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Background Participants in two recent National Academy of Medicine workshops identified a need for more multi-disciplinary professionals on teams to assist oncology clinicians in precision oncology. Methods We developed a graduate school course to prepare biomedical students and pharmacy students to work within a multidisciplinary team of oncology clinicians, pathologists, radiologists, clinical pharmacists, and genetic counselors. Students learned precision oncology skills via case-based learning, hands-on data analyses, and presentations to peers. After the course, a focus group session was conducted to gain an in-depth student perspective on their interprofessional training experience, achievement of the course learning outcomes, ways to improve the course design in future offerings, and how the course could improve future career outcomes. A convenience sampling strategy was used for recruitment into the focus group session. A thematic content analysis was then conducted using the constant comparative method. Results Major themes arising from student feedback were (1) appreciation of a customized patient case-based teaching approach, (2) more emphasis on using data analysis tools, (3) valuing interdisciplinary inclusion, and (4) request for more student discussion with advanced preparation materials. Conclusions Feedback was generally positive and supports the continuation and expansion of the precision oncology course to include more hands-on instruction on the use of clinical bioinformatic tools.

Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients diagnosed with a psychiatric disorder at the Loyola University Medical Center, for whom PGx testing was performed. Information collected included demographics at the time of testing, psychiatric diagnosis, medical and psychiatric history and medications prior and after PGx testing. Of the 592 charts analyzed, the most common primary diagnoses were depression (52%) and anxiety (12%). Prior to PGx testing, 72% of patients were prescribed three or more medications, whereas, after testing, only 44% were prescribed three or more medications included in the test panel (p &lt, 0.0001). The most common clinical consideration on the PGx reports was recommendation to reduce dosages (33%). After PGx testing, the proportion of patients taking incongruent medications decreased from 26% to 19% and that of patients taking congruent medications increased from 74% to 81% (p = 0.006). The results from this retrospective data analysis demonstrated a reduction in polypharmacy and an increase in recommendation-congruent medication prescribing resulting from implementation of PGx testing.

IMPORTANCE: Smoking quitline programs effectively promote smoking cessation in outpatient primary care settings. OBJECTIVE: To examine the factors associated with smoking quitline engagement and smoking cessation among patients undergoing thoracic surgery who consented to a quitline electronic referral. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted from January 1, 2014, to December 31, 2018, among 111 active smoking patients referred to the quitline from a thoracic surgery outpatient clinic visit. Patients were divided into operative and nonoperative cohorts. MAIN OUTCOMES AND MEASURES: Primary outcomes were engagement rates in the quitline program and successful smoking cessation. Secondary outcomes were self-reported point prevalence abstinence at 1 month and 6 months after the smoking quit date. RESULTS: Of 111 patients (62 men; mean [SD] age, 61.8 [11.2] years) who had a quitline referral, 58 (52%) underwent surgery, and 32 of these 58 patients (55%) participated in the program. Of the 53 nonoperative patients (48%), 24 (45%) participated in the program. In the operative cohort, there was no difference in the smoking cessation rate between quitline participants and nonparticipants (21 of 32 [66%] vs 16 of 6 [62%]; P = .79) or in point prevalence abstinence at 1 month (23 of 32 [72%] vs 14 of 25 [56%]; P = .27) or 6 months (14 of 28 [50%] vs 6 of 18 [33%]; P = .36). Similarly, in the nonoperative cohort, there was no difference in the smoking cessation rate between quitline participants and nonparticipants (8 of 24 [33%] vs 11 of 29 [38%]; P = .78) or in point prevalence abstinence at 1 month (7 of 24 [29%] vs 8 of 27 [30%]; P = .99) or 6 months (6 of 23 [26%] vs 6 of 25 [24%]; P = .99). Regardless of quitline participation, operative patients had a 1.8-fold higher proportion of successful smoking cessation compared with nonoperative patients (37 of 58 [64%] vs 19 of 53 [36%]; P = .004) as well as a 2.2-fold higher proportion of 1-month point prevalence abstinence (37 of 57 [65%] vs 15 of 51 [29%]; P

Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies.We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage.Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively.A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC3 cm, even in the absence of nodal involvement.

Background The role of sublobar resection in the treatment of pulmonary typical carcinoids is controversial. This study aims to compare long-term outcomes between sublobar and lobar resections in patients with peripheral typical carcinoid. Methods We retrospectively compared consecutive patients who underwent curative sublobar resection with patients who underwent lobectomy for cT1-3 N0 M0 peripheral pulmonary typical carcinoid in eight centers between 2000 and 2015. Primary outcomes were rates and patterns of recurrence and overall survival. Cox regression modeling was performed to identify factors influencing overall survival and recurrence. Propensity score analysis was done, and overall survival was compared between the two groups. Results In all, 177 patients were analyzed, consisting of 74 sublobar resections and 103 lobectomies, with a total of 857 person-years of follow-up. The R1 resection rates were 7% and 1% after sublobar resection and lobectomy, respectively (P = .08). One of 5 patients with sublobar R1 resection had recurrence. Recurrence rate was 0.02 (95% confidence interval [CI]: 0.009 to 0.044) per person-year of follow-up after sublobar resection and 0.008 (95% CI: 0.003 to 0.02) after lobectomy (P = .15). Five-year survival rates were 91.7% (95% CI: 78.5% to 96.9%) and 97.4% (95% CI: 90.1% to 99.4%) after sublobar and lobar resection, respectively (P = .08). Extent of resection was not a predictor of recurrence or survival. Propensity score analysis confirmed a similar survival and freedom from recurrence between the two groups. Conclusions Sublobar resection of peripheral cT1-3 N0 M0 pulmonary typical carcinoid was not associated with worse short- or long-term outcomes compared with lobectomy. In select patients, sublobar resection may be considered for treatment of peripheral typical carcinoids if an R0 resection is obtained.

Management of any disaster event (i.e., hurricanes, flooding, wildfires, viral pandemic) is a complicated task. An important and frequently overlooked aspect of efficient disaster response is effective information exchange among emergency managers, aging and social service providers, and those impacted by the disaster. Breakdowns in communication are regularly cited as failures in actual emergency situations. Older adults have unique challenges to effective communication during a disaster event. Further, messaging platforms may be inaccessible to older adults. Given the lack of data collected on the role of effective communication for older adults in a disaster event, we developed this symposium to highlight lessons learned for facilitating disaster communication among older community members and discuss how policy can further disaster communication efforts. The first presentation highlights the advantages of using targeted marketing communication channels to encourage older adults to prepare and recover from a disaster, as well as the value of collaborative partnerships in this communication. The second presentation introduces results from research collected from older adults on their use of social media to stay informed before and after Hurricane Matthew. The third presentation explores whether assisted living communities in Florida’s affected counties evacuated or sheltered in place in the context of emergency management communications concerning evacuation. The fourth presentation highlights the experiences of older persons in Houston’s communication post-Hurricane Harvey from an aging service provider’s perspective. The final presentation discusses disaster literacy and how this model can be used to enhance outcomes at all phases of a disaster. Disasters and Older Adults Interest Group Sponsored Symposium.

Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secrete extracellular vesicles (EVs) was not pursued until recently due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following their discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteria are implicated in virulence, toxin release, and transference to host cells, eliciting immune responses, and spread of antibiotic resistance. Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis. Here we report that L. monocytogenes produces EVs with diameters ranging from 20 to 200 nm, containing the pore-forming toxin listeriolysin O (LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Cell-free EV preparations were toxic to mammalian cells, the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion of plcA increased EV toxicity, suggesting PI-PLC reduced LLO activity. Using simultaneous metabolite, protein, and lipid extraction (MPLEx) multiomics we characterized protein, lipid, and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Using immunogold EM we detected LLO at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released from L. monocytogenes during infection. Our findings demonstrate that L. monocytogenes uses EVs for toxin release and implicate these structures in mammalian cytotoxicity.

The influence of existing vulnerabilities on the medium to long term effects of disasters are examined in this study of older adults living through the 2010–2011 Canterbury earthquake series. Data were provided by participants responding to the New Zealand Health, Work and Retirement longitudinal surveys conducted in 2010, 2012 and 2014 (n = 428; aged 50–83) who lived in the Canterbury region during the 2010–2011 earthquakes. Latent profile growth analyses were used to identify respondents who had similar physical and mental health profiles pre- and post-disaster. Groups were compared in terms of demographic factors, medium- and long-term impact of the earthquakes. Groups did not differ in their experiences of threat or disruption, however those in poorest health reported greatest distress and a more negative overall impact of the earthquake. Results suggest existing vulnerabilities were associated with medium and long-term distress of older adults post-disaster.

Multipoint linkage analysis is an important approach for localizing disease-associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use marker allele frequencies determined by admixture proportions averaged over the entire sample. However, admixture proportions vary among pedigrees and throughout the genome in a family-specific manner. Here, we evaluate several approaches to model admixture in linkage analysis, providing different levels of detail about ancestral origin. To perform our evaluations, for specification of marker allele frequencies, we used data on 67 Caribbean Hispanic admixed families from the Alzheimer's Disease Sequencing Project. Our results show that choice of admixture model has an effect on the linkage analysis results. Variant-specific admixture proportions, computed for individual families, provide the most detailed regional admixture estimates, and, as such, are the most appropriate allele frequencies for linkage analysis. This likely decreases the number of false-positive results, and is straightforward to implement.

Objective Neuroendocrine tumors of the lung are currently staged with the 7th edition TNM non–small cell lung cancer staging system. This decision, based on data analysis without data on histology or disease-specific survival, makes its applicability limited. This study proposes a specific staging system for these tumors. Methods We retrospectively analyzed 510 consecutive patients (female/male, 313/197; median age, 61 years; interquartile range, 51-70) undergoing lung resection for a primary neuroendocrine tumor between 2000 and 2015 in 8 centers. Multivariable analysis was performed using a Cox proportional hazard model to identify factors associated with disease-specific survival. A new staging system was proposed on the basis of the results of this analysis. Kaplan–Meier disease-specific survival was analyzed by stage using the proposed and the 7th TNM staging system. Results Follow-up was completed in 490 of 510 patients at a median of 51 months (interquartile range, 18-99). Histology (G1-typical carcinoid vs G2-atypical carcinoid vs G3-large-cell neuroendocrine carcinoma) and pT were independently associated with survival, but pN was not. After regrouping histology and pT, we proposed the following staging system: IA (pT1-2G1), IB (pT3G1, pT1G2), IIA (pT4G1, pT2-3G2, pT1G3), IIB (pT4G2, pT2-3G3), and III (pT4G3). The 5-year survivals were 97.9%, 81.0%, 69.1%, 51.8%, and 0%, respectively. By using the 7th TNM, 5-year survivals were 95.0%, 92.3%, 67.7%, 70.9%, and 65.1% for stage IA, IB, IIA, IIB, and III, respectively. Conclusions Incorporating histology and regrouping tumor stage create a unique neuroendocrine tumor staging system that seems to predict survival better than the 7th TNM classification.

Financial literacy is defined as “the ability to use knowledge and skills to manage financial resources effectively for a lifetime of financial well-being.” The Money Smart Peer-to-Peer Program (MSP) was developed by the FDIC for use with diverse populations. MSP was culturally adapted for use in Jamaica using the Johns Hopkins DIME process. Peer counselling programs consistently demonstrate that they are acceptable and effective with adults who have limited education and low-income by overcoming barriers that are typically encountered when people attempt to access unfamiliar services or guidance from a professional. Research conducted with the MSP program reveals that program participants were more likely to open and save using deposit accounts, use and adhere to a budget, and have increased confidence in their financial abilities 6 to 12 months after completing the course. Implementation of MSP increases the likelihood that people can retire with dignity and financial security.

Pseudomonas stutzeri strain 19 is a Gram-negative bacterium capable of degrading aromatic hydrocarbons. The draft genome of P. stutzeri 19 is estimated to be 5.1 Mb, containing 4,652 protein-coding genes and a G+C content of 63.3%. Multiple genes responsible for the degradation of aromatics are present in this strain.

Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secreted extracellular vesicles (EVs) was not pursued due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteriaare implicated in virulence, toxin release and transference to host cells, eliciting immune responses, and spread of antibiotic resistance.Listeria monocytogenesis a Gram-positive bacterium that is the etiological agent of listeriosis. Here we report thatL. monocytogenesproduces EVs with diameter ranging from 20-200 nm, containing the pore-forming toxin listeriolysin O(LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Using simultaneousmetabolite,protein, andlipidextraction (MPLEx) multi-omics we characterized protein, lipid and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Cell-free EV preparations were toxic to the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion ofplcAincreased EV toxicity, suggesting PI-PLC can restrain LLO activity. Using immunogold electron microscopy we detect LLO localization at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released fromL. monocytogenesthat colocalize with LLO during infection. Our findings demonstrate thatL. monocytogenesutilize EVs for toxin release and implicate these structures in mammalian cytotoxicity.

Disasters are catastrophic events that suddenly and adversely affect populations. International humanitarian support is routinely offered after disasters to alleviate human suffering and facilitate the recovery process. Policymakers and responders use their knowledge and experiences to develop and implement systematized strategies that can be followed during disasters. Yet despite these efforts, the rate of disaster-related morbidity and mortality for older adults remains significantly higher than the general population. Because disasters occur without warning it is difficult to test and enhance strategies and protocols that are intended to mitigate threats and hazards and to quickly and effectively resolve their negative consequences. By identifying persistent challenges encountered during disasters and considering issues facing an aging population, organizations responsible for disaster response may be better attuned to the changing needs of the population and more able to address older adults in their planning and training processes. This symposium will feature five speakers representing Cameroon, Jamaica, Japan, New Zealand, Nepal, Philippines, and the United States. Presentations will describe actual disasters and the challenges and opportunities for preparing and responding to older adults during disasters in countries with varied financial, material, and human resources. Older adults displaced during disasters, assistance during displacement, as well as during return and reintegration after the event will be described. Finally, we will discuss why so many identified problems remain unresolved over time and how disaster managers might adapt lessons learned into processes so that they are culturally sensitive, relevant, and useful in affected regions.

Depression as well as dissatisfaction with sexual wellbeing is common in older lesbian women and gay men. This study explored the relationship of sexual functioning and satisfaction with depression severity in lesbians and gay men who were ages 55 years and older. As part of a larger study, 32 lesbian women and 44 gay men were given the Center for Epidemiological Studies Depression Scale, Changes in Sexual Functioning Questionnaire, and questions regarding sexual satisfaction and frequency of current sexual activity. In gay men, depression severity was significantly correlated with sexual functioning (r=-.448, p=.015) but not with general sexual satisfaction (r=-.212, p=.287). When examining specific items of sexual satisfaction, enjoyment, frequency, desire, and thoughts and pleasure of thoughts of sexual activity were significantly negatively correlated with depression severity. As for sexual functioning, only ability and frequency of ejaculation and pleasure in orgasm was negatively correlated with depression severity in gay men. In lesbian women, depression was not significantly correlated with sexual functioning or satisfaction or to specific items of sexual satisfaction and functioning. Results suggest that depression severity was negatively correlated with sexual satisfaction but less so with functioning in gay men. However, no significant relationships were found between sexual functioning and satisfaction with depression in lesbian women. These findings suggest that sexual satisfaction and functioning may play an important role in the emotional wellbeing of older gay men, but not in older lesbian women.

Prior GWAS have identified loci associated with red blood cell (RBC) traits in populations of European, African, and Asian ancestry. These studies have not included individuals with an Amerindian ancestral background, such as Hispanics/Latinos, nor evaluated the full spectrum of genomic variation beyond single nucleotide variants. Using a custom genotyping array enriched for Amerindian ancestral content and 1000 Genomes imputation, we performed GWAS in 12,502 participants of Hispanic Community Health Study and Study of Latinos (HCHS/SOL) for hematocrit, hemoglobin, RBC count, RBC distribution width (RDW), and RBC indices. Approximately 60% of previously reported RBC trait loci generalized to HCHS/SOL Hispanics/Latinos, including African ancestral alpha- and beta-globin gene variants. In addition to the known 3.8kb alpha-globin copy number variant, we identified an Amerindian ancestral association in an alpha-globin regulatory region on chromosome 16p13.3 for mean corpuscular volume and mean corpuscular hemoglobin. We also discovered and replicated three genome-wide significant variants in previously unreported loci for RDW (SLC12A2 rs17764730, PSMB5 rs941718), and hematocrit (PROX1 rs3754140). Among the proxy variants at the SLC12A2 locus we identified rs3812049, located in a bi-directional promoter between SLC12A2 (which encodes a red cell membrane ion-transport protein) and an upstream anti-sense long-noncoding RNA, LINC01184, as the likely causal variant. We further demonstrate that disruption of the regulatory element harboring rs3812049 affects transcription of SLC12A2 and LINC01184 in human erythroid progenitor cells. Together, these results reinforce the importance of genetic study of diverse ancestral populations, in particular Hispanics/Latinos., Author summary Red blood cells (RBC) are important for transport of oxygen to tissues throughout the body. Distribution of RBC traits differs by ethnicity and gender, and both genetic and acquired factors likely contribute to these differences. Prior genetic studies have identified physical regions of the genome associated with RBC traits in populations with European, African, and Asian ancestry. These studies have not included individuals with ancestry from the American continents (Amerindian ancestry), such as Hispanics/Latinos. In an analysis of RBC traits in up to 19,608 Hispanics/Latinos, we identified an Amerindian-ancestry genetic association in a known alpha-globin regulatory region. We also identified three new RBC trait associations, including a regulatory variant of SLC12A2 that encodes a RBC membrane ion-transport protein. Experimental disruption of this regulatory element led to reduced expression of both SLC12A2 and an adjacent long non-coding RNA in human erythroid progenitor cells. These results contribute to understanding the physiology of red blood cells and reinforce the importance of genetic study of diverse ancestry populations, in particular Hispanics/Latinos.

Circulating white blood cell (WBC) counts (neutrophils, monocytes, lymphocytes, eosinophils, basophils) differ by ethnicity. The genetic factors underlying basal WBC traits in Hispanics/Latinos are unknown. We performed a genome-wide association study of total WBC and differential counts in a large, ethnically diverse US population sample of Hispanics/Latinos ascertained by the Hispanic Community Health Study and Study of Latinos (HCHS/SOL). We demonstrate that several previously known WBC-associated genetic loci (e.g. the African Duffy antigen receptor for chemokines null variant for neutrophil count) are generalizable to WBC traits in Hispanics/Latinos. We identified and replicated common and rare germ-line variants at FLT3 (a gene often somatically mutated in leukemia) associated with monocyte count. The common FLT3 variant rs76428106 has a large allele frequency differential between African and non-African populations. We also identified several novel genetic loci involving or regulating hematopoietic transcription factors (CEBPE-SLC7A7, CEBPA and CRBN-TRNT1) associated with basophil count. The minor allele of the CEBPE variant associated with lower basophil count has been previously associated with Amerindian ancestry and higher risk of acute lymphoblastic leukemia in Hispanics. Together, these data suggest that germline genetic variation affecting transcriptional and signaling pathways that underlie WBC development and lineage specification can contribute to inter-individual as well as ethnic differences in peripheral blood cell counts (normal hematopoiesis) in addition to susceptibility to leukemia (malignant hematopoiesis).

Graphical abstract, Many intracellular bacterial pathogens naturally release membrane vesicles (MVs) under a variety of growth environments. For pathogenic bacteria there are strong evidences that released MVs are a delivery mechanism for the release of immunologically active molecules that contribute to virulence. Identification of membrane vesicle-associated proteins that can act as immunological modulators is crucial for opening up new horizons for understanding the pathogenesis of certain bacteria and for developing novel vaccines. In this protocol, we provide all the details for isolating MVs secreted by either mycobacteria or Gram-positive bacteria and for the subsequent identification of the protein content of the MVs by mass spectrometry. The protocol is adapted from Gram-negative bacteria and involves four main steps: (1) isolation of MVs from the culture media; (2) purification of MVs by density gradient ultrucentrifugation; (3) acetone precipitation of the MVs protein content and in-solution trypsin digestion and (4) mass spectrometry analysis of the generated peptides and protein identification. Our modifications are:•Growing Mycobacteria in a chemically defined media to reduce the number of unrelated bacterial components in the supernatant.•The use of an ultrafiltration system, which allows concentrating larger volumes.•In solution digestion of proteins followed by peptides purification by ziptip.

The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African-Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and nonrandom mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD can incorporate either local or chromosome-wide ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican-American (MXL) and African-American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions, assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample (p=1e−5), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample.

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16× 10(-28)) in ACTN1, agene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.

Pseudomonas frederiksbergensis strain SI8 is a psychrotrophic bacterium capable of efficient aerobic degradation of aromatic hydrocarbons. The draft genome of P. frederiksbergensis SI8 is 6.57 Mb in size, with 5,904 coding sequences and 60.5% G+C content. The isopropylbenzene (cumene) degradation pathway is predicted to be present in P. frederiksbergensis SI8.

Extravascular lung water index (EVLWI) can be measured at the bedside using the transpulmonary thermodilution technique (TPTD). The goal of this study was to compare EVLWI values with a chest x-ray score of pulmonary edema and markers of oxygenation in critically ill children.This was a prospective observational study in a pediatric intensive care unit of a university hospital. We included 27 critically ill children with an indication for advanced invasive hemodynamic monitoring. No specific interventions for the purpose of the study were carried out. Measurements included EVLWI and other relevant hemodynamic variables. Blood gas analysis, ventilator parameters, chest x-ray and TPTD measurements were obtained within a three-hour time frame. Two radiologists assessed the chest x-ray and determined a score for pulmonary edema.A total of 103 measurements from 24 patients were eligible for final analysis. Mean age was two years (range: two months to eight years). Median cardiac index was 4.00 (range: 1.65 to 10.85) l/min/m2. Median EVLWI was 16 (range: 6 to 31) ml/kg. The weighted kappa between the chest x-ray scores of the two radiologists was 0.53. There was no significant correlation between EVLWI or chest x-ray score and the number of ventilator days, severity of illness or markers of oxygenation. There was no correlation between EVLWI and the chest x-ray score. EVLWI was significantly correlated with age and length (r2 of 0.47 and 0.67 respectively).The extravascular lung water index in critically ill children does not correlate with a chest x-ray score of pulmonary edema, nor with markers of oxygenation.

Background Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are characterized by pulmonary oedema, measured as extravascular lung water (EVLW). The chest radiograph (CXR) can potentially estimate the quantity of lung oedema while the transpulmonary thermodilution method measures the amount of EVLW. This study was designed to determine whether EVLW as estimated by a CXR score predicts EVLW measured by the thermodilution method and whether changes in EVLW by either approach predict mortality in ALI/ARDS. Methods Clinical data were collected within 48 hours of ALI/ARDS diagnosis and daily up to 14 days on 59 patients with ALI/ARDS. Two clinicians scored each CXR for the degree of pulmonary oedema, using a validated method. EVLW indexed to body weight was measured using the single indicator transpulmonary thermodilution technique. Results The CXR score had a modest, positive correlation with the EVLWI measurements (r = 0.35, p p Conclusion EVLW measured by CXR was modestly correlated with thermodilution measured EVLW. Unlike CXR findings, transpulmonary thermodilution EVLWI measurements over time predicted mortality in patients with ALI/ARDS.