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DMF use was predictive of higher persistence at 12 and 24 months, but not at last follow-up when azathioprine and glatiramer acetate showed the highest persistence compared to other DMTs. Side effects represented the main reason of discontinuation. CONCLUSION The use of the new oral DMTs greatly increased since their approval but persistence in the long-term is not better than with old drugs. The treatment choice is still a challenge both for patients and their doctors. Early Levallois core technology is usually dated in Europe to the end of Marine Isotope Stage (MIS) 9 and particularly from the beginning of MIS 8 to MIS 6. This technology is considered as one of the markers of the transition from lower to Middle Paleolithic or from Mode 2 to Mode 3. Recent discoveries show that some lithic innovations actually appeared earlier in western Europe, from MIS 12 to MIS 9, contemporaneous with changes in subsistence strategies and the first appearance of early Neanderthal anatomical features. Among these discoveries, there is the iconic Levallois core technology. A selection of well-dated assemblages in the United Kingdom, France, and Italy dated from MIS 12 to 9, which include both cores and flakes with Levallois features, has been described and compared with the aim of characterizing this technology. The conclusion supports the interpretation that several technical features may be attributed to a Levallois technology similar to those observed in younger Middle Paleolithic sites, distinct from the main associated core technologies in each level. Some features in the sample of sites suggest a gradual transformation of existing core technologies. The small evidence of Levallois could indicate occasional local innovations from different technological backgrounds and would explain the diversity of Levallois methods that is observed from MIS 12. The technological roots of Levallois technology in the Middle Pleistocene would suggest a multiregional origin and diffusion in Europe and early evidence of regionalization of local traditions through Europe from MIS 12 to 9. The relationships of Levallois technology with new needs and behaviors are discussed, such as flake preference, functional reasons related to hunting and hafting, an increase in the use of mental templates in European populations, and changes in the structure of hominin groups adapting to climatic and environmental changes. Almost all of global maternal mortality caused by HDP occurs in low to middle-income countries (LMIC). However, limited guidance is available to local primary care practitioners who are usually the main health care providers. This review examined existing international practice guidelines to identify potential practices to improve HDP management in Indonesian primary care settings. We performed structured literature search strategies and snowballing searches in six databases (MEDLINE, Web of Science, EMBASE, CINAHL, Cochrane reviews and Google Scholar) for guidelines that were published between 2007 and 2018 using relevant keywords and phrases of 'guidelines', 'hypertensive disorders of pregnancy' or 'preeclampsia' and 'primary care'. The AGREE II instrument was used to assess quality and reporting of the eligible guidelines. Thematic analysis was performed on all of the guidelines and the results were discussed among the project investigators. Sixteen international practice guidelines or similar management recommendations were reviewed. Almost all of them were partially applicable, with some managements potentially able to be adopted to Indonesian primary care settings. Three main themes for improving HDP management were identified, namely clinical management, care planning, and professional communication. These potential improvements in managing women with HDP in Indonesia may also be relevant in other LMIC. Further contextualisation is required to facilitate their adoption in practice settings. Paranthropus boisei was first described in 1959 based on fossils from the Olduvai Gorge and now includes many fossils from Ethiopia to Malawi. Knowledge about its postcranial anatomy has remained elusive because, until recently, no postcranial remains could be reliably attributed to this taxon. Here, we report the first associated hand and upper limb skeleton (KNM-ER 47000) of P. boisei from 1.51 to 1.53 Ma sediments at Ileret, Kenya. While the fossils show a combination of primitive and derived traits, the overall anatomy is characterized by primitive traits that resemble those found in Australopithecus, including an oblique scapular spine, relatively long and curved ulna, lack of third metacarpal styloid process, gracile thumb metacarpal, and curved manual phalanges. Very thick cortical bone throughout the upper limb shows that P. boisei had great upper limb strength, supporting hypotheses that this species spent time climbing trees, although probably to a lesser extent than earlier australopiths. Hand anatomy shows that P. boisei, like earlier australopiths, was capable of the manual dexterity needed to create and use stone tools, but lacked the robust thumb of Homo erectus, which arguably reflects adaptations to the intensification of precision grips and tool use. KNM-ER 47000 provides conclusive evidence that early Pleistocene hominins diverged in postcranial and craniodental anatomy, supporting hypotheses of competitive displacement among these contemporaneous hominins. click here STUDY OBJECTIVES Early life determinants of sleep problems are mostly unknown. The first 1000 days of life (ie, the time between conception and a child's second birthday) is a period where the foundations for optimum health, growth and neurodevelopment are established. The aim of this explorative study is to identify potential early life determinants of sleep problems at age 7-8 years. METHODS Data from the Amsterdam Born Children and their Development cohort study (n = 2746) were analyzed. Sleep problems at age 7-8 years were reported by the caregiver in the 'Child Sleep Habits Questionnaire'. A higher total score indicates more sleep problems. After multiple imputation (n = 20), we studied multivariable associations between all potential determinants and sleep problems using regression analysis. RESULTS A higher pre-pregnancy body mass index (BMI) was associated with more sleep problems at age 7-8 years [β 0.12 (95% CI 0.05, 0.18)]. Children of mothers with symptoms of anxiety during pregnancy [β 0.06 (95% CI 0.