Maxillofacial haemorrhagic symptoms in emergency department patients: impact of antithrombotics.

PURPOSE: To investigate the effect of antithrombotics on the occurrence of maxillofacial haemorrhagic symptoms, and to determine if these haemorrhagic symptoms are predictors of maxillofacial fractures. METHOD: A prospective cohort study was conducted of consecutive patients with maxillofacial trauma who had been admitted to the emergency department of four hospitals in the Netherlands. This study compared five haemorrhagic symptoms (peri-orbital haematoma, raccoon eyes, epistaxis, subconjunctival ecchymosis, and intra-oral haematoma) between patients not-using (NUA) and using (UA) of antithrombotics, and whether these maxillofacial haemorrhagic symptoms served as predictors for maxillofacial fractures. RESULTS: Out of the 1005 patients, 812 (81%) belonged to the NUA group, and 193 (19%) to the UA group. UA patients exhibited higher frequencies of peri-orbital hematoma (54% vs. 39%, p < 0.001), raccoon eyes (10% vs. 5%, p = 0.01), and subconjunctival ecchymoses (16% vs. 7%, p < 0.001). In NUA, peri-orbital hematoma (OR = 2.5, p < 0.001), epistaxis (OR = 4.1, p < 0.001), subconjunctival ecchymosis (OR = 2.3, p = 0.02), and intra-oral hematoma (OR = 7.1, p < 0.001) were significant fracture predictors. Among UA, peri-orbital hematoma (OR = 2.2, p = 0.04), epistaxis (OR = 5.4, p < 0.001), subconjunctival ecchymosis (OR = 3.7, p = 0.008), and intra-oral hematoma (OR = 22.0, p < 0.001) were significant fracture predictors. CONCLUSION: Maxillofacial haemorrhagic symptoms were observed more frequently in the UA group than in the NUA group. However, in both groups, maxillofacial haemorrhagic symptoms appear to be predictors of maxillofacial fractures. Caution is warranted in attributing these symptoms solely to antithrombotic use during emergency department assessments.

Implementing microwell slides for detection and isolation of single circulating tumor cells from complex cell suspensions.

Cell loss during detection and isolation of circulating tumor cells (CTCs) is a challenge especially when label-free pre-enrichment technologies are used without the aid of magnetic particles. Although microfluidic systems can remove the majority of "contaminating" white blood cells (WBCs), their remaining numbers are still impeding single CTC isolation, thus making additional separation steps needed. This study aimed to develop a workflow from blood-to-single CTC for complex cell suspensions by testing two microwell formats. In the first step, different cell lines were used to compare the performances of Sievewell™ 370 K (TOK, Japan) and CellCelector™ Nanowell U25 (ALS Automated Lab Solutions, Germany) slides for cell labelling and single-cell micromanipulation. Confounding levels of auto-fluorescence inherent to different plastic materials used to cast the microwells, staining recovery rates, and cell isolation rates were determined. In the second step, three different blood preservation tubes were tested for RNA analysis. Lastly, the established workflow was applied to isolate CTCs from peripheral blood samples obtained from metastasized breast cancer (mBC) patients for single-cell DNA and RNA analysis. The detection of CTCs in Sievewell slides profit from better signal-to-noise ratios in the fluorescence channels mainly used for CTC detection. In addition, due to its design, Sievewell supports direct in situ CTC labelling, which minimizes cell loss and leads to single-cell recovery rates after staining of approx. 94%. Detection of PIK3CA mutations in single CTCs verified the applicability of the workflow for the analysis of genomic DNA of CTCs. Furthermore, combined with blood preservation up to 48 h at room temperature in LBguard tubes, panel RT-PCR transcript analysis was successful for single cell line cells and CTCs, respectively. The combined use of Sievewell microwell slides and CellCelector™ automated micromanipulation system improves single CTC detection, labelling and isolation from complex cell suspensions. This approach is especially valuable when samples of high cellular content are processed.

Maxillofacial Fractures in Electric and Conventional Bicycle-Related Accidents.

PURPOSE: With the increased use of both e-bike and conventional bicycle, the number of bicycle-related accidents has increased accordingly. To determine whether there are differences in maxillofacial injuries between these 2 types of bicycle accidents, e-bike and conventional bicycle accidents were compared. MATERIAL AND METHODS: A retrospective cohort study was conducted for all the consecutive patients with maxillofacial injury due to e-bike and conventional bicycle accidents attending the emergency department of 4 hospitals in the Netherlands between May 2018 and October 2019. Primary outcomes are maxillofacial fractures present or absent and the severity of maxillofacial injury using the Maximum Abbreviated Injury Scale and Facial Injury Severity Scale (FISS) after e-bike and conventional bicycle accidents. A binary logistic regression analysis was used to assess differences in risk between an e-bike and conventional bicycle accident, where age, alcohol use, and comorbidities were added as covariates, for maxillofacial fractures, dental injury, and severe maxillofacial fractures. RESULTS: In total, 311 patients were included (73 e-bikers and 238 conventional cyclists). Sex distribution was equal in both groups (45% male vs 55% female). The e-bike group was older (66 vs 53 median age in years, P < .001) and had more comorbidities (0 vs 1, P < .001), while alcohol use was higher in the conventional bicycle group (32% vs 16%, P = .008). e-Bikers sustained midfacial fractures more frequently (47% vs 34%, P = .04), whereas conventional cyclists more often had mandibular fractures (1% vs 11%, P = .01). Although median Maximum Abbreviated Injury Scale and FISS scores did not differ between e-bike and conventional bicycle accidents, severe maxillofacial fractures (FISS score ≥ 2) were observed more often in the conventional cyclists (45% vs 25%, P = .04). No significant differences in risk of midfacial, mandibular, and severe maxillofacial fractures were found between e-bikers and conventional cyclists irrespective of their age, alcohol use, and comorbidities. CONCLUSION: Both the distribution and the severe maxillofacial fractures differed between the e-bike and conventional bicycle accident patients. Patient-specific characteristics, such as age, alcohol use, and comorbidities, may have a greater influence on sustaining maxillofacial fractures than the type of bicycle ridden.

Intraoperative imaging in pathology-assisted surgery.

The pathological assessment of surgical specimens during surgery can reduce the incidence of positive resection margins, which otherwise can result in additional surgeries or aggressive therapeutic regimens. To improve patient outcomes, intraoperative spectroscopic, fluorescence-based, structural, optoacoustic and radiological imaging techniques are being tested on freshly excised tissue. The specific clinical setting and tumour type largely determine whether endogenous or exogenous contrast is to be detected and whether the tumour specificity of the detected biomarker, image resolution, image-acquisition times or penetration depth are to be prioritized. In this Perspective, we describe current clinical standards for intraoperative tissue analysis and discuss how intraoperative imaging is being implemented. We also discuss potential implementations of intraoperative pathology-assisted surgery for clinical decision-making.

The clam and the dam: A Bayesian belief network approach to environmental flow assessment in a data scarce region.

The Volta clam, Galatea paradoxa, is a freshwater macrobenthic bivalve which is endemic to the Lower Volta River in Ghana. The range of occurrence of the clam has been influenced by the flow regime in the Lower Volta which is in turn controlled by operation of two dams located upstream. Previous research has documented the changes to the Lower Volta due to the dams and attempts have been made to design environmental flows (e-flows), freshwater flows to sustain ecosystems, to inform the re-operation of the dams. The past attempts were based on the pre-dam, natural flow regime of the Lower Volta. In this study, a designer e-flow approach is explored using the Volta clam as an indicator species. Using knowledge garnered from various sources on the lifecycle, habitat and the local conditions corresponding to historical and current states of the Volta clams, the factors influencing its extent are visualized and quantified in a Bayesian belief network (BBN). Based on this BBN, an e-flow recommendation for the Lower Volta is for low flows, between 50 m3/s and 330 m3/s, for four months during the Volta clam veliger larva and recruitment life stages which occur in November to March. In addition, it is recommended that full breaching of the sandbar which regularly builds up at the Volta Estuary is done annually and that sand winning on the river bed is prohibited. These e-flow and management recommendations will have consequences for other water users and these have to be investigated, for instance by flow experiments and trade-off analysis. The results show that a BBN is potentially suitable for modelling the linkages between flows, management practices and the status of ecological indicators for the development of e-flows for highly modified rivers in data scarce regions.

Combined transmission, dark field and fluorescence microscopy for intact, 3D tissue analysis of biopsies.

SIGNIFICANCE: Currently, tissue biopsies are sectioned into 3- to 5-µm-thick slices that are used for conventional pathology analysis. Previous work by confocal microscopy and light-sheet microscopy has shown that analyzing biopsies intact in three-dimensions (3D) is possible and may lead to a better understanding of cancer growth patterns. Although accurate, these methods require fluorescent staining of the tissue, in addition to tissue clearing. If the 3D biopsy analysis could be done sufficiently swiftly, this approach may be used for on-site assessment of the adequacy of a biopsy taken. AIM: We aim to show that, by transmission microscopy of optically cleared tissue punches, the tissue architecture can be determined without the need for fluorescent staining. APPROACH: Transmission microscopy is used by combining bright field microscopy with dark field and epifluorescent microscopy to compare samples that have also been analyzed by fluorescent confocal microscopy. RESULTS: With increasing distance to the focal plane, the higher-frequency part of the spatial frequency spectrum of transmitted light is attenuated increasingly. This property is exploited for tissue segmentation, detecting whether tissue is present at a certain position in the focal plane image. Using this approach, we show that a 3D rendering of the internal cavity or tubules structure of punch biopsies, which are up to 1-mm thick, can be acquired in ≈1 min scan time per imaging modality. The images of the overall tissue architecture that are obtained are similar to those from the confocal microscopy benchmark, without requiring fluorescent staining. CONCLUSIONS: Images of the overall tissue architecture can be obtained from transmission microcopy; they are similar to those from the confocal microscopy benchmark without requiring fluorescent staining. Tissue clearing is still needed. The total scan time of the present method is significantly shorter at a fraction of the device costs.

A system dynamics model to quantify the impacts of restoration measures on the water-energy-food nexus in the Urmia lake Basin, Iran.

Water scarcity exacerbated by growing demand in different sectors has created environmental, social, and economic challenges in the Urmia Lake Basin, Iran. Tackling this problem requires an integrated approach considering the basin as an interconnected system where a change in one sector affects others. Here, a System Dynamics Model is developed to simulate the water-energy-food nexus in the Urmia Lake Basin as a holistic multi-sectoral system and to assess the impacts of proposed lake restoration measures, especially looking for trade-offs. Besides considering climate change impacts, the effect of different sets of measures including increasing irrigation efficiency, increasing return flows, inter-basin water transfers, crop land retirement, and reviving a portion of the lake on the natural resources and socio-economic state of the basin are analysed. Results show that Urmia Lake level is sensitive to climate change scenarios. A holistic restoration approach could be effective in increasing the lake level to the proposed ecological level by 2040. However, in doing so, electricity demand in the agricultural sector could grow significantly. It is shown that a 20% retirement of irrigated wheat lands to curb water demand, if coupled with a 20% increase in yield on 80% and 50% of irrigated and rain-fed fields respectively, will not reduce wheat production in the basin. The effectiveness of water demand management measures is highly dependent on continuous monitoring and enforcement, particularly in restricting growth in agricultural water consumption. This study considered all nexus sectors in a holistic way to assess the total impact of proposed measures which on paper look positive, but may have unexpected consequences such as increasing energy demand for electric pumps. In dialogue with Urmia Lake restoration practitioners, this work can feed in to inform effective decisions for the restoration of Urmia Lake.

Sequencing of human genomes extracted from single cancer cells isolated in a valveless microfluidic device.

Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 ± 0.06%) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as the lysis is in sub-nanoliter volumes. Our data thus demonstrates that high quality whole genome sequencing of single cells can be achieved using a relatively simple, inexpensive and scalable device. Detection of genetic heterogeneity at the single cell level, as we have demonstrated for freshly obtained single cancer cells, could soon become available as a clinical tool to precisely match treatment with the properties of a patient's own tumor.

Towards benchmarking citizen observatories: Features and functioning of online amateur weather networks.

Crowd-sourced environmental observations are increasingly being considered as having the potential to enhance the spatial and temporal resolution of current data streams from terrestrial and areal sensors. The rapid diffusion of ICTs during the past decades has facilitated the process of data collection and sharing by the general public and has resulted in the formation of various online environmental citizen observatory networks. Online amateur weather networks are a particular example of such ICT-mediated observatories that are rooted in one of the oldest and most widely practiced citizen science activities, namely amateur weather observation. The objective of this paper is to introduce a conceptual framework that enables a systematic review of the features and functioning of these expanding networks. This is done by considering distinct dimensions, namely the geographic scope and types of participants, the network's establishment mechanism, revenue stream(s), existing communication paradigm, efforts required by data sharers, support offered by platform providers, and issues such as data accessibility, availability and quality. An in-depth understanding of these dimensions helps to analyze various dynamics such as interactions between different stakeholders, motivations to run the networks, and their sustainability. This framework is then utilized to perform a critical review of six existing online amateur weather networks based on publicly available data. The main findings of this analysis suggest that: (1) there are several key stakeholders such as emergency services and local authorities that are not (yet) engaged in these networks; (2) the revenue stream(s) of online amateur weather networks is one of the least discussed but arguably most important dimensions that is crucial for the sustainability of these networks; and (3) all of the networks included in this study have one or more explicit modes of bi-directional communication, however, this is limited to feedback mechanisms that are mainly designed to educate the data sharers.

Inequalities in microbial contamination of drinking water supplies in urban areas: the case of Lilongwe, Malawi.

Over past decades strategies for improving access to drinking water in cities of the Global South have mainly focused on increasing coverage, while water quality has often been overlooked. This paper focuses on drinking water quality in the centralized water supply network of Lilongwe, the capital of Malawi. It shows how microbial contamination of drinking water is unequally distributed to consumers in low-income (unplanned areas) and higher-income neighbourhoods (planned areas). Microbial contamination and residual disinfectant concentration were measured in 170 water samples collected from in-house taps in high-income areas and from kiosks and water storage facilities in low-income areas between November 2014 and January 2015. Faecal contamination (Escherichia coli) was detected in 10% of the 40 samples collected from planned areas, in 59% of the 64 samples collected from kiosks in the unplanned areas and in 75% of the 32 samples of water stored at household level. Differences in water quality in planned and unplanned areas were found to be statistically significant at p < 0.05. Finally, the paper shows how the inequalities in microbial contamination of drinking water are produced by decisions both on the development of the water supply infrastructure and on how this is operated and maintained.

An ecological economic assessment of flow regimes in a hydropower dominated river basin: the case of the lower Zambezi River, Mozambique.

The flow regime of rivers, being an integral part of aquatic ecosystems, provides many important services benefiting humans in catchments. Past water resource developments characterized by river embankments and dams, however, were often dominated by one (or few) economic use(s) of water. This results in a dramatically changed flow regime negatively affecting the provision of other ecosystem services sustained by the river flow. This study is intended to demonstrate the value of alternative flow regimes in a river that is highly modified by the presence of large hydropower dams and reservoirs, explicitly accounting for a broad range of flow-dependent ecosystem services. In this study, we propose a holistic approach for conducting an ecological economic assessment of a river's flow regime. This integrates recent advances in the conceptualization and classification of ecosystem services (UK NEA, 2011) with the flow regime evaluation technique developed by Korsgaard (2006). This integrated approach allows for a systematic comparison of the economic values of alternative flow regimes, including those that are considered beneficial for aquatic ecosystems. As an illustration, we applied this combined approach to the Lower Zambezi Basin, Mozambique. Empirical analysis shows that even though re-operating dams to create environmentally friendly flow regimes reduces hydropower benefits, the gains to goods derived from the aquatic ecosystem may offset the forgone hydropower benefits, thereby increasing the total economic value of river flow to society. The proposed integrated flow assessment approach can be a useful tool for welfare-improving decision-making in managing river basins.

Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries.

Microarray-based enrichment of selected genomic loci is a powerful method for genome complexity reduction for next-generation sequencing. Since the vast majority of exons in vertebrate genomes are smaller than 150 nt, we explored the use of short fragment libraries (85-110 bp) to achieve higher enrichment specificity by reducing carryover and adverse effects of flanking intronic sequences. High enrichment specificity (60-75%) was obtained with a relative even base coverage. Up to 98% of the target-sequence was covered more than 20x at an average coverage depth of about 200x. To verify the accuracy of SNP/mutation detection, we evaluated 384 known non-reference SNPs in the targeted regions. At approximately 200x average sequence coverage, we were able to survey 96.4% of 1.69 Mb of genomic sequence with only 4.2% false negative calls, mostly due to low coverage. Using the same settings, a total of 1197 novel candidate variants were detected. Verification experiments revealed only eight false positive calls, indicating an overall false positive rate of less than 1 per approximately 200,000 bp. Taken together, short fragment libraries provide highly efficient and flexible enrichment of exonic targets and yield relatively even base coverage, which facilitates accurate SNP and mutation detection. Raw sequencing data, alignment files and called SNPs have been submitted into GEO database http://www.ncbi.nlm.nih.gov/geo/ with accession number GSE18542.