Pretest expectations strongly influence interpretation of abnormal laboratory results and further management

Contains fulltext : 89631.pdf (publisher's version ) (Open Access)BACKGROUND: Abnormal results of diagnostic laboratory tests can be difficult to interpret when disease probability is very low. Although most physicians generally do not use Bayesian calculations to interpret abnormal results, their estimates of pretest disease probability and reasons for ordering diagnostic tests may--in a more implicit manner--influence test interpretation and further management. A better understanding of this influence may help to improve test interpretation and management. Therefore, the objective of this study was to examine the influence of physicians' pretest disease probability estimates, and their reasons for ordering diagnostic tests, on test result interpretation, posttest probability estimates and further management. METHODS: Prospective study among 87 primary care physicians in the Netherlands who each ordered laboratory tests for 25 patients. They recorded their reasons for ordering the tests (to exclude or confirm disease or to reassure patients) and their pretest disease probability estimates. Upon receiving the results they recorded how they interpreted the tests, their posttest probability estimates and further management. Logistic regression was used to analyse whether the pretest probability and the reasons for ordering tests influenced the interpretation, the posttest probability estimates and the decisions on further management. RESULTS: The physicians ordered tests for diagnostic purposes for 1253 patients; 742 patients had an abnormal result (64%). Physicians' pretest probability estimates and their reasons for ordering diagnostic tests influenced test interpretation, posttest probability estimates and further management. Abnormal results of tests ordered for reasons of reassurance were significantly more likely to be interpreted as normal (65.8%) compared to tests ordered to confirm a diagnosis or exclude a disease (27.7% and 50.9%, respectively). The odds for abnormal results to be interpreted as normal were much lower when the physician estimated a high pretest disease probability, compared to a low pretest probability estimate (OR = 0.18, 95% CI = 0.07-0.52, p < 0.001). CONCLUSIONS: Interpretation and management of abnormal test results were strongly influenced by physicians' estimation of pretest disease probability and by the reason for ordering the test. By relating abnormal laboratory results to their pretest expectations, physicians may seek a balance between over- and under-reacting to laboratory test results

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Fungal infestation boosts fruit aroma and fruit removal by mammals and birds

For four decades, an influential hypothesis has posited that competition for food resources between microbes and vertebrates selects for microbes to alter these resources in ways that make them unpalatable to vertebrates. We chose an understudied cross kingdom interaction to experimentally evaluate the effect of fruit infection by fungi on both vertebrate (mammals and birds) fruit preferences and on ecologically relevant fruit traits (volatile compounds, toughness, etc). Our well-replicated field experiments revealed that, in contrast to previous studies, frugivorous mammals and birds consistently preferred infested over intact fruits. This was concordant with the higher level of attractive volatiles (esters, ethanol) in infested fruits. This investigation suggests that vertebrate frugivores, fleshyfruited plants, and microbes form a tripartite interaction in which each part could interact positively with the other two (e.g. both orange seeds and fungal spores are likely dispersed by mammals). Such a mutualistic view of these complex interactions is opposed to the generalized idea of competition between frugivorous vertebrates and microorganisms. Thus, this research provides a new perspective on the widely accepted plant evolutionary dilemma to make fruits attractive to mutualistic frugivores while unattractive to presumed antagonistic microbes that constrain seed dispersalinfo:eu-repo/semantics/publishedVersio

Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction

In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score ≥11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection

Effector diversification within compartments of the Leptosphaeria maculans genome affected by Repeat-Induced Point mutations

Fungi are of primary ecological, biotechnological and economic importance. Many fundamental biological processes that are shared by animals and fungi are studied in fungi due to their experimental tractability. Many fungi are pathogens or mutualists and are model systems to analyse effector genes and their mechanisms of diversification. In this study, we report the genome sequence of the phytopathogenic ascomycete Leptosphaeria maculans and characterize its repertoire of protein effectors. The L. maculans genome has an unusual bipartite structure with alternating distinct guanine and cytosine-equilibrated and adenine and thymine (AT)-rich blocks of homogenous nucleotide composition. The AT-rich blocks comprise one-third of the genome and contain effector genes and families of transposable elements, both of which are affected by repeat-induced point mutation, a fungal-specific genome defence mechanism. This genomic environment for effectors promotes rapid sequence diversification and underpins the evolutionary potential of the fungus to adapt rapidly to novel host-derived constraints

Extreme genomic erosion after recurrent demographic bottlenecks in the highly endangered Iberian lynx

Background: Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns of genomic erosion that might limit their viability, and offer tools for their effective conservation. The Iberian lynx (Lynx pardinus) is the most endangered felid and a unique example of a species on the brink of extinction. Results: We generate the first annotated draft of the Iberian lynx genome and carry out genome-based analyses of lynx demography, evolution, and population genetics. We identify a series of severe population bottlenecks in the history of the Iberian lynx that predate its known demographic decline during the 20th century and have greatly impacted its genome evolution. We observe drastically reduced rates of weak-to-strong substitutions associated with GC-biased gene conversion and increased rates of fixation of transposable elements. We also find multiple signatures of genetic erosion in the two remnant Iberian lynx populations, including a high frequency of potentially deleterious variants and substitutions, as well as the lowest genome-wide genetic diversity reported so far in any species. Conclusions: The genomic features observed in the Iberian lynx genome may hamper short- and long-term viability through reduced fitness and adaptive potential. The knowledge and resources developed in this study will boost the research on felid evolution and conservation genomics and will benefit the ongoing conservation and management of this emblematic species

Effects of in vitro metabolism of a broccoli leachate, glucosinolates and S-methylcysteine sulphoxide on the human faecal microbiome

Purpose: Brassica are an important food source worldwide and are characterised by the presence of compounds called glucosinolates. Studies indicate that the glucosinolate derived bioactive metabolite sulphoraphane can elicit chemoprotective benefits on human cells. Glucosinolates can be metabolised in vivo by members of the human gut microbiome, although the prevalence of this activity is unclear. Brassica and Allium plants also contain S-methylcysteine sulphoxide (SMCSO), that may provide additional health benefits but its metabolism by gut bacteria is not fully understood. Methods: We examined the effects of a broccoli leachate (BL) on the composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO. Results: Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in the levels of lactate and short-chain fatty acids. Members of Escherichia isolated from these faecal communities were found to bioconvert glucosinolates and SMCSO to their reduced analogues. Conclusion: This study uses a broccoli leachate to investigate the bacterial-mediated bioconversion of glucosinolates and SMCSO, which may lead to further products with additional health benefits to the host. We believe that this is the first study that shows the reduction of the dietary compound S-methylcysteine sulphoxide by bacteria isolated from human faeces

Use of twitter data for waste minimisation in beef supply chain

Approximately one third of the food produced is discarded or lost, which accounts for 1.3 billion tons per annum. The waste is being generated throughout the supply chain viz. farmers, wholesalers/processors, logistics, retailers and consumers. The majority of waste occurs at the interface of retailers and consumers. Many global retailers are making efforts to extract intelligence from customer’s complaints left at retail store to backtrack their supply chain to mitigate the waste. However, majority of the customers don’t leave the complaints in the store because of various reasons like inconvenience, lack of time, distance, ignorance etc. In current digital world, consumers are active on social media and express their sentiments, thoughts, and opinions about a particular product freely. For example, on an average, 45,000 tweets are tweeted daily related to beef products to express their likes and dislikes. These tweets are large in volume, scattered and unstructured in nature. In this study, twitter data is utilised to develop waste minimization strategies by backtracking the supply chain. The execution process of proposed framework is demonstrated for beef supply chain. The proposed model is generic enough and can be applied to other domains as well

Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism

Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders