HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes

HOXA10 is necessary for embryonic patterning of skeletal elements, but its function in bone formation beyond this early developmental stage is unknown. Here we show that HOXA10 contributes to osteogenic lineage determination through activation of Runx2 and directly regulates osteoblastic phenotypic genes. In response to bone morphogenic protein BMP2, Hoxa10 is rapidly induced and functions to activate the Runx2 transcription factor essential for bone formation. A functional element with the Hox core motif was characterized for the bone-related Runx2 P1 promoter. HOXA10 also activates other osteogenic genes, including the alkaline phosphatase, osteocalcin, and bone sialoprotein genes, and temporally associates with these target gene promoters during stages of osteoblast differentiation prior to the recruitment of RUNX2. Exogenous expression and small interfering RNA knockdown studies establish that HOXA10 mediates chromatin hyperacetylation and trimethyl histone K4 (H3K4) methylation of these genes, correlating to active transcription. HOXA10 therefore contributes to early expression of osteogenic genes through chromatin remodeling. Importantly, HOXA10 can induce osteoblast genes in Runx2 null cells, providing evidence for a direct role in mediating osteoblast differentiation independent of RUNX2. We propose that HOXA10 activates RUNX2 in mesenchymal cells, contributing to the onset of osteogenesis, and that HOXA10 subsequently supports bone formation by direct regulation of osteoblast phenotypic genes. <br/

Using social networking sites for communicable disease control: innovative contact tracing or breach of confidentiality?

Social media applications such as Twitter, YouTube and Facebook have attained huge popularity, with more than three billion people and organizations predicted to have a social networking account by 2015. Social media offers a rapid avenue of communication with the public and has potential benefits for communicable disease control and surveillance. However, its application in everyday public health practice raises a number of important issues around confidentiality and autonomy. We report here a case from local level health protection where the friend of an individual with meningococcal septicaemia used a social networking site to notify potential contacts

Opening science to society:how to progress societal engagement into (open) science policies

A broad understanding of the aims and objectives of the international open science movement was recently adopted with the 2021 UNESCO Recommendation on Open Science, expanding the focus of open science to include scientific knowledge, infrastructures, knowledge systems and the open engagement of societal actors. In response, recent discussions on science policy practice are shifting to the implementation of open science via national policy. While policy instruments to support some aspects of open science are well-studied, guidance on the emerging ‘social’ aspects of open science has lagged, prompting UNESCO to generate guidance. In this paper, authors of a UNESCO Open Science Toolkit guidance document on ‘Engaging societal actors in Open Science’ synthesize the scholarly underpinnings behind the guidance document's recommendations. This work draws upon a targeted search from academic, policy, and grey literature in the fields of open science and community engagement, with a special focus on citizen science, to derive guidance on how to overcome barriers to the uptake of societal engagement approaches. The results present building blocks of what an enabling environment for the open engagement of societal actors could look like, identifying key considerations and reflecting on opportunities and challenges for progressing and evaluating sound open engagement of societal actors into regional &amp; national (open) science policies

Opening science to society:how to progress societal engagement into (open) science policies

A broad understanding of the aims and objectives of the international open science movement was recently adopted with the 2021 UNESCO Recommendation on Open Science, expanding the focus of open science to include scientific knowledge, infrastructures, knowledge systems and the open engagement of societal actors. In response, recent discussions on science policy practice are shifting to the implementation of open science via national policy. While policy instruments to support some aspects of open science are well-studied, guidance on the emerging ‘social’ aspects of open science has lagged, prompting UNESCO to generate guidance. In this paper, authors of a UNESCO Open Science Toolkit guidance document on ‘Engaging societal actors in Open Science’ synthesize the scholarly underpinnings behind the guidance document's recommendations. This work draws upon a targeted search from academic, policy, and grey literature in the fields of open science and community engagement, with a special focus on citizen science, to derive guidance on how to overcome barriers to the uptake of societal engagement approaches. The results present building blocks of what an enabling environment for the open engagement of societal actors could look like, identifying key considerations and reflecting on opportunities and challenges for progressing and evaluating sound open engagement of societal actors into regional &amp; national (open) science policies

COEXISTING PROSTATE CANCER FOUND AT THE TIME OF HOLMIUM LASER ENUCLEATION OF THE PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA: PREDICTING ITS PRESENCE AND GRADE IN ANALYZED TISSUE

Objective: To determine the incidence of prostate cancer identified on holmium laser enucleation of the prostate (HoLEP) specimens and evaluate variables associated with prostate cancer identification. Patients and Methods: All patients undergoing HoLEP between 1998 and 2013 were identified. Patients with a known history of prostate cancer were excluded. Multivariable logistic regression assessed variables associated with identification of prostate cancer on HoLEP specimens and Gleason 7 or higher prostate cancer among the malignant cases. The Gleason grade was used as a proxy for disease severity. Each of the models was adjusted for age, preoperative prostate-specific antigen (PSA), and HoLEP specimen weight. Results: The cohort comprised 1272 patients, of whom 103 (8.1%) had prostate cancer identified. Prostate cancer cases had higher pre-HoLEP PSA (p=0.06) but lower HoLEP specimen weight (p=0.01). On multivariate logistic regression, age and preoperative PSA were associated with increased odds of prostate cancer being present (p<0.01 each), while increasing HoLEP specimen weight was associated with decreased odds of prostate cancer (p<0.001). Men older than 80 had 20% predicted probability of being diagnosed with prostate cancer. Seventy-eight percent of prostate cancer cases were Gleason 6 or less. The pre-HoLEP PSA was associated with increased adjusted odds of intermediate- or high-grade prostate cancer. Conclusion: Prostate cancer identified by HoLEP is not uncommon, but is generally a low-risk disease. Older patients with smaller prostate glands have the highest odds of prostate cancer identification

The political views of doctors in the United Kingdom: A cross sectional study

Background: Little is known about the political views of doctors in the United Kingdom, despite their importance in the functioning of the National Health Service. Methods: Survey-based cross-sectional study in which we asked questions about voting behaviour in 2015 and 2017 UK general elections and 2016 referendum on leaving the European Union (Brexit) and questions relating to recent health policies. Results: 1,172 doctors (45.1% women) from 1,295 responded to an online survey. 60.5% described their political views as ‘left-wing’ and 62.2% described themselves as ‘liberal’. 79.4% of respondents voted to remain in the EU in the 2016 referendum compared to 48.1% of voters as a whole (χ2=819.8, p<0.001). 98.6% of respondents agreed that EU nationals working in the NHS should be able to remain in the UK after Brexit. The median score for the impact of Brexit on the NHS on a scale of 0 (worst impact) to 10 (best impact) was 2 (IQR=1-4). Most respondents agreed with the introduction of minimum alcohol pricing in the UK (73.9%), charging patients who are not eligible for NHS treatment for non-urgent care (70.6%) and protecting a portion of national spending for the NHS (87.1%). 65.8% thought there was too much use of NHS-funded private sector provision in their medical practice. Specialty, income and grade were associated with divergent opinions. Conclusions: UK doctors are left-leaning and liberal in general, which is reflected in their opinions on topical health policy issues. Doctors in the UK voted differently from the general electorate in recent polls

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

Innovating Interdisciplinarity in Higher Education: Exploring the Impact of a Grassroots Community of Practice

Skills in interdisciplinary collaboration are required to address many complex problems facing society. As such, interdisciplinarity is a critical competency for students to develop. However, teachers’ effectiveness in teaching interdisciplinarity is often hindered by silo structures within university faculties. To address this in the Experts in Teamwork (EiT) programme, a MSc in a Norwegian university that develops students’ interdisciplinary teamwork skills through projects that address real-world challenges, a community of practice (CoP) evolved among teachers from different EiT classes. Over 20 months, CoP members participated in digital and in-person discussions, lecture exchanges, student and professional conferences, and co-evaluation of student work, with an aim of better understanding interdisciplinarity and approaches for teaching it to students. The success of the CoP in achieving these aims was evaluated through a series of focus groups consisting of members of the CoP. The CoP achieved some success in fostering pedagogical conversations that were transformative for participants’ understanding of interdisciplinarity in their practice. Participants reported that CoP participation influenced their interactions with students, ultimately helping students to develop a better understanding of interdisciplinarity. However, participants reported limitations in the CoP as a professional development resource, citing its newness and the required time commitment. Participants felt that these issues could be addressed via greater institutional support

The need for consensus on delineation and dose constraints of dentofacial structures in paediatric radiotherapy: Outcomes of a SIOP Europe survey.

BACKGROUND AND PURPOSE: Children receiving radiotherapy for head-and-neck tumours often experience severe dentofacial side effects. Despite this, recommendations for contouring and dose constraints to dentofacial structures are lacking in clinical practice. We report on a survey aiming to understand current practice in contouring and dose assessment to dentofacial structures. METHODS: A digital survey was distributed to European Society for Paediatric Oncology members of the Radiation Oncology Working Group, and member-affiliated centres in Europe, Australia, and New Zealand. The questions focused on clinical practice and aimed to establish areas for future development. RESULTS: Results from 52 paediatric radiotherapy centres across 27 countries are reported. Only 29/52 centres routinely delineated some dentofacial structures, with the most common being the mandible (25 centres), temporo-mandibular joint (22), dentition (13), orbit (10) and maxillary bone (eight). For most bones contoured, an 'As Low As Reasonably Achievable' dose objective was implemented. Only four centres reported age-adapted dose constraints.The largest barrier to clinical implementation of dose constraints was firstly, the lack of contouring guidance (49/52, 94%) and secondly, that delineation is time-consuming (33/52, 63%). Most respondents who routinely contour dentofacial structures (25/27, 90%) agreed a contouring atlas would aid delineation. CONCLUSION: Routine delineation of dentofacial structures is infrequent in paediatric radiotherapy. Based on survey findings, we aim to 1) define a consensus-contouring atlas for dentofacial structures, 2) develop auto-contouring solutions for dentofacial structures to aid clinical implementation, and 3) carry out treatment planning studies to investigate the importance of delineation of these structures for planning optimisation