. This seems to be related to difficulties in accessing materials, finances and insufficient high school preparation.</p> <p>Medical students recognize the public sector demand but their expectations are to combine public sector practice with private work, in order to improve their earnings. Salary expectations of students vary between the three countries.</p> <p>Approximately 75% want to train as hospital specialists and to follow a hospital-based career. A significant proportion is unsure about their future area of specialization, which for many students is equated with migration to study abroad.</p> <p>Conclusions</p> <p>Medical education is an important national investment, but the returns obtained are not as efficient as expected. Investments in high-school preparation, tutoring, and infrastructure are likely to have a significant impact on the success rate of medical schools. Special attention should be given to the socialization of students and the role model status of their teachers.</p> <p>In countries with scarce medical resources, the hospital orientation of students' expectations is understandable, although it should be associated with the development of skills to coordinate hospital work with the network of peripheral facilities. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country.</p

Investigating organizational quality improvement systems, patient empowerment, organizational culture, professional involvement and the quality of care in European hospitals: the 'Deepening our Understanding of Quality Improvement in Europe (DUQuE)' project

BACKGROUND: Hospitals in European countries apply a wide range of quality improvement strategies. Knowledge of the effectiveness of these strategies, implemented as part of an overall hospital quality improvement system, is limited. METHODS/DESIGN: We propose to study the relationships among organisational quality improvement systems, patient empowerment, organisational culture, professionals' involvement with the quality of hospital care, including clinical effectiveness, patient safety and patient involvement. We will employ a cross-sectional, multi-level study design in which patient-level measurements are nested in hospital departments, which are in turn nested in hospitals in different EU countries. Mixed methods will be used for data collection, measurement and analysis. Hospital/care pathway level constructs that will be assessed include external pressure, hospital governance, quality improvement system, patient empowerment in quality improvement, organisational culture and professional involvement. These constructs will be assessed using questionnaires. Patient-level constructs include clinical effectiveness, patient safety and patient involvement, and will be assessed using audit of patient records, routine data and patient surveys. For the assessment of hospital and pathway level constructs we will collect data from randomly selected hospitals in eight countries. For a sample of hospitals in each country we will carry out additional data collection at patient-level related to four conditions (stroke, acute myocardial infarction, hip fracture and delivery). In addition, structural components of quality improvement systems will be assessed using visits by experienced external assessors. Data analysis will include descriptive statistics and graphical representations and methods for data reduction, classification techniques and psychometric analysis, before moving to bi-variate and multivariate analysis. The latter will be conducted at hospital and multilevel. In addition, we will apply sophisticated methodological elements such as the use of causal diagrams, outcome modelling, double robust estimation and detailed sensitivity analysis or multiple bias analyses to assess the impact of the various sources of bias. DISCUSSION: Products of the project will include a catalogue of instruments and tools that can be used to build departmental or hospital quality and safety programme and an appraisal scheme to assess the maturity of the quality improvement system for use by hospitals and by purchasers to contract hospitals

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Development of a novel small antibody that retains specificity for tumor targeting

<p>Abstract</p> <p>Background</p> <p>For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.</p> <p>Methods</p> <p>In this study, authors developed a novel mimetic in the form of V_HFR1_C-10-V_HCDR1-V_HFR2-V_LCDR3-V_LFR4_N-10for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells <it>in vitro</it>. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.</p

Multiscale models for movement in oriented environments and their application to hilltopping in butterflies

Hilltopping butterflies direct their movement in response to topography, facilitating mating encounters via accumulation at summits. In this paper, we take hilltopping as a case study to explore the impact of complex orienteering cues on population dynamics. The modelling employs a standard multiscale framework, in which an individual's movement path is described as a stochastic 'velocity-jump' process and scaling applied to generate a macroscopic model capable of simulating large populations in landscapes. In this manner, the terms and parameters of the macroscopic model directly relate to statistical inputs of the individual-level model (mean speeds, turning rates and turning distributions). Applied to hilltopping in butterflies, we demonstrate how hilltopping acts to aggregate populations at summits, optimising mating for low-density species. However, for abundant populations, hilltopping is not only less effective but also possibly disadvantageous, with hilltopping males recording a lower mating rate than their non-hilltopping competitors. © 2013 Springer Science+Business Media Dordrecht