Search

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 μm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 μm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo. [ABSTRACT FROM AUTHOR]

Objectives: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 crisis many have opinionated on how it may affect society's response to climate change. Two key questions here are how COVID-19 is expected to influence climate action by citizens and by the government. We answer these by applying topic modelling to textual responses from a survey of Spanish citizens. The identified topics tend to be more negative than positive, and more optimistic concerning future climate action by citizens. Positive views involve increasing pro-environmental behavior and are more common among younger, higher educated and male respondents as well as among those who perceive climate change as a serious threat or positively assessed COVID-19 confinement. Negative topics express concern that financial resources for climate action will be limited due to a focus on healthcare and economic recovery. In addition, they mention government mismanagement and waste due to use of protective measures like masks and gloves as impediments to effective climate action., Competing Interests: The authors have declared that no competing interests exist.

The megalithic jar sites of Laos (often referred to as the Plain of Jars) remain one of Southeast Asia's most mysterious and least understood archaeological cultures. The sites, recently inscribed as UNESCO World Heritage, host hollowed stone jars, up to three metres in height, which appear scattered across the landscape, alone or clustered in groups of up to more than 400. Until now, it has not been possible to estimate when the jars were first placed on the landscape or from where the stone was sourced. Geochronological analysis using the age of detrital zircons demonstrates a likely quarry source for one of the largest megalithic jar sites. Optically Stimulated Luminescence (OSL) dating suggests the jars were positioned at the sites potentially as early as the late second millennium BC. Radiocarbon dating of skeletal remains and charcoal samples places mortuary activity around the jars from the 9-13th century AD, suggesting the sites have maintained ritual significance from the period of their initial placement until historic times., Competing Interests: The authors have declared that no competing interests exist.

The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as "IL-15 DCs", with the capacity to stimulate NK cells. In a head-to-head comparison with "IL-4 DCs" used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on "gold-standard" IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies.

The Eastern Atlantic and Mediterranean stock of Bluefin tuna Thunnus thynnus (BFTE) has long been considered overfished and at risk of collapse. Although ICCAT quotas for this stock have decreased considerably over the past years, uncertainty exists about the degree of catch beyond this quota. The extent of such catch is an important piece of information in stock assessment models as well as being an indicator of the effectiveness of fisheries management. We present a model using Bluefin tuna trade data to infer actual catches. Basing our calculations on 25 countries involved in BFTE trade, we estimate that between 2005 and 2011, allowable quotas were exceeded by 44 percent. This gap between catch and quotas has slightly increased over past years, leading to estimated excess catches of 57 percent for the period between 2008 and 2011. To improve assessments, preparation and design of BFTE management, we suggest that the estimated total removals reported in this paper be included in stock assessment models for BFTE. An implication of our findings is that ICCAT member states should take stronger measures to monitor and enforce compliance with quotas.