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Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Mixed flora in urine cultures usually occur due to preanalytic contamination. In our outpatient urology clinic, we detected a high prevalence of mixed flora (46.2%), which was associated with female sex and older age. Patient education did not influence the rate of mixed flora. Future efforts should target high-risk patients.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$11–18 arcsec, resulting in a catalogue of $\sim$220 000 sources, of which $\sim$180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
To understand how the different data collections methods of the Alberta Health Services Infection Prevention and Control Program (IPC) and the National Surgical Quality Improvement Program (NSQIP) are affecting reported rates of surgical site infections (SSIs) following total hip replacements (THRs) and total knee replacements (TKRs).
Design:
Retrospective cohort study.
Setting:
Four hospitals in Alberta, Canada.
Patients:
Those with THR or TKR surgeries between September 1, 2015, and March 31, 2018.
Methods:
Demographic information, complex SSIs reported by IPC and NSQIP were compared and then IPC and NSQIP data were matched with percent agreement and Cohen’s κ calculated. Statistical analysis was performed for age, gender and complex SSIs. A P value <.05 was considered significant.
Results:
In total, 7,549 IPC and 2,037 NSQIP patients were compared. The complex SSI rate for NSQIP was higher compared to IPC (THR: 1.19 vs 0.68 [P = .147]; TKR: 0.92 vs 0.80 [P = .682]). After matching, 7 SSIs were identified by both IPC and NSQIP; 3 were identified only by IPC, and 12 were identified only by NSQIP (positive agreement, 0.48; negative agreement, 1.0; κ = 0.48).
Conclusions:
Different approaches to monitor SSIs may lead to different results and trending patterns. NSQIP reports total SSI rates that are consistently higher than IPC. If systems are compared at any point in time, confidence on the data may be eroded. Stakeholders need to be aware of these variations and education provided to facilitate an understanding of differences and a consistent approach to SSI surveillance monitoring over time.
Operators are mindful of the balloon-to-aortic annulus ratio when performing balloon aortic valvuloplasty. The method of measurement of the aortic valve annulus has not been standardised.
Methods and results:
Patients who underwent aortic valvuloplasty at two paediatric centres between 2007 and 2014 were included. The valve annulus measured by echocardiography and angiography was used to calculate the balloon-to-aortic annulus ratio and measurements were compared. The primary endpoint was an increase in aortic insufficiency by ≥2 degrees. Ninety-eight patients with a median age at valvuloplasty of 2.1 months (Interquartile range (IQR): 0.2–105.5) were included. The angiographic-based annulus was 8.2 mm (IQR: 6.8–16.0), which was greater than echocardiogram-based annulus of 7.5 mm (IQR: 6.1–14.8) (p < 0.001). This corresponded to a significantly lower angiographic balloon-to-aortic annulus ratio of 0.9 (IQR: 0.9–1.0), compared to an echocardiographic ratio of 1.1 (IQR: 1.0–1.1) (p < 0.001). The degree of discrepancy in measured diameter increased with smaller valve diameters (p = 0.041) and in neonates (p = 0.044). There was significant disagreement between angiographic and echocardiographic balloon-to-aortic annulus ratio measures regarding “High” ratio of >1.2, with angiographic ratio flagging only 2/12 (16.7%) of patients flagged by echocardiographic ratio as “High” (p = 0.012). Patients who had an increase in the degree of aortic insufficiency post valvuloplasty, only 3 (5.5%) had angiographic ratio > 1.1, while 21 (38%) had echocardiographic ratio >1.1 (p < 0.001). Patients with resultant ≥ moderate insufficiency more often had an echocardiographic ratio of >1.1 than angiographic ratio of >1.1 There was no association between increase in balloon-to-aortic annulus ratio and gradient reduction.
Conclusions:
Angiographic measurement is associated with a greater measured aortic valve annulus and the development of aortic insufficiency. Operators should use caution when relying solely on angiographic measurement when performing balloon aortic valvuloplasty.
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.
Methods:
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.
Results:
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.
Conclusions:
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.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Background:
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
Methods:
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
Results:
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Conclusions:
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
Concentrations of total organic carbon (TOC), total petroleum hydrocarbons, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were determined in 84 near-surface soils (5–20cm depth) taken from a 255km2 area of Glasgow in the Clyde Basin, UK, during July 2011. Total petroleum hydrocarbon range was 79–2,505mgkg–1 (mean 388mgkg–1; median 272mgkg–1) of which the aromatic fraction was 13–74 % (mean 44 %, median 43 %) and saturates were 28–87 % (mean 56 %, median 57 %). ∑16 PAH varied from 2–653mgkg–1 (mean 32.4mgkg–1; median 12.5mgkg–1) and ∑31 PAH range was 2.47–852mgkg–1 (mean 45.4mgkg–1; median 19.0mgkg–1). ∑PCBtri-hepta range was 2.2–1052μgkg–1 (mean 32.4μgkg–1; median 12.7μgkg–1) and the ∑PCB7 range was 0.3–344μgkg–1 (mean 9.8μgkg–1; median 2.7μgkg–1). The concentration, distribution and source of the persistent organic pollutants were compared with those found in urban soils from other cities and to human health assessment criteria for chronic exposure to chemicals in soil. Total concentrations encountered were generally similar to other urban areas that had a similar industrial history. Benzo[a]pyrene concentrations were assessed against four different land use scenarios (irrespective of current land use) using generic assessment criteria resulting in six of 84 samples exceeding the residential criteria. Isomeric PAH ratios and relative abundance of perylene suggest multiple and environmentally modified pyrogenic PAH sources, inferred to be representative of diffuse pollution. ∑PCB7 concentrations were exceeded in 10 % of sites using the Dutch target value of 20μgkg–1. PCB congener profiles were environmentally attenuated and generally dominated by penta-, hexa- and hepta-chlorinated congeners.
This study tested a transactional hypothesis predicting early adult sexual coercion from family maltreatment, early adolescent gang affiliation, and socialization of adolescent friendships that support coercive relationship norms. The longitudinal study of a community sample of 998 11-year-olds was intensively assessed in early and middle adolescence and followed to 23–24 years of age. At age 16–17 youth were videotaped with a friend, and their interactions were coded for coercive relationship talk. Structural equation modeling revealed that maltreatment predicted gang affiliation during early adolescence. Both maltreatment and gang affiliation strongly predicted adolescent sexual promiscuity and coercive relationship norms with friends at age 16–17 years. Adolescent sexual promiscuity, however, did not predict sexual coercion in early adulthood. In contrast, higher levels of observed coercive relationship talk with a friend predicted sexual coercion in early adulthood for both males and females. These findings suggest that peers have a socialization function in the development of norms prognostic of sexual coercion, and the need to consider peers in the promotion of healthy relationships.
Poly[sulfur-random-1,3-diisopropenylbenzene (DIB)] copolymers synthesized via inverse vulcanization form electrochemically active polymers used as cathodes for high-energy density Li–S batteries, capable of enhanced capacity retention (1005 mAh/g at 100 cycles) and lifetimes of over 500 cycles. In this prospective, we demonstrate how analytical electron microscopy can be employed as a powerful tool to explore the origins of the enhanced capacity retention. We analyze morphological and compositional features when the copolymers, with DIB contents up to 50% by mass, are blended with carbon nanoparticles. Replacing the elemental sulfur with the copolymers improves the compatibility and interfacial contact between active sulfur compounds and conductive carbons. There also appears to be improvements of the cathode mechanical stability that leads to less cracking but preserving porosity. This compatibilization scheme through stabilized organosulfur copolymers represents an alternative strategy to the nanoscale encapsulation schemes which are often used to improve the cycle life in high-energy density Li–S batteries.
Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue. Although the precise mechanism is unclear, the presence of reactive aldehydes produced through polyamine metabolism, such as 3-aminopropanal and acrolein, have been shown to correlate with the incidence of cerebral vasospasm, disruption of oxidative metabolism and mitochondrial functioning, and disturbance of cellular calcium ion channels. Regulation of the polyamine metabolic pathway, therefore, may have the potential to limit injury following cerebral ischemia. To this end, we review this pathway in detail with an emphasis on clinical applicability.
Edited by
Fiona Jenkins, Australian National University, Canberra,Mark Nolan, Australian National University, Canberra,Kim Rubenstein, Australian National University, Canberra
In Korean Paleolithic archaeology, it is traditionally thought that the Late Paleolithic stone tool industries were in some way derived from the Shuidonggou site in northern China. The latter site has long been considered to be the type site of the eastern Asian Late Paleolithic blade technology. However, recent studies suggest that a number of Korean Late Paleolithic sites probably predate Shuidonggou, some by several thousands of years. Here, we present a series of accelerator mass spectrometry (AMS) dates recently analyzed by the AMS laboratory at Seoul National University and discuss further the possibility that the introduction of blade (and later microblade) technologies into Korea may have originated directly from Mongolia, Siberia, and possibly other areas of northeast China, rather than from Shuidonggou.