Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Iridium-catalysed ortho-H/D and -H/T exchange under basic conditions : C-H activation of unprotected tetrazoles

The first examples of selective ortho-directed C-H activation with unprotected 2-aryltetrazoles are described. A new base-assisted protocol for iridium (I) hydrogen isotope exchange catalysis allows access to ortho-deuterated and tritiated tetrazoles, including the tetrazole-containing pharmaceutical, Valsartan. Preliminary mechanistic studies are also presented

The development of QUADAS : a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

BACKGROUND: In the era of evidence based medicine, with systematic reviews as its cornerstone, adequate quality assessment tools should be available. There is currently a lack of a systematically developed and evaluated tool for the assessment of diagnostic accuracy studies. The aim of this project was to combine empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. METHODS: We conducted a Delphi procedure to develop the quality assessment tool by refining an initial list of items. Members of the Delphi panel were experts in the area of diagnostic research. The results of three previously conducted reviews of the diagnostic literature were used to generate a list of potential items for inclusion in the tool and to provide an evidence base upon which to develop the tool. RESULTS: A total of nine experts in the field of diagnostics took part in the Delphi procedure. The Delphi procedure consisted of four rounds, after which agreement was reached on the items to be included in the tool which we have called QUADAS. The initial list of 28 items was reduced to fourteen items in the final tool. Items included covered patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool is presented together with guidelines for scoring each of the items included in the tool. CONCLUSIONS: This project has produced an evidence based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Further work to determine the usability and validity of the tool continue

The Otterbein Miscellany - December 1980

https://digitalcommons.otterbein.edu/miscellany/1014/thumbnail.jp

Identification of shared single copy nuclear genes in Arabidopsis, Populus, Vitis and Oryza and their phylogenetic utility across various taxonomic levels

<p>Abstract</p> <p>Background</p> <p>Although the overwhelming majority of genes found in angiosperms are members of gene families, and both gene- and genome-duplication are pervasive forces in plant genomes, some genes are sufficiently distinct from all other genes in a genome that they can be operationally defined as 'single copy'. Using the gene clustering algorithm MCL-tribe, we have identified a set of 959 single copy genes that are shared single copy genes in the genomes of <it>Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera </it>and <it>Oryza sativa</it>. To characterize these genes, we have performed a number of analyses examining GO annotations, coding sequence length, number of exons, number of domains, presence in distant lineages, such as <it>Selaginella </it>and <it>Physcomitrella</it>, and phylogenetic analysis to estimate copy number in other seed plants and to demonstrate their phylogenetic utility. We then provide examples of how these genes may be used in phylogenetic analyses to reconstruct organismal history, both by using extant coverage in EST databases for seed plants and <it>de novo </it>amplification via RT-PCR in the family Brassicaceae.</p> <p>Results</p> <p>There are 959 single copy nuclear genes shared in <it>Arabidopsis</it>, <it>Populus</it>, <it>Vitis </it>and <it>Oryza </it>["APVO SSC genes"]. The majority of these genes are also present in the <it>Selaginella </it>and <it>Physcomitrella </it>genomes. Public EST sets for 197 species suggest that most of these genes are present across a diverse collection of seed plants, and appear to exist as single or very low copy genes, though exceptions are seen in recently polyploid taxa and in lineages where there is significant evidence for a shared large-scale duplication event. Genes encoding proteins localized in organelles are more commonly single copy than expected by chance, but the evolutionary forces responsible for this bias are unknown.</p> <p>Regardless of the evolutionary mechanisms responsible for the large number of shared single copy genes in diverse flowering plant lineages, these genes are valuable for phylogenetic and comparative analyses. Eighteen of the APVO SSC single copy genes were amplified in the Brassicaceae using RT-PCR and directly sequenced. Alignments of these sequences provide improved resolution of Brassicaceae phylogeny compared to recent studies using plastid and ITS sequences. An analysis of sequences from 13 APVO SSC genes from 69 species of seed plants, derived mainly from public EST databases, yielded a phylogeny that was largely congruent with prior hypotheses based on multiple plastid sequences. Whereas single gene phylogenies that rely on EST sequences have limited bootstrap support as the result of limited sequence information, concatenated alignments result in phylogenetic trees with strong bootstrap support for already established relationships. Overall, these single copy nuclear genes are promising markers for phylogenetics, and contain a greater proportion of phylogenetically-informative sites than commonly used protein-coding sequences from the plastid or mitochondrial genomes.</p> <p>Conclusions</p> <p>Putatively orthologous, shared single copy nuclear genes provide a vast source of new evidence for plant phylogenetics, genome mapping, and other applications, as well as a substantial class of genes for which functional characterization is needed. Preliminary evidence indicates that many of the shared single copy nuclear genes identified in this study may be well suited as markers for addressing phylogenetic hypotheses at a variety of taxonomic levels.</p

Predicting Romantic Interest and Decisions in the Very Early Stages of Mate Selection: Standards, Accuracy, and Sex Differences

In the current study, opposite-sex strangers had 10-min conversations with a possible further date in mind. Based on judgments from partners and observers, three main findings were produced. First, judgments of attractiveness/vitality perceptions (compared with warmth/trustworthiness and status/resources) were the most accurate and were predominant in influencing romantic interest and decisions about further contact. Second, women were more cautious and choosy than men—women underestimated their partner’s romantic interest, whereas men exaggerated it, and women were less likely to want further contact. Third, a mediational model found that women (compared with men) were less likely to want further contact because they perceived their partners as possessing less attractiveness/vitality and as falling shorter of their minimum standards of attractiveness/vitality, thus generating lower romantic interest. These novel results are discussed in terms of the mixed findings from prior research, evolutionary psychology, and the functionality of lay psychology in early mate-selection contexts. </jats:p

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

Preface

1. The issue The present special issue is developed from a workshop entitled Bantu Universals and Variation at the 10th World Congress of African Linguistics (WOCAL10) held online at Leiden University in June 2021. It includes a selection of papers presented at the workshop, as well as papers submitted in response to an open call for papers. The resultant special issue brings together new perspectives on universals and variation in the Bantu language family, with regards to morphosyntax, sema..

Bantu word order between discourse and syntactic relations

Discourse function has often been noticed to be a strong factor in conditioning Bantu word order. The importance of discourse function for determining the word order of Bantu languages is visible for example in locative inversion and dedicated focus positions. As a result of such phenomena, it has been proposed that Bantu word order is best captured by reference to discourse roles, e.g. Topic-Verb-Nontopic. Nevertheless, we typically see statements describing Bantu word order in relation to grammatical roles (e.g. “SVO”), and the notions “subject” and “object” remain core in analyses of Bantu. In this paper we present the result of a study reconsidering Bantu word order from a discourse-configurational perspective, asking how far we can get without reference to grammatical roles. We use a parametric approach to investigate this syntactic variation, presenting new discourse-oriented field data collected on 9 Bantu languages. We show how these parameters highlight variation within the family, with each language sitting at a different point on a continuum between grammatical role-oriented and discourse role-oriented. We therefore argue against a one-size-fits-all account of Bantu word order and advocate for approaches that include both grammatical and discourse roles.La fonction discursive a souvent été identifiée comme un facteur important dans le conditionnement de l’ordre des mots en bantou. L’importance de la fonction discursive dans la détermination de l’ordre des mots des langues bantoues est visible par exemple dans l’inversion locative et les positions du focus. À la suite de tels phénomènes, il a été proposé que l’ordre des mots en bantou est mieux représenté par les rôles discursifs, par ex. Topique-Verbe-Non-topique. Néanmoins, nous observons généralement des déclarations décrivant l’ordre des mots bantou par rapport aux rôles grammaticaux (par exemple « SVO »), et les notions de « sujet » et « objet » restent au cœur des analyses du bantou. Dans cet article, nous présentons les résultats d’une étude reconsidérant l’ordre des mots bantou dans une perspective des configurations discursives, en nous demandant jusqu’où nous pouvons aller sans référence aux rôles grammaticaux. Nous utilisons une approche paramétrique pour étudier cette variation syntaxique, en présentant de nouvelles données de terrain, axées sur le discours, recueillies sur 9 langues bantoues. Nous montrons comment ces paramètres mettent en évidence la variation au sein de la famille, chaque langue se situant à un point différent sur un continuum entre les rôles grammaticaux et les rôles discursifs. Nous nous opposons donc à une description unique de l’ordre des mots bantou et préconisons des approches qui incluent à la fois les rôles grammaticaux et discursifs