Vector Transmission of Leishmania Abrogates Vaccine-Induced Protective Immunity

Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is “leishmanization,” in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania

Prevalence and factors associated with disturbed sleep in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review

This review explores the prevalence and factors associated with disturbed sleep for patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis in order to clarify consistent findings in this otherwise disparate research field. The association of physical, demographic and psychological factors correlating with poor sleep was explored, and the effectiveness of interventions assessed. Ten electronic databases were searched: AMED, CINAHL, Embase, Medline, PsycINFO, PubMed, Scopus, Web of Science, OpenGrey and BASE. Following application of inclusion and exclusion criteria, 29 articles were critically assessed on the basis of methodology, experimental design, ethics and quality of sleep data, leading to the selection of 15 studies for final review. Poor sleep was reported in 35–90% of patients with axial spondyloarthritis and is more prevalent within this clinical population compared to healthy control subjects. Disturbed sleep is an important aspect of disease for patients and reflects the severity of disease activity, pain, fatigue and functional disability. However, the direction of this relationship is undetermined. Associations with age, gender, years spent in education, quality of life and depression have also been demonstrated. Anti-TNF medication is effective in reducing poor sleep, and exercise has also produced beneficial results. Future research into poor sleep should take account of its multifactorial nature. There is also a current lack of research investigating non-pharmacological interventions or combination therapies. A standardised, validated measurement of poor sleep, appropriate for regular patient screening, would be a useful first step for future research

Managerial challenges of Industry 4.0: an empirically backed research agenda for a nascent field

The increasing intelligence of products and systems, their intra-company cross-linking and their cross-company integration into value creation networks is referred to as Industry 4.0. Academics and practitioners, largely agreeing on the global importance of this proclaimed industrial revolution, have published many contributions on the topic. Research, however, is rather focused on investigating single technologies in quite specific application domains and largely neglects the profound managerial challenges underlying Industry 4.0. Given the recent plea for a more active contribution from the management science community, we strive to establish Industry 4.0 as a challenging but promising field for management research, and aim to assist scholars in engaging with the topic. Therefore, we first gather and analyze extant contributions by means of a systematic literature review and synthesize the information gained into 18 managerial challenges of Industry 4.0 falling into six interrelated clusters: (1) strategy and analysis, (2) planning and implementation, (3) cooperation and networks, (4) business models, (5) human resources and (6) change and leadership. Considering that Industry 4.0 is still an emerging topic and publications may therefore not always be found in highly ranked journals, we aimed to increase the confidence in our findings and triangulated our data by conducting an online survey of industry experts and academics that allows us to qualify the identified challenges in terms of importance and future research need. On this basis, we present an empirically backed research agenda and suggest fruitful avenues for future research in three basic categories: practice-enhancing research, knowledge-enhancing research, and high-impact research