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The morphology and growth habits of Evactinopora species of the Evactinoporidae (new family) are documented. This distinctive family of free-living bryozoans has a radial colony form at all growth stages. During a brief attachment phase on a hard substrate, the colony morphology grew as an expanding cone with vertical folds. Following detachment of the nascent colony from this hard substrate, it settled on soft sediment and the free-living expanding colony acquired a star-like form by producing slender outrigger rays. Continued growth produced a radial array of vertical vanes containing feeding autozooecia. The colony maintained a vertical orientation on soft sediment by means of outrigger rays and secretion of solid skeleton on the colony base that provided ballast. The radial growth pattern, outrigger rays, and vertical vanes developed as adaptive characters suitable for free-living life on soft sediment. North American species of Evactinopora are redefined and described taxonomically on the basis of zoarial and zooecial characters and a new species, Evactinopora mangeri, erected. The new family Evactinoporidae is established on the basis of the novel characters of early colony detachment from a hard surface, radial growth pattern through life, generation of outrigger rays, and growth of vertical vanes from the top of rays.
Alternatives to skin preparation with conventional preoperative antiseptics are required because of adverse reactions and the potential emergence of resistance. Here, we present 2 phase 2 studies of ZuraGard (ZG), a novel formulation of isopropyl alcohol and functional excipients developed for preoperative skin antisepsis.
Microbial skin flora on abdominal and inguinal sites in healthy volunteers were quantitatively assessed following application of ZG versus a negative control (ZV) and a chlorhexidine/alcohol preparation, Chloraprep (CP). In trial 1, ZG administered for both recommended and abbreviated application times was compared with CP and ZV via bacterial reductions at 10 minutes, and 6 hours, 12 hours, and 24 hours following application. In trial 2, the 10-minute postapplication responder rates (RRs) for ZG, participants with abdominal ≥2 log10 per cm2, and inguinal ≥3 log10 per cm2 reductions in colony-forming units (CFU) were compared to RRs of participants treated with CP.
In trial 1, ZG at the recommended application time reduced mean bacterial counts by ~3.18 log10 CFU/cm2 and ~2.98 log10 CFU/cm2 at abdominal and inguinal sites, respectively. Qualitatively similar reductions were observed for the abbreviated ZG application time and all CP applications. Application of ZV was ineffective. In trial 2, 10-minute RRs for ZG and CP exceeded 90% at abdominal sites. At inguinal sites, RRs were 83.3% for ZG and 86.7% for CP. No skin irritation or other adverse events were observed.
ZG matched CP efficacy under these experimental conditions with immediate and persistent microbial reductions, including abbreviated application times. Further clinical studies of this novel preoperative antiseptic are merited.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Introduction: Capitalizing on the success of Simulation-Based Education (SBE) in residency-training programs, simulation has been gradually integrated into Continued Professional Development (CPD) programs for Emergency Physicians (EPs) in Canada. This study sought to characterize how Canadian academic emergency medicine (EM) departments have implemented SBE for CPD. Methods: We conducted two national surveys: 1) the National Faculty Simulation Status Assessment Survey, administered by telephone to the simulation directors (or equivalent) at 20 Canadian academic EM sites and 2) the Faculty Simulation Needs Assessment Survey administered online to all full-time EPs across 9 Canadian academic EM sites. Results: The response rates for the National Status and Needs Assessment Surveys were 100% (20/20), and 40% (252/635), respectively. The majority (60%) of Canadian academic EM sites reported utilizing SBE for CPD, though only 30% reported dedicated funding support. EPs reported participating in a median of 3 hours per year of SBE (IQR 1-6 hours). Reported incentivization offered in the form of continued medical education credits varied between simulation directors (67%) and EPs (44%). Simulation directors identified several significant barriers to SBE including a lack of faculty time, fear of peer judgment, and faculty inexperience. In contrast, EP-identified barriers included time commitments outside of shift, lack of opportunities, and lack of departmental. The three most common topics of interest for SBE by EPs were performance of rare procedures, pediatric resuscitation, and neonatal resuscitation. Interprofessional involvement in SBE CPD was valued by both simulation directors and EPs, with most EPs (79%) indicating it is useful. Conclusion: Most Canadian EPs and simulation directors recognize the value of SBE for CPD, yet it is only utilized, infrequently, by 67% of Canadian academic EM departments for this purpose. This may be explained, in part, by poor incentivization for participation. Simulation directors and EPs noted different barriers to SBE implementation for CPD suggesting the need for dialogue to improve utilization. As SBE for CPD is incorporated more frequently, and at more sites, content should be guided by local needs assessments with an emphasis on interprofessional participation.
Introduction: Simulation has assumed an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High quality simulation-based research (SBR) is required to ensure the effective and efficient use of this tool. This study sought to establish national SBR priorities and describe the barriers and facilitators of SBR in Emergency Medicine (EM) in Canada. Methods: Simulation leads (SLs) from all fourteen Canadian Departments or Divisions of EM associated with an adult FRCP-EM training program were invited to participate in three surveys and a final consensus meeting. The first survey documented active EM SBR projects. Rounds two and three established and ranked priorities for SBR and identified the perceived barriers and facilitators to SBR at each site. Surveys were completed by SLs at each participating institution, and priority research themes were reviewed by senior faculty for broad input and review. Results: Twenty SLs representing all 14 invited institutions participated in all three rounds of the study. 60 active SBR projects were identified, an average of 4.3 per institution (range 0-17). 49 priorities for SBR in Canada were defined and summarized into seven priority research themes. An additional theme was identified by the senior reviewing faculty. 41 barriers and 34 facilitators of SBR were identified and grouped by theme. Fourteen SLs representing 12 institutions attended the consensus meeting and vetted the final list of eight priority research themes for SBR in Canada: simulation in CBME, simulation for interdisciplinary and inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology. Conclusion: Conclusion: This study has summarized the current SBR activity in EM in Canada, as well as its perceived barriers and facilitators. We also provide a consensus on priority research themes in SBR in EM from the perspective of Canadian simulation leaders. This group of SLs has formed a national simulation-based research group which aims to address these identified priorities with multicenter collaborative studies.
OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.
Objectives: Individuals with moderate–severe traumatic brain injury (TBI) experience a transitory state of impaired consciousness and confusion often called posttraumatic confusional state (PTCS). This study examined the neuropsychological profile of PTCS. Methods: Neuropsychometric profiles of 349 individuals in the TBI Model Systems National Database were examined 4 weeks post-TBI (±2 weeks). The PTCS group was subdivided into Low (n=46) and High Performing PTCS (n=45) via median split on an orientation/amnesia measure, and compared to participants who had emerged from PTCS (n=258). Neuropsychological patterns were examined using multivariate analyses of variance and mixed model analyses of covariance. Results: All groups were globally impaired, but severity differed across groups (F(40,506)=3.44; p<.001; ŋp2 =.206). Rate of forgetting (memory consolidation) was impaired in all groups, but failed to differentiate them (F(4,684)=0.46; p=.762). In contrast, executive memory control was significantly more impaired in PTCS groups than the emerged group: Intrusion errors: F(2,343)=8.78; p<.001; ŋp2=.049; False positive recognition errors: F(2,343)=3.70; p<.05; ŋp2=.021. However, non-memory executive control and other executive memory processes did not differentiate those in versus emerged from PTCS. Conclusions: Executive memory control deficits in the context of globally impaired cognition characterize PTCS. This pattern differentiates individuals in and emerged from PTCS during the acute recovery period following TBI. (JINS, 2019, 25, 302–313)
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
High-intensity femtosecond laser–plasma interaction experiments were performed to investigate laser–plasma wakefield acceleration in the “bubble” regime. Using a 15 TW laser pulse, the emission of side-scattered radiation was spectrally and spatially resolved and was consequently used to diagnose the evolution of the laser pulse during the acceleration process. Side-scattered emission was observed immediately before wavebreaking at a frequency of ωL + 1.7ωp (where ωL is the laser frequency and ωp is the background plasma frequency). This emission may result from scattering of laser light by large amplitude plasma oscillations generated in the shell of the wakefield “bubble” and which occurs immediately prior to the wavebreaking/injection process. The observed variation of the frequency of scattered light with electron density agrees with theoretical estimates.
Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
Objectives: As the number of adolescents and young adults (AYAs) surviving congenital heart disease (CHD) grows, studies of long-term outcomes are needed. CHD research documents poor executive function (EF) and cerebellum (CB) abnormalities in children. We examined whether AYAs with CHD exhibit reduced EF and CB volumes. We hypothesized a double dissociation such that the posterior CB is related to EF while the anterior CB is related to motor function. We also investigated whether the CB contributes to EF above and beyond processing speed. Methods: Twenty-two AYAs with CHD and 22 matched healthy controls underwent magnetic resonance imaging and assessment of EF, processing speed, and motor function. Volumetric data were calculated using a cerebellar atlas (SUIT) developed for SPM. Group differences were compared with t tests, relationships were tested with Pearson’s correlations and Fisher’s r to z transformation, and hierarchical regression was used to test the CB’s unique contributions to EF. Results: CHD patients had reduced CB total, lobular, and white matter volume (d=.52–.99) and poorer EF (d=.79–1.01) compared to controls. Significant correlations between the posterior CB and EF (r=.29–.48) were identified but there were no relationships between the anterior CB and motor function nor EF. The posterior CB predicted EF above and beyond processing speed (ps<.001). Conclusions: This study identified a relationship between the posterior CB and EF, which appears to be particularly important for inhibitory processes and abstract reasoning. The unique CB contribution to EF above and beyond processing speed alone warrants further study. (JINS, 2018, 24, 939–948)
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
We present a multi-frequency study of the intermediate spiral SAB(r)bc type galaxy NGC 6744, using available data from the Chandra X-Ray telescope, radio continuum data from the Australia Telescope Compact Array and Murchison Widefield Array, and Wide-field Infrared Survey Explorer infrared observations. We identify 117 X-ray sources and 280 radio sources. Of these, we find nine sources in common between the X-ray and radio catalogues, one of which is a faint central black hole with a bolometric radio luminosity similar to the Milky Way’s central black hole. We classify 5 objects as supernova remnant (SNR) candidates, 2 objects as likely SNRs, 17 as H ii regions, 1 source as an AGN; the remaining 255 radio sources are categorised as background objects and one X-ray source is classified as a foreground star. We find the star-formation rate (SFR) of NGC 6744 to be in the range 2.8–4.7 M⊙~yr − 1 signifying the galaxy is still actively forming stars. The specific SFR of NGC 6744 is greater than that of late-type spirals such as the Milky Way, but considerably less that that of a typical starburst galaxy.
The abundances of Ni, Fe, Cr, Mn, P, Cu, K, Na, Ga, Ge, Se, Zn, S, Br, and C were measured in interplanetary dust particles (IDPs) collected from the Earth's stratosphere. All elements with nebular condensation temperatures lower than Mn, except S, were enriched relative to the most volatile-rich type of meteorite while the refractory elements Cr and Ni were present at chondritic abundances. This element abundance pattern is consistent with nebular condensation, suggesting the IDPs condensed at either a different location or time in the evolving solar nebula than do the meteorites. The enrichments of the major elements C, Na, P, and K exclude the possibility that the volatile enrichment in IDPs results from a minor amount of contamination.