Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study.

Objective: Approximately 30% of patients with type 2 diabetes mellitus have knee osteoarthritis. IA corticosteroids used to manage osteoarthritis pain can elevate blood glucose in these patients. We compared blood glucose levels following intra-articular injection of triamcinolone acetonide extended-release (TA-ER), an extended-release, microsphere-based triamcinolone acetonide formulation, vs standard triamcinolone acetonide crystalline suspension (TAcs) in patients with knee osteoarthritis and comorbid type 2 diabetes. Methods: In this double-blind, randomized, parallel-group, phase 2 study (NCT02762370), 33 patients with knee osteoarthritis (American College of Rheumatology criteria) and type 2 diabetes mellitus (HbA1c 6.5-9.0% [48-75 mmol/mol]; 1-2 oral hypoglycaemic agents) were treated with intra-articular TA-ER (32 mg n = 18) or TAcs 40 mg (n = 15). Continuous glucose monitoring-measured glucose (CGMG) was assessed from 1 week pre-injection through 2 weeks postinjection. Endpoints included change in average daily CGMG from baseline (days -3 to -1) to days 1-3 postinjection (CGMGdays1-3) (primary) and percent time average hourly CGMG levels remained in prespecified glycaemic ranges. Results: The change CGMGdays1-3 was significantly lower following TA-ER vs TAcs (14.7 vs 33.9 mg/dl, least-squares-mean-difference [95% CI]: -19.2 [-38.0, -0.4]; P = 0.0452). The percentage of time over days 1-3 that CGMG was in the target glycaemic range (70-180 mg/dl) was numerically greater for TA-ER (63.3%) vs TAcs (49.7%), and that CGMG was >180 mg/dl was lower for TA-ER (34.5%) vs TAcs (49.9%). Non-glycaemic adverse events were mild and comparable between groups. Conclusion: TA-ER may enable intra-articular corticosteroid treatment with minimal blood glucose disruption in patients with knee osteoarthritis and type 2 diabetes mellitus. Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02762370.

Chronological and environmental context of the first hominin dispersal into Western Europe: The case of Barranco León (Guadix-Baza Basin, SE Spain).

The early Pleistocene site of Barranco León (Guadix-Baza Basin, SE Spain), dated to 1.4 Ma (millions of years ago), records the oldest hominin occurrence in Western Europe, as evidenced by the discovery of one tooth and thousands of Mode 1 stone tools. In this paper a detailed analysis of the microvertebrate content of the D1 and D2 units from this site is presented. The early Pleistocene in the Guadix-Baza Basin is characterized by a sharp climatic deterioration, which possibly impeded the settlement of this region by the early hominin population from the southern Caucasus. Shortly afterwards, when the climatic conditions were again favorable, a hominin presence is suddenly evidenced at the units D1 and D2 of Barranco León. According to the microvertebrate analysis of these units, the mean annual temperature at the time of deposition was significantly higher than 13 °C, with prevalent humid conditions. However, although most of the species were inhabitants of water edges, an open landscape was present in the vicinity of the lake. The data reported here clearly support the idea that the early hominin occupation of Europe was strongly constrained by climatic and environmental conditions, rather than by physiography or cultural factors.

The lithic industry of Sima del Elefante (Atapuerca, Burgos, Spain) in the context of Early and Middle Pleistocene technology in Europe.

This paper presents the lithic assemblages documented at Sima del Elefante (TE) and their importance in the context of the Early and Middle Pleistocene human occupation of Europe. We also study changes in human behaviour within the context of the palaeoenvironmental evolution of the Sierra de Atapuerca. This site has characteristics that are of great value for the study of human evolution. The lower levels of TE (Units TE7-TE14) are an essential reference for understanding the early stages of the colonization of Europe. The TE9c level has provided stone tools (Mode 1), faunal remains, and human fossils dated to 1.22 Ma (millions of years ago). Moreover, this is one of the few European sites with a stratigraphic sequence that includes remains of human occupations predating the Jaramillo subchron (Early Pleistocene) and from the Late Middle Pleistocene (Units TE18-TE19). Despite this, the presence of archaeologically sterile units (TE15-17) prevents us from establishing a continuous relationship between the Early and Middle Pleistocene human settlements and, consequently, between their technological and behavioural differences. We can, however compare the technological and palaeoeconomic strategies adopted by different species of hominins during two key phases of the occupation of Europe.

The first hominin of Europe.

The earliest hominin occupation of Europe is one of the most debated topics in palaeoanthropology. However, the purportedly oldest of the Early Pleistocene sites in Eurasia lack precise age control and contain stone tools rather than human fossil remains. Here we report the discovery of a human mandible associated with an assemblage of Mode 1 lithic tools and faunal remains bearing traces of hominin processing, in stratigraphic level TE9 at the site of the Sima del Elefante, Atapuerca, Spain. Level TE9 has been dated to the Early Pleistocene (approximately 1.2-1.1 Myr), based on a combination of palaeomagnetism, cosmogenic nuclides and biostratigraphy. The Sima del Elefante site thus emerges as the oldest, most accurately dated record of human occupation in Europe, to our knowledge. The study of the human mandible suggests that the first settlement of Western Europe could be related to an early demographic expansion out of Africa. The new evidence, with previous findings in other Atapuerca sites (level TD6 from Gran Dolina), also suggests that a speciation event occurred in this extreme area of the Eurasian continent during the Early Pleistocene, initiating the hominin lineage represented by the TE9 and TD6 hominins.

Hemoglobin A1C, mean glucose, and persistence of glycation ratios in insulin-treated diabetes.

OBJECTIVE: Determine the relationship between mean glucose (MG), as assessed by continuous glucose monitoring (CGM), and hemoglobin A1c (A1C) in insulin-requiring adults in a clinical practice setting and examine the persistence of this relationship over time. METHODS: In this retrospective record review in a diabetes practice, a linear regression model was developed using data sets from all patients with ≥1 available download of a Dexcom SevenPlus CGM device in which there was >50% utilization in the 60 days prior to a laboratory A1C. Persistence of the MG to A1C relationship was examined in patients with ≥2 data sets available. RESULTS: A total of 139 patients had ≥1 data set available for evaluation, and 101 patients had ≥2 data sets (range, 2 to 6; total, 279). The slope of the MG versus A1C curve was 19.5 mg/dL for each 1% change in A1C, with an intercept of 17.7 mg/dL. Although 88% of the measured MG values were within 15% of the A1C-predicted MG, there was substantial variation in individuals, with differences as large as ±26%. The MG to A1C (MG:A1C) ratio, which is a measure of glycation, was normally distributed, with a median of 21.6. Spearman correlation coefficients for the MG:A1C ratio on repeated measures ranged from 0.52 to 0.73, demonstrating persistence. CONCLUSION: The relationship between MG and A1C is linear in a population but can vary between individuals. The MG:A1C ratio was normally distributed, tended to persist in individuals over time, and thus could be useful to identify apparent high and low glycators. Glycemic goals may need to be modified in such patients.

Potential Scenarios and Hazards in the Work of the Future: A Systematic Review of the Peer-Reviewed and Gray Literatures.

It would be useful for researchers, practitioners, and decision-makers to anticipate the hazards that workers will face in the future. The focus of this study is a systematic review of published information to identify and characterize scenarios and hazards in the future of work. Eleven bibliographic databases were systematically searched for papers and reports published from 1999 to 2019 that described future of work scenarios or identified future work-related hazards. To compile a comprehensive collection of views of the future, supplemental and ad hoc searches were also performed. After screening all search records against a set of predetermined criteria, the review yielded 36 references (17 peer-reviewed, 4 gray, and 15 supplemental) containing scenarios. In these, the future of work was described along multiple conceptual axes (e.g. labor market changes, societal values, and manual versus cognitive work). Technology was identified as the primary driver of the future of work in most scenarios, and there were divergent views in the literature as to whether technology will create more or fewer jobs than it displaces. Workforce demographics, globalization, climate change, economic conditions, and urbanization were also mentioned as influential factors. Other important themes included human enhancement, social isolation, loneliness, worker monitoring, advanced manufacturing, hazardous exposures, sustainability, biotechnology, and synthetic biology. Pandemics have not been widely considered in the future of work literature, but the recent COVID-19 pandemic illustrates that was short-sighted. Pandemics may accelerate future of work trends and merit critical consideration in scenario development. Many scenarios described 'new' or 'exacerbated' psychosocial hazards of work, whereas comparatively fewer discussed physical, chemical, or biological hazards. Various preventive recommendations were identified. In particular, reducing stress associated with precarious work and its requirements of continual skill preparation and training was acknowledged as critical for protecting and promoting the health and well-being of the future workforce. In conclusion, the future of work will be comprised of diverse complex scenarios and a mosaic of old and new hazards. These findings may serve as the basis for considering how to shape the future of work.

Limestone percussion tools from the late Early Pleistocene sites of Barranco León and Fuente Nueva 3 (Orce, Spain).

In recent years, there is growing interest in the study of percussion scars and breakage patterns on hammerstones, cores and tools from Oldowan African and Eurasian lithic assemblages. Oldowan stone toolkits generally contain abundant small-sized flakes and their corresponding cores, and are characterized by their structural dichotomy of heavy- and light-duty tools. This paper explores the significance of the lesser known heavy-duty tool component, providing data from the late Lower Pleistocene sites of Barranco León and Fuente Nueva 3 (Orce, Spain), dated 1.4-1.2 Myr. Using quantitative and qualitative data from the large-sized limestone industries from these two major sites, we present a new methodology highlighting their morpho-technological features. In the light of the results, we discuss the shortfalls of extant classificatory methods for interpreting the role of percussive technology in early toolkits. This work is rooted in an experimental program designed to reproduce the wide range of percussion marks observed on the limestone artefacts from these two sites. A visual and descriptive reference is provided as an interpretative aid for future comparative research. Further experiments using a variety of materials and gestures are still needed before the elusive traces yield the secrets of the kinds of percussive activities carried out by hominins at these, and other, Oldowan sites.