Perfectionism and PERMA: The Benefits of Other-Oriented Perfectionism

The two-factor theory of perfectionism differentiates between positive and negative forms, yet some researchers still argue that perfectionism, as a whole, is detrimental to wellbeing. To this end, the present study investigated the relationship between the tripartite model of perfectionism and the PERMA model of wellbeing, with specific attention given to the relationship each form of perfectionism had with each element of wellbeing. Ninety-two participants (M age= 24.99) completed online self-report measures of perfectionism (self-oriented, other-oriented, and socially prescribed) and PERMA (positive emotion, engagement, relationships, meaning and accomplishment). Results showed that perfectionism accounted for a substantial amount of variance in all elements of wellbeing. A series of multiple regressions showed that socially prescribed perfectionism negatively predicted all PERMA elements. Self-oriented perfectionism positively predicted positive emotion, engagement, meaning and accomplishment. Other-oriented perfectionism positively predicted meaning and accomplishment. As for overall wellbeing, socially prescribed perfectionism was a negative predictor whereas self-oriented and other-oriented perfectionism were positive predictors. The findings indicate that self-oriented perfectionism is an adaptive form of perfectionism conducive to flourishing whereas socially prescribed perfectionism is a maladaptive form which undermines it. As for other-oriented perfectionism, the findings indicate it is an adaptive form and challenge the view that this “dark” form of perfectionism cannot enhance wellbeing

Does ‘Scientists believe…’ imply ‘All scientists believe...’? Individual differences in the interpretation of generic news headlines

Media headlines reporting scientific research frequently include generic phrases such as “Scientists believe x” or “Experts think y”. These phrases capture attention and succinctly communicate science to the public. However, by generically attributing beliefs to ‘Scientists’, ‘Experts’ or ‘Researchers’ the degree of scientific consensus must be inferred by the reader or listener (do all scientists believe x, most scientists, or just a few?). Our data revealed that decontextualized generic phrases such as “Scientists say…” imply consensus among a majority of relevant experts (53.8% in Study 1 and 60.7-61.8% in Study 2). There was little variation in the degree of consensus implied by different generic phrases, but wide variation between different participants. These ratings of decontextualized phrases will inevitably be labile and prone to change with the addition of context, but under controlled conditions people interpret generic consensus statements in very different ways. We tested the novel hypothesis that individual differences in consensus estimates occur because generic phrases encourage an intuitive overgeneralization (e.g., Scientists believe = All scientists believe) that some people revise downwards on reflection (e.g., Scientists believe = Some scientists believe). Two pre-registered studies failed to support this hypothesis. There was no significant relationship between reflective thinking and consensus estimates (Study 1) and enforced reflection did not cause estimates to be revised downwards (Study 2). Those reporting scientific research should be aware that generically attributing beliefs to ‘Scientists’ or ‘Researchers’ is ambiguous and inappropriate when there is no clear consensus among relevant experts

When 'Scientists say' coffee is good for you one day and bad for you the next: Do generic attributions to ‘Scientists’ and ‘Experts’ amplify perceived conflict?

News consumers are frequently exposed to seemingly conflicting claims about the risks or benefits of activities such as eating meat and drinking coffee, which can lead to confusion and backlash against expert advice. One factor that may artificially inflate perceived conflict is the tendency for news headlines to generically attribute such claims to ‘Scientists’, ‘Experts’ or ‘Researchers’. This can create the perception that scientific consensus frequently changes, with ‘experts’ saying one thing one day (e.g., “Fasting diet could regenerate pancreas and reverse diabetes, researchers say”) and another the next (“Fasting diets may raise risk of diabetes, researchers warn”). We predicted that hedging news headlines with the qualifier ‘some’ (e.g., ...some researchers say) would reduce perceived contradiction and backlash by triggering the scalar inference “some but not all…”. We presented participants with a series of conflicting headlines or non-conflicting headlines about health and nutrition. These were presented in either their original generic format (e.g., Researchers say...) or in a qualified format (e.g., Some researchers say…). Those that saw conflicting headlines felt they were more contradictory, more confusing and resulted in us knowing less about how to be healthy than those who saw the non-conflicting headlines (Experiment 1, N=294). In Experiment 2 (N=400), the same conflict manipulation had no effect on more general beliefs about nutrition or the development of science. When our conflict manipulation did affect beliefs (Experiment 1) the effect of conflict was not moderated by headline format. Our results suggest that replacing generic consensus claims (e.g., Researchers say...) with qualified consensus claims (e.g., Some researchers say…) does not reduce the perceived contradiction and confusion that are typically associated with conflicting news reports

Pharmacodynamics of the Orotomides against Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease.

F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding of the pharmacodynamics (PD) of F901318 is required for selection of effective regimens for study in phase II and III clinical trials. Neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. The relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, and histopathology were determined. The results were benchmarked against a clinically relevant exposure of posaconazole. In the murine model, administration of a total daily dose of 24 mg/kg of body weight produced consistently better responses with increasingly fractionated regimens. The ratio of the minimum total plasma concentration/MIC (Cmin/MIC) was the PD index that best linked drug exposure with observed effect. An average Cmin (mg/liter) and Cmin/MIC of 0.3 and 9.1, respectively, resulted in antifungal effects equivalent to the effect of posaconazole at the upper boundary of its expected human exposures. This pattern was confirmed in a rabbit model, where Cmin and Cmin/MIC targets of 0.1 and 3.3, respectively, produced effects previously reported for expected human exposures of isavuconazole. These targets were independent of triazole susceptibility. The pattern of maximal effect evident with these drug exposure targets was also apparent when survival and histopathological clearance were used as study endpoints. F901318 exhibits time-dependent antifungal activity. The PD targets can now be used to select regimens for phase II and III clinical trials.IMPORTANCE Invasive fungal infections are common and often lethal. There are relatively few antifungal agents licensed for clinical use. Antifungal drug toxicity and the emergence of drug resistance make the treatment of these infections very challenging. F901318 is the first in a new class of antifungal agents called the orotomides. This class has a novel mechanism of action that involves the inhibition of the fungal enzyme dihydroorotate dehydrogenase. F901318 is being developed for clinical use. A deep understanding of the relationship between dosages, drug concentrations in the body, and the antifungal effect is fundamental to the identification of the regimens to administer to patients with invasive fungal infections. This study provides the necessary information to ensure that the right dose of F901318 is used the first time. Such an approach considerably reduces the risks in drug development programs and ensures that patients with few therapeutic options can receive potentially life-saving antifungal therapy at the earliest opportunity

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

Association with pathogenic bacteria affects life-history traits and population growth in Caenorhabditis elegans.

Determining the relationship between individual life-history traits and population dynamics is an essential step to understand and predict natural selection. Model organisms that can be conveniently studied experimentally at both levels are invaluable to test the rich body of theoretical literature in this area. The nematode Caenorhabditis elegans, despite being a well-established workhorse in genetics, has only recently received attention from ecologists and evolutionary biologists, especially with respect to its association with pathogenic bacteria. In order to start filling the gap between the two areas, we conducted a series of experiments aiming at measuring life-history traits as well as population growth of C. elegans in response to three different bacterial strains: Escherichia coli OP50, Salmonella enterica Typhimurium, and Pseudomonas aeruginosa PAO1. Whereas previous studies had established that the latter two reduced the survival of nematodes feeding on them compared to E. coli OP50, we report for the first time an enhancement in reproductive success and population growth for worms feeding on S. enterica Typhimurium. Furthermore, we used an age-specific population dynamic model, parameterized using individual life-history assays, to successfully predict the growth of populations over three generations. This study paves the way for more detailed and quantitative experimental investigation of the ecology and evolution of C. elegans and the bacteria it interacts with, which could improve our understanding of the fate of opportunistic pathogens in the environment.We thank Andrew Grant and Craig Winstanley for providing strains and reagents. Some C. elegans and bacterial strains were provided by the Caenorhabditis Genetics Centre, which is funded by NIH’s Office of Research Infrastructure Programs (P40 OD010440). This research was funded by a grant from the Biotechnology and Biological Sciences Research Council (grant number BB/I012222/1) to O.R. O.R. also acknowledges funding from the Royal Society (University Research Fellowship). EQM was supported by a scholarship from the Winston Churchill Foundation of the United States, and EGR by an EUfunded Erasmus bursary (Lifelong Learning Programme). We also thank two anonymous referees for their valuable comments.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/ece3.1461/abstract

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers

Growth rate after limb deformity correction by the Ilizarov method with or without knee joint distraction: Lengthening in 30 children followed for at least 2 years

Background and purpose Growth inhibition and stimulation have both been reported after juvenile limb lengthening. Distraction of a joint usually suspends and unloads the growth plate and may stimulate growth. We investigated the influence of knee joint distraction on the speed of growth after limb lengthening

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate