Does replication groups scoring reduce false positive rate in SNP interaction discovery?

BACKGROUNG. Computational methods that infer single nucleotide polymorphism (SNP) interactions from phenotype data may uncover new biological mechanisms in non-Mendelian diseases. However, practical aspects of such analysis face many problems. Present experimental studies typically use SNP arrays with hundreds of thousands of SNPs but record only hundreds of samples. Candidate SNP pairs inferred by interaction analysis may include a high proportion of false positives. Recently, Gayan et al. (2008) proposed to reduce the number of false positives by combining results of interaction analysis performed on subsets of data (replication groups), rather than analyzing the entire data set directly. If performing as hypothesized, replication groups scoring could improve interaction analysis and also any type of feature ranking and selection procedure in systems biology. Because Gayan et al. do not compare their approach to the standard interaction analysis techniques, we here investigate if replication groups indeed reduce the number of reported false positive interactions. RESULTS. A set of simulated and false interaction-imputed experimental SNP data sets were used to compare the inference of SNP-SNP interactions by means of replication groups to the standard approach where the entire data set was directly used to score all candidate SNP pairs. In all our experiments, the inference of interactions from the entire data set (e.g. without using the replication groups) reported fewer false positives. CONCLUSIONS. With respect to the direct scoring approach the utility of replication groups does not reduce false positive rates, and may, depending on the data set, often perform worse

Does replication groups scoring reduce false positive rate in SNP interaction discovery?

<p>Abstract</p> <p>Background</p> <p>Computational methods that infer single nucleotide polymorphism (SNP) interactions from phenotype data may uncover new biological mechanisms in non-Mendelian diseases. However, practical aspects of such analysis face many problems. Present experimental studies typically use SNP arrays with hundreds of thousands of SNPs but record only hundreds of samples. Candidate SNP pairs inferred by interaction analysis may include a high proportion of false positives. Recently, Gayan et al. (2008) proposed to reduce the number of false positives by combining results of interaction analysis performed on subsets of data (replication groups), rather than analyzing the entire data set directly. If performing as hypothesized, replication groups scoring could improve interaction analysis and also any type of feature ranking and selection procedure in systems biology. Because Gayan et al. do not compare their approach to the standard interaction analysis techniques, we here investigate if replication groups indeed reduce the number of reported false positive interactions.</p> <p>Results</p> <p>A set of simulated and false interaction-imputed experimental SNP data sets were used to compare the inference of SNP-SNP interactions by means of replication groups to the standard approach where the entire data set was directly used to score all candidate SNP pairs. In all our experiments, the inference of interactions from the entire data set (e.g. without using the replication groups) reported fewer false positives.</p> <p>Conclusions</p> <p>With respect to the direct scoring approach the utility of replication groups does not reduce false positive rates, and may, depending on the data set, often perform worse.</p

The Chemistry of Organo Halogenic Molecules. 155. The Role of Reagent Structure in Halogenation of 9-Substituted Phenanthrenes

9-Substituted phenanthrenes were used as target molecules in investigations of the effect of the reagent structure and reaction conditions on halogenation with bromine (1), CsSO4F (2) and F-TEDA (1-chloromethyl-4-fluoro-1,4-diazoniabicycloe[2,2,2]octane bis(tetra- fluoroborate), (3). 9-Methoxyphenanthrene (4) was converted to 9- bromo-10-methoxyphenanthrene (6a) and 9-bromo-10-hydroxy- phenanthrene (7a), while the amount of dealkylation depended on the solvent and was more pronounced in methanol than in acetonitrile, but no adduct was observed. Addition reaction became a major process in fluorination with CsS04F (2) in methanol and 88% of 9-fluoro-10,10-dimethoxy-9,10-dihydrophenanthrene (8b) was formed, while dealkylation occurred in acetonitrile. The course of fluorination of 9-methoxyphenanthrene with F-TEDA (3) could be completely manipulated by the choice of solvent and 9,9-difluoro- 10-oxo-9,10-dihydrophenanthrene (9b) was formed in acetonitrile, 9-fluoro-10-methoxyphenanthrene (6b) in trifluoroacetic acid and 9-fluoro-10,10-dimethoxy-9,10-dihydrophenanthrene (8b) in methanol. Bromination of 9-hydroxyphenanthrene (5) in acetonitrile resulted only in the substitution process, while 9-fluoro-10-hydroxyphenanthrene (7b) formed in the reaction with CsSO4F and F-TEDA was more reactive than the starting hydroxy derivative and, using a 2 molar ratio of F-TEDA, only 9,9-difluoro-10-oxo- 9,10-dihydrophenanthrene (9b) was formed

Fractionation of potentially toxic elements in urban soils from five European cities by means of a harmonised sequential extraction procedure

The revised (four-step) BCR sequential extraction procedure has been applied to fractionate the chromium, copper, iron, manganese, nickel, lead and zinc contents in urban soil samples from public-access areas in five European cities. A preliminary inter-laboratory comparison was conducted and showed that data obtained by different laboratories participating in the study were sufficiently harmonious for comparisons to be made between cities and land types (e.g. parks, roadside, riverbanks, etc.). Analyte recoveries by sequential extraction, with respect to direct aqua regia digestion, were generally acceptable (100 ± 15%). Iron, nickel and, at most sites, chromium were found mainly in association with the residual phase of the soil matrix. Copper was present in the reducible, oxidisable and residual fractions, whilst zinc was found in all four sequential extracts. Manganese was strongly associated with reducible material as, in some cities, was lead. This is of concern because high lead concentrations were present in some soils (>500 mg kg−1) and the potential exists for remobilisation under reducing conditions. As would be expected, extractable metal contents were generally highest in older, more heavily industrialised cities. Copper, lead and zinc showed marked (and often correlated) variations in concentrations between sites within the same city whereas manganese and, especially, iron, did not. No overall relationships were, however, found between analyte concentrations and land use, nor between analyte partitioning and land use

Antithrombotic management in patients undergoing cardiac implantable electronic device implantation

Cardiac implantable electronic devices (CIEDs) are an established treatment option for arrhythmias, sudden cardiac death prevention, and heart failure. Approximately 1000 devices are implanted per million inhabitants in European countries each year. However, the main concern in patients with an indication for CIED implantation is frequently associated with comorbidities requiring antithrombotic medications. The invasive device implantation procedure represents a bleeding risk ranging from pocket hematoma to cardiac tamponade. On the other hand, temporary interruption of antithrombotic therapy increases the risk for thromboembolic events. Implanting CIEDs in patients on antithrombotic medications incites several clinical dilemmas of balancing thromboembolic risk against bleeding risk, as complications are associated with higher mortality rates in both aspects. The most common bleeding complication is pocket haematoma formation, which is associated with a prolonged hospital stay, higher cost, higher risk of pocket infection, and thus higher morbidity and mortality. Studies have shown that the heparin bridging strategy in patients on oral anticoagulants imposes a greater risk for pocket haematoma formation and no benefit in reducing thromboembolic events. Most procedures of CIED implantation can be performed safely with uninterrupted oral anticoagulants. Dual antiplatelet therapy increases the risk of pocket haematoma and should be avoided whenever possible

To prevent or to cure: How people use traditional, complementary and alternative medicine

To understand the reasons behind the trend of growing use of traditional, complementary and alternative (TCAM) practices we should first reflect on how people use them - to prevent disease/promote health, to treat medical conditions by complementing official medical treatments, or as an alternative to them. A total of N = 583 (Mage = 39.01 years, SDage = 12.10; 74.4% females) participants from Serbia completed an online survey including a list of 24 TCAM practices, grouped into four domains: Alternative Medical Systems (e.g., acupuncture, homeopathy), Natural product-based practices (e.g., herbal extracts/supplements), New Age medicine (e.g., yoga, mindfulness) and Rituals/Customs (e.g., visiting monasteries for health). Participants who indicated using a certain practice in the past year were asked to consider their most recent experience with that practice and choose only one option for how they used it: for preventive purposes/advancing health, at the same time with official medicine therapy, instead of official medicine therapy. Participants also provided information on whether a TCAM practitioner was involved in their last use of any of the TCAM practices and how often, in general, they consult TCAM practitioners. Overall, 63%, 95%CI [60, 65] of participants used TCAM practices for preventive purposes, 31% [29, 34] in parallel with, and 6% [5, 8] as an alternative to official treatments. Of the four domains of TCAM use, New Age medicine and Rituals/Customs were most frequently used for prevention, with 78% [74, 83] and 77% [72, 82], respectively, while Natural product-based practices were used for prevention in 57% [54, 60] and Alternative Medical Systems in 41% [33, 49] of the cases. Alternative use of TCAM practices was the most common in the case of Alternative Medical Systems (21% [14, 28]), while it amounted to no more than 7% of participants for any of the other domains. For 24% of participants, a TCAM practitioner was present during their last TCAM use, 10% reported a practitioner previously prescribing the practice, while 66% of participants reported no practitioner involvement. The results suggest the importance of treating different domains of TCAM practices separately, as they may have different impacts on people’s health behavior. We especially point to the importance of monitoring adherence to alternative medical systems, as they may potentially distract patients from official therapies and thus further compromise their health.Saopšetenje sa međunarodnog skupa Empirical Studies in Psychology održanog od 31. marta do 02. aprila 2023. godine štampano u izvodu

The latent structure of traditional, complementary, and alternative medicine practices based on patterns of use

Despite unknown efficiency, known risks, and associated adverse effects of certain traditional, complementary, and alternative medicine (TCAM) practices, the number of people using them appears to be on the rise. Existing taxonomies of TCAM practices mostly relied on either conceptual reasons, or they relied on attitudes toward TCAM, rather than its actual use. In this study, we sought to group TCAM practices based on their patterns of use. A sample of N = 583 (Mage = 39.01 years, SDage = 12.10; 74.4% females) participants residing in Serbia completed an online survey including a list of 71 TCAM practices. For each practice, they indicated if and when they used it to promote their own or their children's health (options: never heard about it/never used it/more than a year ago/in the past year/during the past two weeks). To evaluate the lifetime use of TCAM, we binarized all TCAM items to reflect whether participants have ever used a given practice (never using a practice was coded as 0, using it at least once as 1). After excluding items with frequencies below 5%, we performed an exploratory factor analysis on the tetrachoric correlation matrix for the remaining 49 items. Using a minimum residual method of extraction and oblimin rotation, we identified four meaningful factors explaining 42% of total variance: 1) Natural product-based practices (NP) comprising the use of products such as extracts and supplements of herbal and non-herbal origin; 2) Rituals/Customs (RC) which reflected the use of traditional medicine and religious practices, such as visiting monasteries; 3) New age medicine (NA) incorporating mind-body therapies and energy medicine practices; and 4) Alternative medical systems (AMS) such as acupuncture, homeopathy, quantum medicine, and osteopathy/chiropractic. Factor correlations ranged from r = .18, p <.001 for RC and AMS to r = .30, p < .001 for NA and AMS. The latent structure we obtained based on the pattern of TCAM use corresponds closely to existing conceptual typologies, as well as to those based on attitudes toward TCAM. This suggests that consumers are sensitive to common characteristics of certain TCAM treatments and are more likely to resort to similar types of TCAM practices to promote their health. The existence of relatively independent factors of TCAM use opens the possibility of differential patterns of their psychological predictors and health-related outcomes

REASON4HEALTH: Rationale and impact

Non-adherence to medical recommendations (NAR) leads to increasing mortality/disease rates and raises the costs of treatments, thus it is a burden on the healthcare system. Typically viewed as harmless, the use of traditional/complementary/alternative medicine (TM/CAM) can lead to adverse health events, but also to avoidance of official treatment or undesirable interaction with it. Thus, there is an increasing call in the medical community to promote evidence-based use of TM/CAM and adherence to official advice; understanding why consumers opt for questionable health practices can contribute to this call. We put forward a comprehensive program to study the psychological roots of these two broad categories of questionable health practices. The program offers a framework for concepts from cognitive, personality, social, and health psychology. We propose that an irrational mindset (a system of irrational thinking and beliefs), rooted in basic psychological dispositions (personality, thinking styles) makes certain consumers susceptible to NAR and TM/CAM practices. We plan to: a. explore the media environment the consumers are exposed to (e.g. predatory practices in advertising TM/CAM), b. identify the large spectrum of NAR and TM/CAM typical for the local cultural context, c. test whether irrational beliefs of very different content really form a mindset (how they are interrelated), d. measure the prevalence of NAR and TM/CAM and relate them to irrational mindset and further to personality traits, and e. test whether the TM/CAM proneness can be affected by manipulating irrational beliefs. The results will be useful to stakeholders in different ways: information on the prevalence of TM/CAM and NAR in Serbia is useful by itself, but identifying their underlying psychological mechanisms will help in understanding the most vulnerable portions of the population. In addition, we will provide useful input for designing interventions that will support consumers in making rational health decisions

To prevent or to cure: How people use traditional, complementary and alternative medicine

To understand the reasons behind the trend of growing use of traditional, complementary and alternative (TCAM) practices this study sought to uncover how people use them - to prevent disease/promote health, to treat medical conditions by complementing official medical treatments, or as an alternative to them. A sample of N = 583 Serbian citizens completed an online questionnaire assessing four TCAM domains: Alternative medical systems (AMS), Natural product-based practices (NP), New Age medicine (NA), and Rituals/Customs (RC). Participants indicated whether they had used a given practice in the past year, and if yes, how they used it. Overall, participants used TCAM preventively in two-thirds of cases, but we also found a significant association between TCAM domain and way of use. AMS was used alternatively more than any other TCAM domain, NP was the most prevalent complementary treatment, while NA and RC were predominantly used preventively. Our results suggest that different domains of TCAM practices may impact people’s health differently, depending on how they are used, which should inform interventions.Saopšetenje sa međunarodnog skupa Empirical Studies in Psychology održanog od 31. marta do 02. aprila 2023. godine štampano u celini

Snowmass Theory Frontier: Effective Field Theory

We summarize recent progress in the development, application, and understanding of effective field theories and highlight promising directions for future research. This Report is prepared as the TF02 "Effective Field Theory" topical group summary for the Theory Frontier as part of the Snowmass 2021 process.Comment: 12 page