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The interfacial characteristics of GaInP GaAs heterostructures reveals that a photoluminescence (PL) peak having an energy of 1.425 electron volts is found in samples with GaInP-to-GaAs interfaces. The interfacial characteristics are determined by performing PL measurements. The PL peak is caused by the excitonic recombination in the heterostructures.

Sophie A Derksen, Xenia Brancart, Gina Rossi Department of Psychology, Personality and Psychopathology Research Group (PEPS), Vrije Universiteit Brussel (VUB), Brussels, BelgiumCorrespondence: Sophie A Derksen, PE-PEPS, Vrije Universiteit Brussel (VUB), Pleinlaan 2, Brussels, 1050, Belgium, Email sophiederksen@outlook.comIntroduction: With a rapidly aging population, age-neutrality of psychological instruments is becoming ever more important for accurate assessment of older adults. This study aims to test the age-neutrality of the Dutch Behavioral Inhibition System/Behavioral Approach System (BIS/BAS) scales by means of Differential Item Functioning (DIF) and Differential Test Functioning (DTF) analyses.Methods: DIF and DTF analyses were conducted using an odds ratio approach. Potential DIF was examined for the two primary scales and three BAS subscales in 390 Dutch-speaking participants divided over three age groups.Results: Overall, the BIS-BAS scales lacked age-neutrality when comparing older adults to young adults: eight out of 20 items (ie, 40%) displayed DIF according to the adjusted Bonferroni corrected cut-offs, which exceeds the threshold of 25% for large DIF. Thus, for 40% of the test items, items were differently endorsed by young and older adults with the same position on the construct measured by the item. Therefore, the implications of the item-level DIF on the scale level were investigated across age groups. DTF analyses revealed large DTF for all BIS and BAS scales according to the adjusted Bonferroni corrected cut-offs.Discussion: DIF found in items on the BIS scale and BAS-Drive and BAS-Fun Seeking scale can probably be explained by a difference in degree of expression across age groups. A solution could be the development of age-specific norms. DIF on BAS-Reward Responsiveness subscale could be partly due to measuring a different construct across age groups. Rephrasing or replacing such items with DIF may increase age-neutrality of the BIS/BAS Scales.Keywords: older adults, BIS/BAS questionnaire, personality, assessment, differential item functioning

STUDY OBJECTIVE: We identify factors that define frequent and highly frequent emergency department (ED) users. METHODS: Administrative health care records were used to define less frequent (1 to 6 visits), frequent (7 to 17 visits), and highly frequent (>=18 visits) ED users. Analyses were conducted to determine the most unique demographic, disease, and health care use features of these groups. RESULTS: Frequent users composed 9.9% of all ED visits, whereas highly frequent users composed 3.6% of visits. Compared with less frequent users, frequent users were defined most strongly by their substance abuse challenges and by their many visits to primary care and specialist physicians. Substance abuse also distinguished highly frequent from frequent ED users strongly; 67.3% versus 35.9% of these patient groups were substance abusers, respectively. Also, 70% of highly frequent versus only 17.8% of frequent users had a long history of frequent ED use. Last, highly frequent users did not use other health care services proportionally more than their frequent user counterparts, suggesting that these former patients use EDs as a main source of care. CONCLUSION: This research develops objective thresholds of frequent and highly frequent ED use. Although substance abuse is prominent in both groups, only highly frequent users seem to visit EDs in place of other health care services. Future analyses can investigate these patterns of health care use more closely, including how timely access to primary care affects ED use. Cluster analysis also has value for defining frequent user subgroups who may benefit from different yet equally effective treatment options. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the proportion, geographic variation, and predictors of infant hospital readmission within 6 weeks of the postbirth discharge. METHODS: A cross-sectional, population-based study was conducted of all infants who were born from 1997 through 2001, linkable to the birth mother, and discharged alive from the hospital (N = 68 681) using hospital discharge files in the Canadian province of Manitoba. The following predictors of readmission were examined using logistic regression: preterm, low birth weight, neighborhood income, geographic location (the North, Rural South, and Urban areas of Winnipeg and Brandon), breastfeeding status, length of stay, maternal age, and type of delivery. Using 9 non-Winnipeg regions and 12 Winnipeg subregions, ecologic correlations (1-tailed Spearman) between newborn hospital readmission rates and the following were examined: 1) a region's overall health status, measured by the premature mortality rate (PMR), or death before aged 75 years and 2) a region's socioeconomic risk, using the Socio-Economic Factor Index (SEFI). RESULTS: The proportion of infants who were readmitted to the hospital at least once within 6 weeks of postbirth hospital discharge was 3.95%, with respiratory illness the leading cause (22.3% of readmissions). Risk of readmission was higher for infants who were born preterm (adjusted odds ratio [AOR]: 1.80; 95% confidence interval [CI]: 1.55-2.10), who were of the 3 lowest income quintiles (lowest: AOR: 2.02; 95% CI: 1.77-2.32; low: AOR: 1.48; 95% CI: 1.29-1.71; middle: AOR: 1.26; 95% CI: 1.08-1.47), who resided in the North (AOR: 1.85; 95% CI: 1.66-2.07) or Rural South (AOR: 1.25; 95% CI: 1.14-1.36), who were not breastfed (AOR: 1.32; 95% CI: 1.20-1.44), whose mother's age was 17 or younger (AOR: 1.30; 95% CI: 1.10-1.55), whose mother was 18 to 19 years of age (AOR: 1.25; 95% CI: 1.09-144), or who were born by cesarean section (AOR: 1.30; 95% CI: 1.19-1.43). Regional readmission rates were correlated with PMR (9 non-Winnipeg regions: r = 0.77 for PMR and r = 0.68 for SEFI; 12 Winnipeg Community Areas: r = 0.49 for PMR and r = 0.73 for SEFI). CONCLUSIONS: Income and geography are strongly associated with newborn hospital readmission. Modifiable risk factors include increasing breastfeeding rates, decreasing cesarean section rates, and decreasing adolescent pregnancy rates (or increasing adolescent parental support), but these need additional study to establish causation. [ABSTRACT FROM AUTHOR]

Background: Epilepsy management during pregnancy is crucial for both the mother and fetus. The use of antiseizure medications (ASMs) during pregnancy requires careful consideration due to their potential effects on maternal and fetal health., Methods: This study analyzed trends in ASMs use among pregnant people in four Canadian provinces over 20 years (Manitoba, Saskatchewan, Alberta, and Quebec). Descriptive statistics were utilized to examine the characteristics of the population, with the frequency and patterns of ASM use estimated throughout each trimester. Linear regression models were developed to analyze yearly patterns of ASM utilization for the overall study population, as well as for people with and without epilepsy., Results: Among 1,317,141 pregnant individuals across four provinces, 0.7% had epilepsy. Of the total pregnancies, 1.7% (n = 22,783) were exposed to ASMs, comprising 4,392 from pregnant people with epilepsy (PPWE) and 18,391 from those without epilepsy (PPWOE). Results demonstrated varying trends in ASM usage between provinces, with an overall increase in usage among people without epilepsy in Manitoba, Saskatchewan, and Alberta. ASM use among PPWOE surged significantly in Manitoba (24.2-149.1 per 10,000 pregnant people), Saskatchewan (29.4-107.0 per 10,000), and Alberta (65.7-241.7 per 10,000) ( p < 0.05). In Alberta, PPWE's ASM exposure also rose, from 23.6 in 2008 to 43.0 per 10,000 pregnant people in 2021, while Quebec witnessed a decrease from 59.2 in 1998 to 45.5 per 10,000 pregnancies in 2015. Analysis of ASM use by trimester illustrated a substantial decline among PPWOE from 365 days pre-pregnancy to the third trimester in all provinces. ASM utilization by drug class showcased significant shifts, with second-generation ASMs experiencing a notable rise. Carbamazepine, once prominent, declined, making way for lamotrigine. Regional variations underscore diverse preferences, such as clonazepam's sustained popularity in Manitoba and Quebec., Conclusion: The study identified increasing trends in ASM use, particularly the increased use of second-generation ASMs, and differences in prescription patterns for pregnant individuals with and without epilepsy. These findings reveal changing ASM use patterns, including increased second-generation ASM use and regional disparities, providing valuable insights into real-world prescription practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Peymani, Berard, Winquist, Kaul, Sheehy, Lavu, Leong, Falk, Delaney, Kowalec, Ng, Ruth, Aboulatta, Alessi-Severini, Dragan, Derksen, Barrett, Shams and Eltonsy.)

Purpose: To examine the rates and determinants of breastfeeding initiation (BFI) amongst women with epilepsy (WWE) and women without epilepsy (WWoE) in Manitoba, Canada., Methods: We conducted a retrospective cohort study using province-wide health databases from 1995 to 2019. Annual BFI rates for WWE and WWoE were examined. Multivariable logistic regression models were used to quantify the association between maternal and infant characteristics and BFI in both groups., Results: During the study period, 1,331 pregnant WWE and 357,334 WWoE were examined. Among WWE, 70.9 % initiated breastfeeding compared to 81.8 % among WWoE. We observed a significant small increase in yearly trends of BFI in both WWE (β=0.45, p = 0.008) and WWoE (β=0.23, p < 0.001). In WWE, BFI was associated with caesarean delivery (aOR=0.72,95 % CI: 0.53-0.97), chronic pain (aOR=0.67,95 % Cl: 0.46-0.97), lower income (aOR=0.34,95 % Cl: 0.26-0.44), and gestational age (aOR= 1.09,95 % CI:1.01-1.18). In WWoE, BFI was associated with chronic pain (aOR=0.83,95 % Cl: 0.80-0.86), lower income (aOR=0.45, 95 %CI:0.44-0.46), mood and anxiety disorder (aOR=0.84,95 % CI:0.81-0.86), and gestational age (aOR=1.13,95 % Cl:1.12-1.14). The use of any ASM (aOR=0.66,95 % Cl:0.51-0.85), new generation (aOR=0.86,95 % Cl: 0.62-1.20), polytherapy (aOR=0.46,95 % Cl: 0.31-0.69) and gabapentin (aOR=0.49,95 % Cl: 0.17-1.24) reduced the likelihood of BFI among WWE., Conclusion: BFI was approximately 10 % lower in WWE compared to WWoE. Determinants such as low income, ASM use, and comorbidities were significant contributors to a reduced BFI in both groups. Targeted counselling for WWE on breastfeeding benefits is essential. Further research is needed to investigate breastfeeding continuation in WWE., Competing Interests: Declaration of competing interest All authors declare that they have nothing to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). Although studies have documented lower cancer screening rates, there is limited epidemiological evidence quantifying potential diagnostic delays. This study explores the risk of metastatic cancer stage for people with IDD compared to those without IDD among breast (female), colorectal, and lung cancer patients in Canada., Methods: Separate population-based cross-sectional studies were conducted in Ontario and Manitoba by linking routinely collected data. Breast (female), colorectal, and lung cancer patients were included (Manitoba: 2004-2017; Ontario: 2007-2019). IDD status was identified using established administrative algorithms. Modified Poisson regression with robust error variance models estimated associations between IDD status and the likelihood of being diagnosed with metastatic cancer. Adjusted relative risks were pooled between provinces using random-effects meta-analyses. Potential effect modification was considered., Results: The final cohorts included 115,456, 89,815, and 101,811 breast (female), colorectal, and lung cancer patients, respectively. Breast (female) and colorectal cancer patients with IDD were 1.60 and 1.44 times more likely to have metastatic cancer (stage IV) at diagnosis compared to those without IDD (relative risk [RR], 1.60; 95% confidence interval [CI], 1.16-2.20; RR, 1.44; 95% CI, 1.24-1.67). This increased risk was not observed in lung cancer. Significant effect modification was not observed., Conclusions: People with IDD were more likely to have stage IV breast and colorectal cancer identified at diagnosis compared to those without IDD. Identifying factors and processes contributing to stage disparities such as lower screening rates and developing strategies to address diagnostic delays is critical., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Cancer is a leading cause of death among adults living with intellectual or developmental disabilities (IDD). However, few epidemiological studies exist worldwide quantifying inequalities in cancer stage at diagnosis and survival for people with IDD relative to those without IDD., Methods: A population-based, retrospective cohort study was conducted using provincial health and social administrative data in Manitoba, Canada. Adults (≥18 years) with a cancer diagnosis between 2004 and 2017 were included. Lifetime IDD was identified before the cancer diagnosis using an established algorithm. Modified Poisson regression with robust error variance was used to estimate the association between IDD status and metastatic cancer at diagnosis. Multivariable Cox proportional hazards analyses were used to the effect of IDD on overall survival following the cancer diagnosis., Results: The staging and prognosis cohorts included 62,886 (n = 473 with IDD) and 74,143 (n = 592 with IDD) cancer patients, respectively. People living with IDD were significantly more likely to be diagnosed with metastatic cancer and die following their cancer diagnosis compared to those without IDD (RR=1.20; 95 % CI 1.05-1.38; HR= 1.53; 95 % CI 1.38-1.71). Significant heterogeneity by sex was identified for cancer survival (p = 0.005)., Discussion: People with IDD had more advanced cancer stage at diagnosis and worse survival relative to those without IDD. Identifying and developing strategies to address the factors responsible that contribute to these disparities is required for improving patient-centred cancer care for adults with IDD., Competing Interests: Declaration of Competing Interest DD reports advisory board attendance for Merck Canada, Novartis, Jazz Pharmaceuticals, Pfizer, and AstraZeneca, honoraria for education content from Boehringer-Ingelheim and Bristol Myers Squibb, and a research grant from AstraZeneca. All other authors report having no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

RNA is a vital biomolecule, the function of which is tightly spatiotemporally regulated. RNA organelles are biological structures that either membrane-less or surrounded by membrane. They are produced by the all the cells and indulge in vital cellular mechanisms. They include the intracellular RNA granules and the extracellular exosomes. RNA granules play an essential role in intracellular regulation of RNA localization, stability and translation. Aberrant regulation of RNA is connected to disease development. For example, in microsatellite diseases such as CXG repeat expansion disorders, the mutant CXG repeat RNA's localization and function are affected. RNA is not only transported intracellularly but can also be transported between cells via exosomes. The loading of the exosomes is regulated by RNA-protein complexes, and recent studies show that cytosolic RNA granules and exosomes share common content. Intracellular RNA granules and exosome loading may therefore be related. Exosomes can also transfer pathogenic molecules of CXG diseases from cell to cell, thereby driving disease progression. Both intracellular RNA granules and extracellular RNA vesicles may serve as a source for diagnostic and treatment strategies. In therapeutic approaches, pharmaceutical agents may be loaded into exosomes which then transport them to the desired cells/tissues. This is a promising target specific treatment strategy with few side effects. With respect to diagnostics, disease-specific content of exosomes, e.g., RNA-signatures, can serve as attractive biomarker of central nervous system diseases detecting early physiological disturbances, even before symptoms of neurodegeneration appear and irreparable damage to the nervous system occurs. In this review, we summarize the known function of cytoplasmic RNA granules and extracellular vesicles, as well as their role and dysfunction in CXG repeat expansion disorders. We also provide a summary of established protocols for the isolation and characterization of both cytoplasmic and extracellular RNA organelles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nabariya, Heinz, Derksen and Krauß.)

Objective: To evaluate the effects of early pregnancy loss on subsequent health care use and costs., Data Sources: Linked administrative health databases from Manitoba, Canada., Study Design: This was a population-based cohort study. The exposure of interest was first recorded ectopic pregnancy or miscarriage (EPM). Outcomes included visits to all ambulatory care providers, family physicians (FPs), specialists, and hospitals, as well as the costs associated with these visits. We also assessed the impact of EPM on a global measure of health service utilization and the incidence and costs of psychotropic medications., Data Collection/extraction Methods: We identified women who experienced their first recorded loss (EPM) from 2003-2012 and created a propensity score model to match these women to women who experienced a live birth, with outcome measures available through 31 December 2014. We used a difference in differences approach with multivariable negative binomial models and generalized estimating equations (GEE) to assess the impact of EPM on the aforementioned health care utilization indicators., Principal Findings: EPM was associated with a short-term increase in visits to, and costs associated with, certain ambulatory care providers. These findings were driven in large part by increased visits/costs to FPs (rate difference [RD]: $19.92 [95% CI: $16.33, $23.51]) and obstetrician-gynecologists (OB-GYNs) (RD $9.41 [95% CI: $8.42, $10.40]) in the year immediately following the loss, excluding care associated with the loss itself. We also detected an increase in hospital stays and costs and a decrease in the use of psychotropic medications relative to matched controls., Conclusion: Pregnancy loss may lead to subsequent increases in certain types of health care utilization. While the absolute costs associated with post-EPM care are relatively small, the observed patterns of service utilization are informative for providers and policy makers seeking to support women following a loss., (© 2022 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Bacteria from the genera Paraburkholderia and Herbaspirillum can promote the growth of Sorghum bicolor , but the underlying mechanisms are not yet known. In a pot experiment, sorghum plants grown on sterilized substrate were inoculated with Paraburkholderia tropica strain IAC/BECa 135 and Herbaspirillum frisingense strain IAC/BECa 152 under phosphate-deficient conditions. These strains significantly increased Sorghum bicolor cultivar SRN-39 root and shoot biomass. Shotgun metagenomic analysis of the rhizosphere revealed successful colonization by both strains; however, the incidence of colonization was higher in plants inoculated with P. tropica strain IAC/BECa 135 than in those inoculated with H. frisingense strain IAC/BECa 152. Conversely, plants inoculated with H. frisingense strain IAC/BECa 152 showed the highest increase in biomass. Genomic analysis of the two inoculants implied a high degree of rhizosphere fitness of P. tropica strain IAC/BECa 135 through environmental signal processing, biofilm formation, and nutrient acquisition. Both genomes contained genes related to plant growth-promoting bacterial (PGPB) traits, including genes related to indole-3-acetate (IAA) synthesis, nitrogen fixation, nodulation, siderophore production, and phosphate solubilization, although the P. tropica strain IAC/BECa 135 genome contained a slightly more extensive repertoire. This study provides evidence that complementary mechanisms of growth promotion in Sorghum might occur, i.e., that P. tropica strain IAC/BECa 135 acts in the rhizosphere and increases the availability of nutrients, while H. frisingense strain IAC/BECa 152 influences plant hormone signaling. While the functional and taxonomic profiles of the rhizobiomes were similar in all treatments, significant differences in plant biomass were observed, indicating that the rhizobiome and the endophytic microbial community may play equally important roles in the complicated plant-microbial interplay underlying increased host plant growth., Competing Interests: The authors declare no conflict of interest.

Objectives: To determine if in utero selective serotonin reuptake inhibitor (SSRI) or selective serotonin norepinephrine inhibitor (SNRI) exposure is associated with developmental vulnerability in kindergarten among children whose mothers were diagnosed with prenatal mood or anxiety disorder., Methods: Linkable administrative data were used to create a population-based cohort of 266 479 mother-child dyads of children born in Manitoba, Canada, between 1996 and 2014, with follow-up through 2015. The sample was restricted to mothers who had a mood or anxiety disorder diagnosis between 90 days before conception ( N = 13 818). Exposed women had ≥2 SSRI or SNRI dispensations during pregnancy ( n = 2055); unexposed mothers did not have a dispensation of an SSRI or SNRI during pregnancy ( n = 10 017). The Early Development Instrument (EDI) was used to assess developmental health in kindergarten children. The EDI is a 104-component kindergarten teacher-administered questionnaire, encompassing 5 developmental domains., Results: Of the 3048 children included in the study who met inclusion criteria and had an EDI, 21.43% of children in the exposed group were assessed as vulnerable on 2 or more domains versus 16.16% of children in the unexposed group (adjusted odds ratio = 1.43; 95% confidence interval 1.08-1.90). Children in the exposed group also had a significant risk of being vulnerable in language and/or cognition (adjusted odds ratio = 1.40; 95% confidence interval 1.03-1.90)., Conclusions: Exposure to SSRIs or SNRIs during pregnancy was associated with an increased risk of developmental vulnerability and an increased risk of deficits in language and/or cognition. Replication of results is necessary before clinical implications can be reached., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: In the province of Manitoba, Canada, given that latent tuberculosis infection (LTBI) treatment is provided at no cost to the patient, treatment completion rates should be optimal. The objective of this study was to estimate LTBI treatment completion using prescription drug administrative data and identify patient characteristics associated with completion., Methods: Prescription drug data (1999-2014) were used to identify individuals dispensed isoniazid (INH) or rifampin (RIF) monotherapy. Treatment completion was defined as being dispensed INH for ≥ 180 days (INH180) or ≥ 270 days (INH270) or RIF for ≥ 120 days (RIF120). Logistic regression models tested socio-demographic and comorbidity characteristics associated with treatment completion., Results: The study cohort comprised 4985 (90.4%) persons dispensed INH and 529 (9.6%) RIF. Overall treatment completion was 60.2% and improved from 43.1% in 1999-2003 to 67.3% in 2009-2014. INH180 showed the highest completion (63.8%) versus INH270 (40.4%) and RIF120 (27.0%). INH180 completion was higher among those aged 0-18 years (68.5%) compared with those aged 19+ (61.0%). Sex, geography, First Nations status, income quintile, and comorbidities were not associated with completion., Conclusions: Benchmark 80% treatment completion rates were not achieved in Manitoba. Factors associated with non-completion were older age, INH270, and RIF120. Access to shorter LTBI treatments, such as rifapentine/INH, may improve treatment completion.

Study Objective: This study compares how throughput and output factors affect emergency department (ED) median waiting room time., Methods: Administrative health care use records were used to identify all daytime (8 am to 8 pm) visits made to adult EDs in Winnipeg, Canada, between April 1, 2012, and March 31, 2013. First, we measured the waiting room time (from patient registration until transfer into the ED) of each index visit (incoming patient). We then linked each index visit to a group of existing patients surrounding it and counted the number of existing patients engaged in throughput processes (radiographs, computed tomography [CT] scans, advanced diagnostic tests) and one output process (waiting to be hospitalized). Regression analysis was used to measure how strongly each factor uniquely affected incoming patient median waiting room time, stratified by the acuity level., Results: Analyses were performed on 143,172 index visits. On average, 153.4 radiographs and 48.5 CT scans were conducted daily, whereas 45.3 patients were admitted daily to hospital. Median waiting room time was shortest (8.0 minutes) for the highest-acuity index visits and was not influenced by these throughput or output factors. For all other index visits, median waiting room time was associated strongly with the number of existing patients receiving radiographs, and, to a lesser extent, with the number of existing patients receiving CT scans and waiting for hospital admission., Conclusion: Both throughput and output factors affect how long newly arriving ED patients remain in the waiting room. This suggests that a range of strategies may help to reduce ED wait time, each requiring stronger ED and hospital partnerships., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Scientists have called for strategies to identify ED patients with unmet needs. We identify the unique profile of ED patients who arrive by ambulance and subsequently leave without consulting a provider (ie, a paradoxical visit, PV)., Methods: Using a retrospective cohort design, administrative data from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years old as having zero, single or multiple PVs in 2012/2013. Analyses compare the sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and concurrent healthcare use profile of non-PV, single and multiple PV patients., Results: The study cohort consisted of 122 639 patients with 250 754 ED visits. Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of all ED visits. Descriptively, more single versus non-PV patients lived in urban core and lowest-income areas, were frequent ED users generally, were substance abusers and had seven plus primary care physician visits. Multiple PV patients had a similar but more extreme profile versus their single PV counterparts (eg, 54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges). From multivariate statistics, single versus non-PV patients are defined uniquely by their frequent ED use, by their substance abuse, as living in a core and low income area, and as having multiple visits with primary care physicians., Conclusions: PV patients have needs that do not align with the acute model of ED care. These patients may benefit from a more integrated care approach likely involving allied health professionals., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Improving the scoring functions for small molecule-protein docking is a highly challenging task in current computational drug design. Here we present a novel consensus scoring concept for the prediction of binding modes for multiple known active ligands. Similar ligands are generally believed to bind to their receptor in a similar fashion. The presumption of our approach was that the true binding modes of similar ligands should be more similar to each other compared to false positive binding modes. The number of conserved (consensus) interactions between similar ligands was used as a docking score. Patterns of interactions were modeled using ligand receptor interaction fingerprints. Our approach was evaluated for four different data sets of known cocrystal structures (CDK-2, dihydrofolate reductase, HIV-1 protease, and thrombin). Docking poses were generated with FlexX and rescored by our approach. For comparison the CScore scoring functions from Sybyl were used, and consensus scores were calculated thereof. Our approach performed better than individual scoring functions and was comparable to consensus scoring. Analysis of the distribution of docking poses by self-organizing maps (SOM) and interaction fingerprints confirmed that clusters of docking poses composed of multiple ligands were preferentially observed near the native binding mode. Being conceptually unrelated to commonly used docking scoring functions our approach provides a powerful method to complement and improve computational docking experiments.

Complementarity of molecular surfaces is crucial for molecular recognition. A method for representation of molecular shape is presented. We decompose the molecular surface into commensurate patches with defined shape by fitting hyperbolical paraboloids onto a triangulated isosurface of the Gaussian model of a molecule. As a result of this decomposition we obtain a 3D graph representation of the molecular shape, which can be used for complete and partial shape matching and isosteric group searching. To point out the possibilities and limitations of shape-only models, we challenged our method by three scenarios in a virtual screening contest: rigid body alignment, consensus shape filtering, and target-specific screening.