Characterization of early non-responders within behavioral weight loss treatment.

Objective: Given that low early (4 weeks) weight loss (WL) predicts longer-term WL, the purpose of this study was to identify factors associated with poor early WL. Methods: 438 adults with overweight/obesity participating in an Internet-delivered behavioral WL program provided weights at baseline and 4 weeks. Participants were stratified by percent WL at 4 weeks: LOW: <2% WL, MEDIUM: 2 to <4% WL, HIGH: ≥4% WL and groups were compared on baseline variables (demographics, physical activity, and psychosocial measures) and 4-week intervention adherence. Results: 37.4%, 40.9%, and 21.7% of participants had LOW, MEDIUM, and HIGH early WL respectively. LOW was more likely to be female compared to HIGH and less likely to be non-Hispanic White compared to MEDIUM and HIGH (p's<0.05). After controlling for demographic differences, LOW had lower baseline physical activity compared to HIGH and watched fewer video lessons, self-monitored calorie intake and weight on fewer days, and were less likely to achieve the exercise goal compared to MEDIUM and HIGH (p's<0.05). Conclusion: Findings can inform future adaptive interventions which tailor treatment based upon early WL to improve WL outcomes for more individuals.

An Adaptive Telephone Coaching Intervention for Patients in an Online Weight Loss Program: A Randomized Clinical Trial.

Importance: Weight loss (WL) during the first month of a behavioral program is associated with longer-term WL. Testing of translatable and adaptive obesity programs is needed. Objective: To compare brief, extended, and no telephone coaching for individuals with suboptimal response (ie, 1-month WL <4%) within an online WL program. Design, Setting, and Participants: This randomized clinical trial with enrollment between March 2019 and April 2022 (data collection completed May 2023) was conducted at an academic research center in the US. Eligible participants included adults aged 18 to 70 years with daily access to internet and a body mass index between 25 and 45. Interventions: All participants received an automated online WL program (4 months) and WL maintenance program (8 months), consisting of video lessons, self-monitoring, and personalized feedback. Participants were randomized, such that individuals with suboptimal response received either brief telephone coaching (3 calls during weeks 5-8), extended telephone coaching (12 calls during weeks 5-16), or no coaching (control). Coaching included education, problem solving, and goal setting, and promoted engagement with the online program. Main Outcomes and Measures: The primary outcomes were percent weight change and proportion of participants achieving 5% or greater WL at 4 and 12 months. A priori hypotheses for WL were that WL for extended coaching would be greater than for brief coaching, and both extended and brief coaching would be greater than no coaching (control). A longitudinal mixed-effects model with participant-specific intercept was used to examine intervention effects on percent WL at 4 and 12 months. Secondary analyses focused on program engagement and cost/kilogram of WL. Results: The study included a total of 437 participants who reported WL at 1 month (mean [SD] age, 50.8 [11.4] years; mean [SD] BMI, 34.6 [5.0]; 305 female [69.8%] and 132 male [30.2%]) with 148 randomized to extended coaching, 143 assigned to brief coaching, and 146 assigned to the control group. Of all participants, 346 (79.2%) were considered to have a suboptimal response. WL at 4 months was significantly greater in the extended coaching group (mean [SD] WL, -7.0% [5.1%]) and brief coaching group (mean [SD] WL, -6.2% [4.7%]) vs the control group (mean [SD] WL, -4.5% [4.7%]) (P < .001). Similarly, the proportion of participants achieving 5% or greater WL at 4 months was greater in the extended coaching group (89 participants [65.9%]) and brief coaching group (77 participants [58.5%]) vs control group (46 participants [36.5%]) (P < .001). At 12 months, a similar pattern was observed for achievement of 5% WL or greater (extended coaching, 63 participants [48.1%]; brief coaching, 58 participants [45.9%]; control, 38 participants [32.8%]; P = .03). Percent WL at 12 months was significantly higher in extended coaching vs control (mean [SD] WL for extended coaching, -5.5% [6.7%]; mean [SD] WL for control, -3.9% [7.4%]; P = .03) but not for brief coaching (mean [SD] WL, -4.9% [6.1%]).Both the brief and extended coaching groups watched more lessons and self-monitored on more days compared with the control group. The cost per additional kilogram of WL, beyond that of the control group, was $50.09 for brief coaching and $92.65 for extended coaching. Conclusions and Relevance: In this randomized clinical trial testing an adaptive intervention, the provision of coaching for individuals with suboptimal response improved WL and was cost-effective; further testing in clinical settings (eg, health care systems) is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03867981.

Associations of daily weight management-focused social support with weight loss, activity behaviors, and eating regulation in the context of metabolic and bariatric surgery.

Objective: Greater perceived social support (PSS) is associated with more favorable changes in weight loss, activity behaviors, and eating regulation after metabolic and bariatric surgery (MBS). However, studies have relied on generic, retrospective PSS measures, and stability of PSS levels and relations with weight loss and weight-related behaviors over time is unknown. Using smartphone-based Ecological Momentary Assessment, this study evaluated pre-to 1-year post-MBS changes in daily weight management-focused PSS and associations with weight loss, device-measured activity behaviors, and eating regulation before and during the initial year after MBS. Method: Adult MBS patients (n = 71) received (1) an accelerometer to measure daily moderate-to-vigorous intensity physical activity (MVPA) and sedentary time (ST) minutes/day, and (2) a smartphone to complete morning weight-focused PSS ratings and eating regulation (dietary restraint/disinhibition) ratings at four semi-random times daily for 10 days at pre- and 3, 6, and 12-month postoperative. Generalized linear mixed models analyzed the associations of PSS with total weight loss (%TWL) and activity/eating outcomes. Results: Participants on average reported relatively stable moderate-to-high PSS (3.98 on one to five scale) across assessments. Perceived social support was not related to %TWL, MVPA, or ST. Participants with higher PSS reported lower disinhibition and higher restraint than those with lower PSS (ps < 0.05); however, participants reported higher restraint on days that PSS was lower than their usual levels (p = 0.009). Conclusions: MBS patients on average had stable PSS levels across time. Higher PSS levels were associated with greater resistance to overeating cues (disinhibition) and cognitive control to restrict food intake (restraint) over time. Additionally, participants reported higher restraint when PSS levels were lower than usual. Overall, weight-focused PSS appeared to hold greater importance in relation to regulating eating behavior than engaging in activity behaviors or weight loss among MBS patients during the initial postoperative year. Clinical Trial Registration: NCT02777177.

The NOAA NCEI marine microplastics database.

Microplastics (<5 mm) pollution is a growing problem affecting coastal communities, marine ecosystems, aquatic life, and human health. The widespread occurrence of marine microplastics, and the need to curb its threats, require expansive, and continuous monitoring. While microplastic research has increased in recent years and generated significant volumes of data, there is a lack of a robust, open access, and long-term aggregation of this data. The National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI) now provides a global open access to marine microplastics data on an easily discoverable and accessible GIS web map and data portal ( https://www.ncei.noaa.gov/products/microplastics ). The objective of this data portal is to develop a repository where microplastics data are aggregated, archived, and served in a user friendly, consistent, and reliable manner. This work contributes to NCEI's efforts towards data standardization, integration, harmonization, and interoperability among national and international collaborators for monitoring global marine microplastics. This paper describes the NOAA NCEI global marine microplastics database, its creation, quality control procedures, and future directions.

The prognostic value of Eastern Cooperative Oncology Group performance status on overall survival among patients with metastatic prostate cancer: a systematic review and meta-analysis.

Background: There is heterogeneity in the literature regarding the strength of association between Eastern Cooperative Oncology Group performance status (ECOG PS) and mortality. We conducted a systematic review and meta-analysis of studies reporting the prognostic value of ECOG PS on overall survival (OS) in metastatic prostate cancer (mPC). Methods: PubMed was searched from inception to March 21, 2022. A meta-analysis pooling the effect of ECOG PS categories (≥2 vs. <2, 2 vs. <2, and ≥1 vs. <1) on OS was performed separately for studies including patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) using a random-effects model. Analyses were stratified by prior chemotherapy and study type. Results: Overall, 75 studies, comprising 32,298 patients, were included. Most studies (72/75) included patients with mCRPC. Higher ECOG PS was associated with a significant increase in mortality risk, with the highest estimate observed among patients with mCRPC with an ECOG PS of ≥2 versus <2 (hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.87-2.37). When stratifying by study type, there was a higher risk estimate of mortality among patients with mCRPC with an ECOG PS of ≥1 versus <1 in real-world data studies (HR: 1.98, 95% CI: 1.72-2.26) compared with clinical trials (HR: 1.32, 95% CI: 1.13-1.54; p < 0.001). There were no significant differences in the HR of OS stratified by previous chemotherapy. Conclusion: ECOG PS was a significant predictor of OS regardless of category, previous chemotherapy, and mPC population. Additional studies are needed to better characterize the effect of ECOG PS on OS in mCSPC.

Implementation of a Clinical Decision Support (CDS) Tool for the Management of Functional Constipation in Pediatric Primary Care.

Constipation is common in general pediatrics and often results in potentially unnecessary referrals to pediatric gastroenterology. We hypothesized that a clinical decision-making tool would support primary care providers to manage pediatric constipation, improve workflow, and prevent unnecessary subspecialty care. In this pilot quality improvement initiative, a multidisciplinary team completed a root cause analysis related to challenges with the care of pediatric constipation. The results informed the development of interventions including a Clinical Decision Support tool and patient educational materials embedded within an existing order-set in the electronic health record, which we implemented in our primary care network. The use of the updated order-set continues to increase monthly, and there is reported improved workflow and increased confidence by providers. These interventions demonstrated that it is feasible to implement tools to support primary care clinicians in their management of pediatric patients with constipation.

Associations of physical activity and sedentary behavior with appetite sensations and eating regulation behaviors before and during the initial year following bariatric surgery.

Background: Bariatric surgery produces weight loss in part by impacting appetite and eating behavior. Research suggests physical activity (PA) assists with regulation of appetite and eating during non-surgical weight loss, although whether PA carries similar benefits in the context of bariatric surgery is unknown. Objective: Evaluate associations of moderate-to-vigorous intensity PA (MVPA) and sedentary time (ST) with appetite sensations (hunger [homeostatic/hedonic], satiety) and eating regulation behaviors (restraint, disinhibition) before and during the initial year following bariatric surgery. Method: Adult bariatric patients received an accelerometer to measure MVPA/ST and a smartphone to complete appetite/eating ratings at four semi-random times daily for 10 days at pre- and 3-, 6-, and 12-months post-surgery. Data were analyzed using generalized linear mixed models. Results: Higher MVPA levels related to more satiety across time (p = 0.045) and more restraint at 3-months post-surgery (p < 0.001). At pre-surgery, higher MVPA levels also related to more disinhibition (p's < 0.01), although participants reported more disinhibition on days they performed less MVPA than usual (p = 0.017). MVPA did not relate to hunger. Lower ST levels related to more hedonic hunger (p = 0.003), especially at 12-months post-surgery (p < 0.001), and participants reported more homeostatic hunger on days they accumulated more ST than usual (p = 0.044). Additionally, higher ST levels related to more disinhibition at 3-months post-surgery (p's < 0.01) and lower restraint at pre-surgery (p's < 0.05). ST did not relate to satiety. Conclusions: This study is the first to show that MVPA and ST each associate with appetite and eating regulation in daily life before and during post-surgical weight loss. Results, while preliminary and requiring experimental confirmation, highlight potential for targeting bariatric patients' activity behaviors to enhance modulation of appetite, control of food intake, and resistance to overeating.

Tumor Lysis Syndrome: Implications for Oncology Nursing Practice.

OBJECTIVES: To provide an overview of tumor lysis syndrome, which is one of the metabolic oncologic emergencies. DATA SOURCES: A review and synthesis of empirical articles. CONCLUSION: One of the metabolic oncologic emergencies identified by the Oncology Nursing Society is tumor lysis syndrome. This condition is life-threatening and is characterized by metabolic derangements that can lead to acute kidney injury and multiple organ dysfunction. Normal intracellular components (potassium, phosphorus, and nucleic acids) spill into the bloodstream when cancer cells die. If the tumor is large and highly responsive to chemotherapy, the resulting cascade of dead tumor cells may overwhelm normal homeostatic mechanisms. The cells enter the bloodstream faster than they can be cleared by the kidneys. This results in hyperkalemia and hyperphosphatemia. Nucleic acids convert to uric acid in the liver with a resultant hyperuricemia. Excess uric acid in the kidneys can lead to uric acid nephropathy and renal insufficiency. Phosphorus binds with calcium, leading to hypocalcemia from the formation of calcium phosphate precipitate or crystals. These crystals can also lead to renal insufficiency or acute kidney injury, which can lead to a metabolic acidosis and exacerbation of the hyperkalemic state. These metabolic derangements define presence of tumor lysis syndrome. IMPLICATIONS FOR NURSING PRACTICE: Multidisciplinary collaboration and communication is essential to identifying patients at risk prior to treatment. Meticulous nursing care in terms of prevention and treatment is critical to patient survival.

Relationship between stress and weight management behaviors during the COVID-19 pandemic among those enrolled in an internet program.

BACKGROUND: The COVID-19 pandemic resulted in mandated stay-at-home orders, potentially resulting in changes in mental health (e.g., stress, anxiety) and challenges maintaining healthy dietary and physical activity behaviors. OBJECTIVE: This study examined how stress was associated with mental well-being and weight loss behaviors during the COVID-19 pandemic among adults enrolled in an internet-based weight loss program. METHODS: Participants enrolled in a weight-loss program residing in Rhode Island or Massachusetts, USA, completed a brief survey on their mental health and current weight-loss behaviors during the COVID-19 pandemic. Surveys were completed between 14 April 2020 and 21 April 2020, approximately one month after stay-at-home orders were mandated. Linear regression was used to examine associations between stress, mental health, and weight-loss behaviors. RESULTS: A total of 99 participants completed the survey (79% female, 91% white, 52.2 ± 9.8 years, 34.0 ± 5.2 kg/m2, 77% reported moderate to extreme stress). Greater stress was associated with higher BMI (p = 0.04), higher education (p = 0.04), working more hours (p = 0.003), and having school-age children at home (p = 0.002). Greater stress was also associated with higher levels of anxiety, worry, and concern regarding COVID-19 (p's < 0.001) and having less time to spend on weight-loss efforts (p < 0.001), after controlling for BMI and education. CONCLUSIONS: Many individuals enrolled in a weight-loss program experienced more stress during COVID-19 compared to before the pandemic. This stress was related to more mental health challenges as well as more difficulties finding time for weight management efforts.

Ecological momentary assessment of gastrointestinal symptoms and risky eating behaviors in Roux-en-Y gastric bypass and sleeve gastrectomy patients.

BACKGROUND: Gastrointestinal symptoms (GIS) are common after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). However, little is known about frequencies of GIS and their co-occurrence with risky eating behaviors. OBJECTIVES: Compare RYGB and SG on GIS and risky eating behaviors, and test associations between GIS and behaviors. SETTING: Two university hospitals in Northeastern United States. METHODS: RYGB (n = 18) and SG (n = 53) patients completed smartphone-based ecological momentary assessment of GIS and risky eating behaviors at 4 semi-random times daily for 10 days preoperatively and at 3, 6, and 12 months postoperatively. Study objectives were evaluated using generalized linear mixed-effects models. RESULTS: All available data from each assessment were included in the analysis: participant attrition was 18%, 30%, and 38% at 3, 6, and 12 months. All GIS were reduced at 12 months postoperative. Bloating decreased consistently whereas cramping, dehydration, and dumping first increased at 3 to 6 months then decreased to 12 months. Diarrhea, nausea, reflux, and vomiting decreased to 12 months for RYGB, but first increased at 3 to 6 months then decreased to 12 months for SG. Consumption of carbonated and sugar-sweetened beverages, fatty meats, and sweets decreased to 6 months then rebounded at 12 months. Eating past the first sign of fullness, drinking liquids with meals, not starting meals with protein, and fried foods consumption decreased to 6 months and then rebounded for RYGB only at 12 months. Alcohol consumption did not change. Sweets consumption and eating past the first sign of fullness were most consistently associated with GIS for both RYGB and SG patients. CONCLUSION: GIS and risky eating behaviors improved postoperatively, although patterns of change were variable and occasionally differed between RYGB and SG. Pending replication, patients may benefit from intervention to limit risky behaviors that are tailored to their surgery type.

Comprehensive Genomic Profiling of Adult Renal Sarcomas Provides Insight into Disease Biology and Opportunities for Targeted Therapies.

BACKGROUND: Primary adult renal sarcomas (RSs) are rare aggressive neoplasms. Clinical outcomes are extremely poor, and optimal treatment remains challenging. OBJECTIVE: To identify genomic alterations (GAs) in patients with RSs. DESIGN, SETTING, AND PARTICIPANTS: Comprehensive genomic profiling (CGP) was conducted on DNA/RNA extracted from formalin-fixed paraffin-embedded tissue using the FoundationOne Heme/Sarcoma assay in 13 adult, locally advanced or metastatic RSs of various histologic types. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All classes of GAs, including base substitutions, small indels, rearrangements, copy number alterations, tumor mutational burden (TMB), and microsatellite instability (MSI), were analyzed. RESULTS AND LIMITATIONS: CGP revealed 55 GAs (4.2 per tumor), 29 of which were clinically relevant genomic alterations (CRGAs; 2.2 per tumor). At least one CRGA was detected in nine (69%) cases. High-level amplifications (more than six copies) involving 4q12 amplicon of the KIT and PDGFRA genes were identified in four (31%) cases (two undifferentiated pleomorphic sarcomas [UPSs], one sarcomatoid renal cell carcinoma, and one myxofibrosarcoma). Both UPSs also had KDR gene amplification in addition to KIT and PDGFRA. Additional CRGAs were found in CDKN2A/B (23%), NF1 (23%), and MET (8%). All RSs were MSI stable, the mean TMB was 3.5 mutations/megabase (Mb), and none (0%) featured TMB >10 mutations/Mb. Limitations include the small sample size. CONCLUSIONS: RSs are characterized by diverse histology and genomic profiles including 31% of cases with 4q12 amplification harboring the KIT/PDGFRA/KDR genes. Of the tumors, 69% carry CRGAs, which could lead to potential benefit from targeted therapies; however, a low TMB also suggests that these cases are unlikely to respond to checkpoint inhibitors. PATIENT SUMMARY: This study provides insights into molecular biology of renal sarcoma, a rare aggressive subtype of kidney tumors. We demonstrated that renal sarcomas harbor unique, recurrent, clinically relevant molecular abnormalities that provide new opportunities for targeted therapies.

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BACKGROUND: We determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection. METHODS: A5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid. RESULTS: St A participants had higher levels of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1ß, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections. CONCLUSIONS: Our results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH.

Prolonged sedentary time adversely relates to physical activity and obesity among preoperative bariatric surgery patients.

BACKGROUND: Bariatric surgery patients spend much of their waking time sedentary. Yet, little is known about their patterns of accumulation of sedentary time (ST) and whether more prolonged ST is associated with lower physical activity (PA), independent of total ST, or obesity severity. OBJECTIVES: To characterize variability in prolonged ST among bariatric patients preoperatively and assess the importance of a "prolonger" pattern in relation to PA and weight status. SETTING: Two university hospital clinics, United States. METHODS: Adult patients (n = 76) wore a wrist-based accelerometer for 10 days preoperatively. ST and time spent in light and moderate-to-vigorous PA was determined using validated thresholds. Percent of total ST accumulated in ≥30-consecutive ST minute bouts was calculated, and participants were trichotomized into low, medium, and high "prolongers" based on this value. The associations of prolonged ST with PA and obesity were examined. RESULTS: On average, participants accumulated a mean ± standard deviation of 10.5 ± 2.1 hours of ST per day, 30% of which was prolonged (prolonger groups: low = 7.2%-24.5%, medium = 24.5%-33.0%, and high = 34.0%-52.6% of ST in ≥30-min bouts). Adjusting for covariates including total ST, high prolongers had fewer light PA minutes per day (P < .01), and a greater percentage of prolonged ST related to lower likelihood of meeting the national guideline of ≥150 moderate-to-vigorous PA minutes per week (P = .012). High (versus low) prolongers had more severe obesity (P < .05). CONCLUSIONS: Accumulating a greater percentage of ST in prolonged bouts appears to be adversely related to PA and obesity severity among bariatric patients. Future research should determine whether interrupting prolonged ST with brief breaks can favorably modify PA and weight in this population.

DIAL now protocol: A randomized trial examining the provision of phone coaching to those with sub-optimal early weight loss during an Internet weight management program.

BACKGROUND: While low-intensity Internet-delivered weight loss (IDWL) programs are efficacious, many patients fail to achieve clinically significant weight loss (WL). Given the positive association between 4-week and post-treatment WL, providing a more intensive intervention for those with sub-optimal 4-week WL may improve outcomes for a greater proportion of individuals. This stepped-care approach would minimize cost by reserving more aggressive treatment for those with sub-optimal early WL. OBJECTIVE: This randomized trial examines whether the provision of brief or extended phone coaching for those with sub-optimal early WL improves 4- and 12-month WL when compared to no coaching. Secondary aims include examination of cost/kg WL and intervention engagement. METHODS: 450 individuals (age 18-70 years, BMI: 25-45 kg/m2) will be randomized to: 1) IDWL+3 weeks of coaching ('Brief'), 2) IDWL+12 weeks of coaching ('Extended'), or 3) IDWL only ('Control'). All individuals will receive a 4-month IDWL program followed by an 8-month IDWL maintenance program. At week 4, individuals will be classified as early sub-optimal responders (<4% WL) or initial responders (≥4% WL). Individuals with sub-optimal early WL randomized to 'Brief' or 'Extended' will receive 3 and 12 weeks of phone coaching respectively, starting at week 5. Those with sub-optimal early WL randomized to 'Control', and initial responders will not receive any coaching. Assessments will occur at 4 and 12 months. DISCUSSION: Study findings can inform the development of more effective IDWL programs. This model which provides additional support to those with sub-optimal early WL can easily be translated into healthcare and community settings.

Investigating the culturable atmospheric fungal and bacterial microbiome in West Texas: implication of dust storms and origins of the air parcels.

Individuals often experience ailments such as allergies, asthma and respiratory tract infections throughout the year. Weather reports often include estimations of common allergens that can affect these individuals. To describe the local 'atmospheric microbiome' in Lubbock, Texas, USA, we examined the culturable fungal and bacterial microbiome present in the air on calm and dust storm days using internal transcribed spacer (ITS)-1 and 16S rRNA amplicon sequencing, respectively. While some types of airborne fungi were frequently present throughout the year, distinct differences were also observed between calm and dust storm days. We also observed the influence of the origin of air parcels and wind elevation of the air trajectory. The most abundant genera of fungi identified during the study period were Cryptococcus, Aureobasidium, Alternaria, Cladosporium and Filobasidium. This observation was not surprising considering the agricultural intensive environment of West Texas. Interestingly, Cladosporium, a common allergenic mold, was increased during days with dust storm events. The predominant bacterial genera observed were Bacillus, Pseudomonas, Psychrobacter, Massilia and Exiguobacterium. The relative abundance of the psychrophiles, Psychrobacter and Exiguobacterium, was surprising, given the semi-aridity of West Texas. Coupling our observations with back trajectories of the wind (Hybrid Single-Particle Lagrangian Integrated Trajectory models) demonstrated that dust storms, regional anthropogenic activity and origin of air parcels are important influences on the diversity and temporal presence of the atmospheric microbiome.

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon. EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases. RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months. CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy. IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Prevalence of and Risk Factors for Low Bone Mineral Density in Children With Celiac Disease.

BACKGROUND & AIMS: Celiac disease can reduce bone mineral density. We sought to determine the prevalence and risk factors for low areal bone mineral density (aBMD) in children with celiac disease. METHODS: We performed a retrospective cohort study of 673 children with celiac disease (63% female; median age at diagnosis, 10.6 y; interquartile range, 7.8-13.9) who underwent dual x-ray absorptiometry (DXA) from 2009 through 2016 at the Children's Hospital of Philadelphia. We collected demographic, clinical, and laboratory data from medical records. We performed logistic regression analysis to identify factors associated with low (Z less than -2) lumbar spine aBMD Z (aBMD-Z) scores at initial and subsequent tests. RESULTS: The time between diagnosis of celiac disease and first DXA was 0 days (interquartile range, -11 to 31 d). The mean aBMD-Z score at the children's initial scan was -0.4 ± 1.2; 46 children had aBMD-Z scores less than -2 (6.8%; 95% CI, 5.2%-9.0%). Those who had a second DXA analysis (n = 108; 16.0%) had a significant increase in aBMD-Z score (mean change, 0.29; P = .0005). Higher body mass index (BMI) was associated with lower odds of a low aBMD-Z score at the initial DXA analysis (odds ratio, 0.46, 95% CI, 0.35-0.50). BMI-Z scores greater than -0.4 identified children with a low aBMD-Z at their initial DXA analysis with a 95% negative predictive value. CONCLUSIONS: Approximately 7% of subjects with celiac disease had a low aBMD-Z score, determined by DXA, at the time of diagnosis; this value was nearly 3-fold higher than expected from a population of children of this age and sex distribution. BMI-Z scores could be used to identify children with celiac disease at risk for low BMD who should receive DXA screening.

Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study.

Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies1. Tumor complexity and heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient2-6. To date, precision oncology trials have been based on molecular matching with predetermined monotherapies7-14. Several of these trials have been hindered by very low matching rates, often in the 5-10% range15, and low response rates. Low matching rates may be due to the use of limited gene panels, restrictive molecular matching algorithms, lack of drug availability, or the deterioration and death of end-stage patients before therapy can be implemented. We hypothesized that personalized treatment with combination therapies would improve outcomes in patients with refractory malignancies. As a first test of this concept, we implemented a cross-institutional prospective study (I-PREDICT, NCT02534675 ) that used tumor DNA sequencing and timely recommendations for individualized treatment with combination therapies. We found that administration of customized multidrug regimens was feasible, with 49% of consented patients receiving personalized treatment. Targeting of a larger fraction of identified molecular alterations, yielding a higher 'matching score', was correlated with significantly improved disease control rates, as well as longer progression-free and overall survival rates, compared to targeting of fewer somatic alterations. Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogeneous cancers with combinations of customized agents.