Single-stranded genomic architecture constrains optimal codon usage

Viral codon usage is shaped by the conflicting forces of mutational pressure and selection to match host patterns for optimal expression. We examined whether genomic architecture (single- or double-stranded DNA) influences the degree to which bacteriophage codon usage differ from their primary bacterial hosts and each other. While both correlated equally with their hosts' genomic nucleotide content, the coat genes of ssDNA phages were less well adapted than those of dsDNA phages to their hosts' codon usage profiles due to their preference for codons ending in thymine. No specific biases were detected in dsDNA phage genomes. In all nine of ten cases of codon redundancy in which a specific codon was overrepresented, ssDNA phages favored the NNT codon. A cytosine to thymine biased mutational pressure working in conjunction with strong selection against non-synonymous mutations appears be shaping codon usage bias in ssDNA viral genomes

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence

Current controversies: Null hypothesis significance testing

Traditional null hypothesis significance testing (NHST) incorporating the critical level of significance of 0.05 has become the cornerstone of decision-making in health care, and nowhere less so than in obstetric and gynecological research. However, such practice is controversial. In particular, it was never intended for clinical significance to be inferred from statistical significance. The inference of clinical importance based on statistical significance (p < 0.05), and lack of clinical significance otherwise (p ≥ 0.05) represents misunderstanding of the original purpose of NHST. Furthermore, the limitations of NHST—sensitivity to sample size, plus type I and II errors—are frequently ignored. Therefore, decision-making based on NHST has the potential for recurrent false claims about the effectiveness of interventions or importance of exposure to risk factors, or dismissal of important ones. This commentary presents the history behind NHST along with the limitations that modern-day NHST presents, and suggests that a statistics reform regarding NHST be considered

Preliminary Evidence for the Cross-Cultural Utility of the Type D Personality Construct in the Ukraine

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Clinical and scientific progress related to the interface between cardiology and psychology: lessons learned from 35 years of experience at the Thoraxcenter of the Erasmus Medical Center in Rotterdam

In November 1975, as the first in the Netherlands, a full-time psychologist was employed at the Department of Cardiology of the Thoraxcenter of the Erasmus Medical Center. This innovative decision was consistent with a view to treat the patient as a whole rather than the heart as a single body part in need of repair, combined with the understanding that the heart and mind interact to affect health. The present selective review addresses the broad range of contributions of 35 years of psychology to clinical cardiology and cardiovascular research with a focus on research, teaching, psychological screening and patient care. The review ends with lessons to be learned and challenges for the future with respect to improving the care and management of patients with heart disease in order to enhance secondary prevention and the role of behavioural and psychological factors in this endeavour

Phosphorylation and Activation of the Plasma Membrane Na+/H+ Exchanger (NHE1) during Osmotic Cell Shrinkage

The Na+/H+ Exchanger isoform 1 (NHE1) is a highly versatile, broadly distributed and precisely controlled transport protein that mediates volume and pH regulation in most cell types. NHE1 phosphorylation contributes to Na+/H+ exchange activity in response to phorbol esters, growth factors or protein phosphatase inhibitors, but has not been observed during activation by osmotic cell shrinkage (OCS). We examined the role of NHE1 phosphorylation during activation by OCS, using an ideal model system, the Amphiuma tridactylum red blood cell (atRBC). Na+/H+ exchange in atRBCs is mediated by an NHE1 homolog (atNHE1) that is 79% identical to human NHE1 at the amino acid level. NHE1 activity in atRBCs is exceptionally robust in that transport activity can increase more than 2 orders of magnitude from rest to full activation. Michaelis-Menten transport kinetics indicates that either OCS or treatment with the phosphatase inhibitor calyculin-A (CLA) increase Na+ transport capacity without affecting transport affinity (Km = 44 mM) in atRBCs. CLA and OCS act non-additively to activate atNHE1, indicating convergent, phosphorylation-dependent signaling in atNHE1 activation. In situ 32P labeling and immunoprecipitation demonstrates that the net phosphorylation of atNHE1 is increased 4-fold during OCS coinciding with a more than 2-order increase in Na+ transport activity. This is the first reported evidence of increased NHE1 phosphorylation during OCS in any vertebrate cell type. Finally, liquid chromatography and mass spectrometry (LC-MS/MS) analysis of atNHE1 immunoprecipitated from atRBC membranes reveals 9 phosphorylated serine/threonine residues, suggesting that activation of atNHE1 involves multiple phosphorylation and/or dephosphorylation events

Analytical and numerical study on grating depth effects in grating coupled waveguide sensors

The in-coupling process for grating-coupled planar optical waveguide sensors is investigated in the case of TE waves. A simple analytical model based on the Rayleigh-Fourier-Kiselev method is applied to take into account the depth of the grating coupler, which is usually neglected in the modeling. Analytical expressions are derived both for the position and width of the in-coupling peaks to illustrate the effects of grating depth on the guided mode resonances in grating coupled waveguide sensors. Numerical computations verify the model for shallow gratings both in terms of peak shape and position and provide the limitations for the analytical formulas

Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems

Objective: To evaluate positive predictive value (PPV) of different disease codes and free text in identifying acute myocardial infarction (AMI) from electronic healthcare records (EHRs). Design: Validation study of cases of AMI identified from general practitioner records and hospital discharge diagnoses using free text and codes from the International Classification of Primary Care (ICPC), International Classification of Diseases 9th revision-clinical modification (ICD9-CM) and ICD-10th revision (ICD-10). Setting: Population-based databases comprising routinely collected data from primary care in Italy and the Netherlands and from secondary care in Denmark from 1996 to 2009. Participants: A total of 4 034 232 individuals with 22 428 883 person-years of follow-up contributed to the data, from which 42 774 potential AMI cases were identified. A random sample of 800 cases was subsequently obtained for validation. Main outcome measures: PPVs were calculated overall and for each code/free text. 'Best-case scenario' and 'worst-case scenario' PPVs were calculated, the latter taking into account non-retrievable/non-assessable cases. We further assessed the effects of AMI misclassification on estimates of risk during drug exposure. Results: Records of 748 cases (93.5% of sample) were retrieved. ICD-10 codes had a 'best-case scenario' PPV of 100% while ICD9-CM codes had a PPV of 96.6% (95% CI 93.2% to 99.9%). ICPC codes had a 'best-case scenario' PPV of 75% (95% CI 67.4% to 82.6%) and free text had PPV ranging from 20% to 60%. Corresponding PPVs in the 'worst-case scenario' all decreased. Use of codes with lower PPV generally resulted in small changes in AMI risk during drug exposure, but codes with higher PPV resulted in attenuation of risk for positive associations. Conclusions: ICD9-CM and ICD-10 codes have good PPV in identifying AMI from EHRs; strategies are necessary to further optimise utility of ICPC codes and free-text search. Use of specific AMI disease codes in estimation of risk during drug exposure may lead to small but significant changes and at the expense of decreased precision