The Re-Emergence of H1N1 Influenza Virus in 1977: A Cautionary Tale for Estimating Divergence Times Using Biologically Unrealistic Sampling Dates

In 1977, H1N1 influenza A virus reappeared after a 20-year absence. Genetic analysis indicated that this strain was missing decades of nucleotide sequence evolution, suggesting an accidental release of a frozen laboratory strain into the general population. Recently, this strain and its descendants were included in an analysis attempting to date the origin of pandemic influenza virus without accounting for the missing decades of evolution. Here, we investigated the effect of using viral isolates with biologically unrealistic sampling dates on estimates of divergence dates. Not accounting for missing sequence evolution produced biased results and increased the variance of date estimates of the most recent common ancestor of the re-emergent lineages and across the entire phylogeny. Reanalysis of the H1N1 sequences excluding isolates with unrealistic sampling dates indicates that the 1977 re-emergent lineage was circulating for approximately one year before detection, making it difficult to determine the geographic source of reintroduction. We suggest that a new method is needed to account for viral isolates with unrealistic sampling dates

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

BACKGROUND: There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. METHODS: The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. RESULTS: The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. CONCLUSION: The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women

Pulmonary Arterial Stent Implantation in an Adult with Williams Syndrome

We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. The patient was treated with balloon angioplasty and stent implantation. Short-term follow-up showed a good clinical result with excellent patency of the stents but early restenosis of the segments in which only balloon angioplasty was performed. These stenoses were subsequently also treated successfully by stent implantation. Stent patency was observed 3 years after the first procedure

The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis

Background:To investigate small-nucleolar RNAs (snoRNAs) as reference genes when measuring miRNA expression in tumour samples, given emerging evidence for their role in cancer.Methods:Four snoRNAs, commonly used for normalisation, RNU44, RNU48, RNU43 and RNU6B, and miRNA known to be associated with pathological factors, were measured by real-time polymerase chain reaction in two patient series: 219 breast cancer and 46 head and neck squamous cell carcinoma (HNSCC). SnoRNA and miRNA were then correlated with clinicopathological features and prognosis.Results:Small-nucleolar RNA expression was as variable as miRNA expression (miR-21, miR-210, miR-10b). Normalising miRNA PCR expression data to these recommended snoRNAs introduced bias in associations between miRNA and pathology or outcome. Low snoRNA expression correlated with markers of aggressive pathology. Low levels of RNU44 were associated with a poor prognosis. RNU44 is an intronic gene in a cluster of highly conserved snoRNAs in the growth arrest specific 5 (GAS5) transcript, which is normally upregulated to arrest cell growth under stress. Low-tumour GAS5 expression was associated with a poor prognosis. RNU48 and RNU43 were also identified as intronic snoRNAs within genes that are dysregulated in cancer.Conclusion:Small-nucleolar RNAs are important in cancer prognosis, and their use as reference genes can introduce bias when determining miRNA expression. © 2011 Cancer Research UK All rights reserved

Parenting-by-gender interactions in child psychopathology: attempting to address inconsistencies with a Canadian national database

<p>Abstract</p> <p>Background</p> <p>Research has shown strong links between parenting and child psychopathology. The moderating role of child gender is of particular interest, due to gender differences in socialization history and in the prevalence of psychiatric disorders. Currently there is little agreement on how gender moderates the relationship between parenting and child psychopathology. This study attempts to address this lack of consensus by drawing upon two theories (self-salience vs. gender stereotyped misbehaviour) to determine how child gender moderates the role of parenting, if at all.</p> <p>Methods</p> <p>Using generalized estimating equations (GEE) associations between three parenting dimensions (hostile-ineffective parenting, parental consistency, and positive interaction) were examined in relationship to child externalizing (physical aggression, indirect aggression, and hyperactivity-inattention) and internalizing (emotional disorder-anxiety) dimensions of psychopathology. A sample 4 and 5 year olds from the National Longitudinal Survey of Children and Youth (NLSCY) were selected for analysis and followed over 6 years (N = 1214). Two models with main effects (Model 1) and main effects plus interactions (Model 2) were tested.</p> <p>Results</p> <p>No child gender-by-parenting interactions were observed for child physical aggression and indirect aggression. The association between hostile-ineffective parenting and child hyperactivity was stronger for girls, though this effect did not reach conventional levels of statistical significance (<it>p </it>= .059). The associations between parenting and child emotional disorder did vary as a function of gender, where influences of parental consistency and positive interaction were stronger for boys.</p> <p>Discussion</p> <p>Despite the presence of a few significant interaction effects, hypotheses were not supported for either theory (i.e. self-salience or gender stereotyped misbehaviour). We believe that the inconsistencies in the literature regarding child gender-by-parenting interactions is due to the reliance on gender as an indicator of a different variable which is intended to explain the interactions. This may be problematic because there is likely within-gender and between-sample variability in such constructs. Future research should consider measuring and modelling variables that are assumed to explain such interactions when conducting gender-by-parenting research.</p

Sins of Omission

Little is known about the relative incidence of serious errors of omission versus errors of commission. Objective : To identify the most common substantive medical errors identified by medical record review. Design : Retrospective cohort study. Setting : Twelve Veterans Affairs health care systems in 2 regions. Participants : Stratified random sample of 621 patients receiving care over a 2-year period. Main Outcome Measure : Classification of reported quality problems. Methods : Trained physicians reviewed the full inpatient and outpatient record and described quality problems, which were then classified as errors of omission versus commission. Results : Eighty-two percent of patients had at least 1 error reported over a 13-month period. The average number of errors reported per case was 4.7 (95% confidence intervals [CI]: 4.4, 5.0). Overall, 95.7% (95% CI: 94.9%, 96.4%) of errors were identified as being problems with underuse. Inadequate care for people with chronic illnesses was particularly common. Among errors of omission, obtaining insufficient information from histories and physicals (25.3%), inadequacies in diagnostic testing (33.9%), and patients not receiving needed medications (20.7%) were all common. Out of the 2,917 errors identified, only 27 were rated as being highly serious, and 26 (96%) of these were errors of omission. Conclusions : While preventing iatrogenic injury resulting from medical errors is a critically important part of quality improvement, we found that the overwhelming majority of substantive medical errors identifiable from the medical record were related to people getting too little medical care, especially for those with chronic medical conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74567/1/j.1525-1497.2005.0152.x.pd

A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m−2, respectively) (n=59) or the daily × 5 Mayo Clinic schedule (425 and 20 mg m−2, respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79–1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71–1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred

The development and psychometric properties of a measure of clinicians’ attitudes to depression: the revised Depression Attitude Questionnaire (R-DAQ)

Background: Depression is a common mental disorder associated with substantial disability. It is inadequately recognised and managed, and clinicians’ attitudes to this condition and its treatment may play a part in this. Most research in this area has used the Depression Attitude Questionnaire (DAQ), but analyses have shown this measure to exhibit problems in psychometric properties and suitability for the health professionals and settings where depression recognition may occur. Methods: We revised the DAQ using a pooled review of findings from studies using this measure, together with a Delphi study which sought the opinions of a panel of relevant experts based in the UK, USA, Australia, and European countries (n = 24) using 3 rounds of questioning to consider attitude dimensions, content, and item wording. After item generation, revision and consensus (agreement >70%) using the Delphi panel, the revised DAQ (R-DAQ) was tested with 1193 health care providers to determine its psychometric properties. Finally the test-retest reliability of the R-DAQ was examined with 38 participants. Results: The 22-item R-DAQ scale showed good internal consistency: Cronbach’s alpha coefficient was 0.84; and satisfactory test-retest reliability: intraclass correlation coefficient was 0.62 (95% C.I. 0.37 to 0.78). Exploratory factor analysis favoured a three-factor structure (professional confidence, therapeutic optimism/pessimism, and a generalist perspective), which accounted for 45.3% of the variance. Conclusions: The R-DAQ provides a revised tool for examining clinicians’ views and understanding of depression. It addresses important weaknesses in the original measure whilst retaining items and dimensions that appeared valid. This revised scale is likely to be useful in examining attitudes across the health professional workforce and beyond the confines of the UK, and may be valuable for the purpose of evaluating training that aims to address clinicians’ attitudes to depression. It incorporates key dimensions of attitudes with a modest number of items making it applicable to use in busy clinical settings

Chagas Disease Risk in Texas

Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and human population data at the county level. We modeled the distribution of each vector species using occurrence data from México and the United States and environmental variables. We then computed the ecological risk from the distribution models and combined it with disease incidence data to produce a composite risk map which was subsequently used to calculate the populations expected to be at risk for the disease. South Texas had the highest relative risk. We recommend mandatory reporting of Chagas disease in Texas, testing of blood donations in high risk counties, human and canine testing for Chagas disease antibodies in high risk counties, and that a joint initiative be developed between the United States and México to combat Chagas disease