Acquisition of Mandarin tones by Canadian first graders: Effect of prior exposure to tonal and non-tonal languages.

This study examines the tone productions of school-aged children with and without a tonal language background who are learning Mandarin as a second language (L2) or heritage language in Mandarin-English bilingual schools in Western Canada. Tones are frequently identified as one of the most challenging aspects of phonology for Mandarin L2 learners to acquire. In this study, tone productions of bilingual children from three home language backgrounds, English, Cantonese, and Mandarin Chinese, were compared for transcribed accuracy using mixed effects logistic regression. In addition, the fundamental frequency contours of correct tone productions were fitted with generalized additive mixed models to analyse the acoustic differences between groups. Error patterns were also analysed for possible Cantonese substitutions. Our results suggest that children with a Cantonese background are more accurate in tone productions than children with an English language background, but they also made more errors than their peers with a Mandarin language background. These findings suggest that a tonal language background could result in positive transfer among school-age children who are in the early stages of learning Mandarin as an L2.

The Prevalence and Determinants of NAFLD and MAFLD and Their Severity in the VA Primary Care Setting.

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population. METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 dB/m was used to define NAFLD, whereas MAFLD was defined as controlled attenuation parameter median ≥290 dB/m and either body mass index ≥25 kg/m2 or diabetes, or 2 or more of the following: hypertension, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol. RESULTS: The mean age of participants was 50.9 years, 55.4% were women, 42.8% were white, and 43.8% were Black. The prevalence of NAFLD was 40.6% (82/202). All 82 patients with NAFLD had a body mass index ≥25 kg/m2, and therefore met our criteria for MAFLD (ie, 100% concordance). Compared with patients with no metabolic trait, patients with ≥3 traits had a 48-fold (adjusted odds ratio, 47.6; 95% confidence interval, 11.3-200) higher risk of NAFLD/MAFLD. Overall, 19 participants (9.4% of the total, 15.9% of those with NAFLD) had at least moderate fibrosis. CONCLUSIONS: NAFLD was present in 40% of Veterans registered in primary care; 9.4% of veterans had at least moderate hepatic fibrosis, with most having concurrent NAFLD. There was perfect concordance between NAFLD and the alternative MAFLD definition.

Shake It Off! Acoustic Manipulation of Lipid Vesicles for Mass Spectrometric Analysis.

Analyzing lipid assemblies, including liposomes and extracellular vesicles (EVs), is challenging due to their size, diverse composition, and tendency to aggregate. Such vesicles form with a simple phospholipid bilayer membrane, and they play important roles in drug discovery and delivery. The use of mass spectrometry (MS) allows for broad analysis of lipids from different classes; however, their release from the higher order structural aggregates is typically achieved by chemical means. Mechanical disruption by high frequency surface acoustic waves (SAW) is presented as an appealing alternative to preparing lipid vesicles for MS sampling. In this work, SAWs used to disrupt liposomes allow for the direct analysis of their constituent lipids by employing SAW nebulization with corona discharge (CD) ionization. We explore the effects of duration, frequency, and incorporation of nonpolar lipids, including cholesterol, on the SAW's ability to disrupt the liposome. We also report on the successful MS analysis of liposome-derived lipids along with cytochrome C in solution, thus demonstrating applications to aqueous samples and native MS conditions.

Missed Opportunities for Screening or Surveillance Among Patients with Newly Diagnosed Non-cardia Gastric Adenocarcinoma.

BACKGROUND: Screening for gastric cancer is not recommended despite rising rates in certain U.S. POPULATIONS: We determined possible missed opportunities for the detection and surveillance of preneoplastic lesions among gastric cancer patients in a VA hospital. METHODS: This retrospective cohort study included consecutive, newly diagnosed non-cardia gastric adenocarcinoma patients from 11/2007 to 10/2018 at the Houston VA Hospital. We identified missed opportunities for screening based on risk factors (non-White race, smoking, alcohol, Helicobacter pylori infection, gastric ulcers, family history of gastric cancer). We additionally determined missed opportunities for surveillance of known high-risk lesions. Associations between receipt of prior endoscopy for screening or surveillance and cancer-related outcomes (stage, treatment, survival) were determined using logistic regression models. RESULTS: Among 91 gastric cancer patients, 95.6% were men, 51.6% were black, 12.1% were Hispanic, with mean age of 68.0 years (standard deviation 10.8 years). The most common risk factors included non-white race (68.1%), smoking (76.9%), alcohol use (59.3%) and prior H. pylori (12.1%). Most patients had ≥ 1 risk factor for gastric cancer (92.6%), and 76.9% had ≥ 2 risk factors. Only 25 patients (27.5%) had undergone endoscopy prior to cancer diagnosis. Of 14 with known high-risk lesions (i.e., gastric intestinal metaplasia, dysplasia, ulcer), only 2 (14.3%) underwent surveillance endoscopy. Receipt of prior endoscopy was not associated with differences in cancer outcomes. CONCLUSIONS: Most patients with newly diagnosed gastric cancer had ≥ 2 known risk factors for gastric cancer but never received prior screening endoscopy. Among the few with known prior preneoplastic lesions, endoscopic surveillance was not consistently performed.

Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of MPNST-MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.

Prevalence and Predictors of Missed Dysplasia on Index Barrett's Esophagus Diagnosing Endoscopy in a Veteran Population.

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis. METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up EGD within 3-18 months after index EGD. We used logistic regression models to estimate odds ratios and 95% confidence intervals for risk factors of dysplasia on follow-up EGD. RESULTS: We identified 614 patients who had BE on index EGD. Among those with NDBE and follow-up EGD within 3-18 months (n = 271), 4.1% had definite dysplasia on follow-up, and an additional 14.0% had indefinite dysplasia. Proportions of definite or indefinite dysplasia at follow-up within 3-18 months significantly decreased from 32.6% among patients with index EGD before 2009 to 11.7% among patients with index EGD after 2013 (P for trend = .068). Those with any indefinite or definite dysplastic BE at follow-up within 3-18 months after index EGD (n = 49) were more likely to have BE length ≥3 cm on index EGD (odds ratio, 3.39; 95% confidence interval, 1.63-7.08) than those with persistent NDBE or no BE on follow-up. CONCLUSIONS: The occurrence of missed dysplasia on an index EGD has decreased over time. However, those with long segment BE were more than 3 times as likely to have missed dysplasia, and this group could benefit from dysplasia surveillance within 18 months of BE diagnosis.

Race/Ethnicity and Birthplace as Risk Factors for Gastric Intestinal Metaplasia in a Multiethnic United States Population.

INTRODUCTION: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk. METHODS: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed a risk prediction model of GIM risk. We additionally examined for associations using a composite variable combining race/ethnicity and birthplace. RESULTS: Among 267 cases with GIM and 1,842 controls, older age (vs <40 years: 40-60 years adjusted odds ratios (adjORs) 2.02; 95% CI 1.17-3.29; >60 years adjOR 4.58; 95% CI 2.61-8.03), Black race (vs non-Hispanic White: adjOR 2.17; 95% CI 1.31-3.62), Asian race (adjOR 2.83; 95% CI 1.27-6.29), and current smoking status (adjOR 2.04; 95% CI 1.39-3.00) were independently associated with increased GIM risk. Although non-US-born Hispanics had higher risk of GIM (vs non-Hispanic White: adjOR 2.10; 95% CI 1.28-3.45), we found no elevated risk for US-born Hispanics (adjOR 1.13; 95% CI 0.57-2.23). The risk prediction model had area under the receiver operating characteristic of 0.673 (95% CI 0.636-0.710) for discriminating GIM. DISCUSSION: We found that Hispanics born outside the United States were at increased risk of GIM, whereas Hispanics born in the United States were not, independent of Helicobacter pylori infection. Birthplace may be more informative than race/ethnicity when determining GIM risk among US populations.

IN SITU MASS SPECTROMETERS FOR APPLICATIONS IN SPACE.

Mass spectrometry (MS) has played a remarkable role in exploring the chemical make-up of our solar system. In situ probes were historically developed to analyze inorganic/elemental compositions while leveraging native ions or harsh ionization methods to aid in exploring astrophysics applications (e.g., heliophysics). The part played by MS is demonstrated in a majority of scientific payloads focused on exploration, particularly at the turn of the century with missions including Cassini-Huygens, Rosetta, and now Mars Science Laboratory. Plasma mass spectrometers have grown more sophisticated to interrogate fundamental inorganic analysis (e.g., solar wind and magnetospheres) including both native ions and neutrals. Cosmic dust floating in-between and orbiting planetary bodies has been targeted by unique sampling via impact ionization. More complex systems rely on landed planetary instrumentation with lessons learned from pioneering missions in the 1970s and 1980s to near neighbors Mars and Venus. Modern probes have expanded applicable target chemicals by recognizing the needs to provide for molecular analyses, extended mass range, and high resolution to provide unequivocal detection and identification. Notably, as the field surrounding astrobiology has gained momentum, so has the in situ detection of complex molecular chemistry including the chemical evolution of organic molecules. Mission context often includes long term timelines from spacecraft launch to arrival and additionally the diverse target environments across various planets. Therefore, customized experimental designs for space MS have been born of necessity. To this point, the development of MS instrumentation on Earth has now far outpaced development for experiments in space. Therefore, exciting developments lie ahead among various international space agencies conducting current and future mission planning with increasingly enhanced instrumentation. For instance, near-neighbor Mars has entertained considerable attention with complex MS instrumentation with laser desorption ionization aboard the Mars Organic Molecule Analyzer instrument. To study comets, the Rosetta mission employs a secondary ionization mechanism. Meanwhile, the various moons of Jupiter and Saturn have intriguing surface and subsurface properties that warrant more advanced analyzer systems. Instrumentation design will continue to evolve as requirements develop and this review serves as a reflection of the contribution of in situ MS to space exploration in the past 20 years and the anticipated contribution yet to come. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.

External validation of a model determining risk of neoplastic progression of Barrett's esophagus in a cohort of U.S. veterans.

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients. METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence of high-grade dysplasia (HGD) or EAC on initial EGD. We performed an external validation study of a risk model containing sex, smoking, BE length, and low-grade dysplasia (LGD) status and assessed discriminatory ability using the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 608 BE patients, 24 progressed to HGD/EAC. The points-based model discriminated well with an AUROC of .72 (95% confidence interval [CI], .63-.82). When categorized into low-, intermediate-, and high-risk groups according to published cutoffs, the AUROC was poor at .57. Restructured into low-risk versus high-risk groups, the AUROC was .72 (95% CI, .64-.80). Excluding baseline LGD did not reduce discriminatory ability (AUROC, .73; 95% CI, .64-.82). CONCLUSIONS: This external validation provides further evidence that the model including sex, LGD status, smoking status, and BE length may help to risk stratify BE patients. A simplified version excluding LGD status and/or reducing the number of risk groups has increased utility in clinical practice without loss of discriminatory ability.

Risk Score Using Demographic and Clinical Risk Factors Predicts Gastric Intestinal Metaplasia Risk in a U.S. Population.

BACKGROUND/AIMS: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S. METHODS: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. pylori infection alone and a baseline model including remaining terms without H. pylori. RESULTS: Male sex, older age, non-white race/ethnicity, smoking status, and H. pylori were associated with GIM risk. The expanded model including these terms had AUROC 0.73 (95%CI 0.71-0.76) for predicting GIM and AUROC 0.82 (95%CI 0.79-0.86) for extensive GIM. This model discriminated better than a model including only H. pylori (AUROC 0.66; 95%CI 0.63-0.68) and the baseline model (AUROC 0.67; 95%CI 0.64-0.70). The expanded model performed similarly among primary care (AUROC 0.75) and endoscopy (AUROC 0.73) patients. The expanded model showed sufficient internal validity (cross-validation AUROC 0.72) with little evidence of over-fitting. CONCLUSIONS: We develop and validate a non-invasive risk model for GIM detection in a U.S. population that included terms for sex, age, race/ethnicity, smoking status, and H. pylori infection. Validated risk models would identify individuals with GIM who should be referred for endoscopic screening.

Opportunities to expand access to mental health services: A case for the role of online peer support communities.

This study investigated whether with disruptions in care due to the COVID-19 pandemic, persons who self-identified as living with a mental health condition increased their usage of an online peer support community. We also explored whether study participants who self-reported usage of online peer support communities were interested in using these communities to connect with evidence-based interventions and mental health services. This study employed a cross-sectional online survey design. The survey was disseminated by the Inspire online peer support community and Mental Health America through various social media channels. Descriptive and inferential analyses were conducted to summarize participant demographics, investigate patterns of use of online peer support communities, and interest in accessing additional programs through these platforms. There were 369 survey respondents, with a mean age of 49 (SD = 15.6), of which 77% were female. Most respondents self-reported having depression (34%), post-traumatic stress disorder (25%), and anxiety-related conditions (20%). The number of respondents who reported accessing online peer support platforms multiple times a day appeared to double after March 2020. We also found an overall positive association between frequency of community use and self-reported benefit to mental health. Approximately 81% of respondents expressed interest in accessing mental health services via an online peer support community. Persons who self-report living with mental health conditions and who engage in online peer support communities expressed interest in accessing evidence-based interventions via these online platforms. Participants were most interested in services related to enhancing coping mechanisms and skills, enabling overall wellbeing, and accessing therapy.

Identification of Quinolinones as Antivirals against Venezuelan Equine Encephalitis Virus.

Venezuelan equine encephalitis virus (VEEV) is a reemerging alphavirus that can cause encephalitis resulting in severe human morbidity and mortality. Using a high-throughput cell-based screen, we identified a quinolinone compound that protected against VEEV-induced cytopathic effects. Analysis of viral replication in cells identified several quinolinone compounds with potent inhibitory activity against vaccine and virulent strains of VEEV. These quinolinones also displayed inhibitory activity against additional alphaviruses, such as Mayaro virus and Ross River virus, although the potency was greatly reduced. Time-of-addition studies indicated that these compounds inhibit the early-to-mid stage of viral replication. Deep sequencing and reverse genetics studies identified two unique resistance mutations in the nsP2 gene (Y102S/C; stalk domain) that conferred VEEV resistance on this chemical series. Moreover, introduction of a K102Y mutation into the nsP2 gene enhanced the sensitivity of chikungunya virus (CHIKV) to this chemical series. Computational modeling of CHIKV and VEEV nsP2 identified a highly probable docking alignment for the quinolinone compounds that require a tyrosine residue at position 102 within the helicase stalk domain. These studies identified a class of compounds with antiviral activity against VEEV and other alphaviruses and provide further evidence that therapeutics targeting nsP2 may be useful against alphavirus infection.

Prevalence of Gastric Intestinal Metaplasia in a Multiethnic US Veterans Population.

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, from February 2008 to August 2013. All participants completed a study questionnaire on sociodemographic and clinical characteristics and underwent upper endoscopy with gastric mapping (7 biopsy sites). Cases were classified as having gastric intestinal metaplasia if intestinal metaplasia was detected in 1 or more noncardia gastric biopsies; noncases were participants without evidence of gastric intestinal metaplasia. We used logistic regression models to estimate odds ratios (ORs) and 95% CI values to examine the association between race or ethnicity and gastric intestinal metaplasia and performed a mediation analysis to determine whether H pylori and gastritis affected observed associations. RESULTS: We included 415 cases with gastric intestinal metaplasia and 1764 noncases. The prevalence of gastric intestinal metaplasia was highest among Hispanic patients (29.5%; 95% CI, 23.7%-36.1%), followed by African American (25.5%; 95% CI, 22.4%-28.9%) and non-Hispanic white patients (13.7%; 95% CI, 11.9%-15.7%). After we adjusted for age, sex, and smoking, African American (OR, 1.87; 95% CI, 1.44-2.44) and Hispanic race or ethnicity (OR, 2.32; 95% CI, 1.61-3.34) and H pylori infection (OR, 3.65; 95% CI, 2.79-4.55) were associated with an increased risk of gastric intestinal metaplasia. H pylori infection alone accounted for 33.6% of the association of race or ethnicity with gastric intestinal metaplasia, and 55.5% of the association when combined with acute and chronic gastritis. CONCLUSIONS: Hispanic and African American patients have an increased risk for gastric intestinal metaplasia, determined by upper endoscopy biopsy analysis, compared with non-Hispanic white patients. This increase in risk was partially independent of H pylori infection.

Unsupervised Reconstruction of Analyte-Specific Mass Spectra Based on Time-Domain Morphology with a Modified Cross-Correlation Approach.

Concomitant species that appear at the same or very similar times in a mass-spectral analysis can clutter a spectrum because of the coexistence of many analyte-related ions (e.g., molecular ions, adducts, fragments). One method to extract ions stemming from the same origin is to exploit the chemical information encoded in the time domain, where the individual temporal appearances inside the complex structures of chronograms or chromatograms differ with respect to analytes. By grouping ions with very similar or identical time-domain structures, single-component mass spectra can be reconstructed, which are much easier to interpret and are library-searchable. While many other approaches address similar objectives through the Pearson's correlation coefficient, we explore an alternative method based on a modified cross-correlation algorithm to compute a metric that describes the degree of similarity between features inside any two ion chronograms. Furthermore, an automatic workflow was devised to be capable of categorizing thousands of mass-spectral peaks into different groups within a few seconds. This approach was tested with direct mass-spectrometric analyses as well as with a simple, fast, and poorly resolved LC-MS analysis. Single-component mass spectra were extracted in both cases and were identified based on accurate mass and a mass-spectral library search.

Prevalence of Barrett's esophagus and performance of societal screening guidelines in an unreferred primary care population of U.S. veterans.

BACKGROUND AND AIMS: Less than 10% of patients diagnosed with esophageal adenocarcinoma have a pre-existing Barrett's esophagus (BE) diagnosis, possibly because of suboptimal performance of guidelines. We examined the prevalence of BE in a previously unscreened primary care population and the potential yield of practice BE screening guidelines. METHODS: This was a retrospective analysis of a prospective cross-sectional study of consecutively recruited unreferred patients from primary care clinics who underwent study upper endoscopy. We examined the performance of BE screening guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology (BSG), American Society for Gastrointestinal Endoscopy (ASGE), American College of Gastroenterology (ACG), American Gastroenterological Association (AGA), and our own modification of guidelines. RESULTS: We identified 44 BE cases and 469 control subjects (prevalence, 8.6%). Among 371 patients without GERD symptoms, 25 (6.7%) had BE. The AGA guidelines requiring ≥2 BE risk factors had sensitivity of 100% and specificity of only .2%, whereas ACG, ASGE, ESGE, and BSG guidelines (all requiring GERD first) had low sensitivities (38.6%-43.2%), specificities ranging from 67.4% to 76.5%, and area under the receiver operating curve (AUROC) of .50 to .60. Our 2-pronged approach depending on presence or absence of GERD symptoms but with other risk factors achieved sensitivity of 81.8%, specificity of 51.2%, and AUROC of .66. CONCLUSIONS: Over half of BE cases were without frequent GERD symptoms, but virtually all had at least 1 known BE risk factor. Practice guidelines requiring GERD symptoms have low sensitivity, whereas those not requiring GERD have low specificity. We have proposed a screening guideline with better use of known risk factors.

Six-step etoposide desensitization protocol: A pediatric, adolescent, and young adult case series.

Etoposide administration can be complicated by hypersensitivity reactions. Desensitization may provide a strategy to prevent hypersensitivity recurrence. One challenge with desensitization is regimen complexity. This case series describes 12 pediatric, adolescent, and young adult patients who received a simplified six-step etoposide desensitization protocol. This protocol contains 50% fewer titration steps compared with previously described protocols and eliminates infusion rate changes during titration. Simplified titration may minimize risk of error during administration and improve safety. This protocol was tolerated by 92% of patients. Given increasing frequency and duration of drug shortages, a simplified desensitization protocol provides a valuable treatment option.

Dietary Potassium Intake and Mortality in a Prospective Hemodialysis Cohort.

OBJECTIVES: Among hemodialysis patients, clinical practice guidelines recommend dietary potassium restriction given concerns about potential hyperkalemia leading to malignant arrhythmias and mortality. However, there are sparse data informing recommendations for dietary potassium intake in this population. We thus sought to examine the relationship between dietary potassium intake and death risk in a prospective cohort of hemodialysis patients. DESIGN AND METHODS: Among 415 hemodialysis patients from the prospective "Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease" cohort recruited across 16 outpatient dialysis clinics, information regarding dietary potassium intake was obtained using Food Frequency Questionnaires administered over October 2011 to March 2015. We first examined associations of baseline dietary potassium intake categorized as tertiles with mortality risk using Cox regression. We then examined clinical characteristics associated with low dietary potassium intake (defined as the lowest tertile) using logistic regression. RESULTS: In expanded case-mix Cox analyses, patients whose dietary potassium intake was in the lowest tertile had higher mortality (ref: highest tertile) (adjusted hazard ratio 1.74, 95% confidence interval 1.14-2.66). These associations had even greater magnitude of risk following adjustment for laboratory and nutritional covariates (adjusted hazard ratio 2.65, 95% confidence interval 1.40-5.04). In expanded case-mix restricted cubic spline analyses, there was a monotonic increase in mortality risk with incrementally lower dietary potassium intake. In expanded case-mix logistic regression models, female sex; higher serum bicarbonate; and lower dietary energy, protein, and fiber intake were associated with low dietary potassium intake. CONCLUSIONS: In a prospective cohort of hemodialysis patients, lower dietary potassium intake was associated with higher mortality risk. These findings suggest that excessive dietary potassium restriction may be deleterious in hemodialysis patients, and further studies are needed to determine the optimal dietary potassium intake in this population.

Performance on the mouse vibration actuating search task is compromised by sleep deprivation.

As we go about our daily routines we are continuously bombarded with environmental feedback that requires appraisal and response. Sleep loss can compromise the efficiency by which these cognitive processes function. Operationally, poor performance caused by insufficient sleep translates to increased health and safety risks in settings where attention and timely and/or accurate decisions to respond are critical (e.g., at work, on the road, etc.). Current rodent tasks that assess altered cognition after sleep deprivation (SD) do not accurately model the continuous multisensory feedback that informs goal-oriented behavior in humans. Herein, we describe the vibration actuating search task (VAST), which consists of a vibrating open field with pseudo-randomly selected entrance and target destination points. To successfully complete a trial, mice use feedback from rotary motor-induced floor vibrations to navigate from the entrance point to the target destination. Sets of 20 trials were conducted on 3 consecutive days, and before testing on the third day control mice were undisturbed while other mice were sleep deprived for 10 h. On the first 2 days mice learned the task with high success rates. Alternatively, VAST performance was compromised following SD as measured by increased failures in task completion, time to target, time spent immobile, and decreased speed as compared with undisturbed mice. The VAST enables the analysis of continuous feedback via multiple sensory modalities in mice and is applicable to a variety of operational settings.NEW & NOTEWORTHY The vibration actuating search task (VAST) is a novel performance assay that uses continuous auditory and haptic feedback to motivate and direct search behaviors in mice. The VAST is rapidly acquired by mice and performance is disrupted by sleep deprivation. The VAST has practical application in occupational settings. The cognitive aspects of the sensorimotor integration in the VAST may prove useful for rodent models of neurodegenerative disease.

Enabling Field Asymmetric Ion Mobility Spectrometry Separation of Fentanyl-Related Compounds Using Controlled Humidity.

Due to the widespread abuse of opioids in recent years, the development of quick and reliable methods for analyzing compounds such as fentanyl and its derivatives is increasingly important. Ahead of online mass spectrometric analysis, field asymmetric ion mobility spectrometry (FAIMS) has previously been used for rapid ion prefiltering and demonstrated significantly improved peak capacity with the addition of vapor modifiers to the carrier gas. The application of FAIMS-mass spectrometry (MS) in the analysis of fentanyl and related compounds is presented herein with the use of a water vapor modifier. The inclusion of the water vapor modifier to the FAIMS methodology is made more robust with the incorporation of a humidity sensor. A dramatic improvement in the separation of fentanyl, alfentanil, 4-aminophenyl-1-phenethylpiperidine (4-ANPP), norfentanyl, and heroin has been achieved, and the ability to distinguish the isobars in a mixture, alfentanil and ortho-isopropyl furanyl fentanyl, is demonstrated without lengthy chromatography.

Inexpensive Ultrasonic Nebulization Coupled with Direct Current Corona Discharge Ionization Mass Spectrometry for Liquid Samples and Its Fundamental Investigations.

The concept of direct mass-spectrometric analysis, especially exploited by ambient desorption/ionization (ADI) methods, provides numerous means for convenient sample analysis. While many simple and versatile ionization sources have been developed, challenges lay in achieving efficient sample introduction. In previous work, a sample introduction method employing direct current corona discharge (CD) coupled to a surface acoustic wave nebulization (SAWN) device enhanced sampling performance for both polar and nonpolar analytes by up to 4 orders of magnitude. In fact, the SAWN-CD method generated a multiply charged peptide ion signal comparable to that of conventional ESI. Unfortunately, the high cost of the SAWN devices themselves limits their accessibility. Herein, we report on an analogous implementation of CD with an inexpensive ultrasonic nebulizer (USN) on the basis of a commercial room humidifier demonstrating equivalent exemplary performance. We subsequently compare the two methods of SAWN-CD and USN-CD in a screening application of milk for the detection of two antibiotic drugs, ciprofloxacin and ampicillin. Finally, we further investigate the relative softness of these CD-coupled acoustic nebulization methods in comparison to that of ESI using a survival yield study of the thermometer ion nitrobenzylpyridinium.