Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/

Understanding the Role of Molecular Diffusion and Catalytic Selectivity in Liquid-Phase Beckmann Rearrangement

Understanding the role of diffusion in catalysis is essential in the design of highly active, selective, and stable industrial heterogeneous catalysts. By using a combination of advanced in situ spectroscopic characterization tools, particularly quasi-elastic and inelastic neutron scattering, we outline the crucial differences in diffusion modes and molecular interactions of active sites within solid-acid catalysts. This, coupled with 2D solid-state NMR and probe-based FTIR spectroscopy, reveals the nature of the active site in our SAPO-37 catalyst and affords detailed information on the evolution of solid-acid catalysts that can operate at temperatures as low as 130 °C, for the Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam (precursor for Nylon-6). The versatility of this approach leads to structure−property correlations that contrast the dynamics of the diffusion process in the different materials studied. Our results illustrate the power of these techniques in unravelling the interplay between active site and molecular diffusion in single-site heterogeneous catalysts, which can play a vital role in designing low-temperature, sustainable catalytic processes

Why do patients want to have their blood tested? A qualitative study of patient expectations in general practice

BACKGROUND: General practitioners often take their impression of patients' expectations into account in their decision to have blood tests done. It is commonly recommended to involve patients in decision-making during consultations. The study aimed to obtain detailed information on patients' expectations about blood tests. METHODS: Qualitative study among patients in waiting rooms of general practices. Each patient was presented with a short questionnaire about their preferences in terms of diagnostics. Patients who would like blood tests to be done were interviewed. RESULTS: Fifty-seven (26%) of the 224 respondents wanted blood tests. Twenty-two were interviewed. Patients overestimated the qualities of blood tests. Favourable test results were regarded as proof of good health. Patients regarded blood tests as a useful instrument to screen for serious disorders, and were confirmed in this belief by people in their social environment and by the media. Many patients expected their GP to take an active test ordering approach, though some indicated that they might be convinced if their GP proposed a wait-and-see policy. CONCLUSIONS: GPs' perceptions about patient expectations seem justified: patients appear to have high hopes for testing as a diagnostic tool. They expect diagnostic certainty without mistakes and a proof of good health. The question is whether it would be desirable to remove patients' misconceptions, allowing them to participate in policy decisions on the basis of sound information, or whether it would be better to leave the misconceptions uncontested, in order to retain the 'magic' of additional tests and reassure patients. We expect that clarifying the precise nature of patients' expectations by the GP may be helpful in creating a diagnostic strategy that satisfies both patients and GPs. GPs will have to balance the benefits of reassuring their patients by means of blood tests which may be unnecessary against the benefits of avoiding unnecessary tests. Further research is needed into the effects of different types of patient information and the effects of testing on satisfaction and anxiety

Do coder characteristics influence validity of ICD-10 hospital discharge data?

<p>Abstract</p> <p>Background</p> <p>Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (≥13,000 vs. <13,000 records), 2) coders' employment status (full- vs. part-time), and 3) hospital type.</p> <p>Methods</p> <p>This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics.</p> <p>Results</p> <p>422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics.</p> <p>Conclusions</p> <p>This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.</p

Pharmacokinetics, safety, and tolerability of a depot formulation of naltrexone in alcoholics: an open-label trial

BACKGROUND: Naltrexone is an effective medication for treatment of alcohol dependence, but its efficacy is limited by lack of adherence to the oral dosage form. A long-acting depot formulation of naltrexone may increase adherence. METHODS: A single site, 6-week open label study was conducted with 16 alcohol dependent subjects each receiving 300 mg of Naltrexone Depot by intramuscular injection. The main outcomes were safety and tolerability of the Naltrexone Depot formulation, blood levels of naltrexone and its main metabolite 6-beta naltrexol, and self-reported alcohol use. All subjects received weekly individual counseling sessions. RESULTS: The medication was well tolerated with 88% of subjects completing the 6-week trial. The most common side effect experienced was injection site complications. There were no serious adverse events. Subjects had naltrexone and 6-beta-naltrexol concentrations throughout the trial with mean values ranging from 0.58 ng/mL to 2.04 ng/mL and 1.51 ng/mL to 5.52 ng/mL, respectively, at each sampling time following administration. Compared to baseline, subjects had significantly reduced number of drinks per day, heavy drinking days and proportion of drinking days. CONCLUSION: Naltrexone Depot is safe and well tolerated in alcoholics and these findings support the further investigation of its utility in larger double-blind placebo controlled trials

Alcohol policy enforcement and changes in student drinking rates in a statewide public college system: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Heavy alcohol use among U.S. college students is a major contributor to young adult morbidity and mortality. The aim of this study was to examine whether college alcohol policy enforcement levels predict changes in student drinking and related behaviors in a state system of public colleges and universities, following a system-wide change to a stricter policy.</p> <p>Methods</p> <p>Students and administrators at 11 Massachusetts public colleges/universities completed surveys in 1999 (N of students = 1252), one year after the policy change, and again in 2001 (N = 1074). We calculated policy enforcement scores for each school based on the reports of deans of students, campus security chiefs, and students, and examined the correlations between perceived enforcement levels and the change in student drinking rates over the subsequent two year period, after weighting the 2001 data to adjust for demographic changes in the student body.</p> <p>Results</p> <p>Overall rates of any past-30-days drinking, heavy episodic drinking, and usual heavy drinking among past-30-days drinkers were all lower in 2001 compared to 1999. School-level analyses (N = 11) found deans' baseline reports of stricter enforcement were strongly correlated with subsequent declines in heavy episodic drinking (Pearson's r = -0.73, p = 0.011). Moreover, consistently high enforcement levels across time, as reported by deans, were associated with greater declines in heavy episodic drinking. Such relationships were not found for students' and security chiefs' reports of enforcement. Marijuana use did not rise during this period of decline in heavy drinking.</p> <p>Conclusions</p> <p>Study findings suggest that stronger enforcement of a stricter alcohol policy may be associated with reductions in student heavy drinking rates over time. An aggressive enforcement stance by deans may be an important element of an effective college alcohol policy.</p

Peer substance use overestimation among French university students: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use.</p> <p>Methods</p> <p>12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use.</p> <p>Results</p> <p>Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline.</p> <p>Conclusions</p> <p>Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.</p

Data-driven approach for creating synthetic electronic medical records

<p>Abstract</p> <p>Background</p> <p>New algorithms for disease outbreak detection are being developed to take advantage of full electronic medical records (EMRs) that contain a wealth of patient information. However, due to privacy concerns, even anonymized EMRs cannot be shared among researchers, resulting in great difficulty in comparing the effectiveness of these algorithms. To bridge the gap between novel bio-surveillance algorithms operating on full EMRs and the lack of non-identifiable EMR data, a method for generating complete and synthetic EMRs was developed.</p> <p>Methods</p> <p>This paper describes a novel methodology for generating complete synthetic EMRs both for an outbreak illness of interest (tularemia) and for background records. The method developed has three major steps: 1) synthetic patient identity and basic information generation; 2) identification of care patterns that the synthetic patients would receive based on the information present in real EMR data for similar health problems; 3) adaptation of these care patterns to the synthetic patient population.</p> <p>Results</p> <p>We generated EMRs, including visit records, clinical activity, laboratory orders/results and radiology orders/results for 203 synthetic tularemia outbreak patients. Validation of the records by a medical expert revealed problems in 19% of the records; these were subsequently corrected. We also generated background EMRs for over 3000 patients in the 4-11 yr age group. Validation of those records by a medical expert revealed problems in fewer than 3% of these background patient EMRs and the errors were subsequently rectified.</p> <p>Conclusions</p> <p>A data-driven method was developed for generating fully synthetic EMRs. The method is general and can be applied to any data set that has similar data elements (such as laboratory and radiology orders and results, clinical activity, prescription orders). The pilot synthetic outbreak records were for tularemia but our approach may be adapted to other infectious diseases. The pilot synthetic background records were in the 4-11 year old age group. The adaptations that must be made to the algorithms to produce synthetic background EMRs for other age groups are indicated.</p