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  1. Subramanian P, Allcock N, James V, Lathlean J
    J Clin Nurs, 2012 May;21(9-10):1254-62.
    PMID: 21777315 DOI: 10.1111/j.1365-2702.2011.03789.x
    To explore nurses' challenges in managing pain among ill patients in critical care.
  2. James V, Kee CY, Ong GY
    J Emerg Med, 2019 Apr;56(4):421-425.
    PMID: 30638645 DOI: 10.1016/j.jemermed.2018.12.015
    BACKGROUND: Point-of-care ultrasonography (POCUS) is increasingly used for both diagnostic and guided procedures. Increasingly, POCUS has been used for identification of pneumonia and to assist in the differentiation of pleural effusions, as well as to guide thoracentesis. As such, there is a need for training with ideally high-fidelity lung ultrasound phantoms to ensure ultrasound proficiency and procedural competency. Unfortunately, most commercial ultrasound phantoms remain expensive and may have limited fidelity.

    OBJECTIVE: Our aim was to create and describe a homemade, high-fidelity ultrasound phantom model for demonstrating pneumonia with pleural effusions for teaching purposes.

    DISCUSSION: An ultrasound phantom was constructed using a water-filled latex glove with a sliver of meat in it, covered over by a palm-sized piece of meat (skin and ribs are optional to increase ultrasonographic details and realism). This would appear like parapneumonic effusions with organized pneumonia under ultrasound examination. Creamer (or talc) can be added to the water in the glove to simulate empyema. The model can also be used to teach simple effusions and for ultrasound-guided thoracentesis and in clinical decision making.

    CONCLUSIONS: Easily prepared, homemade high-fidelity ultrasound phantom models for instructions on identification of pleural effusions and ultrasound-guided pleural tap of parapneumonic effusion were made.

  3. James V, Samuel J, Kee CY, Ong GY
    Ultrasound J, 2020 Dec 03;12(1):51.
    PMID: 33270182 DOI: 10.1186/s13089-020-00199-y
    BACKGROUND: The presence of intra-abdominal calcification in the pediatric population can be due to a wide range of conditions. Calcification in the abdomen can be seen in normal or abnormal anatomical structures. In some patients, abnormal calcification points towards the pathology; whereas in others, calcification itself is the pathology. After a thorough history and clinical examination, point-of-care ultrasound (POCUS) would complement the assessment of acute abdominal pain, based on the list of differentials generated as per the abdominal region. The main objective of this article is to review commonly encountered causes of intra-abdominal calcifications in the pediatric population and help in clinical decision-making in a Pediatric Emergency Department.

    CASE PRESENTATION: We describe a series of pediatric patients who presented to the Pediatric Emergency Department with acute abdominal pain, in whom point-of-care ultrasound helped expedite the diagnosis by identifying varying types of calcification and associated sonological findings. For children who present to the Pediatric Emergency Department with significant abdominal pain, a rapid distinction between emergencies and non-emergencies is vital to decrease morbidity and mortality.

    CONCLUSIONS: In a child presenting to the Pediatric Emergency Department with abdominal pain, POCUS and the findings of calcifications can narrow or expand the differential diagnosis when integrated with history and physical exam, to a specific anatomic structure. Integrating these findings with additional sonological findings of an underlying pathology might raise sufficient concerns in the emergency physicians to warrant further investigations for the patient in the form of a formal radiological ultrasound and assist in the patient's early disposition. The use of POCUS might also help to categorize the type of calcification to one of the four main categories of intra-abdominal calcifications, namely concretions, conduit wall calcification, cyst wall calcification, and solid mass-type calcification. POCUS used thoughtfully can give a diagnosis and expand differential diagnosis, reduce cognitive bias, and reduce physician mental load. By integrating the use of POCUS with the history and clinical findings, it will be possible to expedite the management in children who present to the Pediatric Emergency Department with acute abdominal pain.

  4. Ong YN, James V, Lau KS, Chor YK, Ong GY
    Pediatr Emerg Care, 2022 Apr 01;38(4):183-186.
    PMID: 34608058 DOI: 10.1097/PEC.0000000000002555
    Abdominal pain is one of the most common presenting complaints encountered in the pediatric emergency department. The use of point-of-care ultrasonography by emergency physicians has been shown to expedite the diagnosis of a large variety of conditions and can be used to accurately identify intra-abdominal pathology in children. We describe the case of a pediatric patient who presented to the pediatric emergency department with acute abdominal pain, in whom point-of-care ultrasonography helped expedite the diagnosis of acute portal vein thrombosis and liver abscess.
  5. Chave J, Condit R, Muller-Landau HC, Thomas SC, Ashton PS, Bunyavejchewin S, et al.
    PLoS Biol, 2008 Mar 04;6(3):e45.
    PMID: 18318600 DOI: 10.1371/journal.pbio.0060045
    In Amazonian tropical forests, recent studies have reported increases in aboveground biomass and in primary productivity, as well as shifts in plant species composition favouring fast-growing species over slow-growing ones. This pervasive alteration of mature tropical forests was attributed to global environmental change, such as an increase in atmospheric CO2 concentration, nutrient deposition, temperature, drought frequency, and/or irradiance. We used standardized, repeated measurements of over 2 million trees in ten large (16-52 ha each) forest plots on three continents to evaluate the generality of these findings across tropical forests. Aboveground biomass increased at seven of our ten plots, significantly so at four plots, and showed a large decrease at a single plot. Carbon accumulation pooled across sites was significant (+0.24 MgC ha(-1) y(-1), 95% confidence intervals [0.07, 0.39] MgC ha(-1) y(-1)), but lower than reported previously for Amazonia. At three sites for which we had data for multiple census intervals, we found no concerted increase in biomass gain, in conflict with the increased productivity hypothesis. Over all ten plots, the fastest-growing quartile of species gained biomass (+0.33 [0.09, 0.55] % y(-1)) compared with the tree community as a whole (+0.15 % y(-1)); however, this significant trend was due to a single plot. Biomass of slow-growing species increased significantly when calculated over all plots (+0.21 [0.02, 0.37] % y(-1)), and in half of our plots when calculated individually. Our results do not support the hypothesis that fast-growing species are consistently increasing in dominance in tropical tree communities. Instead, they suggest that our plots may be simultaneously recovering from past disturbances and affected by changes in resource availability. More long-term studies are necessary to clarify the contribution of global change to the functioning of tropical forests.
  6. Park J, Choi JY, Choi J, Chung S, Song N, Park SK, et al.
    Cancers (Basel), 2021 May 14;13(10).
    PMID: 34069208 DOI: 10.3390/cancers13102370
    In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10-3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10-4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
  7. Zanti M, O'Mahony DG, Parsons MT, Li H, Dennis J, Aittomäkkiki K, et al.
    Hum Mutat, 2023;2023.
    PMID: 38725546 DOI: 10.1155/2023/9961341
    A large number of variants identified through clinical genetic testing in disease susceptibility genes, are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion), can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analyses of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC), and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity - findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared to classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and pre-formatted excel calculators for implementation of the method for rare variants in BRCA1, BRCA2 and other high-risk genes with known penetrance.
  8. Morra A, Jung AY, Behrens S, Keeman R, Ahearn TU, Anton-Culver H, et al.
    Cancer Epidemiol Biomarkers Prev, 2021 Apr;30(4):623-642.
    PMID: 33500318 DOI: 10.1158/1055-9965.EPI-20-0924
    BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

    METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

    RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

    CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

    IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

  9. Delavaux CS, Crowther TW, Zohner CM, Robmann NM, Lauber T, van den Hoogen J, et al.
    Nature, 2023 Sep;621(7980):773-781.
    PMID: 37612513 DOI: 10.1038/s41586-023-06440-7
    Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.
  10. Delavaux CS, Crowther TW, Zohner CM, Robmann NM, Lauber T, van den Hoogen J, et al.
    Nature, 2023 Oct;622(7982):E2.
    PMID: 37752352 DOI: 10.1038/s41586-023-06654-9
  11. Mo L, Zohner CM, Reich PB, Liang J, de Miguel S, Nabuurs GJ, et al.
    Nature, 2023 Dec;624(7990):92-101.
    PMID: 37957399 DOI: 10.1038/s41586-023-06723-z
    Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2-5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151-363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.
  12. Ma H, Crowther TW, Mo L, Maynard DS, Renner SS, van den Hoogen J, et al.
    Nat Plants, 2023 Nov;9(11):1795-1809.
    PMID: 37872262 DOI: 10.1038/s41477-023-01543-5
    Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.
  13. Mueller SH, Lai AG, Valkovskaya M, Michailidou K, Bolla MK, Wang Q, et al.
    Genome Med, 2023 Jan 26;15(1):7.
    PMID: 36703164 DOI: 10.1186/s13073-022-01152-5
    BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.

    METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.

    RESULTS: In European ancestry samples, 14 genes were significantly associated (q 

  14. Baxter JS, Johnson N, Tomczyk K, Gillespie A, Maguire S, Brough R, et al.
    Am J Hum Genet, 2021 Jul 01;108(7):1190-1203.
    PMID: 34146516 DOI: 10.1016/j.ajhg.2021.05.013
    A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
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