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OBJECTIVE: To reweight the Agency for Healthcare Research and Quality Patient Safety for Selected Indicators Composite (Patient Safety Indicator [PSI] 90) from weights based solely on the frequency of component PSIs to those that incorporate excess harm reflecting patients' preferences for outcome‐related health states. DATA SOURCES: National administrative and claims data involving hospitalizations in nonfederal, nonrehabilitation, acute care hospitals. STUDY DESIGN: We estimated the average excess aggregate harm associated with the occurrence of each component PSI using a cohort sample for each indicator based on denominator‐eligible records. We used propensity scores to account for potential confounding in the risk models for each PSI and weighted observations to estimate the “average treatment effect in the treated” for those with the PSI event. We fit separate regression models for each harm outcome. Final PSI weights reflected both the disutilities and the frequencies of the harms. DATA COLLECTION/EXTRACTION METHODS: We estimated PSI frequencies from the 2012 Healthcare Cost and Utilization Project State Inpatient Databases with present on admission data and excess harms using 2012–2013 Centers for Medicare & Medicaid Services Medicare Fee‐for‐Service data. PRINCIPAL FINDINGS: Including harms in the weighting scheme changed individual component weights from the original frequency‐based weighting. In the reweighted composite, PSIs 11 (“Postoperative Respiratory Failure”), 13 (“Postoperative Sepsis”), and 12 (“Perioperative Pulmonary Embolism or Deep Vein Thrombosis”) contributed the greatest harm, with weights of 29.7%, 21.1%, and 20.4%, respectively. Regarding reliability, the overall average hospital signal‐to‐noise ratio for the reweighted PSI 90 was 0.7015. Regarding discrimination, among hospitals with greater than median volume, 34% had significantly better PSI 90 performance, and 41% had significantly worse performance than benchmark rates (based on percentiles). CONCLUSIONS: Reformulation of PSI 90 with harm‐based weights is feasible and results in satisfactory reliability and discrimination, with a more clinically meaningful distribution of component weights.

Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma that generally originates from Schwann cells. The prognosis for this type of malignancy is relatively poor due to complicated genetic alterations and the lack of specific targeted therapy. Chromosome fragment 4q22-23 is frequently deleted in MPNSTs and other human tumors, suggesting tumor suppressor genes may reside in this region. Here, we provide evidence that SMARCAD1, a known chromatin remodeler, is a novel tumor suppressor gene located in 4q22-23. We identified two human homologous smarcad1 genes (smarcad1a and smarcad1b) in zebrafish, and both genes share overlapping expression patterns during embryonic development. We demonstrated that two smarcad1a loss-of-function mutants, sa1299 and p403, can accelerate MPNST tumorigenesis in the tp53 mutant background, suggesting smarcad1a is a bona fide tumor suppressor gene for MPNSTs. Moreover, we found that DNA double-strand break (DSB) repair might be compromised in both mutants compared to wildtype zebrafish, as indicated by pH2AX, a DNA DSB marker. In addition, both SMARCAD1 gene knockdown and overexpression in human cells were able to inhibit tumor growth and displayed similar DSB repair responses, suggesting proper gene expression level or gene dosage is critical for cell growth. Given that mutations of SMARCAD1 sensitize cells to PARP inhibitors in yeast and the human U2OS osteosarcoma cell line, the identification of SMARCAD1 as a novel tumor suppressor gene might contribute to the development of new cancer therapies for MPNSTs. This article is protected by copyright. All rights reserved.

The origins of geographic races in wide-ranging species are poorly understood. In Texas, the texanus subspecies of Helianthus annuus has long been thought to have acquired its defining phenotypic traits via introgression from a local congener, H. debilis, but previous tests of this hypothesis were inconclusive. Here, we explore the origins of H. a. texanus using whole genome sequencing data from across the entire range of H. annuus and possible donor species, as well as phenotypic data from a common garden study. We found that although it is morphologically convergent with H. debilis, H. a. texanus has conflicting signals of introgression. Genome wide tests (Patterson's D and TreeMix) only found evidence of introgression from H. argophyllus (sister species to H. annuus and also sympatric), but not H. debilis, with the exception of one individual of 109 analysed. We further scanned the genome for localized signals of introgression using PCAdmix and found minimal but nonzero introgression from H. debilis and significant introgression from H. argophyllus in some populations. Given the paucity of introgression from H. debilis, we argue that the morphological convergence observed in Texas is probably from standing genetic variation. We also found that genomic differentiation in H. a. texanus is mostly driven by large segregating inversions, several of which have signatures of natural selection based on haplotype frequencies.

OBJECTIVE: Obstructive sleep apnea (OSA) is common among bariatric surgery patients and is associated with perioperative risk. Preoperative screening is recommended, but some screening tools lack validation, and their relative performance is unclear in this population. The study objective was to compare the ability of four existing tools (STOP-BANG, NO-OSAS, No-Apnea, and the Epworth Sleepiness Scale [ESS]) to screen for moderate to severe OSA in a diverse bariatric cohort. METHODS: Data from patients presenting for first-time bariatric surgery who underwent a sleep study within 1 year of the initial encounter were retrospectively reviewed. Performance of the four tools for detecting moderate to severe OSA was compared based on the area under the receiver operating characteristic curves (AUC). RESULTS: Of the included 214 patients (83.2% female, median age 39 years), 45.3% had moderate to severe OSA. Based on AUC, STOP-BANG (0.75 [95% CI: 0.68–0.81], N = 185), NO-OSAS (0.76 [95% CI: 0.69–0.82], N = 185), and No-Apnea (0.69 [95% CI: 0.62–0.76], N = 190) had similar performance (P > 0.16). Compared with STOP-BANG and NO-OSAS, ESS (0.61 [95% CI: 0.54–0.68], N = 198) had a significantly lower AUC (P < 0.01). Hispanic/Latino self-identification, sex, or obesity class did not significantly modify test performance. CONCLUSIONS: STOP-BANG and NO-OSAS may be preferable to No-Apnea and ESS when screening bariatric surgery patients for moderate to severe OSA. Efforts to screen bariatric patients for OSA are recommended.

Obstructive and central sleep apnea affects ~1 billion people globally and may lead to serious cardiovascular and neurocognitive consequences, but treatment options are limited. High loop gain (ventilatory instability) is a major pathophysiological mechanism underlying both types of sleep apnea and can be lowered pharmacologically with acetazolamide, thereby improving sleep apnea severity. However, individual responses vary and are strongly correlated with the loop gain reduction achieved by acetazolamide. To aid with patient selection for long‐term trials and clinical care, our goal was to understand better the factors that determine the change in loop gain following acetazolamide in human subjects with sleep apnea. Thus, we (i) performed several meta‐analyses to clarify how acetazolamide affects ventilatory control and loop gain (including its primary components controller/plant gain), and based on these results, we (ii) performed physiological model simulations to assess how different baseline conditions affect the change in loop gain. Our results suggest that (i) acetazolamide primarily causes a left shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; and (ii) higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline result in a more pronounced loop gain reduction with acetazolamide. In summary, the combination of mechanistic meta‐analyses with model simulations provides a unified framework of acetazolamide’s effects on ventilatory control and revealed physiological predictors of response, which are consistent with empirical observations of acetazolamide's effects in different sleep apnea subgroups. Prospective studies are needed to validate these predictors and assess their value for patient selection., (a) Based on mechanistic meta‐analyses in patients with sleep apnea, acetazolamide primarily causes a left‐shift of the chemosensitivity line thus lowering plant gain without substantially affecting controller gain; the net effect is a relative reduction in overall loop gain similar to the reduction in plant gain. (b) Based on model simulations, a higher controller gain, higher paCO2 at eupneic ventilation, and lower CO2 production at baseline each result in a more pronounced loop gain reduction with acetazolamide, and thus may predict response to acetazolamide.

AIM: The geographic range and ecological niche of species are widely used concepts in ecology, evolution and conservation and many modelling approaches have been developed to quantify each. Niche and distribution modelling methods require a litany of design choices; differences among subdisciplines have created communication barriers that increase isolation of scientific advances. As a result, understanding and reproducing the work of others is difficult, if not impossible. It is often challenging to evaluate whether a model has been built appropriately for its intended application or subsequent reuse. Here, we propose a standardized model metadata framework that enables researchers to understand and evaluate modelling decisions while making models fully citable and reproducible. Such reproducibility is critical for both scientific and policy reports, while international standardization enables better comparison between different scenarios and research groups. INNOVATION: Range modelling metadata (RMMS) address three challenges: they (a) are designed for convenience to encourage use, (b) accommodate a wide variety of applications, and (c) are extensible to allow the research community to steer them as needed. RMMS are based on a metadata dictionary that specifies a hierarchical structure to catalogue different aspects of the range modelling process. The dictionary balances a constrained, minimalist vocabulary to improve standardization with flexibility for users to modify and extend. To facilitate use, we have developed an R package, rangeModelMetaData, to build templates, automatically fill values from common modelling objects, check for inconsistencies with standards, and suggest values. MAIN CONCLUSIONS: Range Modelling Metadata tools foster cross‐disciplinary advances in biogeography, conservation and allied disciplines by improving evaluation, model sharing, model searching, comparisons and reproducibility among studies. Our initially proposed standards here are designed to be modified and extended to evolve with research trends and needs.

We dedicate this paper to John Clamp, who was an integral part of the research and writing of this paper. Clamp passed while this manuscript was under review. He was a professor at North Carolina Central University for more than 30 yr, devoting his outstanding research to evolutionary biology, and particularly the study of ciliated protists. He was a larger‐than‐life character and will be greatly missed as friend and mentor. This work was supported by the Ministerio de Economia y Competitividad, Espanola (MINECO, grant number CGL2013‐40851‐P/ BOS) to MMC, and travel support from the Research Coordination Network for Biodiversity of Ciliates (National Science Foundation grant number DEB 1136580) from the U.S. National Science Foundation to JC. RAJW was supported by the Crafoord Foundation, Sweden (grant numbers 20160971 and 20170671), while completing this manuscript.

Despite the fact that income smoothing by managers is a pervasive phenomenon that has been widely researched, extant literature provides incomplete evidence on how smoothing is associated with cost of debt in general, and in the private loan market in particular. The institutional factors associated with private loan contracts, combined with the theoretical motivations for smoothing, make it unclear whether smoothing will be positively, negatively, or not associated with loan spread. Using both cross-country and within-country analyses on an international sample of private loans, we predict and provide evidence that income smoothing is associated with lower cost of debt when the threat of private benefits consumption by managers is low, but is associated with higher cost of debt when the threat of private benefits consumption by managers is high. We provide the first evidence in the literature that the garbling effect of smoothing can predictably dominate the signaling view of smoothing in debt contract design, and we identify private benefits consumption threat as the feature of the contracting environment that empirically reveals a sign reversal in the relation between smoothing and cost of debt. This article is protected by copyright. All rights reserved

This study examines whether key characteristics of analysts’ forecasts—timeliness, accuracy, and informativeness—change when investor demand for information is likely to be especially high, i.e., during periods of high uncertainty. Findings reveal that when uncertainty is high, analysts’ forecasts are more timely but less accurate. However, analysts’ forecasts are also more informative to the market, which is consistent with investors’ demand for timely information, even if it is less accurate. We observe these findings when market prices are increasing and decreasing, consistent with the findings resulting from uncertainty in general rather than just uncertainty associated with market declines. We also examine how timeliness, accuracy, and informativeness change in response to elevated levels of three sources of uncertainty—market, industry, and firm-level. We predict and find that analysts are better able to deal with heightened industry uncertainty, as reflected by greater timeliness with no loss in forecast accuracy. In contrast, analysts have greater difficulty dealing with heightened market uncertainty, as both timeliness and forecast accuracy decline. This article is protected by copyright. All rights reserved

Asthma, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are the most common respiratory disorders worldwide. Given demographic and environmental changes, prevalence for each is likely to increase. Although exact numbers are not known, based on chance alone, many people will be affected by both lower airways obstruction and concomitant upper airway obstruction during sleep. Some recent studies suggest that there is a reciprocal interaction, with chronic lung disease predisposing to OSA, and OSA worsening control and outcomes from chronic lung disease. Thus, the combination of wake and sleep respiratory disorders can create an overlap syndrome with unique pathophysiological, diagnostic and therapeutic concerns. Although much work needs to be done, given the above, Respirologists, Sleep Medicine and Primary Care providers must be vigilant for overlap syndromes. Accurate diagnosis of, for example, OSA as a cause of nocturnal symptoms in a patient with asthma is likely to limit further ineffective titration of medications for asthma. Moreover, prompt treatment of OSA in the overlap syndromes will not only offer symptomatic benefit of OSA, but also improve symptoms and healthcare resource utilization attributable to obstructive lung disease, and in COPD, it may reduce mortality.

Recent policies by public and private payers have increased incentives to reduce hospital admissions. Using data from four states from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project, this study compared the payer-specific population-based rates of adults using inpatient, observation, and emergency department (ED) services for 10 common medical conditions in 2009 and in 2013. Patients had an expected primary payer of private insurance, Medicare, Medicaid, or no insurance. Across all four payer populations, inpatient admissions declined, and care shifted toward treat-and-release observation stays and ED visits. The percentage of hospitalizations that began with an observation stay increased. Implications for quality of care and costs to patients warrant further examination. Journal of Hospital Medicine 2017;12:443-446.

Understanding the frequency of and reasons for postpartum revisits, which occur more often for women with delivery complications than for those without, can help identify risk and inform discharge care. The objective of this study was to examine the rate of and reasons for inpatient and emergency department (ED) revisits 7 days and 42 days following deliveries with and without severe maternal morbidity (SMM). Retrospective conveys the intended meaning. cohort study using data from the Agency for Healthcare Research and Quality’s 2016‐2017 Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases from 14 states with de‐identified patient linkage numbers and adequate race/ethnicity coding (AR, FL, GA, IA, MD, MS, MO, NV, OR, SC, SD, TN, VT, and WI). The analysis consisted of delivery hospitalizations and postpartum inpatient and ED revisits for women aged 12‐55 years. SMM conditions at delivery were grouped into eight types: severe cardiac conditions, sickle cell disease with crisis, severe hypertensive disorders, severe respiratory conditions, sepsis, severe hemorrhage, other severe obstetric conditions, and other severe medical conditions. Outcomes included 7‐day and 42‐day inpatient and ED age‐adjusted revisit rates and the reason for the revisit. A total of 9164 index deliveries with an SMM condition and 1 406 582 deliveries without an SMM condition at delivery were included. Of those deliveries with an SMM condition, 35.0% were for black women and 23.1% were for women aged 35 years and older compared with 22.4% and 15.2% of deliveries without an SMM condition, respectively. Overall, 73.2 per 1000 deliveries with an SMM condition had an inpatient or ED revisit within 7 days and one in five women returned within 42 days postpartum (207.0 revisits per 1000 deliveries). These rates were more than twice as high as those for deliveries without an SMM condition (32.1 and 87.7 per 1000, respectively). Among women with only one SMM type at delivery, the 42‐day revisit rate for inpatient or ED care was as high as 445.5 per 1000 deliveries with sickle cell disease with crisis, followed by 250.9 per 1000 deliveries with severe cardiac conditions. An additional 2400 women without an SMM condition diagnosed at delivery had an inpatient readmission within 7 days for an SMM‐related condition. Women with the highest postpartum revisit rates included those with a diagnosis of SMM at delivery overall and specifically those with sickle cell disease with crisis and severe cardiac conditions. A number of women with SMM conditions were diagnosed at a postpartum readmission and not at the delivery. Examining revisits during the postpartum period is an important consideration when studying SMM. This study can help identify women at high risk of postpartum revisits. The data can be used to inform the scheduling and content of coordinated discharge care, assist with resource allocation, and identify research priorities for maternal care. Future research is needed to examine the contributions of clinical factors at delivery, expected payer, and hospital and community characteristics in explaining disparities in the risk of postpartum readmission. Agency for Healthcare Research and Quality.

Introduction The Paris System for classifying urine cytology emphasizes identification of high-grade urothelial carcinoma (HGUC). The causes of false-negative urine cytologies (UC) within this system are not well described. Material and Methods We identified 660 cases between 2005 and 2013 with both UC and subsequent cystoscopic biopsies. UC were classified as either Negative for HGUC or “Abnormal” (“Atypical”, “Suspicious”, and “Malignant”). Apparent false-negative cases were reviewed in a nonblinded fashion by two cytopathologists and two subspecialized genitourinary pathologists. Results A total of 199 of the 660 cases (30%) were histologically diagnosed as HGUC. The UC were “Abnormal” in 170/199 cases (sensitivity/specificity of 86%/71%). Twenty four apparent false negative cases were available for retrospective review. Five of 24 (21%) cystoscopic biopsies were found not to be HGUC on review (one false positive and four low-grade urothelial carcinoma (LGUC on review). Of the remaining 19 UC, 7 (29%) cytology samples were found to be truly negative on review, 11 (46%) were found to be Atypical, and 1 (4%) suspicious. Of the 12 UC that were at least “Atypical” with histologic HGUC on review: six misses (half) were attributed to obscuring inflammation/blood, four to poor preservation, eight to paucity of abnormal cells, and 1 case to interpretive error; many cases demonstrated overlapping reasons. Conclusion About one fifth of apparent false negative diagnoses for HGUC can be because of overdiagnosis of HGUC by surgical pathologists. If poor preservation or obscured samples are called nondiagnostic, the sensitivity/specificity of UC for HGUC can be as high as 94%/71%. Diagn. Cytopathol. 2016;44:994–999. © 2016 Wiley Periodicals, Inc.

During invasion, colonizing species can hybridize with native species, potentially swamping out native genomes. However, theory predicts that introgression will often be biased into the invading species. Thus, empirical estimates of gene flow between native and invasive species are important to quantify the actual threat of hybridization with invasive species. One classic example of introgression occurs in California, where Helianthus bolanderi was thought to be a hybrid between the serpentine endemic Helianthus exilis and the congeneric invader Helianthus annuus. We used genotyping by sequencing to look for signals of introgression and population structure. We find that H. bolanderi and H. exilis form one genetic clade, with weak population structure that is associated with geographic location rather than soil composition and likely represent a single species, not two. Additionally, while our results confirmed early molecular analysis and failed to support the hybrid origin of H. bolanderi, we did find evidence for introgression mainly into the invader H. annuus, as predicted by theory.

BACKGROUND Cervical cancer screening and follow-up guidelines have changed considerably in recent years, but to the authors' knowledge few published reports exist to estimate the impact of these changes in community-based settings. The authors examined the patterns and results of cervical cancer testing and follow-up over a decade in 4 geographically diverse US health care systems to inform the future evaluation of changes resulting from increased uptake of the human papillomavirus (HPV) vaccination. METHODS The authors studied women aged 21 to 65 years who were members of one of these health systems at any time between 1998 and 2007. Data were collected and standardized across sites, based on receipt of Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap testing, HPV testing, and cervical biopsy and treatment procedures were calculated. Screening intervals and trends in the results of screening Pap tests and cervical biopsies also were examined. RESULTS Pap testing rates decreased (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and HPV testing rates increased over the study period. Screening frequency varied across health care systems, and many women continued to receive annual testing. All 4 sites moved to less frequent screening over the study period without marked changes in the overall use of cervical biopsy or treatment. CONCLUSIONS Despite differences over time and across health plans in rates of cervical cancer testing and follow-up cervical procedures, the authors found no notable differences in Pap test results, diagnostic or treatment procedure rates, or pathological outcomes. This finding suggests that the longer screening intervals did not lead to more procedures or more cancer diagnoses. Cancer 2015;121:2976–2983. © 2015 American Cancer Society.

BACKGROUND To the authors' knowledge, few studies to date have examined adherence to recommended guidelines for follow-up and outcomes after an unsatisfactory Papanicolaou (Pap) test (UPT) with liquid-based technologies. METHODS Within 4 US health plans, the median time to follow-up and the percentage of patients with follow-up testing by 120 days was calculated after a UPT. Multivariable analyses evaluated the association between clinical factors and follow-up testing. The authors compared the risk of a diagnosis of cervical intraepithelial neoplasia of type 2 or worse (CIN2+) after a UPT with the risk after a satisfactory Pap test while controlling for study site, test year, and other covariates. RESULTS A total of 634,644 Pap tests performed between 2004 and 2010 were included in the current study. Of 1442 UPTs, 53.4% had follow-up testing within 120 days; follow-up differed across the health plans (P

Oxygen therapy is known to reduce loop gain (LG) in patients with obstructive sleep apnoea (OSA), yet its effects on the other traits responsible for OSA remain unknown. Therefore, we assessed how hyperoxia and hypoxia alter four physiological traits in OSA patients. Eleven OSA subjects underwent a night of polysomnography during which the physiological traits were measured using multiple 3-min 'drops' from therapeutic continuous positive airway pressure (CPAP) levels. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Pharyngeal collapsibility was quantified as the ventilation at CPAP of 0 cmH2O. Upper airway responsiveness was defined as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was estimated as the level of ventilatory drive associated with arousal. On separate nights, subjects were submitted to hyperoxia (n = 9; FiO2 ∼0.5) or hypoxia (n = 10; FiO2 ∼0.15) and the four traits were reassessed. Hyperoxia lowered LG from a median of 3.4 [interquartile range (IQR): 2.6-4.1] to 2.1 (IQR: 1.3-2.5) (P

BACKGROUND Sleep is known to be poor in the hospital. Patients frequently request pharmacological sleep aids, despite the risk of altered mental status (delirium) and falls. Little is known about the scope of pharmacological sleep aid use in hospitalized patients. METHODS We performed a single center, retrospective review of all patients admitted to the general adult (age >18 years) medical and surgical units of a tertiary care center during a recent 2-month period (January 2013–February 2013). Review of the electronic medication administration system was performed to assess for medications administered for sleep. RESULTS Of 642 unique admissions, 168 patients (26.2%) received a medication for sleep. Most (n = 115, 68.5%) had no known history of insomnia or regular prior sleep medication use. Patients most frequently were treated with trazodone (30.4%; median dose, 50 mg; range, 12.5–450 mg), lorazepam (24.4%; median, 0.5 mg; range, 0.25–2 mg), and zolpidem tartrate (17.9%; median, 10 mg; range, 2.5–10 mg). Of the medications given, 36.7% were given early (before 9 pm) or late (after midnight). Of patients not known to be previously taking a pharmacological sleep aid, 34.3% of them were discharged with a prescription for one. CONCLUSIONS Despite increasing evidence of risks such as delirium or falls, pharmacological sleep aid use in general wards remains common, even in elderly patients. Medication administration time is frequently suboptimal. Many previously sleep medication-naive patients leave the hospital with a sleep aid prescription. Further research is needed to understand the factors that contribute to the high rate of sleep medication use in hospitalized patients. Journal of Hospital Medicine 2014;9:652–657. © 2014 Society of Hospital Medicine

The repeated evolution of traits in organisms facing similar environmental conditions is considered to be fundamental evidence for the role of natural selection in moulding phenotypes. Yet, aside from case studies of parallel evolution and its genetic basis, the repeatability of evolution at the level of the whole genome remains poorly characterized. Here, through the use of transcriptome sequencing, we examined genomic divergence for three pairs of sister species of sunflowers. Two of the pairs (Helianthus petiolaris - H. debilis and H. annuus - H. argophyllus) have diverged along a similar latitudinal gradient and presumably experienced similar selective pressure. In contrast, a third species pair (H. exilis - H. bolanderi) diverged along a longitudinal gradient. Analyses of divergence, as measured in terms of FST, indicated little repeatability across the three pairs of species for individual genetic markers (SNPs), modest repeatability at the level of individual genes and the highest repeatability when large regions of the genome were compared. As expected, higher repeatability was observed for the two species pairs that have diverged along a similar latitudinal gradient, with genes involved in flowering time among the most divergent genes. Genes showing extreme low or high differentiation were more similar than genes showing medium levels of divergence, implying that both purifying and divergent selection contributed to repeatable patterns of divergence. The location of a gene along the chromosome also predicted divergence levels, presumably because of shared heterogeneity in both recombination and mutation rates. In conclusion, repeated genome evolution appeared to result from both similar selective pressures and shared local genomic landscapes.

Despite numerous advances in "omics" research, early detection of ovarian cancer still remains a challenge. The aim of this study was to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy could characterise alterations in the biomolecular signatures of human blood plasma/serum obtained from ovarian cancer patients compared to non-cancer controls. Blood samples isolated from ovarian cancer patients (n = 30) and healthy controls (n = 30) were analysed using ATR-FTIR spectroscopy. For comparison, a smaller cohort of samples (n = 8) were analysed using an InVia Renishaw Raman spectrometer. Resultant spectra were pre-processed prior to being inputted into principal component analysis (PCA) and linear discriminant analysis (LDA). Statistically significant differences (P < 0.001) were observed between spectra of ovarian cancer versus control subjects for both biospectroscopy methods. Using a support vector machine classifier for Raman spectra of blood plasma, a diagnostic accuracy of 74% was achieved, while the same classifier showed 93.3% accuracy for IR spectra of blood plasma. These observations suggest that a biospectroscopy approach could be applied to identify spectral alterations associated with the presence of insidious ovarian cancer.

Hybrid sterility is an important species barrier, especially in plants where hybrids can often form between divergent taxa. Here we explore how life history affects the acquisition of hybrid sterility in two groups in the sunflower family. We analyzed genetic distance and F1 pollen sterility for interspecific crosses in annual and perennial groups. We find that reproductive isolation is acquired in a steady manner and that annual species acquire hybrid sterility barriers faster than perennial species. Potential causes of the observed sterility pattern are discussed.

BACKGROUND Pap test (PT) interpretations of low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion (HSIL), or LSIL-H, are used in many laboratories; however monitoring its usage for quality assurance purposes is understudied. METHODS PTs from 2005 to 2010 were collected, and yearly frequencies of LSIL, HSIL, LSIL-H, and atypical squamous cells, cannot exclude HSIL (ASC-H) as a function of total PTs and total squamous intraepithelial lesions (SILs) were calculated. Two-year risk of cervical intraepithelial neoplasia 2 (CIN2) or worse (CIN2+) and CIN 3 or worse (CIN3+) was calculated. RESULTS A total of 352,220 PTs were identified including 17,301 abnormal PTs. LSIL-H usage increased from 2005 to 2010 (from 0.28% of total PTs in 2005 to 0.61% in 2010, P

BACKGROUND Atypical glandular cells (AGC) is a very important diagnosis in gynecological cytology. In the current study, the authors investigated the usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou (Pap) tests. METHODS A total of 148 patients with an AGC diagnosis based on Pap tests by cytotechnologists and referred to cytopathologists were studied. Among these patients, there were 68 patients with CB preparations and 80 patients with Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1 month-36 months). RESULTS Of the 68 patients with CBs, 31 (46%) were reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30 patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%) were given specific diagnoses of high-grade intraepithelial lesion (3 patients), endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3 patients). On follow-up, the CB-AGC group was found to have a significantly lower rate of negative/low-grade squamous intraepithelial lesion diagnoses compared with the TP-AGC group (55% vs 85%; P = .006). The CB-AGC group had a significantly higher rate of endocervical or endometrial adenocarcinoma compared with the TP-AGC group (36% vs 8%; P = .003) at the time of follow-up. The rates of high-grade squamous intraepithelial lesion were not found to be statistically different between these 2 groups (9% vs 7%; P = .66). CONCLUSIONS The Cellient CB is a useful technique to further categorize a diagnosis of AGC on Pap tests. Using the Cellient CB system, the pathologist has the ability to improve the diagnostic accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be avoided. Cancer (Cancer Cytopathol) 2014;122:8–14. © 2013 American Cancer Society.

Calcium isotopic compositions of sixteen Ca-bearing USGS geological reference materials including igneous and sedimentary rocks are reported. Calcium isotopic compositions were determined in two laboratories (GPMR, State Key Laboratory of Geological Processes and Mineral Resources, China University of Geosciences, Wuhan; and CIG, Centre for Isotope Geochemistry, University of California, Berkeley) using the 42Ca-48Ca double-spike technique by thermal ionisation mass spectrometry. As opposed to common cation exchange resin, a micro-column filled with Ca-selective resin (DGA resin) was used in order to achieve high recovery (> 96%) and efficient separation of Ca from the sample matrix. The intermediate measurement precision was evaluated at 0.14‰ (2s) for δ44/40CaSRM915a at GPMR, based on replicate measurements of pure Ca reference material NIST SRM 915a, NIST SRM 915b and seawater. Overall, the measurement uncertainties in both laboratories were better than 0.15‰ at the 2s level. Result validation was carried out for all available data sets. The Ca isotopic compositions of USGS reference materials are not only in agreement between GPMR and CIG, but also in agreement with previously published data within quoted uncertainties. The comprehensive data set reported in this study serves as a reference for both quality assurance and interlaboratory comparison of high precision Ca isotopic study.

Background Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesives (glue) or clips. This process helps the cut edges heal together and is called 'healing by primary intention'. However, a minority of surgical wounds are not closed in this way. Where the risk of infection is high or there has been significant loss of tissue, wounds may be left open to heal by the growth of new tissue rather than by primary closure; this is known as 'healing by secondary intention'. There is a risk of infection in open wounds, which may impact on wound healing, and antiseptic or antibiotic treatments may be used with the aim of preventing or treating such infections. This review is one of a suite of Cochrane reviews investigating the evidence on antiseptics and antibiotics in different types of wounds. It aims to present current evidence related to the use of antiseptics and antibiotics for surgical wounds healing by secondary intention (SWHSI). Objectives To assess the effects of systemic and topical antibiotics, and topical antiseptics for the treatment of surgical wounds healing by secondary intention. Search methods In November 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions with respect to language, date of publication or study setting. Selection criteria Randomised controlled trials which enrolled adults with a surgical wound healing by secondary intention and assessed treatment with an antiseptic or antibiotic treatment. Studies enrolling people with skin graft donor sites were not included, neither were studies of wounds with a non-surgical origin which had subsequently undergone sharp or surgical debridement or other surgical treatments or wounds within the oral or aural cavities. Data collection and analysis Two review authors independently performed study selection, risk of bias assessment and data extraction. Main results Eleven studies with a total of 886 participants were included in the review. These evaluated a range of comparisons in a range of surgical wounds healing by secondary intention. In general studies were small and some did not present data or analyses that could be easily interpreted or related to clinical outcomes. These factors reduced the quality of the evidence. Two comparisons compared different iodine preparations with no antiseptic treatment and found no clear evidence of effects for these treatments. The outcome data available were limited and what evidence there was low quality. One study compared a zinc oxide mesh dressing with a plain mesh dressing. There was no clear evidence of a difference in time to wound healing between groups. There was some evidence of a difference in measures used to assess wound infection (wound with foul smell and number of participants prescribed antibiotics) which favoured the zinc oxide group. This was low quality evidence. One study reported that sucralfate cream increased the likelihood of healing open wounds following haemorrhoidectomy compared to a petrolatum cream (RR: 1.50, 95% CI 1.13 to 1.99) over a three week period. This evidence was graded as being of moderate quality. The study also reported lower wound pain scores in the sucralfate group. There was a reduction in time to healing of open wounds following haemorrhoidectomy when treated with Triclosan post-operatively compared with a standard sodium hypochlorite solution (mean difference -1.70 days, 95% CI -3.41 to 0.01). This was classed as low quality evidence. There was moderate quality evidence that more open wounds resulting from excision of pyomyositis abscesses healed when treated with a honey-soaked gauze compared with a EUSOL-soaked gauze over three weeks' follow-up (RR: 1.58, 95% CI 1.03 to 2.42). There was also some evidence of a reduction in the mean length of hospital stay in the honey group. Evidence was taken from one small study that only had 43 participants. There was moderate quality evidence that more Dermacym®-treated post-operative foot wounds in people with diabetes healed compared to those treated with iodine (RR 0.61, 95% CI 0.40 to 0.93). Again estimates came from one small study with 40 participants. Authors' conclusions There is no robust evidence on the relative effectiveness of any antiseptic/antibiotic/anti-bacterial preparation evaluated to date for use on SWHSI. Where some evidence for possible treatment effects was reported, it stemmed from single studies with small participant numbers and was classed as moderate or low quality evidence. This means it is likely or very likely that further research will have an important impact on our confidence in the estimate of effect, and may change this estimate.

BACKGROUND: The most important indicator for urologic surgeons at The Johns Hopkins Hospital to have a patient undergo cystoscopy is a cytologic diagnosis of high-grade urothelial carcinoma. The template was designed to standardize diagnostic categories so clinicians can manage their patients uniformly. The template was based in part on the Bethesda System for cervical cytology. METHODS: According to the template, reactive/inflammatory changes were included in the negative group (no urothelial atypia or malignancy identified). The category atypical urothelial cells of undetermined significance (AUC-US) was akin to atypical squamous cells of undetermined significance (ASC-US), as was the category of atypical urothelial cells, favor high-grade carcinoma (AUC-H). The categories high-grade urothelial carcinoma (HGUC) and low-grade urothelial carcinoma also were added. RESULTS: The Pathology Data System at the Johns Hopkins Hospital was searched for cases that met the following criteria over a period from July 1, 2007 to June 30, 2009: all cytologic specimens from the urinary tract and all surgical specimens with a diagnosis of HGUC, regardless of invasion status. All cytologic specimens were then matched with biopsies during the same period, and all surgical specimens from patients who had a cytologic diagnosis of AUC-US or AUC-H were retrieved for 18 months after the end of the 2-year study period. Greater than 50% of patients who had biopsy-confirmed HGUC had a preceding cytologic diagnosis of AUC-H or HGUC. When patients with AUC-US were added to the analysis, 80% of patients with HGUC had at least 1 abnormal urinary cytology result. Of those patients who had a diagnosis of AUC-H, 38% had urothelial cancer discovered at biopsy compared with only 10% of those with an AUC-US diagnosis. CONCLUSIONS: The authors concluded that their template is effective in targeting those patients who need to undergo cystoscopy. Cancer (Cancer Cytopathol) 2013;121:15–20 © 2012 American Cancer Society.

Urine cytology continues to play an important role in the diagnosis and management of urothelial carcinoma, a common cancer of adults with significant morbidity and mortality. Because of its high sensitivity for high-grade urothelial tumors, including lesions that may be cystoscopically occult, urine cytology nicely compliments cystoscopic examination, a method that detects most low-grade tumors. Over the decades, several reporting schemes for urine cytology have been published in the literature, each of which has relative strengths and weaknesses. Unlike cervical cytology, there has not been widespread acceptance and use of any particular reporting scheme for urine cytology studies. Thus, terminology and criteria for urine cytology reporting are not uniform among pathologists, which can frustrate clinicians and hinders interlaboratory comparisons.

There is some evidence to suggest that acetazolamide may improve obstructive sleep apnoea (OSA).However, how acetazolamide affects the key traits causing OSA remains uncertain. We aimed to investigate the effect of acetazolamide on the traits contributing to OSA and its severity. Acetazolamide (500 mg twice daily) was administered for 1 week to 13 OSA subjects. Pharyngeal anatomy/collapsibility, loop gain (LG), upper-airway muscle responsiveness (gain) and the arousal threshold were determined using multiple 3 min 'CPAP pressure drops': pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP=0. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Upper-airway gain was taken as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was quantified as the level of ventilatory drive associated with arousal. The apnoea-hypopnoea index (AHI)was assessed on separate nights using standard polysomnography. Acetazolamide reduced the median [interquartile range] LG (3.4 [2.4-5.4] versus 2.0 [1.4-3.5]; P

BACKGROUND: Intrapancreatic accessory spleen (IPAS) is a rare benign lesion of the pancreas that frequently clinically and radiographically mimics a solid neoplasm. Very rarely, epidermoid cysts may form in IPAS and be mistaken for a cystic neoplasm of the pancreas on radiographic imaging. IPAS and epidermoid cyst involving intrapancreatic cyst (ECIPAS) are benign, and, if recognized, do not require surgical intervention. There are few reports of the cytopathologic features of IPAS diagnosed by fine-needle aspiration (FNA). METHODS: Here we report a series of 6 cases of endoscopic ultrasound (EUS)-guided FNA of IPAS, 3 of which had histological confirmation, including 1 case of histologically confirmed ECIPAS. RESULTS: Cytomorphologic features of IPAS include a polymorphous population of hematopoietic cells, including lymphocytes, eosinophils, histiocytes, plasma cells, and red blood cells, admixed with numerous small blood vessels representing splenic sinusoids. CD8 immunostaining of cell block or core biopsy material highlights splenic endothelial cells and confirms the diagnosis. FNA of ECIPAS reveals predominantly macrophages and proteinaceous debris. CONCLUSIONS: Diagnostic pitfalls include pancreatic neuroendocrine tumor. If IPAS is recognized as a diagnostic consideration on EUS-FNA, unnecessary surgical resection may be avoided. Cancer (Cancer Cytopathol) 2012;120:261-8. V C 2012 American Cancer Society. Accessory spleens are estimated to be present in approximately 10% of the general population and 15%20% of accessory spleens are present in the pancreatic tail, 1 as portions of splenic tissue become trapped in the dorsal pancreatic bud during embryologic development. IPASs are benign and do not require surgical intervention unless the spleen is involved by a secondary process such as lymphoma or idiopathic thrombocytopenic purpura. The fine-needle aspiration (FNA) findings of intrapancreatic accessory spleen (IPAS) have rarely been reported. 2-4 Epidermoid cyst in an IPAS (ECIPAS) was first reported by Davidson et al 5 in 1980, and fewer than 25 cases have been reported in the English literature. 6-10 The FNA findings of a histopathologically confirmed ECIPAS have not been previously described to our knowledge. With the increased use of imaging for screening, diagnosis, and monitoring of many conditions, as well as use of multiphase computed tomography (CT) and magnetic resonance imaging (MRI) with improved contrast and spatial resolution, the incidental detection of masses in many organs, including pancreas, has

Background Sickle cell disease (SCD) is characterized by frequent disease-related events that require acute care. It is unknown to what extent patients utilize multiple hospitals for acute care. We examined the continuity pattern of acute care visits to the hospital or emergency department. We hypothesized that among patients with multiple SCD related acute care visits, children experience more concentrated hospital care than adults and privately insured patients experience more concentrated hospital care than publicly insured patients. Procedure We conducted a retrospective cohort study using data from the 2005 and 2006 Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases. Subjects included patients with SCD =1 year of age. The primary outcome was proportion of patients with multiple acute care visits to a single hospital. Results A total of 13,533 patients made =2 acute SCD-related visits. Of the 5,030 children, 77.3% went to the same hospital for all visits. In contrast, of the 8,503 adults, only 51.3% visited the same hospital. Adolescents were more likely than adults to go to one hospital [adjusted relative risk (ARR) 1.40, confidence interval (CI) 1.351.45]. Those with public insurance and the uninsured had a decreased probability of using one hospital (ARR 0.96, CI 0.940.99, and ARR 0.83, CI 0.790.88, respectively). Conclusions Adults and patients with public insurance or no insurance are more likely to use multiple hospitals for acute care. By receiving acute care at multiple hospitals, patients with SCD experience dispersed and fragmented care potentially leading to decreased care quality. Pediatr Blood Cancer 2012;59:685689. (c) 2011 Wiley Periodicals, Inc.

The demands on emergency services have grown relentlessly, and the Institute of Medicine (IOM) has asserted the need for "regionalized, coordinated, and accountable emergency care systems throughout the country." There are large gaps in the evidence base needed to fix the problem of how emergency care is organized and delivered, and science is urgently needed to define and measure success in the emerging network of emergency care. In 2010, Academic Emergency Medicine convened a consensus conference entitled "Beyond Regionalization: Integrated Networks of Emergency Care." This article is a product of the conference breakout session on "Defining and Measuring Successful Networks"; it explores the concept of integrated emergency care delivery and prioritizes a research agenda for how to best define and measure successful networks of emergency care. The authors discuss five key areas: 1) the fundamental metrics that are needed to measure networks across time-sensitive and non-time-sensitive conditions; 2) how networks can be scalable and nimble and can be creative in terms of best practices; 3) the potential unintended consequences of networks of emergency care; 4) the development of large-scale, yet feasible, network data systems; and 5) the linkage of data systems across the disease course. These knowledge gaps must be filled to improve the quality and efficiency of emergency care and to fulfill the IOM's vision of regionalized, coordinated, and accountable emergency care systems.

Congenital heart disease is the most common birth defect in the United States, with an estimated frequency of approximately 12-14 of 1000 live births per year. Neonates with congenital heart disease often need palliative or corrective surgery requiring cardiopulmonary bypass during the first weeks of life. The neonate undergoing cardiopulmonary bypass surgery experiences a more profound metabolic response to stress than that seen in older children and adults undergoing surgery. However, compared with older children and adults, the neonate has less metabolic reserves and is extremely vulnerable to the negative metabolic impact induced by stress, which can lead to suboptimal wound healing and growth failure. There are complications associated with the metabolic derangements of neonatal surgery requiring cardiopulmonary bypass, including but not limited to acute renal failure, chylothorax, and neurological dysfunction. This article discusses the importance of nutrition and metabolic support for the neonate undergoing cardiopulmonary bypass and the immediate postoperative nutrition needs of such a patient. Also, this article uses a case study to examine the feeding methodology used at one particular institution after neonatal cardiac surgery. The purpose of the case study is to provide an illustration of the many factors and obstacles that clinicians often face in the provision and timing of nutrition support.

Recent work in Barrovian metamorphic terranes has found that rocks experience peak metamorphic temperatures across several grades at similar times. This result is inconsistent with most geodynamic models of crustal over-thickening and conductive heating, wherein rocks which reach different metamorphic grades generally reach peak temperatures at different times. Instead, the presence of additional sources of heat and ⁄ or focusing mechanisms for heat transport, such as magmatic intrusions and ⁄ or advection by metamorphic fluids, may have contributed to the contemporaneous development of several different metamorphic zones. Here, we test the hypothesis of temporally focussed heating for the Wepawaug Schist, a Barrovian terrane in Connecticut, USA, using Sm-Nd ages of prograde garnet growth and U-Pb zircon crystallization ages of associated igneous rocks. Peak temperature in the biotite-garnet zone was dated (via Sm-Nd on garnet) at 378.9 ± 1.6 Ma (2r), whereas peak temperature in the highest grade staurolite-kyanite zone was dated (via Sm-Nd on garnet rims) at 379.9 ± 6.8 Ma (2r). These garnet ages suggest that peak metamorphism was pene-contemporaneous (within error) across these metamorphic grades. Ion microprobe U-Pb ages for zircon from igneous rocks hosted by the metapelites also indicate a period of syn-metamorphic peak igneous activity at 380.6 ± 4.7 Ma (2r), indistinguishable from the peak ages recorded by garnet. A 388.6 ± 2.1 Ma (2r) garnet core age from the staurolite-kyanite zone indicates an earlier episode of growth (coincident with ages from texturally early zircon and a previously published monazite age) along the prograde regional metamorphic T-t path. The timing of peak metamorphism and igneous activity, as well as the occurrence of extensive syn-metamorphic quartz vein systems and pegmatites, best supports the hypothesis that advective heating driven by magmas and fluids focussed major mineral growth into two distinct episodes: the first at c. 389 Ma, and the second, corresponding to the regionally synchronous peak metamorphism, at c. 380 Ma.

Atomic scale molecular dynamics simulation is used to investigate how alkali concentrations in glass adjacent to interfaces with crystal surfaces, might differ from those within the interior of a bulk glass. A sodium, lithium alkali-borosilicate glass and its interfaces with the (1 0 0) and (1 1 0) surfaces of MgO, CaO, and SrO are considered. These six interfaces were formed by melt-quenching the glass in the presence of the crystal surface, providing glass alkali ions with the opportunity to either migrate towards or away from the crystal surface. The resulting alkali contents adjacent to the interface are found to differ depending on crystal composition and surface orientation.

Objectives: There is substantial variation in the emergency department (ED) disposition of patients with transient ischemic attack (TIA), and the factors responsible for this variation have not been determined. In this study, the authors examined the influence of clinical, sociodemographic, and hospital characteristics on ED disposition. Methods: All ED-treated TIA cases from community hospitals in 11 states were identified from the 2002 Healthcare Cost and Utilization Project (HCUP). Using the aggregate data, descriptive analyses compared admitted and discharged cases. Pearson’s chi-square test was used to determine the statistical significance of these comparisons. Based on the results of the bivariate analyses, logistic regression models of the likelihood of hospital admission were derived, using a stepwise selection process. Adjusted risk ratios and 95% confidence intervals (CI) were calculated from the logistic regression models. Results: A total of 34,843 cases were identified in the 11 states, with 53% of cases admitted to the hospital. In logistic regression models, differences in admission status were found to be strongly associated with clinical characteristics such as age and comorbidities. After controlling for comorbidities, differences in admission status were also found to be associated to hospital type and with sociodemographic characteristics, including county of residence and insurance status. Conclusions: While clinical factors predictably and appropriately impact the ED disposition of patients diagnosed with TIA, several nonclinical factors are also associated with differences in disposition. Additional research is needed to better understand the basis for these disparities and their potential impact on patient outcomes.

BACKGROUND. Deep fibromatosis or desmoid tumor (DF/DT) is a low-grade, soft tissue lesion that is notable for its infiltration and local recurrence and its inability to metastasize. Although the histologic features of DF/DT are well described, there is a paucity of literature regarding cytologic findings. METHODS. The surgical pathology files of The Johns Hopkins Hospital revealed 17 patients with a diagnosis of DF/DT with prior cytology in a 16-year period (1989–2005). The clinicoradiologic findings were noted, and the fine-needle aspiration (FNA) slides were available for review in 8 patients. In patients with archived tissue, an immunohistochemical panel was performed that included β-catenin, desmin, CD-34, and c-kit. RESULTS. There was a wide age range and a wide range of anatomic distribution for DF/DT in this series. Eleven patients (65%) had a prior history of surgery at or near the site of DF/DT. Radiologically, 5 of 11 patients (45%) who had in-house studies available and no history of DF/DT were diagnosed as suspicious for malignancy. Predominantly bland spindled cells with long, fusiform nuclei and metachromatic matrix material were present in most tumors. The tumor cells were present both singly and as fragments embedded in the matrix. Nine patients had paraffin-embedded tissue samples available for immunohistochemical staining. Six of those samples demonstrated nuclear β-catenin reactivity, and all 9 samples were negative for desmin, CD-34, and c-kit. CONCLUSIONS. The current results indicated that clinical history in patients with suspected DF/DT is important. Because of the infiltrative nature of DF/DT, the radiographic impression often is over-called as suspicious for malignancy. The cytomorphology is nonspecific, often resulting in descriptive diagnoses. Immunohistochemical stains increase the yield of FNA. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.