Preparing Low-Skilled Workers for the Jobs of Tomorrow

Identifies ways for state policies to leverage technology-based economic development by preparing low-skilled workers for middle-skill, technical jobs in the fields of science, technology, engineering, and math (STEM). Outlines current state initiatives

Antiresorptive-associated spontaneous fractures of both tibiae, followed by an atypical femur fracture during the sequential treatment with alendronate, denosumab then teriparatide.

A 35-year-old man with juvenile idiopathic arthritis since childhood presented with bilateral atypical tibial fractures, followed by a later, single atypical fracture of the femur. The fractures were associated with 6 years of oral alendronate treatment immediately followed by subcutaneous denosumab therapy and later teriparatide therapy for osteoporosis. Atypical fractures are known to occur in the femur following bisphosphonate therapy; however, there are only a few documented cases of atypical fractures in the tibia. Our case highlights a rare but serious complication of a commonly prescribed antiresorptive agent. It also shows that teriparatide, while helpful in increasing bone mass, does not fully prevent the development of atypical fractures. Careful investigation should be considered in patients on long-term antiresorptive therapy presenting with bony tenderness to exclude an atypical fracture.Cambridge NIHR Biomedical Research Centr

The Effects on the Femoral Cortex of a 24 Month Treatment Compared to an 18 Month Treatment with Teriparatide: A Multi-Trial Retrospective Analysis.

BACKGROUND: Teriparatide (TPTD) is an anabolic agent indicated for the treatment of severely osteoporotic patients who are at high risk of fragility fractures. The originally approved duration of TPTD treatment in several regions, including Europe, was 18 months. However, studies of areal bone mineral density (aBMD) showed additional benefit when treatment is continued beyond 18 months, and the drug is currently licenced for 24 months. Improvements in cortical structure at the proximal femur have already been shown in patients given TPTD for 24 months using quantitative computed tomography (QCT). Here, we investigate whether cortical and endocortical trabecular changes differ between an 18- and 24-month treatment. METHODS: Since an 18- versus 24-month TPTD study using QCT has not been conducted, we studied combined QCT data from four previous clinical trials. Combined femoral QCT data from three 18-month TPTD studies ('18-month group') were compared with data from a fourth 24-month trial ('24-month group'). Cortical parameters were measured over the entire proximal femur which allowed for a comparison of the mean changes as well as a visual comparison of the colour maps of changes after 18 and 24 months TPTD. RESULTS: For both the combined 18-month group and the 24-month group, overall cortical thickness and endocortical trabecular density increased, while overall cortical bone mineral density decreased. While the changes in the 24-month group were of greater magnitude compared to the 18-month group, the differences were only significant for the endocortical trabecular density (ECTD), corrected for age, weight, femoral neck T-score, total hip T-score and the baseline mean ECTD. CONCLUSION: Although the combination of data from different clinical trials is not optimal, these data support the concept that the duration of TPTD in the 18-24 month phase is of clinical relevance when considering improvement in hip structure.This study was funded by Eli Lilly. TW, GMT, AHG and KESP received research grants from Eli Lilly. KESP is also funded by the Cambridge NIHR Biomedical research Centre. The Evelyn Trust funded GMT. The funders had no role in study design, data analysis or decision to publish, but were involved in collection of data and had the chance to review the manuscript once written.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014772

Mapping Bone Changes at the Proximal Femoral Cortex of Postmenopausal Women in Response to Alendronate and Teriparatide Alone, Combined or Sequentially.

Combining antiresorptive and anabolic drugs for osteoporosis may be a useful strategy to prevent hip fractures. Previous studies comparing the effects of alendronate (ALN) and teriparatide (TPTD) alone, combined or sequentially using quantitative computed tomography (QCT) in postmenopausal women have not distinguished cortical bone mineral density (CBMD) from cortical thickness (CTh) effects, nor assessed the distribution and extent of more localized changes. In this study a validated bone mapping technique was used to examine the cortical and endocortical trabecular changes in the proximal femur resulting from an 18-month course of ALN or TPTD. Using QCT data from a different clinical trial, the global and localized changes seen following a switch to TPTD after an 18-month ALN treatment or adding TPTD to the ALN treatment were compared. Ct.Th increased (4.8%, p < 0.01) and CBMD decreased (-4.5%, p < 0.01) in the TPTD group compared to no significant change in the ALN group. A large Ct.Th increase could be seen for the switch group (2.8%, p < 0.01) compared to a significantly smaller increase for the add group (1.5%, p < 0.01). CBMD decreased significantly for the switch group (-3.9%, p < 0.01) and was significantly different from no significant change in the add group. Ct.Th increases were shown to be significantly greater for the switch group compared to the add group at the load bearing regions. This study provides new insights into the effects of ALN and TPTD combination therapies on the cortex of the proximal femur and supports the hypothesis of an increased bone remodeling by TPTD being mitigated by ALN.This is the accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2454/abstract

Prevalence of axial spondyloarthritis in patients with inflammatory bowel disease using cross-sectional imaging: a systematic literature review.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA. METHODS: PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging. RESULTS: A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17-26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn's disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics. CONCLUSION: This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk

Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed tomography.

OBJECTIVE: To assess the relationship between proximal femoral cortical bone thickness and radiological hip osteoarthritis using quantitative 3D analysis of clinical computed tomography (CT) data. METHODS: Image analysis was performed on clinical CT imaging data from 203 female volunteers with a technique called cortical bone mapping (CBM). Colour thickness maps were created for each proximal femur. Statistical parametric mapping was performed to identify statistically significant differences in cortical bone thickness that corresponded with the severity of radiological hip osteoarthritis. Kellgren and Lawrence (K&L) grade, minimum joint space width (JSW) and a novel CT-based osteophyte score were also blindly assessed from the CT data. RESULTS: For each increase in K&L grade, cortical thickness increased by up to 25 % in distinct areas of the superolateral femoral head-neck junction and superior subchondral bone plate. For increasing severity of CT osteophytes, the increase in cortical thickness was more circumferential, involving a wider portion of the head-neck junction, with up to a 7 % increase in cortical thickness per increment in score. Results were not significant for minimum JSW. CONCLUSIONS: These findings indicate that quantitative 3D analysis of the proximal femur can identify changes in cortical bone thickness relevant to structural hip osteoarthritis. KEY POINTS: • CT is being increasingly used to assess bony involvement in osteoarthritis • CBM provides accurate and reliable quantitative analysis of cortical bone thickness • Cortical bone is thicker at the superior femoral head-neck with worse osteoarthritis • Regions of increased thickness co-locate with impingement and osteophyte formation • Quantitative 3D bone analysis could enable clinical disease prediction and therapy development.TT acknowledges the support of an Evelyn Trust Clinical Training Fellowship award (RG65411). KP acknowledges support of an Arthritis Research UK Research Progression award (RG66087), and the Cambridge NIHR Biomedical Research Centre (RG64245). None of the funding sources had a role in study design, data handling, writing of the report, or decision to submit the paper for publication.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00330-015-4048-

A SQUAMOSA MADS-box gene involved in the regulation of anthocyanin accumulation in bilberry fruits

Anthocyanins are important health promoting phytochemicals that are abundant in many fleshy fruits. Bilberry (Vaccinium myrtillus L.) is one of the best sources of these compounds. Here we report on the expression pattern and functional analysis of a SQUAMOSA (SQUA) class MADS-box transcription factor, VmTDR4, associated with anthocyanin biosynthesis in bilberry. Levels of VmTDR4 expression were spatially and temporally linked with colour development and anthocyanin-related gene expression. Virus induced gene silencing (VIGS) was used to suppress VmTDR4 expression in bilberry resulting in substantial reduction in anthocyanin levels in fully ripe fruits. Chalcone synthase was used a positive control in the VIGS experiments. Additionally, in sectors of fruit tissue in which the expression of the VmTDR4 gene was silenced, the expression of R2R3 MYB family transcription factors related to the biosynthesis of flavonoids were also altered. We conclude that VmTDR4 plays an important role in the accumulation of anthocyanins during normal ripening in bilberry; probably through direct or indirect control of transcription factors belonging to the R2R3 MYB family

Targeted regeneration of bone in the osteoporotic human femur.

We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness