Tolerability of the Oscar 2 ambulatory blood pressure monitor among research participants: a cross-sectional repeated measures study

<p>Abstract</p> <p>Background</p> <p>Ambulatory blood pressure monitoring (ABPM) is increasingly used to measure blood pressure (BP) in research studies. We examined ease of use, comfort, degree of disturbance, reported adverse effects, factors associated with poor tolerability, and association of poor tolerability with data acquisition of 24-hour ABPM using the Oscar 2 monitor in the research setting.</p> <p>Methods</p> <p>Sixty adults participating in a research study of people with a history of borderline clinic BP reported on their experience with ABPM on two occasions one week apart. Poor tolerability was operationalized as an overall score at or above the 75th percentile using responses to questions adapted from a previously developed questionnaire. In addition to descriptive statistics (means for responses to Likert-scaled "0 to 10" questions and proportions for Yes/No questions), we examined reproducibility of poor tolerability as well as associations with poor tolerability and whether poor tolerability was associated with removal of the monitor or inadequate number of BP measurements.</p> <p>Results</p> <p>The mean ambulatory BP of participants by an initial ABPM session was 148/87 mm Hg. After wearing the monitor the first time, the degree to which the monitor was felt to be cumbersome ranged from a mean of 3.0 to 3.8, depending on whether at work, home, driving, or other times. The most bother was interference with normal sleeping pattern (mean 4.2). Wearers found the monitor straightforward to use (mean 7.5). Nearly 67% reported that the monitor woke them after falling asleep, and 8.6% removed it at some point during the night. Reported adverse effects included pain (32%), skin irritation (37%), and bruising (7%). Those categorized as having poor tolerability (kappa = 0.5 between sessions, p = 0.0003) were more likely to report being in fair/poor health (75% vs 22%, p = 0.01) and have elevated 24-hour BP average (systolic: 28% vs 17%, p = 0.56; diastolic: 30% vs 17%, p = 0.37). They were also more likely to remove the monitor and have inadequate numbers of measurements.</p> <p>Conclusions</p> <p>The Oscar 2 ABPM device is straightforward to use but can interfere with sleep. Commonly reported adverse effects include pain, skin irritation, and bruising. Those who tolerate the monitor poorly are more likely to report being in fair or poor health and to remove it, particularly at night.</p

The logic of the future in quantum theory

According to quantum mechanics, statements about the future made by sentient beings like us are, in general, neither true nor false; they must satisfy a many-valued logic. I propose that the truth value of such a statement should be identified with the probability that the event it describes will occur. After reviewing the history of related ideas in logic, I argue that it gives an understanding of probability which is particularly satisfactory for use in quantum mechanics. I construct a lattice of future-tense propositions, with truth values in the interval $[0,1]$, and derive logical properties of these truth values given by the usual quantum-mechanical formula for the probability of a history

A T3 and T7 Recombinant Phage Acquires Efficient Adsorption and a Broader Host Range

It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress

Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ2 statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set

Recombination Phenotypes of Escherichia coli greA Mutants

<p>Abstract</p> <p>Background</p> <p>The elongation factor GreA binds to RNA polymerase and modulates transcriptional pausing. Some recent research suggests that the primary role of GreA may not be to regulate gene expression, but rather, to promote the progression of replication forks which collide with RNA polymerase, and which might otherwise collapse. Replication fork collapse is known to generate dsDNA breaks, which can be recombinogenic. It follows that GreA malfunction could have consequences affecting homologous recombination.</p> <p>Results</p> <p><it>Escherichia coli </it>mutants bearing substitutions of the active site acidic residues of the transcription elongation factor GreA, D41N and E44K, were isolated as suppressors of growth inhibition by a toxic variant of the bacteriophage lambda Red-beta recombination protein. These mutants, as well as a D41A <it>greA </it>mutant and a <it>greA </it>deletion, were tested for proficiency in recombination events. The mutations were found to increase the efficiency of RecA-RecBCD-mediated and RecA-Red-mediated recombination, which are replication-independent, and to decrease the efficiency of replication-dependent Red-mediated recombination.</p> <p>Conclusion</p> <p>These observations provide new evidence for a role of GreA in resolving conflicts between replication and transcription.</p

Physiological Benefits of Being Small in a Changing World: Responses of Coho Salmon (Oncorhynchus kisutch) to an Acute Thermal Challenge and a Simulated Capture Event

Evidence is building to suggest that both chronic and acute warm temperature exposure, as well as other anthropogenic perturbations, may select for small adult fish within a species. To shed light on this phenomenon, we investigated physiological and anatomical attributes associated with size-specific responses to an acute thermal challenge and a fisheries capture simulation (exercise+air exposure) in maturing male coho salmon (Oncorhynchus kisutch). Full-size females were included for a sex-specific comparison. A size-specific response in haematology to an acute thermal challenge (from 7 to 20°C at 3°C h−1) was apparent only for plasma potassium, whereby full-size males exhibited a significant increase in comparison with smaller males (‘jacks’). Full-size females exhibited an elevated blood stress response in comparison with full-size males. Metabolic recovery following exhaustive exercise at 7°C was size-specific, with jacks regaining resting levels of metabolism at 9.3±0.5 h post-exercise in comparison with 12.3±0.4 h for full-size fish of both sexes. Excess post-exercise oxygen consumption scaled with body mass in male fish with an exponent of b = 1.20±0.08. Jacks appeared to regain osmoregulatory homeostasis faster than full-size males, and they had higher ventilation rates at 1 h post-exercise. Peak metabolic rate during post-exercise recovery scaled with body mass with an exponent of b∼1, suggesting that the slower metabolic recovery in large fish was not due to limitations in diffusive or convective oxygen transport, but that large fish simply accumulated a greater ‘oxygen debt’ that took longer to pay back at the size-independent peak metabolic rate of ∼6 mg min−1 kg−1. Post-exercise recovery of plasma testosterone was faster in jacks compared with full-size males, suggesting less impairment of the maturation trajectory of smaller fish. Supporting previous studies, these findings suggest that environmental change and non-lethal fisheries interactions have the potential to select for small individuals within fish populations over time

NleG Type 3 Effectors from Enterohaemorrhagic Escherichia coli Are U-Box E3 Ubiquitin Ligases

NleG homologues constitute the largest family of type 3 effectors delivered by pathogenic E. coli, with fourteen members in the enterohaemorrhagic (EHEC) O157:H7 strain alone. Identified recently as part of the non-LEE-encoded (Nle) effector set, this family remained uncharacterised and shared no sequence homology to other proteins including those of known function. The C-terminal domain of NleG2-3 (residues 90 to 191) is the most conserved region in NleG proteins and was solved by NMR. Structural analysis of this structure revealed the presence of a RING finger/U-box motif. Functional assays demonstrated that NleG2-3 as well as NleG5-1, NleG6-2 and NleG9′ family members exhibited a strong autoubiquitination activity in vitro; a characteristic usually expressed by eukaryotic ubiquitin E3 ligases. When screened for activity against a panel of 30 human E2 enzymes, the NleG2-3 and NleG5-1 homologues showed an identical profile with only UBE2E2, UBE2E3 and UBE2D2 enzymes supporting NleG activity. Fluorescence polarization analysis yielded a binding affinity constant of 56±2 µM for the UBE2D2/NleG5-1 interaction, a value comparable with previous studies on E2/E3 affinities. The UBE2D2 interaction interface on NleG2-3 defined by NMR chemical shift perturbation and mutagenesis was shown to be generally similar to that characterised for human RING finger ubiquitin ligases. The alanine substitutions of UBE2D2 residues Arg5 and Lys63, critical for activation of eukaryotic E3 ligases, also significantly decreased both NleG binding and autoubiquitination activity. These results demonstrate that bacteria-encoded NleG effectors are E3 ubiquitin ligases analogous to RING finger and U-box enzymes in eukaryotes