Revealing Site Occupancy in a Complex Oxide: Terbium Iron Garnet.

Complex oxide films stabilized by epitaxial growth can exhibit large populations of point defects which have important effects on their properties. The site occupancy of pulsed laser-deposited epitaxial terbium iron garnet (TbIG) films with excess terbium (Tb) is analyzed, in which the terbium:iron (Tb:Fe)ratio is 0.86 compared to the stoichiometric value of 0.6. The magnetic properties of the TbIG are sensitive to site occupancy, exhibiting a higher compensation temperature (by 90 K) and a lower Curie temperature (by 40 K) than the bulk Tb3 Fe5 O12 garnet. Data derived from X-ray core-level spectroscopy, magnetometry, and molecular field coefficient modeling are consistent with occupancy of the dodecahedral sites by Tb3+ , the octahedral sites by Fe3+ , Tb3+ and vacancies, and the tetrahedral sites by Fe3+ and vacancies. Energy dispersive X-ray spectroscopy in a scanning transmission electron microscope provides direct evidence of TbFe antisites. A small fraction of Fe2+ is present, and oxygen vacancies are inferred to be present to maintain charge neutrality. Variation of the site occupancies provides a path to considerable manipulation of the magnetic properties of epitaxial iron garnet films and other complex oxides, which readily accommodate stoichiometries not found in their bulk counterparts.

Adenoma Detection is Increased in the Setting of Melanosis Coli.

GOALS: To compare the adenoma detection rate (ADR) during colonoscopy in patients with melanosis coli against matched controls without melanosis. BACKGROUND: Melanosis coli is a colonoscopic finding in which the colon wall appears darkly pigmented, most often due to extended laxative use, and is considered benign. The pigmentation spares adenomas, which should therefore be more readily detectable in melanosis coli. STUDY: We identified all patients with melanosis on colonoscopy at our institution over a 5-year period. We matched each patient with 2 controls by age, gender, and endoscopist. We compared the prevalence of adenomas between groups, and used multivariable analysis, adjusting for procedure indication and bowel preparation quality, to determine the independent association of melanosis with adenoma detection. RESULTS: At least 1 adenoma was detected in 34.7% of melanosis patients and 26.5% of controls [odds ratio (OR)=1.52; 95% confidence interval (CI), 1.04-2.24; P=0.03]. On multivariable analysis, the presence of melanosis remained associated with increased adenoma detection (OR=1.56; 95% CI, 1.05-2.33; P=0.03). Melanosis patients were more likely to have an adenoma ≤5 mm (OR=1.62; 95% CI, 1.04-2.51; P=0.03), but not adenomas 6 to 9 mm or ≥10 mm. CONCLUSIONS: Melanosis coli is associated with a significant increase in ADR during colonoscopy compared with controls. The increased visibility of adenomas given their contrast with the pigmented background is a likely explanation. Future efforts to identify bowel preparation agents that can induce a similar effect could improve ADRs during colonoscopy.

Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer.

Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. This phase II trial assessed the overall response rate, safety, and pharmacokinetics (PK) of LY2603618 and pemetrexed in patients with non-small cell lung cancer (NSCLC). Methods In this open-label, single-arm trial, patients with advanced or metastatic NSCLC progressing after a prior first-line treatment regimen (not containing pemetrexed) and Eastern Cooperative Oncology Group performance status ≤2 received pemetrexed (500 mg/m(2), day 1) and LY2603618 (150 mg/m(2), day 2) every 21 days until disease progression. Safety was assessed using Common Terminology Criteria for Adverse Events v3.0. Serial blood samples were collected for PK analysis after LY2603618 and pemetrexed administration. Expression of p53, as measured by immunohistochemistry and genetic variant analysis, was assessed as a predictive biomarker of response. Results Fifty-five patients were enrolled in the study. No patients experienced a complete response; a partial response was observed in 5 patients (9.1 %; 90 % CI, 3.7-18.2) and stable disease in 20 patients (36.4 %). The median progression-free survival was 2.3 months (range, 0-27.1). Safety and PK of LY2603618 in combination with pemetrexed were favorable. No association between p53 status and response was observed. Conclusions There was no significant clinical activity of LY2603618 and pemetrexed combination therapy in patients with advanced NSCLC. The results were comparable with historical pemetrexed single-agent data, with similar safety and PK profiles being observed.

Chiral Selective Chemistry Induced by Natural Selection of Spin-Polarized Electrons.

The search to understand the origin of homochirality in nature has been ongoing since the time of Pasteur. Previous work has shown that DNA can act as a spin filter for low-energy electrons and that spin-polarized secondary electrons produced by X-ray irradiation of a magnetic substrate can induce chiral selective chemistry. In the present work it is demonstrated that secondary electrons from a substrate that are transmitted through a chiral overlayer cause enantiomeric selective chemistry in an adsorbed adlayer. We determine the quantum yields (QYs) for dissociation of (R)- or (S)-epichlorohydrin adsorbed on a chiral self-assembled layer of DNA on gold and on bare gold (for control). The results show that there is a significant difference in the QYs between the two enantiomers when adsorbed on DNA, but none when they are adsorbed on bare Au. We propose that the effect results from natural spin filtering effects cause by the chiral monolayer.

Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.

BACKGROUND: Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue. METHODS: We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations. RESULTS: We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib. CONCLUSIONS: This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.

Spin-polarized electron induced asymmetric reactions in chiral molecules.

Understanding the origin of chirality in nature has been an active area of research since the time of Pasteur. In this chapter we examine one possible route by which this asymmetry could have arisen, namely chiral-specific chemistry induced by spin-polarized electrons. The various sources of spin-polarized electrons (parity violation, photoemission, and secondary processes) are discussed. Experiments aimed at exploring these interactions are reviewed starting with those based on the Vester-Ulbricht hypothesis through recent studies of spin polarized secondary electrons from a magnetic substrate. We will conclude with a discussion of possible new avenues of research that could impact this area.

Effect of a patient navigator program on the volume and quality of colonoscopy.

BACKGROUND AND GOALS: To increase colorectal cancer screening among urban minorities, New York Presbyterian Hospital/Columbia University, with support from the New York City Department of Health and the Citywide Colon Cancer Control Coalition (C5), instituted a patient navigation and direct endoscopic referral system. We assessed the effect of this program on the volume of colonoscopy in this institution, which caters to a socioeconomically diverse patient population. STUDY: We compared colonoscopy volume during the first year of the navigator program with the volume during the year before this program. We stratified on Medicaid status to assess the secular trend of screening rates. To assess quality during this period, we measured cecal intubation rates, preparation quality, and adenoma detection rates. RESULTS: Of the 749 patients assessed by the patient navigators, 678 (91%) underwent colonoscopy. Colonoscopy volume among the Medicaid outpatients increased by 56% (957 to 1489). Adenoma detection was 27% and the cecal intubation rate was 97%. Comparing navigated patients with the nonnavigated Medicaid outpatients, preparation quality was superior (34% vs. 40% suboptimal, P=0.0282), although preparation quality remained inferior to that of private patients (20% suboptimal, P<0.0001). CONCLUSIONS: Volume of the colonoscopy increased, coinciding with the onset of the patient navigation program. This increase was nearly entirely owing to a rise in the colonoscopies among Medicaid outpatients, the principal focus of the navigator program. This increase in quantity was accomplished while maintaining an overall high level of quality as measured by cecal intubation rates and adenoma detection, although preparation quality requires further efforts at improvement.

Thermal and electron-induced decomposition of 2-butanol on Pt(111).

The adsorption, thermal evolution, and electron irradiation of 2-butanol on Pt(111) were investigated with reflection absorption infrared spectroscopy (RAIRS). A simulated vibrational spectrum of a single 2-butanol molecule was calculated using density functional theory to facilitate vibrational assignments. Exposures of 0.2 Langmuir (L) and lower result in both isolated 2-butanol molecules with minimal lateral interactions and hydrogen-bonded clusters. The thermal evolution following a 4.0 L exposure shows that the hydrogen-bonded multilayer desorbs around 170 K, leaving a 2-butanol monolayer where hydrogen bonding still exists. At 190 K, a new feature at 1699 cm(-1) is attributed to the formation of butanone. Irradiation with 750 or 100 eV electrons leads to 2-butanol desorption and partial conversion to butanone, as indicated by the appearance of a peak at 1709 cm(-1).

Emergence of Subsurface Oxygen on Rh(111).

Oxygen atoms on transition metal surfaces are highly mobile under the demanding pressures and temperatures typically employed for heterogeneously catalyzed oxidation reactions. This mobility allows for rapid surface diffusion of oxygen atoms, as well as absorption into the subsurface and reemergence to the surface, resulting in variable reactivity. Subsurface oxygen atoms play a unique role in the chemistry of oxidized metal catalysts, yet little is known about how subsurface oxygen is formed or returns to the surface. Furthermore, if oxygen diffusion between the surface and subsurface is mediated by defects, there will be localized changes in the surface chemistry due to the elevated oxygen concentration near the emergence sites. We observed that oxygen atoms emerge preferentially along the boundary between surface phases and that subsurface oxygen is depleted before the surface oxide decomposes.

Increased Healthcare Utilization by Patients With Inflammatory Bowel Disease Covered by Medicaid at a Tertiary Care Center.

BACKGROUND: Low socioeconomic status has been linked with numerous poor health outcomes, but data are limited regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by IBD patients based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status. METHODS: We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid with all other patients. RESULTS: Of 947 patients with IBD, 221 (23%) had been enrolled in Medicaid. Compared with patients with other insurance types, patients with Medicaid had higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, and ethnicity, patients with Medicaid had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Patients with Medicaid had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001), and after adjusting for the same factors, the odds of requiring steroids in the patients with Medicaid was increased (OR 3.77; 95% CI 2.53-5.62). CONCLUSIONS: Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often.

Trainee colonoscopy quality is influenced by the independent and unobserved performance characteristics of supervising physicians.

Background Endoscopy training remains an apprenticeship, and the characteristics that facilitate transfer of high quality procedural skills from role models to trainees are unknown. We sought to determine whether unobserved supervisor performance influences the quality of colonoscopy performed by trainees, by studying how supervisors perform alone and how trainees perform while under those same supervisors. Methods This was a retrospective cross-sectional study conducted among ambulatory adults ≥ 50 years old who underwent colonoscopy for cancer screening or polyp surveillance from 2006 to 2015 at one academic medical center. The primary exposures were the colonoscopy withdrawal time (WT) and adenoma detection rate (ADR) of supervisors while performing colonoscopies alone. The primary outcomes were the WT and ADR of trainees performing colonoscopies under supervision. Results Data were included from 22 attending gastroenterologist supervisors, 56 gastroenterology fellow trainees, and 2777 adults undergoing 3094 colonoscopy procedures. Among all supervised colonoscopies, mean trainee WT was 12.7 minutes (SD 4.9) and trainee ADR was 33.5 %. The trainee WT was 0.42 minutes longer (standard error = 0.16, P  = 0.01) per minute increase in supervisor WT. Similarly, trainee ADR was higher under a high ADR supervisor, and the odds ratio of high compared to low supervisor ADR category was 1.28 (95 %CI 1.01 - 1.62, P  = 0.04) after adjusting for other factors. Conclusions The unobserved performance characteristics of supervising endoscopists may influence the quality of colonoscopy performed by trainees.

Inter-rater agreement for visual discrimination of phasic and tonic electromyographic activity in sleep.

Study Objectives: The objective of this study was to determine the confidence of expert raters in discriminating phasic and tonic electromyographic (EMG) activity. We undertook this study because we suspected that even expert scorers may disagree on whether a given EMG segment contained phasic activity, tonic activity, or both. Methods: Six individuals holding either Fellowship status in the American Academy of Sleep Medicine or Board Certification in Sleep Medicine with at least 5 years experience in interpreting polysomnography visually examined 60 segments containing EMG activity. Raters determined their relative confidence that each segment contained phasic and tonic activity by noting whether they were highly certain or somewhat certain that the segment contained such activity or somewhat certain or highly certain that each segment did not contain such activity. Every segment was rated by every rater twice, once for phasic and once for tonic activity. Results: Substantial differences among raters existed in certainty regarding presence/absence of both phasic and tonic activity, although raters agreed on segments far above chance. Consensus was higher on certainty regarding presence of phasic, relative to tonic, activity. Conclusions: These findings indicate the limitations of visual analyses for discriminating abnormal muscle activity during sleep. Conversely, when expert judgments are combined with digitized measurements of EMG activity in sleep (e.g. REM atonia index), some allowance must be made for the unique contribution of visual analyses to such judgments, most notably for short duration EMG signals. These results may have relevance for polysomnographic interpretation in suspected synucleinopathies.

Time-resolved synchrotron radiation excited optical luminescence: light-emission properties of silicon-based nanostructures.

The recent advances in the study of light emission from matter induced by synchrotron radiation: X-ray excited optical luminescence (XEOL) in the energy domain and time-resolved X-ray excited optical luminescence (TRXEOL) are described. The development of these element (absorption edge) selective, synchrotron X-ray photons in, optical photons out techniques with time gating coincide with advances in third-generation, insertion device based, synchrotron light sources. Electron bunches circulating in a storage ring emit very bright, widely energy tunable, short light pulses (<100 ps), which are used as the excitation source for investigation of light-emitting materials. Luminescence from silicon nanostructures (porous silicon, silicon nanowires, and Si-CdSe heterostructures) is used to illustrate the applicability of these techniques and their great potential in future applications.

Low adherence to national guidelines for proton-pump inhibitor prescription in patients receiving combination aspirin and anticoagulation.

BACKGROUND: Aspirin, when used with concurrent anticoagulation, increases the risk of gastrointestinal bleeding (GIB). Therefore, multisociety guidelines recommend prophylactic proton-pump inhibitors (PPIs) for patients receiving aspirin and anticoagulation. We aimed to determine rates and predictors of adherence to these recommendations. METHODS: All adult inpatients discharged from the hospital on aspirin and anticoagulation from July 2009 to June 2014 were retrospectively evaluated for PPI prescription on discharge instructions. We used univariate and multivariate logistic regression to test for predictors of PPI prescription. RESULTS: A total of 2422 patients were discharged on aspirin and anticoagulation; the mean age was 68 years and 53.2% were male; 42.2% were prescribed a PPI at discharge. On univariate analysis, factors associated with discharge PPI prescription included increased age (47.1% versus 37.9%), white race (47.3% versus 37.1-40.2%), higher aspirin dose (55.1% versus 39.4%), being married (46.2% versus 39.4%) and preadmission PPI use (96.6% versus 23.4%). On multivariate analysis, significant predictors of discharge PPI prescription were age 60-69 years [odds ratio (OR) 1.61] and 70-79 years (OR 1.48), and preadmission PPI use (OR 120.03). Lower odds of discharge PPI prescription included Medicaid (OR 0.55) or Medicare (OR 0.71) insurance, Spanish language (OR 0.63), and lower dose aspirin (81 mg) (OR 0.40). CONCLUSIONS: A total of 42.2% of patients discharged on aspirin and anticoagulation were prescribed PPIs. Older age and preadmission PPI use were predictive of PPI prescription, while Medicaid/Medicare insurance, Spanish language, and lower dose aspirin decreased the likelihood of discharge PPI prescription. This creates an opportunity to improve primary GIB prevention through quality improvement interventions.

The American Academy of Sleep Medicine Inter-scorer Reliability program: respiratory events.

STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) Inter-scorer Reliability program provides a unique opportunity to compare a large number of scorers with varied levels of experience to determine agreement in the scoring of respiratory events. The objective of this paper is to examine areas of disagreement to inform future revisions of the AASM Manual for the Scoring of Sleep and Associated Events. METHODS: The sample included 15 monthly records, 200 epochs each. The number of scorers increased steadily during the period of data collection, reaching more than 3,600 scorers by the final record. Scorers were asked to identify whether an obstructive, mixed, or central apnea; a hypopnea; or no event was seen in each of the 200 epochs. The "correct" respiratory event score was defined as the score endorsed by the most scorers. Percentage agreement with the majority score was determined for each epoch and the mean agreement determined. RESULTS: The overall agreement for scoring of respiratory events was 93.9% (κ = 0.92). There was very high agreement on epochs without respiratory events (97.4%), and the majority score for most of the epochs (87.8%) was no event. For the 364 epochs scored as having a respiratory event, overall agreement that some type of respiratory event occurred was 88.4% (κ = 0.77). The agreement for epochs scored as obstructive apnea by the majority was 77.1% (κ = 0.71), and the most common disagreement was hypopnea rather than obstructive apnea (14.4%). The agreement for hypopnea was 65.4% (κ = 0.57), with 16.4% scoring no event and 14.8% scoring obstructive apnea. The agreement for central apnea was 52.4% (κ = 0.41). A single epoch was scored as a mixed apnea by a plurality of scorers. CONCLUSIONS: The study demonstrated excellent agreement among a large sample of scorers for epochs with no respiratory events. Agreement for some type of event was good, but disagreements in scoring of apnea vs. hypopnea and type of apnea were common. A limitation of the analysis is that most of the records had normal breathing. A review of controversial events yielded no consistent bias that might be resolved by a change of scoring rules.

Fecal-based colorectal cancer screening among the uninsured in northern Manhattan.

BACKGROUND: Colorectal cancer (CRC) screening reduces CRC mortality; however, for many reasons, uninsured individuals are less likely to utilize CRC screening tests. PURPOSE: To compare CRC screening behaviors and outcomes with guaiac fecal occult blood testing (gFOBT) from 1998 to 2006 and fecal immunochemical testing (FIT) from 2006 to 2010 in a community-based program serving uninsured patients in northern Manhattan. METHODS: In 2013, we conducted a retrospective record review of individuals aged ≥50 years who received fecal-based CRC screening at the Northern Manhattan Cancer Screening Partnership between 1998 and 2010. Included were those with household income ≤250% of the federal poverty level, no medical insurance coverage, and who were not up to date with CRC screening. We assessed screening positivity rate, positive predictive value, differences in the use of diagnostic colonoscopy, colonoscopic findings, and adenoma detection rates for gFOBT versus FIT. RESULTS: In total, 7,710 patients completed CRC screenings (4,951 gFOBT and 2,759 FIT). The majority were female, Hispanic, foreign born, and young at age of first screening. Compared to gFOBT, FIT detected twice as many positive tests (3.2% vs 1.5%, p≤0.001) and had a higher adenoma detection rate (18.2 vs 11.8, p=0.002). CONCLUSIONS: The improved positivity and adenoma detection rates with greater number of screening tests over time favor the use of FIT over gFOBT for colorectal screening among uninsured populations in northern Manhattan.

Assessing bowel preparation quality using the mean number of adenomas per colonoscopy.

INTRODUCTION: The quality of the bowel preparation directly influences colonoscopy effectiveness. Quality indicators are widely employed to monitor operator performance and to gauge colonoscopy effectiveness. Some have suggested that the enumeration of the mean number of adenomas per colonoscopy (MNA) may be a more useful measure of bowel preparation quality, but evidence of the utility of this metric is limited. The relationship between bowel preparation quality and MNA was assessed. METHODS: Records of adult patients, aged 50-74 years, who had undergone a screening colonoscopy in a 6 month period at a hospital-based endoscopy suite in New York City were examined. Excluded were those who were symptomatic or having a colonoscopy for surveillance. Patient and procedural characteristics and clinical findings were abstracted from the endoscopy database. Bowel preparation quality was recorded as excellent, good, fair and poor. Histology and size of polyps removed were gathered from pathology reports. MNA was calculated and incident rate ratios assessing the relationship between bowel preparation quality, MNA, and covariates was calculated using Poisson regression. RESULTS: A total of 2422 colonoscopies were identified; 815 (33.6%) were screening colonoscopies among average risk individuals, 50-74 years; 203 (24.9%) had ≥1 adenomas; and 666 (81.7%) had excellent/good preparation quality. Overall MNA was 0.34 [standard deviation (SD) 0.68] and MNA was greater among those >60 years [incident rate ratio (IRR) 1.89, 95% confidence interval (CI) 1.48-2.42), males (IRR 1.60, 95%CI 1.26-2.04) and those with good bowel preparation (IRR 2.54, 95%CI 1.04-6.16). Among those with ≥1 adenomas, MNA was 1.48 (SD 1.05) for excellent and 1.00 (SD 0.00) for poor quality preparation (p = 0.55). CONCLUSIONS: We found that MNA is sensitive to changes in bowel preparation with higher MNA among those with good bowel preparation compared with those with poor preparation. Our evidence suggests MNA was particularly sensitive when restricted to only those in whom adenomas were seen.

The American Academy of Sleep Medicine inter-scorer reliability program: sleep stage scoring.

STUDY OBJECTIVES: The program provides a unique opportunity to compare a large number of scorers with varied levels of experience to determine sleep stage scoring agreement. The objective is to examine areas of disagreement to inform future revisions of the AASM Manual for the Scoring of Sleep and Associated Events. METHODS: The sample included 9 record fragments, 1,800 epochs and more than 3,200,000 scoring decisions. More than 2,500 scorers, most with 3 or more years of experience, participated. The analysis determined agreement with the score chosen by the majority of scorers. RESULTS: Sleep stage agreement averaged 82.6%. Agreement was highest for stage R sleep with stages N2 and W approaching the same level. Scoring agreement for stage N3 sleep was 67.4% and was lowest for stage N1 at 63.0%. Scorers had particular difficulty with the last epoch of stage W before sleep onset, the first epoch of stage N2 after stage N1 and the first epoch of stage R after stage N2. Discrimination between stages N2 and N3 was particularly difficult for scorers. CONCLUSIONS: These findings suggest that with current rules, inter-scorer agreement in a large group is approximately 83%, a level similar to that reported for agreement between expert scorers. Agreement in the scoring of stages N1 and N3 sleep was low. Modifications to the scoring rules to improve scoring during sleep stage transitions may result in improvement.