Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

Background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition

Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca²+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca²+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain

A collaborative approach to designing an intervention for patients with atrial fibrillation

Background: Patients diagnosed with atrial fibrillation (AF) have an increased risk of stroke, and need to adhere to treatment and lifestyle recommendations to reduce likelihood of adverse events. AF patients are often highly symptomatic relying on subjective indicators to manage their illness. Method: Intervention design comprised two parallel processes: (1) targeting theoretical constructs within the common sense model and (2) piloting intervention materials, using expert patient panels (2 focus groups with 6 patients), individual patient interviews (n 1⁄4 6) and expert cardiologist feedback. Findings: Each component of the intervention was adapted and moderated following patient and cardiologist feedback, e.g. presentation of risk information. The final intervention comprises DVD (including patient narratives), worksheets, patient education booklet and a self-monitoring diary. It is currently being evaluated in a randomised control trial [ISRCTN93952605]. Discussion: Health psychologists play an intrinsic role in this collaborative process, whereby intervention development evolves through theoretical and pragmatic piloting.peer-reviewe

Geological Field Trips

This field trip guide organized in the framework of the Goldschmidt Conference 2013, held in Florence from August 25 to 30, 2013, is here presented. The two-days field trip, shows some of the many geological, naturalistic and cultural features in the Fiorano area (Modena), in which history, geology and passion for Ferrari come together in a perfect marriage. The first excursion day is dedicated to visit the Natural Reserve of Salse di Nirano, where the mud volcanoes, produced by the cold mud, salt water and hydrocarbons - mainly methane- can be observed. The second day is devoted to visit the Ferrari Museum and goes on at the Spezzano Castle, hosting the Ceramics Museum. Clays are, in fact, abundant in the hilly margin, where they form badlands, characteristic narrow crests washed out by running waters. In the Castle there is also a Balsamic Vinegar producing Consortium, it’s a peculiar and typical product of Modena province. The itinerary ends with the tour to Enzo Ferrari’s Birthplace at Modena

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown

Engaging rural Australian communities in National Science Week helps increase visibility for women researchers

During a week-long celebration of science, run under the federally-supported National Science Week umbrella, the Catch a Rising Star: women in Queensland research (CaRS) program flew scientists who identify as women to regional and remote communities in the Australian State of Queensland. The aim of the project was twofold: first, to bring science to remote and regional communities in a large, economically diverse state; and second, to determine whether media and public engagement provide career advancement opportunities for women scientists. This paper focuses on the latter goal. The data show: 1) a substantial majority (> 80%) of researchers thought the training and experience provided by the program would help develop her career as a research scientist in the future; 2) the majority (65%) thought the program would help relate her research to end users, industry partners, or stakeholders in the future; and, 3) analytics can help create a compelling narrative around engagement metrics and help to quantify influence. During the weeklong project, scientists reached 600,000 impressions on one social media platform (Twitter) using a program hashtag. The breadth and depth of the project outcomes indicate funding bodies and employers could use similar data as an informative source of metrics to support hiring and promotion decisions. Although this project focused on researchers who identify as women, the lessons learned are applicable to researchers representing a diverse range of backgrounds. Future surveys will help determine whether the CaRS program provided long-term career advantages to participating scientists and communities

Prescribing cycle training intensity from the six-minute walk test for patients with COPD

Background: Cycle training intensity for patients with chronic obstructive pulmonary disease (COPD) is normally based on an incremental cycle test. Such tests are expensive and not readily available to clinicians. The six-minute walk test (6MWT) has been proposed as an alternative to an incremental cycle test for this purpose, based on the findings of previous research that the peak oxygen consumption (VO2peak) for the incremental cycle test and the 6MWT was equivalent in participants with COPD. A regression equation relating distance walked on the 6MWT and peak work rate (Wpeak) on the incremental cycle test has been described. The aim of this study is to measure the physiological responses to constant load cycle exercise performed at an intensity of 60% Wpeak determined from the 6MWT in participants with stable COPD. Methods/Design: This study is a prospective, repeated measures design. Thirty-five participants with stable COPD and mild to severe lung disease will be recruited from referrals to pulmonary rehabilitation. Subjects with co-morbidities limiting exercise performance will be excluded. Two 6MWTs will be performed. The better 6MWT will be used to calculate Wpeak for cycle exercise from a regression equation. After 30 minutes rest, subjects will perform ten minutes of constantload cycle exercise at 60% of the calculated Wpeak. During all exercise, cardiorespiratory and metabolic data (Cosmed K4b2), dyspnoea and rate of perceived exertion (RPE) will be recorded. The VO2 measured at the end of cycle exercise will be compared to VO2peak of the 6MWT (VO2bike/ VO2walk). Pearson's correlation coefficient will be calculated for the relationship between VO2bike and VO2walk. A one-way analysis of variance (ANOVA), with Bonferroni correction, will be performed to determine whether the ratio of VO2bike/VO2walk is affected by disease severity. Discussion: This novel study will measure the physiological responses to cycle exercise, in terms of VO2peak, performed at an intensity determined from the 6MWT in participants with COPD. Positive findings will enable clinicians to more precisely prescribe cycle training intensity by utilising a simple, reliable and inexpensive 6MWT, thus providing a better standard of care for patients with COPD referred to pulmonary rehabilitation

Sequence and tectonostratigraphy of the Neoproterozoic (Tonian-Cryogenian) Amundsen Basin prior to supercontinent (Rodinia) breakup

Intracontinental basins that lack obvious compartmentalization and extensional faults may lie inboard of, and have the same timing as, rifted continental margins. Neoproterozoic successions of northwest Laurentia are an example where rift and intracontinental basins are spatially and temporally related. This study describes Tonian-Cryogenian pre-rift strata of the upper Shaler Supergroup, deposited in the Amundsen Basin (Victoria Island, Canada), in which five transgressive-regressive (T-R) cycles are identified. The pre-breakup succession in the Amundsen Basin has stratigraphic architecture that differs from adjacent, fault-bound rift basins. There is little evidence for extensive progradation, which resulted in broad, layer-cake stratigraphy where shallow-water facies predominate, deposited on a storm-dominated ramp. Correlation between the Amundsen and Fifteenmile (Yukon) basins is complicated by differing rates and regimes of subsidence, with the exception of a basin-deepening event that occurred in both basins and correlates with the global Bitter Springs isotope stage, initiating sometime after ~811 Ma. Contrary to previous correlations, we propose that the upper Shaler Supergroup and Little Dal Group of the Mackenzie Mountains Supergroup (Mackenzie Basin) are equivalent to the entire Fifteenmile Group. The identification of cycles and subsidence patterns in the Amundsen Basin prior to Rodinia break-up has implications for understanding the stratigraphic architecture of other intracontinental sag basins. We recognize three tectonostratigraphic units for the upper Shaler Supergroup that record an initial sag basin, followed by early extension and thermal doming, and finally rifting of the Amundsen Basin. Subsidence possibly was related to multiple cycles of intra-plate extension that complemented coeval fault-controlled subsidence. Analysis of pre-rift strata in the Amundsen Basin supports multi-phase, non-correlative break-up of Rodinia along the northwest margin of Laurentia

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production

Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development