Delivery of pain-free dentistry is crucial for reducing fear and anxiety, completion of treatment, and increasing acceptance of future dental treatment in children. Local anaesthetic (LA) facilitates ...this pain-free approach but it remains challenging. A number of interventions to help children cope with delivery of LA have been described, with no consensus on the best method to increase its acceptance.
To evaluate the effects of methods for acceptance of LA in children and adolescents during dental treatment.
Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health's Trials Register (to 24 May 2019); the Cochrane Central Register of Controlled Trials (CENTRAL; 2019 Issue 4) in the Cochrane Library (searched 24 May 2019); MEDLINE Ovid (1946 to 24 of May 2019); Embase Ovid (1980 to 24 May 2019); and Web of Science (1900 to 24 May 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and World Health Organization International Clinical Trials Registry Platform were also searched to 24 May 2019. There were no restrictions on language or date of publications.
Parallel randomised controlled trials (RCTs) of interventions used to increase acceptance of dental LA in children and adolescents under the age of 18 years.
We used standard methodological procedures expected by Cochrane. We performed data extraction and assessment of risk of bias independently and in duplicate. We contacted authors for missing information. We assessed the certainty of the body of evidence using GRADE.
We included 26 trials with 2435 randomised participants aged between 2 and 16 years. Studies were carried out between 2002 and 2019 in dental clinics in the UK, USA, the Netherlands, Iran, India, France, Egypt, Saudi Arabia, Syria, Mexico, and Korea. Studies included equipment interventions (using several LA delivery devices for injection or audiovisual aids used immediately prior to or during LA delivery or both) and dentist interventions (psychological behaviour interventions delivered in advance of LA (video modelling), or immediately prior to or during delivery of LA or both (hypnosis, counter-stimulation). We judged one study to be at low risk and the rest at high risk of bias. Clinical heterogeneity of the included studies rendered it impossible to pool data into meta-analyses. None of the studies reported on our primary outcome of acceptance of LA. No studies reported on the following secondary outcomes: completion of dental treatment, successful LA/painless treatment, patient satisfaction, parent satisfaction, and adverse events. Audiovisual distraction compared to conventional treatment: the evidence was uncertain for the outcome pain-related behaviour during delivery of LA with a reduction in negative behaviour when 3D video glasses where used in the audiovisual distraction group (risk ratio (RR) 0.13, 95% confidence interval (CI) 0.03 to 0.50; 1 trial, 60 participants; very low-certainty evidence). The wand versus conventional treatment: the evidence was uncertain regarding the effect of the wand on pain-related behaviour during delivery of LA. Four studies reported a benefit in using the wand while the remaining studies results suggested no difference between the two methods of delivering LA (six trials, 704 participants; very low-certainty evidence). Counter-stimulation/distraction versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with children experiencing less pain when counter-stimulation was used (RR 0.12, 95% CI 0.04 to 0.34; 1 trial, 134 participants; very low-certainty evidence). Hypnosis versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with participants in the hypnosis group experiencing less pain (mean difference (MD) -1.79, 95% CI -3.01 to -0.57; 1 trial, 29 participants; very low-certainty evidence). Other comparisons considered included pre-cooling of the injection site, the wand versus Sleeper One, the use of a camouflage syringe, use of an electrical counter-stimulation device, and video modelling acclimatisation, and had a single study each. The findings from these other comparisons were insufficient to draw any affirmative conclusions about their effectiveness, and were considered to be very low-certainty evidence.
We did not find sufficient evidence to draw firm conclusions as to the best interventions to increase acceptance of LA in children due to variation in methodology and nature/timing of outcome measures. We recommend further parallel RCTs, reported in line with the CONSORT Statement. Care should be taken when choosing outcome measures.
Programmed cell death (PCD) is a genetically controlled pathway that plants can use to selectively eliminate redundant or damaged cells. In addition to its fundamental role in plant development, PCD ...can often be activated as an essential defense response when dealing with biotic and abiotic stresses. For example, localized, tightly controlled PCD can promote plant survival by restricting pathogen growth, driving the development of morphological traits for stress tolerance such as aerenchyma, or triggering systemic pro-survival responses. Relatively little is known about the molecular control of this essential process in plants, especially in comparison to well-described cell death models in animals. However, the networks orchestrating transcriptional regulation of plant PCD are emerging. Transcription factors (TFs) regulate the clusters of stimuli inducible genes and play a fundamental role in plant responses, such as PCD, to abiotic and biotic stresses. Here, we discuss the roles of different classes of transcription factors, including members of NAC, ERF and WRKY families, in cell fate regulation in response to environmental stresses. The role of TFs in stress-induced mitochondrial retrograde signaling is also reviewed in the context of life-and-death decisions of the plant cell and future research directions for further elucidation of TF-mediated control of stress-induced PCD events are proposed. An increased understanding of these complex signaling networks will inform and facilitate future breeding strategies to increase crop tolerance to disease and/or abiotic stresses.
Recruitment of circulating monocytes is critical for tumour angiogenesis. However, how human monocyte subpopulations extravasate to tumours is unclear. Here we show mechanisms of extravasation of ...human CD14
CD16
patrolling and CD14
CD16
intermediate proangiogenic monocytes (HPMo), using human tumour xenograft models and live imaging of transmigration. IFNγ promotes an increase of the chemokine CX3CL1 on vessel lumen, imposing continuous crawling to HPMo and making these monocytes insensitive to chemokines required for their extravasation. Expression of the angiogenic factor VEGF and the inflammatory cytokine TNF by tumour cells enables HPMo extravasation by inducing GATA3-mediated repression of CX3CL1 expression. Recruited HPMo boosts angiogenesis by secreting MMP9 leading to release of matrix-bound VEGF-A, which amplifies the entry of more HPMo into tumours. Uncovering the extravasation cascade of HPMo sets the stage for future tumour therapies.
To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different ...meta-analytic strategies.
Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding.
We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding.
We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques.
Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding.
Purpose
The purpuse of this study is to answer the following two questions. Do conflict management efforts mitigate the recurrence and severity of civil conflict? If so, how? Do some conflict ...management strategies fare better than others in these tasks? This study theorizes about the connection between the costliness of a conflict management strategy – with respect to both the disputants and third parties – and civil conflict outcomes. This theory produces two contradictory predictions: that more costly strategies either increase or decrease violence. This study not only adjudicates between these two possibilities but also incorporates the role of timing. The early use of more costly strategies, for example, may encourage disputants to reduce violence in civil conflicts.
Design/methodology/approach
To evaluate the predications that the authors derive from their theoretical argument, the authors quantitatively analyze the effect of conflict management strategies’ relative cost on various measures of civil conflict recurrence and severity. The authors first identify the set of international–civil militarized conflicts (I-CMCs) during the period 1946–2010. I-CMCs contain two dimensions – interstate and intrastate – making them the most complex and dangerous form of militarized conflict. To each I-CMC, the authors then link all third-party attempts to manage the I-CMC’s civil conflict dimension. Finally, after developing quantitative indicators, a series of regression equations explore the relationships of primary interest.
Findings
Two main findings emerge. First, when third parties use a relatively more costly conflict management strategy to manage a civil conflict (e.g. a peace operation or military intervention, as opposed to mediation), the severity of the conflict increases, while conflict recurrence rates remain unchanged. Second, this study uncovers a trade-off. The early use of a relatively more costly management strategy lowers a civil conflict’s severity in the short-term. It also, however, increases the likelihood – and speed with which – civil conflict recurs. The timing of certain conflict management strategies matters.
Originality/value
Scholars typically isolate conflict management strategies in number (i.e. consider efforts as independent of one another, even those within the same conflict) and kind (i.e. examine mediation but not peace operations). This study, in contrast, includes the following: the full menu of conflict management strategies available to third parties – negotiation, mediation, adjudication/arbitration, peace operations, sanctions and military intervention – over a lengthy time period (1946–2010); theorizes about the relative merits of these strategies; and considers the timing of certain conflict management efforts. In so doing, it highlights a policy trade-off and proposes promising areas for future research.
Natural ventilation (NV) is a sustainable solution to improve building energy efficiency and reduce carbon emission. In this study, we quantified the impact of air pollution and noise pollution on ...the NV potential at both city scale and building scale in London. At city scale, the loss of annual cooling energy saving potential due to noise pollution (8.1 kWh/m2) was found to be comparable to that due to air pollution (9.0 kWh/m2). At building scale, we selected a naturally ventilated office building in central London with two windows facing a noisy and polluted traffic road and one window overlooking a quiet and clean courtyard for case study. By coupling EnergyPlus simulation with advanced wind tunnel experiments, we identified the prevailing inflow directions and cooling energy saving potentials of 26 NV modes with different window combinations. It was found that cross ventilation with stack effects is the most efficient NV mode for indoor-outdoor exchanges and prevailing building inflow direction can be regulated by optimising window openings at different heights. Particularly for the case study building, we can save cooling energy by up to 5.6 kWh/m2 per month in the optimal NV mode while minimising the negative health impact of ambient pollution by introducing more fresh air from the cleaner side. In addition, local urban morphological changes such as the presence of a tall building or the expansion of an adjacent road were also found to be influential on NV performances.
•The impact of air and noise pollution on natural ventilation potential was quantified at both city and building scales.•The prevailing inflow directions were identified by coupling EnergyPlus model with advanced wind tunnel experiments.•Window optimisation strategies were proposed by considering the trade-offs between energy efficiency and health impact.•An additional 20 kWh/m2 can be saved per annum via natural ventilation upon further reduction of air and noise pollution.
Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Drusen accumulation is the major pathological hallmark common to both dry and wet AMD. Although ...activation of the immune system has been implicated in disease progression, the pathways involved are unclear. Here we show that drusen isolated from donor AMD eyes activates the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, causing secretion of interleukin-1b (IL-1b) and IL-18. Drusen component C1Q also activates the NLRP3 inflammasome. Moreover, the oxidative-stress-related protein-modification carboxyethylpyrrole (CEP), a biomarker of AMD, primes the inflammasome. We found cleaved caspase-1 and NLRP3 in activated macrophages in the retinas of mice immunized with CEP-adducted mouse serum albumin, modeling a dry-AMD–like pathology. We show that laser-induced choroidal neovascularization (CNV), a mouse model of wet AMD, is exacerbated in Nlrp3(-/-) but not Il1r1(-/-) mice, directly implicating IL-18 in the regulation of CNV development. These findings indicate a protective role for NLRP3 and IL-18 in the progression of AMD.
Mammalian phenylalanine hydroxylase (PheH) is an allosteric enzyme that catalyzes the first step in the catabolism of the amino acid phenylalanine. Following allosteric activation by high ...phenylalanine levels, the enzyme catalyzes the pterin-dependent conversion of phenylalanine to tyrosine. Inability to control elevated phenylalanine levels in the blood leads to increased risk of mental disabilities commonly associated with the inherited metabolic disorder, phenylketonuria. Although extensively studied, structural changes associated with allosteric activation in mammalian PheH have been elusive. Here, we examine the complex allosteric mechanisms of rat PheH using X-ray crystallography, isothermal titration calorimetry (ITC), and small-angle X-ray scattering (SAXS). We describe crystal structures of the preactivated state of the PheH tetramer depicting the regulatory domains docked against the catalytic domains and preventing substrate binding. Using SAXS, we further describe the domain movements involved in allosteric activation of PheH in solution and present the first demonstration of chromatography-coupled SAXS with Evolving Factor Analysis (EFA), a powerful method for separating scattering components in a model-independent way. Together, these results support a model for allostery in PheH in which phenylalanine stabilizes the dimerization of the regulatory domains and exposes the active site for substrate binding and other structural changes needed for activity.
As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening.
Mortality, causes of death, and lung cancer findings are ...reported to explore the effect of computed tomography (CT) screening.
A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group).
Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group.
No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).
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