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Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.
After reading this article you will be able to:
•understand the relative incidence of cardiotoxic side-effects of the various SGAs
•perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs
•understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.
While hot-water drilling is a well-established technique used to access the subsurface of ice masses, drilling into high-elevation (≳ 4000 m a.s.l.) debris-covered glaciers faces specific challenges. First, restricted transport capacity limits individual equipment items to a volume and mass that can be slung by small helicopters. Second, low atmospheric oxygen and pressure reduces the effectiveness of combustion, limiting a system's ability to pump and heat water. Third, thick supraglacial debris, which is both highly uneven and unstable, inhibits direct access to the ice surface, hinders the manoeuvring of equipment and limits secure sites for equipment placement. Fourth, englacial debris can slow the drilling rate such that continued drilling becomes impracticable and/or boreholes deviate substantially from vertical. Because of these challenges, field-based englacial and subglacial data required to calibrate numerical models of high-elevation debris-covered glaciers are scarce or absent. Here, we summarise our experiences of hot-water drilling over two field seasons (2017–2018) at the debris-covered Khumbu Glacier, Nepal, where we melted 27 boreholes up to 192 m length, at elevations between 4900 and 5200 m a.s.l. We describe the drilling equipment and operation, evaluate the effectiveness of our approach and suggest equipment and methodological adaptations for future use.
Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants.
Using a mixed-methods design, health researchers (N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers.
Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers.
Study findings add to literature on research dissemination by documenting health researchers’ perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants.
Intertidal biofilms are a diverse mixture of bacteria, algae as well as sporelings of macroalgae embedded in a polysaccharid matrix. As the primary colonisers of newly formed surfaces, biofilms undergo a succession of different microbe assemblage until the mature state is reached. A biofilm can act as primary producers and as such recycle nutrients in a habitat. It will influence macrobiota by providing a food source or sending out cues to settlers. Biofilms themselves will be controlled by these settlers. This interaction between bottom-up and top-down plays a crucial part for the functioning of the rocky shore ecosystems. However, the diversity of biolfilms as well as it nature to react quickly to environmental changes makes identification and quantification of the individual compounds a difficult task. Subsequently, the understanding of biofilms in general and intertidal, rocky shore microbe assemblages has always tied to techniques and methods available at the time of study. This chapter focusses on the techniques that have greatly contributed to increasing knowledge of biofilms and discusses their findings. Nonetheless, newly developed methods promise to further this knowledge of the ecological role of biofilms on rocky coastlines.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The major facilitator superfamily domain 2a protein was identified recently as a lysophosphatidylcholine (LPC) symporter with high affinity for LPC species enriched with DHA (LPC-DHA). To test the hypothesis that reproductive state and choline intake influence plasma LPC-DHA, we performed a post-hoc analysis of samples available through 10 weeks of a previously conducted feeding study, which provided two doses of choline (480 and 930 mg/d) to non-pregnant (n=21), third-trimester pregnant (n=26), and lactating (n=24) women; all participants consumed 200 mg of supplemental DHA and 22% of their daily choline intake as deuterium-labeled choline. The effects of reproductive state and choline intake on total LPC-DHA (expressed as a percentage of LPC) and plasma enrichments of labeled LPC and LPC-DHA were assessed using mixed and generalized linear models. Reproductive state interacted with time (p=0.001) to influence total LPC-DHA, which significantly increased by week 10 in non-pregnant women, but not in pregnant or lactating women. Contrary to total LPC-DHA, patterns of labeled LPC-DHA enrichments were discordant between pregnant and lactating women (p<0.05), suggestive of unique, reproductive state-specific mechanisms that result in the reduced production and/or enhanced clearance of LPC-DHA during pregnancy and lactation. Regardless of reproductive state, women consuming 930 versus 480 mg choline/d exhibited no change in total LPC-DHA but higher d3-LPC-DHA (p=0.02), indicating that higher choline intakes favor production of LPC-DHA from the PEMT pathway of phosphatidylcholine biosynthesis. Our results warrant further investigation into the effect of reproductive state and dietary choline on LPC-DHA dynamics and its contribution to DHA status.
Resumptive pronouns are produced in English in unguarded speech in restrictive relative clauses and appositive relative clauses. However, numerous studies have found that resumptive pronouns in restrictive relative clauses are not acceptable. To our knowledge, no studies have examined the acceptability of resumptive pronouns in appositive relative clauses, despite hints in the literature that they may be more acceptable in appositive than in restrictive relative clauses. This article fills that gap. We found that resumptive pronouns were rated as more natural in appositive relative clauses than in restrictive relative clauses. These findings may be due to which currently undergoing a reanalysis from a relative pronoun to a solely connective word, as has been suggested in the literature. A small-scale corpus search also reveals that appositive relative clauses with resumptive pronouns are increasing in American English.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The aim of this narrative review is to assess and present evidence on the mechanisms of action of probiotics in constipation, their effectiveness and their utilisation by patients and healthcare professionals. Chronic constipation is a common bothersome disorder that has a considerable impact on patients' quality of life. Probiotics have been increasingly investigated for their effectiveness in various disorders, including chronic constipation. Probiotics may affect gut motility and constipation through their impact on the gut microbiota and fermentation, the central and enteric nervous system and the immune system. However, evidence for the effectiveness of probiotics in the management of constipation remains varied, with some strains demonstrating improvements, while others show no effect. Despite the uncertainty in evidence and the fact that the majority of healthcare professionals do not recommend probiotics for constipation, an increased prevalence of probiotic use by people with constipation has been shown. Therefore, there is a need for public health strategies to inform the public about where strong evidence of probiotic effectiveness exist, and where evidence is still weak. Education of healthcare professionals on the increased utilisation of probiotics for constipation by the public and on current evidence for the effectiveness of specific strains is also required.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Concerns exist over the long-term consequences of subclavian artery ligation in subclavian flap repair for coarctation of the aorta. We sought to analyse upper limb structural and functional performance in adults who have had surgery in childhood for coarctation of the aorta, using either subclavian flap repair or end to end aortic anastomosis.
Two-group observational design using anatomical and upper limb functional performance measures. Purposive sampling from our specialist adult congenital heart disease database of patients who received subclavian flap repair or end to end anastomosis for coarctation of the aorta as children. Upper limb measurements were completed using MRI and blood flow velocity with ultrasound imaging. Bilateral standardised upper limb functional testing of assessment of strength, dexterity and a standardised self-report of upper limb disability was completed.
Eighteen right-handed patients, 9 with subclavian repair, (38 ± 12 years, 78% males) were studied. Age at repair was 4.7 ± 5.9 years; mean time from initial repair 32 ± 9 years. The subclavian group had a larger difference between right and left when compared the end to end anastomosis group in: lower arm muscle mass (94.5 ± 42.3 mls versus 37.8 ± 94.5 mls, p = 0.008), lower arm maximal cross-sectional area, (5.9 ± 2.8 cm2 versus 2.9 ± 2.6 cm2, p = 0.038) and grip strength (14.7 ± 8.3 lbs versus 5.9 ± 5.3 lbs, p = 0.016) There were no significant functional differences between groups.
In adults with repaired coarctation of the aorta, those with subclavian flap repair had a greater right to left arm muscle mass and grip strength differential when compared to those with end to end anastomosis repair.
We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).
We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50 in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50 in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.
(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2 s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50 for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM; p = 0.39). (3) The RUC-4 IC50 was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM; p = 0.05; n = 4) or ADP (102±22 vs 54±13; p<0.001; n = 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.
Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.
Localized network processes are central to the study of political science, whether in the formation of political coalitions and voting blocs, balancing and bandwagoning, policy learning, imitation, diffusion, tipping-point dynamics, or cascade effects. These types of processes are not easily modeled using traditional network approaches, which focus on global rather than local structures within networks. We show that localized network processes, in which network edges form in response to the formation of other edges, are best modeled by shifting from the traditional theoretical framework of nodes-as-actors to what we term a nodes-as-actions framework, which allows for zeroing in on relationships among network connections. We show that the proposed theoretical framework is statistically compatible with a local structure graph model (LSGM). We demonstrate the properties of LSGMs using a Monte Carlo experiment and explore action–reaction processes in two empirical applications: formation of alliances among countries and legislative cosponsorships in the US Senate.
Wing shape is an important factor affecting the aerodynamic performance of wings of monocopters and flapping-wing micro air vehicles. Here, an evolutionary structural optimisation method is adapted to optimise wing shape to enhance the lift force due to aerodynamic pressure on the wing surfaces. The pressure distribution is observed to vary with the span-based Reynolds number over a range covering most insects and samaras. Accordingly, the optimised wing shapes derived using this evolutionary approach are shown to adjust with Reynolds number. Moreover, these optimised shapes exhibit significantly higher lift coefficients (
) than the initial rectangular wing forebear. Interestingly, the optimised shapes are found to have a large area outboard, broadly in line with the features of high-lift forewings of multi-winged insects. According to specific aerodynamic performance requirements, this novel method could be employed in the optimisation of improved wing shapes for micro air vehicles.
Roles for pharmacists in general practice are developing in Australia. It is known that pharmacists can provide effective smoking cessation services in other settings but evidence in general practice is lacking.
To determine whether a pharmacist can provide effective smoking cessation services within general practice.
Data from smoking cessation consultations were obtained for 66 consecutive patients seen by one practice pharmacist. The pharmacist tailored interventions to the individual. Medication was offered in collaboration with community pharmacists and general practitioners. Quit coaching, based on motivational interviewing, was conducted. Smoking status was ascertained at least 6 months after the intended quit date and verified by a carbon monoxide breath test where possible.
The patients’ median age was 43 years (range 19–74 years); 42 were females (64%). At baseline, the median (i) number of pack years smoked was 20 (range: 1–75); (ii) Fagerstrom Test of dependence score was 6 (1–10); and (iii) number of previous quit attempts was 3 (0–10). Follow-up after at least 6 months determined a self-reported point prevalence abstinence rate of 30% (20/66). Of all patients who reported to be abstinent, 65% (13/20) were tested for carbon monoxide breath levels and were all below 7 ppm. The biochemically verified smoking abstinence rate was therefore 20% overall (13/66). Successful quit attempts were associated with varenicline recommendation (69% v 25%), increased median number of practice pharmacist consultations (4 v 2 per patient) and mental health diagnosis (85% v 51%).
Our observed abstinence rate was comparable or better than those obtained by practice nurses, community pharmacists and outpatient pharmacists, indicating the general practice pharmacist provided an effective smoking cessation intervention. A larger randomised trial is warranted.