A high throughput array microscope for the mechanical characterization of biomaterials

In the last decade, the emergence of high throughput screening has enabled the development of novel drug therapies and elucidated many complex cellular processes. Concurrently, the mechanobiology community has developed tools and methods to show that the dysregulation of biophysical properties and the biochemical mechanisms controlling those properties contribute significantly to many human diseases. Despite these advances, a complete understanding of the connection between biomechanics and disease will require advances in instrumentation that enable parallelized, high throughput assays capable of probing complex signaling pathways, studying biology in physiologically relevant conditions, and capturing specimen and mechanical heterogeneity. Traditional biophysical instruments are unable to meet this need. To address the challenge of large-scale, parallelized biophysical measurements, we have developed an automated array high-throughput microscope system that utilizes passive microbead diffusion to characterize mechanical properties of biomaterials. The instrument is capable of acquiring data on twelve-channels simultaneously, where each channel in the system can independently drive two-channel fluorescence imaging at up to 50 frames per second. We employ this system to measure the concentration-dependent apparent viscosity of hyaluronan, an essential polymer found in connective tissue and whose expression has been implicated in cancer progression

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Synaptic density in carriers of C9orf72 mutations: a [ 11 C]UCB‐J PET study

Abstract: Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk of frontotemporal dementia from C9orf72 mutation, using [11C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls and one symptomatic patient with behavioural variant frontotemporal dementia. The three pre‐symptomatic C9orf72 carriers showed reduced synaptic density in the thalamus compared to controls, and there was an additional extensive synaptic loss in frontotemporal regions of the symptomatic patient. [11C]UCB‐J PET may facilitate early, pre‐symptomatic assessment, monitoring of disease progression and evaluation of new preventive treatment strategies for frontotemporal dementia

Synaptic density in carriers of C9orf72 mutations: a [ 11 C]UCB‐J PET study

Abstract: Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk of frontotemporal dementia from C9orf72 mutation, using [11C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls and one symptomatic patient with behavioural variant frontotemporal dementia. The three pre‐symptomatic C9orf72 carriers showed reduced synaptic density in the thalamus compared to controls, and there was an additional extensive synaptic loss in frontotemporal regions of the symptomatic patient. [11C]UCB‐J PET may facilitate early, pre‐symptomatic assessment, monitoring of disease progression and evaluation of new preventive treatment strategies for frontotemporal dementia

HIF1α and HIF2α independently activate SRC to promote melanoma metastases

Malignant melanoma is characterized by a propensity for early lymphatic and hematogenous spread. The hypoxia-inducible factor (HIF) family of transcription factors is upregulated in melanoma by key oncogenic drivers. HIFs promote the activation of genes involved in cancer initiation, progression, and metastases. Hypoxia has been shown to enhance the invasiveness and metastatic potential of tumor cells by regulating the genes involved in the breakdown of the ECM as well as genes that control motility and adhesion of tumor cells. Using a Pten -deficient, Braf -mutant genetically engineered mouse model of melanoma, we demonstrated that inactivation of HIF1α or HIF2α abrogates metastasis without affecting primary tumor formation. HIF1α and HIF2α drive melanoma invasion and invadopodia formation through PDGFRα and focal adhesion kinase–mediated (FAK-mediated) activation of SRC and by coordinating ECM degradation via MT1-MMP and MMP2 expression. These results establish the importance of HIFs in melanoma progression and demonstrate that HIF1α and HIF2α activate independent transcriptional programs that promote metastasis by coordinately regulating cell invasion and ECM remodeling

Pangolins in global camera trap data: Implications for ecological monitoring

Despite being heavily exploited, pangolins (Pholidota: Manidae) have been subject to limited research, resulting in a lack of reliable population estimates and standardised survey methods for the eight extant species. Camera trapping represents a unique opportunity for broad-scale collaborative species monitoring due to its largely non-discriminatory nature, which creates considerable volumes of data on a relatively wide range of species. This has the potential to shed light on the ecology of rare, cryptic and understudied taxa, with implications for conservation decision-making. We undertook a global analysis of available pangolin data from camera trapping studies across their range in Africa and Asia. Our aims were (1) to assess the utility of existing camera trapping efforts as a method for monitoring pangolin populations, and (2) to gain insights into the distribution and ecology of pangolins. We analysed data collated from 103 camera trap surveys undertaken across 22 countries that fell within the range of seven of the eight pangolin species, which yielded more than half a million trap nights and 888 pangolin encounters. We ran occupancy analyses on three species (Sunda pangolin Manis javanica, white-bellied pangolin Phataginus tricuspis and giant pangolin Smutsia gigantea). Detection probabilities varied with forest cover and levels of human influence for P. tricuspis, but were low (<0.05) for all species. Occupancy was associated with distance from rivers for M. javanica and S. gigantea, elevation for P. tricuspis and S. gigantea, forest cover for P. tricuspis and protected area status for M. javanica and P. tricuspis. We conclude that camera traps are suitable for the detection of pangolins and large-scale assessment of their distributions. However, the trapping effort required to monitor populations at any given study site using existing methods appears prohibitively high. This may change in the future should anticipated technological and methodological advances in camera trapping facilitate greater sampling efforts and/or higher probabilities of detection. In particular, targeted camera placement for pangolins is likely to make pangolin monitoring more feasible with moderate sampling efforts

Developing a Growth Mindset through outdoor personal development: can an intervention underpinned by psychology increase the impact of an outdoor learning course for young people?

This study considers the impact of using a series of Mindset interventions during a five-day outdoor personal development (OPD) course. Self-efficacy, resilience and Mindset were measured pre course, post course and one month post course. It was hypothesised that both experimental and control groups would increase their self-efficacy and resilience, and that the Mindset (experimental) group would significantly increase beyond the levels of the control group, who took part in the standard OPD course. It was also predicted that the Mindset group would move towards a Growth Mindset, whereas the control group would not show any change in Mindset. Hypotheses were tested using a randomised, quasi-experimental method. Separate mixed analyses of variance were carried out for each dependent variable, followed by planned comparisons and post-hoc tests using a Bonferroni correction. Results showed that both groups increased self-efficacy over time; however, there was no further significance for the experimental group. Resilience only increased significantly in the experimental group while the control group made no significant gain, and students in the experimental group moved significantly towards a Growth Mindset while the control group did not

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe