Adaptive windowing in contrast-enhanced intravascular ultrasound imaging

Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200 µm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2 dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2 dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium

The Significance of African Lions for the Financial Viability of Trophy Hunting and the Maintenance of Wild Land

Recent studies indicate that trophy hunting is impacting negatively on some lion populations, notably in Tanzania. In 2004 there was a proposal to list lions on CITES Appendix I and in 2011 animal-welfare groups petitioned the United States government to list lions as endangered under their Endangered Species Act. Such listings would likely curtail the trophy hunting of lions by limiting the import of lion trophies. Concurrent efforts are underway to encourage the European Union to ban lion trophy imports. We assessed the significance of lions to the financial viability of trophy hunting across five countries to help determine the financial impact and advisability of the proposed trade restrictions. Lion hunts attract the highest mean prices (US$24,000–US$71,000) of all trophy species. Lions generate 5–17% of gross trophy hunting income on national levels, the proportional significance highest in Mozambique, Tanzania, and Zambia. If lion hunting was effectively precluded, trophy hunting could potentially become financially unviable across at least 59,538 km2 that could result in a concomitant loss of habitat. However, the loss of lion hunting could have other potentially broader negative impacts including reduction of competitiveness of wildlife-based land uses relative to ecologically unfavourable alternatives. Restrictions on lion hunting may also reduce tolerance for the species among communities where local people benefit from trophy hunting, and may reduce funds available for anti-poaching. If lion off-takes were reduced to recommended maximums (0.5/1000 km2), the loss of viability and reduction in profitability would be much lower than if lion hunting was stopped altogether (7,005 km2). We recommend that interventions focus on reducing off-takes to sustainable levels, implementing age-based regulations and improving governance of trophy hunting. Such measures could ensure sustainability, while retaining incentives for the conservation of lions and their habitat from hunting

Cancer survivor rehabilitation and recovery: Protocol for the Veterans Cancer Rehabilitation Study (Vet-CaRes)

Background: Cancer survivors are a rapidly growing and aging population in the U.S., but there are many challenges associated with the survivorship experience such as functional disabilities and psychosocial distress. When viewed next to the general population, Veterans are especially at risk for these challenges as they are older and have a high incidence of co-morbid conditions. While the Institute of Medicine (IOM) has called for further cancer survivorship research to address these challenges, we still know little about this experience from the perspective of aging Veterans. Methods/design We conducted a longitudinal, mixed-methods study over the course of three and a half years at the Boston and Houston VA Medical Centers. We recruited 170 Veterans diagnosed with head and neck, colorectal and esophageal/gastric cancers that were identified from the VA tumor registry. Veterans completed three in-depth interviews, conducted at 6, 12 and 18 months after pathology confirmation, measuring the physical, social and psychological factors related to cancer survivorship. The longitudinal design allowed us to assess any changes in cancer related disability and distress over time. Discussion Weekly teleconference study team meetings were a key aspect to the research process. Issues related to recruitment, data management and analysis, and the dissemination of research results was discussed. Interviewers presented detailed case reports of completed interviews that allowed us to refine our interview protocols. We also discussed issues relevant to the Veteran population of which we were previously unaware and some of the challenges of the research process itself. This novel study produced a robust data set that documents the functional and psychosocial cancer survivorship experiences of aging Veterans. The longitudinal design will help us more fully understand the recovery patterns for this specific population, and identify the unique needs and gaps in health services

Nucleation of Dislocations in 3.9 nm Nanocrystals at High Pressure

As circuitry approaches single nanometer length scales, it is important to predict the stability of metals at these scales. The behavior of metals at larger scales can be predicted based on the behavior of dislocations, but it is unclear if dislocations can form and be sustained at single nanometer dimensions. Here, we report the formation of dislocations within individual 3.9 nm Au nanocrystals under nonhydrostatic pressure in a diamond anvil cell. We used a combination of x-ray diffraction, optical absorbance spectroscopy, and molecular dynamics simulation to characterize the defects that are formed, which were found to be surface-nucleated partial dislocations. These results indicate that dislocations are still active at single nanometer length scales and can lead to permanent plasticity.Comment: 33 pages, 12 figure

Hierarchically modelling Kepler dwarfs and subgiants to improve inference of stellar properties with asteroseismology

This work is a part of a project that has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (CartographY; grant agreement ID 804752). AJL, GRD, and WJC acknowledge the support of the Science and Technology Facilities Council. DH acknowledges support from the Alfred P. Sloan Foundation, the National Aeronautics and Space Administration (80NSSC19K0597), and the National Science Foundation (AST-1717000). MBN acknowledges support from the UK Space Agency. RAG acknowledges the funding from the PLATO CNES grant.With recent advances in modelling stars using high-precision asteroseismology, the systematic effects associated with our assumptions of stellar helium abundance (Y) and the mixing-length theory parameter (αMLT) are becoming more important. We apply a new method to improve the inference of stellar parameters for a sample of Kepler dwarfs and subgiants across a narrow mass range (⁠0.8<M<1.2M⊙). In this method, we include a statistical treatment of Y and the αMLT. We develop a hierarchical Bayesian model to encode information about the distribution of Y and αMLT in the population, fitting a linear helium enrichment law including an intrinsic spread around this relation and normal distribution in αMLT. We test various levels of pooling parameters, with and without solar data as a calibrator. When including the Sun as a star, we find the gradient for the enrichment law, ΔY/ΔZ=1.05+0.28−0.25 and the mean αMLT in the population, μα=1.90+0.10−0.09, μα=1.90+0.10−0.09⁠. While accounting for the uncertainty in Y and αMLT, we are still able to report statistical uncertainties of 2.5 per cent in mass, 1.2 per cent in radius, and 12 per cent in age. Our method can also be applied to larger samples that will lead to improved constraints on both the population level inference and the star-by-star fundamental parameters.Publisher PDFPeer reviewe

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs

Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes

In 2012, an international consensus paper reported that medulloblastoma comprises four molecular subgroups (WNT, SHH, Group 3, and Group 4), each associated with distinct genomic features and clinical behavior. Independently, multiple recent reports have defined further intra-subgroup heterogeneity in the form of biologically and clinically relevant subtypes. However, owing to differences in patient cohorts and analytical methods, estimates of subtype number and definition have been inconsistent, especially within Group 3 and Group 4. Herein, we aimed to reconcile the definition of Group 3/Group 4 MB subtypes through the analysis of a series of 1501 medulloblastomas with DNA-methylation profiling data, including 852 with matched transcriptome data. Using multiple complementary bioinformatic approaches, we compared the concordance of subtype calls between published cohorts and analytical methods, including assessments of class-definition confidence and reproducibility. While the lowest complexity solutions continued to support the original consensus subgroups of Group 3 and Group 4, our analysis most strongly supported a definition comprising eight robust Group 3/Group 4 subtypes (types I–VIII). Subtype II was consistently identified across all component studies, while all others were supported by multiple class-definition methods. Regardless of analytical technique, increasing cohort size did not further increase the number of identified Group 3/Group 4 subtypes. Summarizing the molecular and clinico-pathological features of these eight subtypes indicated enrichment of specific driver gene alterations and cytogenetic events amongst subtypes, and identified highly disparate survival outcomes, further supporting their biological and clinical relevance. Collectively, this study provides continued support for consensus Groups 3 and 4 while enabling robust derivation of, and categorical accounting for, the extensive intertumoral heterogeneity within Groups 3 and 4, revealed by recent high-resolution subclassification approaches. Furthermore, these findings provide a basis for application of emerging methods (e.g., proteomics/single-cell approaches) which may additionally inform medulloblastoma subclassification. Outputs from this study will help shape definition of the next generation of medulloblastoma clinical protocols and facilitate the application of enhanced molecularly guided risk stratification to improve outcomes and quality of life for patients and their families

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of &lt; 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age &lt; 3 or &gt; 10 years (11% v 3% and 33% v 23%, respectively; P &lt; .001) and with longer symptom duration ( P &lt; .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Determining seropositivity-A review of approaches to define population seroprevalence when using multiplex bead assays to assess burden of tropical diseases.

BACKGROUND: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays. METHODOLOGY/PRINCIPAL FINDINGS: A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points. CONCLUSIONS/SIGNIFICANCE: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time