Search Results (25)

The problem of estimating the ratio of the means of a two-component Poisson mixture model is considered, when each component is subject to zero-inflation, i.e., excess zero counts. The resulting zero-inflated Poisson mixture (ZIPM) model can be viewed as a three-component Poisson mixture model with one degenerate component. The EM algorithm is applied to obtain frequentist estimators and their standard errors, the latter determined via an explicit expression for the observed information matrix. As an intermediate step, we derive an explicit expression for standard errors in the two-component Poisson mixture model (without zero-inflation), a new result. The ZIPM model is applied to simulated data and real ecological count data of frigatebirds on the Coral Sea Islands off the coast of Northeast Australia. Full article

The kinetic stability provided by the sterically demanding {SiN^Dipp}²⁻ dianion (SiN^Dipp = {CH₂SiMe₂NDipp}₂; Dipp = 2,6-i-Pr₂C₆H₃) is intrinsic to the isolation of not only the group 1 alumanyl reagents ([{SiN^Dipp}AlM]₂; M = K, Rb, Cs) but also facilitates the completely selective oxidative addition of a C-H bond of 1,2-C₂B₁₀H₁₂ to the aluminium centre. In each case, the resultant compounds comprise a four-coordinate o-carboranyl (hydrido)aluminate anion, [(SiN^Dipp)Al(H)(1,2-C₂B₁₀H₁₁)]⁻, in which the carboranyl cage is bonded to aluminium by an Al-C σ bond. Although the anions further assemble as extended network structures based on Al-H∙∙∙M, B-H∙∙∙M, and C-H∙∙∙M interactions, each structure is unique due to the significant variation in M⁺ ionic radius as group 1 is descended. The potassium derivative crystallises as a one-dimensional polymer, its rubidium analogue is a dimer due to the polyhapto-sequestration of a molecule of benzene solvent within the alkali metal coordination sphere, and the caesium species is a two-dimensional assembly of hexameric aggregates. Full article

Accurate hydrological data with high spatial resolution is important for flood risk and water resource management, particularly under the context of climate change. The cost of monitoring networks, as well as the characteristics of the hydrological environment itself, can be a barrier to meeting these data requirements, however. This study covers the design and testing of a low-cost, “build-it-yourself”, instream water depth sensor providing an assessment of its potential in future hydrological monitoring projects. The low-cost sensor was built using an Arduino microcontroller, a differential pressure sensor and a thermistor, a real-time clock, and an SD card module. The low-cost logger was deployed in tandem with a factory-calibrated Solinst^®LevelLogger^® 5 Junior for 6 months in the River Wissey, UK. We found the mean absolute error of the Arduino-based logger relative to the commercial setup to be ±0.69 cm for water depth and ±0.415 °C for water temperature. Economically, the Arduino-based logger offers an advantage, costing a total of £133.35 (USD 168.26 at time of publication) comparative to the industrial comparison’s cost of £408 (USD 514.83 at time of publication). This study concludes that the low cost of the Arduino-based logger gives a strong advantage to its incorporation in hydrological data collection, if the trade-offs (i.e., time investment and accuracy) are considered acceptable and appropriate for a project. Full article

Complex structural chromosome abnormalities such as chromoanagenesis have been reported in acute myeloid leukemia (AML). They are usually not well characterized by conventional genetic methods, and the characterization of chromoanagenesis structural abnormalities from short-read sequencing still presents challenges. Here, we characterized complex structural abnormalities involving chromosomes 2, 3, and 7 in an AML patient using an integrated approach including CRISPR/Cas9-mediated nanopore sequencing, mate pair sequencing (MPseq), and SNP microarray analysis along with cytogenetic methods. SNP microarray analysis revealed chromoanagenesis involving chromosomes 3 and 7, and a pseudotricentric chromosome 7 was revealed by cytogenetic methods. MPseq revealed 138 structural variants (SVs) as putative junctions of complex rearrangements involving chromosomes 2, 3, and 7, which led to 16 novel gene fusions and 33 truncated genes. Thirty CRISPR RNA (crRNA) sequences were designed to map 29 SVs, of which 27 (93.1%) were on-target based on CRISPR/Cas9 crRNA nanopore sequencing. In addition to simple SVs, complex SVs involving over two breakpoints were also revealed. Twenty-one SVs (77.8% of the on-target SVs) were also revealed by MPseq with shared SV breakpoints. Approximately three-quarters of breakpoints were located within genes, especially intronic regions, and one-quarter of breakpoints were intergenic. Alu and LINE repeat elements were frequent among breakpoints. Amplification of the chromosome 7 centromere was also detected by nanopore sequencing. Given the high amplification of the chromosome 7 centromere, extra chromosome 7 centromere sequences (tricentric), and more gains than losses of genomic material, chromoanasynthesis and chromothripsis may be responsible for forming this highly complex structural abnormality. We showed this combination approach’s value in characterizing complex structural abnormalities for clinical and research applications. Characterization of these complex structural chromosome abnormalities not only will help understand the molecular mechanisms responsible for the process of chromoanagenesis, but also may identify specific molecular targets and their impact on therapy and overall survival. Full article

Hydrothermal liquefaction (HTL) is often mooted as a promising and sustainable processing methodology for converting biomass into usable products, including bio-oils, which can potentially alleviate humanity’s reliance on fossil fuels. To date, most HTL development work with novel biomasses has been undertaken at the laboratory scale in batch processes, and the results have been extrapolated to the theoretical continuous flow processes required for industrial uptake. Here, we assess the use of a novel continuous flow HTL system, applying it to Sargassum (seaweed) material and generating a bio-oil, which is assessed against typical crude oil fractions. Full article

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE. Full article

High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and −0.21 respectively) and low (r = −0.46, −0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = −0.11 to −0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature. Full article

Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula. Full article

Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ_½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1–18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ_½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact on muscle metabolism. Full article

Background: A better understanding of neighborhood-level factors’ contribution is needed in order to increase the precision of cancer control interventions that target geographic determinants of cancer health disparities. This study characterized the distribution of neighborhood deprivation in a racially diverse cohort of prostate cancer survivors. Methods: A retrospective cohort of 253 prostate cancer patients who were treated with radical prostatectomy from 2011 to 2019 was established at the Medical University of South Carolina. Individual-level data on clinical variables (e.g., stage, grade) and race were abstracted. Social Deprivation Index (SDI) and Healthcare Professional Shortage (HPS) status was obtained from the Robert Graham Center and assigned to participants based on their residential census tract. Data were analyzed with descriptive statistics and multivariable logistic regression. Results: The cohort of 253 men consisted of 168 white, 81 African American, 1 Hispanic and 3 multiracial men. Approximately 49% of 249 men lived in areas with high SDI (e.g., SDI score of 48 to 98). The mean for SDI was 44.5 (+27.4), and the range was 97 (1–98) for all study participants. African American men had a significantly greater likelihood of living in a socially deprived neighborhood compared to white men (OR = 3.7, 95% C.I. 2.1–6.7, p < 0.01), while men who lived in areas with higher HPS shortage status were significantly more likely to live in a neighborhood that had high SDI compared to men who lived in areas with lower HPS shortages (OR = 4.7, 95% C.I. = 2.1–10.7, p < 0.01). African Americans had a higher likelihood of developing biochemical reoccurrence (OR = 3.7, 95% C.I. = 1.7–8.0) compared with white men. There were no significant association between SDI and clinical characteristics of prostate cancer. Conclusions: This study demonstrates that SDI varies considerably by race among men with prostate cancer treated with radical prostatectomy. Using SDI to understand the social environment could be -particularly useful as part of precision medicine and precision public health approaches and could be used by cancer centers, public health providers, and other health care specialists to inform operational decisions about how to target health promotion and disease prevention efforts in catchment areas and patient populations. Full article

The classification and quantification of fuel is traditionally a labour-intensive, costly and often subjective operation, especially in hazardous vegetation types, such as gorse (Ulex europaeus L.) scrub. In this study, unmanned aerial vehicle (UAV) technologies were assessed as an alternative to traditional field methodologies for fuel characterisation. UAV laser scanning (ULS) point clouds were captured, and a variety of spatial and intensity metrics were extracted from these data. These data were used as predictor variables in models describing destructively and non-destructively sampled field measurements of total above ground biomass (TAGB) and above ground available fuel (AGAF). Multiple regression of the structural predictor variables yielded correlations of R² = 0.89 and 0.87 for destructively sampled measurements of TAGB and AGAF, respectively, with relative root mean square error (RMSE) values of 18.6% and 11.3%, respectively. The best metrics for non-destructive field-measurements yielded correlations of R² = 0.50 and 0.49, with RMSE values of 40% and 30.8%, for predicting TAGB and AGAF, respectively, indicating that ULS-derived structural metrics offer higher levels of precision. UAV-derived versions of the field metrics (overstory height and cover) predicted TAGB and AGAF with R² = 0.44 and 0.41, respectively, and RMSE values of 34.5% and 21.7%, demonstrating that even simple metrics from a UAV can still generate moderate correlations. In further analyses, UAV photogrammetric data were captured and automatically processed using deep learning in order to classify vegetation into different fuel categories. The results yielded overall high levels of precision, recall and F1 score (0.83 for each), with minimum and maximum levels per class of F1 = 0.70 and 0.91. In conclusion, these ULS-derived metrics can be used to precisely estimate fuel type components and fuel load at fine spatial resolutions over moderate-sized areas, which will be useful for research, wildfire risk assessment and fuel management operations. Full article

In the Subantarctic sector of the Southern Ocean, vertical entrainment of iron (Fe) triggers the seasonal productivity cycle but diminishing physical supply during the spring to summer transition forces microbial assemblages to rapidly acclimate. Here, we tested how phytoplankton and bacteria within an isolated eddy respond to different dissolved Fe (DFe)/ligand inputs. We used three treatments: one that mimicked the entrainment of new DFe (Fe-NEW), another in which DFe was supplied from bacterial regeneration of particles (Fe-REG), and a control with no addition of DFe (Fe-NO). After 6 days, 3.5 (Fe-NO, Fe-NEW) to 5-fold (Fe-REG) increases in Chlorophyll a were observed. These responses of the phytoplankton community were best explained by the differences between the treatments in the amount of DFe recycled during the incubation (Fe-REG, 15% recycled c.f. 40% Fe-NEW, 60% Fe-NO). This additional recycling was more likely mediated by bacteria. By day 6, bacterial production was comparable between Fe-NO and Fe-NEW but was approximately two-fold higher in Fe-REG. A preferential response of phytoplankton (haptophyte-dominated) relative to high nucleic acid (HNA) bacteria was also found in the Fe-REG treatment while the relative proportion of diatoms increased faster in the Fe-NEW and Fe-NO treatments. Comparisons between light and dark incubations further confirmed the competition between picophytoplankton and HNA for DFe. Overall, our results demonstrate great versatility by microorganisms to use different Fe sources that results in highly efficient Fe recycling within surface waters. This study also encourages future research to further investigate the interactions between functional groups of microbes (e.g. HNA and cyanobacteria) to better constraint modeling in Fe and carbon biogeochemical cycles. Full article

The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges. Full article

A finite difference model of a heat exchanger (HX) considered maldistribution, axial conduction, heat leak, and the edge effect, all of which are needed to model a high effectiveness HX. An HX prototype was developed, and channel height data were obtained using a computerized tomography (CT) scan from previous work along with experimental results. This study used the core geometry data to model results with the finite difference model, and compared the modeled and experimental results to help improve the expanded microchannel HX (EMHX) prototype design. The root mean square (RMS) error was 3.8%. Manifold geometries were not put into the model because the data were not available, so impacts of the manifold were investigated by varying the temperature conditions at the inlet and exit of the core. Previous studies have not considered the influence of heat transfer in the manifold on the HX effectiveness when maldistribution is present. With no flow maldistribution, manifold heat transfer increases overall effectiveness roughly as would be expected by the greater heat transfer area in the manifolds. Manifold heat transfer coupled with flow maldistribution for the prototype, however, causes a decrease in the effectiveness at high flow rate, and an increase in effectiveness at low flow rate. Full article

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells enter a mechanical microenvironment that is substantially different to that of the primary tumour and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate healthy bone remodelling in response to physical exercise. However, the effects of mechanical loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast (MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress. We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour growth, characterised by reduced proliferation and invasion and increased migration. In breast cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast, conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells. To further investigate these interactions, we developed a microfluidic organ-chip model using the Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate these factors into predictive in vitro models of bone metastasis. Full article