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Objective: The aim of this investigation was to assess the effectiveness of a non‐cross‐linked hyaluronic acid based soft‐tissue filler in the correction of lateral canthal lines and periorbital lines. Material and methods: A total of 59 female Caucasian patients with a mean age of 52.6 ± 9.0 years were enrolled in this prospective open‐label, multicentre study and received intradermal injections of a soft‐tissue filler at baseline, after 3 and 6 weeks. Aesthetic improvement and patient satisfaction, skin hydration, skin firmness and skin elasticity, as well as adverse events were assessed at 3, 6, 8, 12 and 16 weeks. Results: At baseline, the lateral canthal skin firmness was 0.206 ± 0.07 mm and increased after 8 weeks to 0.087 ± 0.08 mm with p < 0.001, while the perioral skin firmness was 0.205 ± 0.09 mm and increased after 8 weeks to 0.116 ± 0.08 mm with p < 0.001. Increases in skin hydration were observed after 8 weeks in both areas, however, did not reach statistical significance at any point. At week 8, 12 and 16 a majority (93.1%, 91.1% and 73.7% respectively) of the patients stated that they were 'satisfied' or 'very satisfied' with the treatment. Conclusion: Overall, the skin firmness and skin visco‐elasticity showed significant increases in the lateral canthal and perioral region. Moreover, albeit not statistically significant, skin hydration increased in both areas after 8 weeks. The procedure has been shown to be safe and satisfactory for the treated patients; however, emergence of oral herpes should be added to the safety profile of intradermally applied hyaluronic acid treatments. [ABSTRACT FROM AUTHOR]

Aims/Purpose: To analyse the effect of the design of FineVision Micro F and AcrySof IQ PanOptix trifocal intraocular lenses on the visual quality of patients under photopic and mesopic illumination conditions. Methods: Observational, prospective, cross‐sectional study. The study was conducted at the Hospital Universitario Sanitas la Moraleja in Madrid. The study followed the principles of the Declaration of Helsinki. The sample included 16 patients who underwent cataract or lensectomy surgery, with bilateral implantation of one of the two intraocular lenses (IOLs) under study: 20 eyes with FineVision Micro F implant and 12 eyes with AcrySof IQ PanOptix. After 30 days after surgery, an assessment of photopic and mesopic, monocular and binocular visual acuity (VA) was performed for three distances: far (4 m), intermediate (66 cm) and near (40 cm) with the ETDRS test. A p‐value <0.05 was considered a criterion for statistical significance. Results: Visual acuity analysis showed significant differences between FineVision Micro F and AcrySof IQ PanOptix lenses, under photopic conditions, for intermediate distance (p‐value 0.014) with means of 0.04 ± 0.05 and 0.11 ± 0.11, respectively and near distance (p‐value 0.001), with means of 0.05 ± 0.06 and 0.12 ± 0.06, respectively. On the other hand, in mesopic conditions, statistically significant differences (p‐value 0.032) were observed in close distance, with means of 0.43 ± 0.3 and 0.52 ± 0.2, respectively. Conclusions: Both FineVision Micro F and AcrySof IQ PanOptix IOL designs provide optimal VA at far distances in both photopic and mesopic illumination conditions. The FineVision Micro F IOL provides better intermediate and near VA in photopic conditions and near distance in mesopic conditions than the AcrySof IQ PanOptix IOL, and this difference is clinically significant. [ABSTRACT FROM AUTHOR]

Aims and objectives: Pressure ulcers (PUs) are a serious health problem. They can be considered as an indicator of the quality of health care and are associated with considerable cost increases for the health care system. The prevention of PUs is a major concern in hospital care. The aim of the study was to reveal the current PU prevention‐related processes and structures with a specific focus on the Accident and Emergency (A&E) Department. Method: In late 2018/early 2019, all German hospitals were invited to participate in a nationwide cross‐sectional survey. One standardized questionnaire was assigned to a representative of each hospital. The representative was asked to state what PU‐related structures and processes are implemented in their hospital, in general and specific to the A&E department. Besides mostly descriptive analysis, PU‐related processes were analysed on PU incidence in a multivariate linear regression model. Results: Two hundred seventy‐six hospitals participated in the survey. 63.4% (n = 175) of the participating hospitals had at least one PU manager. Skin inspection was the most frequently performed procedure. Although not recommended, 1.3% (2.1%) of the facilities still use sheepskins quite often (very often). In the regression model on PU incidence, only the process 'mobilization in bed' was statistically significantly associated. Although the risk of developing a PU in the emergency department is high, more than half of the facilities had no PU guidelines. Conclusion: Even if recommended procedures (skin inspection, 30° positioning) have been used frequently, regular training could help to bring new scientific findings such as the use of local skin protection dressings into clinical practice. Prevention guidelines should be established in all areas of care even for A&E as well as when patients are transferred inside or out of the hospital, where the risk of PU development was considered low. [ABSTRACT FROM AUTHOR]

Statistical inference provides the protocols for conducting rigorous science, but data plots provide the opportunity to discover the unexpected. These disparate endeavours are bridged by visual inference, where a lineup protocol can be employed for statistical testing. Human observers are needed to assess the lineups, typically using a crowd‐sourcing service. This paper describes a new approach for computing statistical significance associated with the results from applying a lineup protocol. It utilizes a Dirichlet distribution to accommodate different levels of visual interest in individual null panels. The suggested procedures facilitate statistical inference for a broader range of data problems. [ABSTRACT FROM AUTHOR]

Aims: Disease‐specific validated questionnaires are used to quantify symptom severity, but they are time consuming to complete and evaluate. A Visual Analogue Scale (VAS) assessment of bother is simpler and faster. The aim of this study is to compare VAS with individual and composite pelvic floor disability index‐short form 20 items in predicting significant pelvic organ prolapse (POP). Methods: A retrospective analysis of data was obtained at a tertiary urogynaecological clinic between February 2017 and August 2018. All women filled out the PFDI‐20 and underwent a standardised physician‐directed interview, POP‐Q and translabial ultrasound. Women with symptoms of POP were asked to indicate the degree of bother using a VAS. Receiver operating characteristic curves were used to evaluate the performance of individual Pelvic Organ Prolapse Distress Inventory (POPDI)‐6 items, the six‐item composite POPDI‐6 score, and VAS in predicting significant POP on clinical and ultrasound examination. Results: The complete data sets of 231 women were analysed. Median VAS for POP was 2.9 (range 0–10). Median POPDI‐6 individual and composite scores for items one to six were 2, 2, 2, 1, 2, 0 (all range 0–4) and 9 (range 0–22), respectively. The majority had significant prolapse on clinical examination (n = 195, 84%) and on ultrasound (n = 192, 83%). The composite POPDI‐6 prolapse score provided areas under the curve of 0.68 and 0.64 for the prediction of clinical and sonographic POP, compared to 0.74 and 0.69, respectively, for VAS. The difference was not significant (P = 0.3 and 0.8, respectively). Conclusions: The VAS score was not inferior to the POPDI‐6 in predicting significant POP. It has the potential to simplify the assessment of symptom severity. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aims to understand early (<24 h post ictus) and late (up to 12 months) survival post aneurysmal subarachnoid haemorrhage (aSAH), with a focus on rurality and socioeconomic status. Methods: A statewide population‐based cohort of aSAH cases in Tasmania, Australia, was established from 2010 to 2014 using multiple overlapping sources. Clinical data were collected from medical records and the Tasmanian Death Registry, with area‐level rurality and socioeconomic status geocoded to participants' residential address. Results: From a cohort of 237 (70% women, 36% disadvantaged, 38% rural) individuals over a 5‐year period, 12‐month mortality was 52.3% with 54.0% of these deaths occurring within 24 h post ictus. In univariable analysis of 12‐month survival, outcome was not influenced by socioeconomic status, but rural geographical location was associated with a non‐significant increase in death (hazard ratio (HR) 1.22; 95% confidence interval (CI) 0.85–1.75) along with hypertension (HR 1.78; 95% CI 1.07–2.98) and hypercholesterolaemia (HR 1.70; 95% CI 0.99–2.91). Multivariable analysis demonstrated a statistically significant increase in death to 12 months after aSAH for both hypertension (HR 1.81; 95% CI 1.08–3.03) and hypercholesterolaemia (HR 1.71; 95% CI 1.00–2.94) but not socioeconomic status or geographic location. Conclusion: We found high early death in this population‐based aSAH Australian population. Survival to 12 months after aSAH was not related to either geographical location or socioeconomic status but modifiable risk factors increased the risk of death. [ABSTRACT FROM AUTHOR]

We introduce and evaluate three tests for publication selection bias based on excess statistical significance (ESS). The proposed tests incorporate heterogeneity explicitly in the formulas for expected and ESS. We calculate the expected proportion of statistically significant findings in the absence of selective reporting or publication bias based on each study's SE and meta‐analysis estimates of the mean and variance of the true‐effect distribution. A simple proportion of statistical significance test (PSST) compares the expected to the observed proportion of statistically significant findings. Alternatively, we propose a direct test of excess statistical significance (TESS). We also combine these two tests of excess statistical significance (TESSPSST). Simulations show that these ESS tests often outperform the conventional Egger test for publication selection bias and the three‐parameter selection model (3PSM). [ABSTRACT FROM AUTHOR]

Objectives: Endocytoscopy (EC) is an ultra‐high magnification endoscopy designed to provide in vivo histologic assessment. This study aimed to evaluate the diagnostic yield of the newly developed fourth‐generation EC for esophageal squamous lesions by using a modified EC classification. Methods: A total of 2548 EC images of 57 esophageal targeted areas between June 2015 and October 2017 were retrospectively collected. Two lesions with low‐quality images were excluded. Only EC images were independently reviewed by two expert and two non‐expert endoscopists. The lesions were classified according to a three‐tier modified EC classification. We used a multilevel logistic regression to analyze the data. Results: The sensitivity and specificity of diagnosing non‐squamous cell cancer (SCC) vs SCC were 82.5% and 83.0% by the experts; 90.1% and 75.0% by non‐experts. The interobserver agreement among the four raters was good (kappa statistic 0.59). The diagnostic accuracy of experts and non‐experts was similar (P = 0.16 for specificity and P = 0.20 for sensitivity). The sensitivity and specificity of EC for non‐neoplasia vs neoplasia were 88.7% and 74.6% by experts; 90.3 and 52.1% by non‐experts. The interobserver agreement among the four raters was moderate (kappa statistic 0.44). The specificity of experts was higher compared to non‐experts, although the difference did not reach statistical significance (P = 0.08 for specificity and P = 0.93 for sensitivity). Conclusions: Fourth‐generation EC offers acceptable diagnostic accuracy and reliability in both experts and non‐experts, especially when diagnosing SCC lesions. [ABSTRACT FROM AUTHOR]

Aims: There is a widespread perception among clinicians and pathologists that the histomorphological assessment of minor salivary gland (MinSG) tumours is more difficult and hampered by more misdiagnoses than that of major salivary gland tumours. This is based on a vague, subjective clinical impression, lacking scientific proof. The aim of the present study was to identify and statistically verify potential reasons that could explain this difference. Methods and results: We identified 14 putative clinical, pathological and combined clinicopathological reasons that, altogether, could explain the phenomenon of the perceived greater diagnostic difficulty associated with MinSG tumours. We performed a comprehensive literature search and a statistical comparison of data from a large personal consultation series (biased for difficult cases) with cumulated data from straightforward, unselected (non‐consultation) series from the literature. By performing this comparison, we identified, with statistical significance, a comprehensive series of reasons, as well as of consequences, of the greater difficulty in diagnosing MinSG tumours. Conclusions: Among the 14 criteria, high frequencies of initial incisional biopsies and of a low‐grade category in malignant tumours emerged as the two most important reasons for enhanced diagnostic difficulty. Very rare entities, unusual locations, shortcomings in clinicopathological communication, and pecularities of the special anatomical location of the hard palate, such as tumour necrosis, mucosal ulceration, pseudoinvasion, and the peculiar phenomenon of 'tumoral–mucosal fusion', contribute to further diagnostic difficulties. The awareness of these shortcomings and pitfalls enables us to provide a series of recommendations for clinicians and pathologists that might aid in assessment and reduce the rate of misdiagnosis of MinSG tumours. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the effectiveness of a low‐dose intravenous S‐ketamine treatment on refractory pain in patients with Complex Regional Pain Syndrome (CRPS). Methods: In this retrospective study, patients with CRPS who received intravenous S‐ketamine from March 2010 to April 2019 were included. According to our inpatient protocol, S‐ketamine dose was increased until pain reduction was achieved or side effects were observed. Maximum dose was 14 mg/h and treatment duration was 7 days. Primary outcome parameters were pain scores (Numeric Rating Scale) at baseline (T0), end of infusion (T1), and approximately 4 weeks postinfusion (T2). Patients were categorized as responder/nonresponder at T1 and T2. Patients were considered a responder in case there was pain score reduction of greater than or equal to 2 points or if treatment was reported as successful. Results: Forty‐eight patients were included. Mean disease duration was 5 years (interquartile range [IQR] = 6 years). Median pain score significantly decreased from 8 (IQR = 2) at T0 to 6 (IQR = 4) at T1 (p < 0.001). At T1, 62% of the patients were responders. At T2, 48% of the patients remained a responder. A significant proportion of the responders at T1 turned into nonresponders at T2 (p = 0.03). Conclusion: In a group of patients with CRPS with refractory pain, low‐dose intravenous S‐ketamine treatment resulted in effective pain relief during infusion. Although a significant proportion of initial responders became nonresponders at follow‐up, half of the patients were still a responder at ~ 4 weeks postinfusion. Further research is needed to investigate mechanisms responsible for pain relief by S‐ketamine infusions and to ascertain possible predictors of response to the treatment. [ABSTRACT FROM AUTHOR]

Summary: High risk of bias associated with missing outcome data (MOD) in meta‐analyses (MAs) of the effects of lifestyle interventions during pregnancy on postpartum weight retention (PPWR) casts doubt on whether such interventions can be relied upon as truly effective. This systematic overview of three MAs (19 RCTs), each with high MOD rates in the subset of RCTs included, examined how MOD were addressed in the estimation of summary intervention effects. All MAs reported beneficial and statistically significant intervention effects estimated based on complete case analyses, deemed valid if MOD was missing at random (MAR). Therefore, we conducted sensitivity analyses using pattern mixture models and informative missingness parameters (describing how the outcome in the missing participants may be related to the outcome in the completers), to ascertain the robustness of the estimates to reasonable deviations from the MAR assumption. In plausible scenarios where the response in intervention group participants with versus without MOD was worse (by just 0.5 kg), effect estimates were attenuated in all MAs and no longer statistically significant in two MAs. Statistical significance was retained when all 19 RCTs identified across MAs were examined together in a broader meta‐analysis: −0.63 kg (95%CI −0.17, −0.08), but the clinical relevancy of effects of this magnitude remains unclear. [ABSTRACT FROM AUTHOR]

Background: Historical and recent literature disagree on whether a higher PO 131I dosage, compared to IV or SC routes, is required for successful resolution of spontaneous hyperthyroidism in cats, necessitating investigation into the effect of PO and injectable radioactive iodine administration on % thyroidal radioactive iodine uptake (RAIU). Hypothesis/Objectives: To investigate the effect of PO and SC routes of 123I administration on paired % thyroidal RAIU in euthyroid cats. Specifically, a 1.5‐fold difference (50% relative change) was hypothesized, which in absolute terms can be expressed as a 3.25% increase in the mean %RAIU of 7.04% after PO 123I administration to 10.56% after SC dosing. Animals Seven healthy euthyroid teaching‐research colony cats. Methods: A randomized, radiologist‐blinded crossover study comparing %RAIU after PO and SC 123I administration. Results: Percentage thyroidal RAIU values (mean ± SD; 95% confidence interval) after PO (4.81% ± 1.63%; 3.30%‐6.23%) and SC (5.26% ± 2.43%; 3.01%‐7.51%) 123I administration were associated with a median within‐pair absolute difference of 0.2% (range: min, 0.1%‐max, 4.9%). Statistical significance was not achieved (P =.45). Six of 7 cats had a within‐pair absolute difference of 0.1% to 0.9% (relative change of 4%‐20%), but a single outlier cat had a within‐pair absolute difference of 4.9% (relative change of 108%). Conclusions and Clinical Importance: This study did not detect an effect of 123I administration route on paired % thyroidal RAIU in euthyroid cats. However, a type 2 statistical error due to small sample size is possible. [ABSTRACT FROM AUTHOR]

Background: Critical care is a stressful workplace for nursing staff. Mindfulness‐based stress reduction programmes are an emerging concept to manage stress in nursing, but little is known about the impact of such interventions, especially in critical care settings. Aims and objectives: A quality improvement initiative was introduced to explore the effects of a mindfulness‐based stress reduction intervention on a cohort of critical care nurses in terms of quality of life, perceived stress, mindfulness awareness, and sickness and absence rates. Methods: A pre‐/post‐interventional design recruited nurses (n = 25) working within a critical care unit to undertake the intervention. Participants were asked to complete psychometric questionnaires at three time points, pre‐course (0 months), immediately post‐course (8 weeks), and at a follow‐up point at month 4. Sickness and absence rates were analysed to detect differences pre‐ and post‐course. Retention rates were ascertained by numbers of participants completing the psychometric tests. Findings Overall, positive correlations were found when comparing pre‐course vs 8‐week mean scores of satisfaction with life (P <.001), reduced perceived stress (P <.001), and mindfulness awareness (P =.002). Bootstrap analysis of the data confirmed that positive outcome measures were more significant at the 4‐month mark in reduced perceived stress and mindfulness awareness (P <.001) compared with the satisfaction with life scale (P =.41). There was no significant change in sickness rates pre‐ and post‐intervention (P =.69). The retention rate was 70% at month 4. Conclusions and recommendations: Mindfulness training is a feasible and accepted intervention that critical care nurses may benefit from in terms of quality of life, perceived stress, and mindfulness awareness. This has positive outcomes for staff and patients. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most commonly occurring malignancy in women. This study aimed to investigate the functions of the long noncoding RNA ZBED3‐AS1 (ZBED3‐AS1) in BC and its molecular mechanisms. qRT‐PCR was conducted to access the expression of ZBED3‐AS1, microRNA‐513a‐5p (miR‐513a‐5p), and Kruppel like factor 6 (KLF6) in BC. Additionally, BC cell viability and proliferative capacity were measured by MTT and 5‐Ethynyl‐20‐deoxyuridine (EdU) assays. A transwell assay was used for evaluating BC cell migration and invasion. The interactions among ZBED3‐AS1, miR‐513a‐5p, and KLF6 in BC were confirmed by dual‐luciferase reporter assay. Furthermore, feedback approaches were performed to determine whether ZBED3‐AS1 influences BC cell behaviors by regulating the miR‐513a‐5p/KLF6 axis. The murine xenograft model was established to assess the effect of ZBED3‐AS1 on tumor growth. The expression of ZBED3‐AS1 and KLF6 was reduced, while miR‐513a‐5p expression was elevated in BC. ZBED3‐AS1 elevation attenuated the malignant behaviors of BC cells, including viability, proliferative capacity, migration, and invasion. Mechanical experiments revealed that ZBED3‐AS1 targeted miR‐513a‐5p, and miR‐513a‐5p targeted KLF6 in BC. Feedback approaches validated that miR‐513a‐5p overexpression or KLF6 depletion reversed the inhibitory effects of ZBED3‐AS1 upregulation on viability, proliferative capacity, migration, and invasion of BC cells. Furthermore, ZBED3‐AS1 elevation attenuated the tumor growth in the murine xenograft model. ZBED3‐AS1 hindered the malignant development of BC cells by regulating the miR‐513a‐5p/KLF6 axis, providing a novel therapeutic target in BC. [ABSTRACT FROM AUTHOR]

Objective: To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose‐response meta‐analysis were conducted. Methods: The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4–0.8, and 0.8–1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random‐effects modeling to estimate the dose‐response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs. Results: A total of 1406 participants (cohort: 466; meta‐analysis: 940) were included. In the cohort study, the 0.4–0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8–1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose‐response meta‐analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non‐linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L). Conclusion: Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4–0.8 mmol/L. [ABSTRACT FROM AUTHOR]

It has been shown that disadvantaged groups who endorse system‐justifying beliefs tend to internalize their state of inferiority by expressing ingroup derogation and opposing collective action for change. In the present research, we recruited women – as disadvantaged group – from different countries (the United States, the United Kingdom, Italy) and examined whether their moral conviction against gender inequality, as an absolute stance that does not tolerate any violation, may interact with and overpower system‐justifying beliefs. Results from three studies provided support for our hypotheses. First, when women held strong moral conviction, they expressed higher identification with their disadvantaged ingroup and, in turn, higher collective action intentions, independent of system‐justifying beliefs. Second, when women held weak moral conviction, higher system‐justifying beliefs reduced women's ingroup identification and, in turn, undermined their collective action intentions. This support is found across different contexts of gender inequality (the gender leadership gap, the gender pay gap, and the gender power imbalance), using different methodological approaches (online survey, online experiment, laboratory experiment). Implications, limits, and future directions are discussed. [ABSTRACT FROM AUTHOR]

Experiences in immersive 3D virtual reality (VR) are more presence‐inducing, and so it may be tempting to claim that content will be learned better in VR. This randomized control trial study on natural selection challenges that assumption. This study answers the question of whether learning STEM in an immersive 3D VR environment is always superior to learning via a 2D monitor (PC). This is a 2 × 2 × 3 design. The first factor is platform immersivity (low = 2D PC, or high = 3D VR), the second factor is level of embodiment (lower = watching playback video, or higher = using mouse/controller to agentically manipulate content), and the third factor is test time (pretest, posttest, and follow‐up). There was a significant main effect for embodiment, the high embodied and agentic groups learned the most. There was not a main effect for platform, because the participants in the low embodied VR group performed significantly worse than the three other groups. Although, the one high embodied, VR group learned and retained the most knowledge. A path‐analysis revealed that the effect of platform was significantly mediated by presence, agency, and engagement. The smaller learning gain in the low embodied VR condition suggests that participants come to the immersive VR experience with expectations about agency and control of the virtual content, and when those expectations were not met, the disconnect was deleterious for learning. More agentic and interactive control of manipulable virtual content is encouraged. Design is critical, and platform is not destiny. Lay Description: What is already known about this topic?: VR has special affordances like presence and embodied content manipulation that can increase learning, if used correctly.Compared to 2D desktop, being in 3D VR generally induces more presence and more engagement.When students physically reenact, using gesture or embodied learning, greater learning gains are often seen. What this paper adds?: The high embodied, active VR group learned the most and reported the most engagement.Overall, being active and embodied resulted in more learning (regardless of the platform of desktop or VR).Embedded and embodied kinesthetic in‐process assessments during gameplay are valid measures of comprehension.The pathways leading to post‐play and 1 week follow‐up knowledge are complex. Implications for practice and/or policy?: Designers should strive to create embodied and agentic tasks in educational VR games.Watching a playback video on a 2D PC (desktop) platform can be appropriate for learning, but passive viewing videos in immersive VR can attenuate learning.Designers should include more embedded, in‐process data gathering during educational gameplay.Some guidelines are given for in‐process assessments, these assessments can lead to more dynamic, adaptive learning. [ABSTRACT FROM AUTHOR]

Tropospheric and lower‐stratospheric motions at mesoscales and larger are a mixture of waves and two‐dimensional (2‐D) turbulence. Determining their relative importance is necessary, since waves are capable of coordinated systematic momentum transport accompanying the wave propagation, and associated wind forcing, in ways that 2‐D turbulence is not. This can impact weather forecasting. Using a network of ten windprofiler radars in eastern Ontario and western Quebec in Canada, plus an additional one in the Arctic, the relative roles of internal gravity (buoyancy) waves and two‐dimensional turbulence are examined at temporal scales from about 3–4 hrs to several tens of hours (horizontal spatial scales of typically one or two hundred kilometres to a few thousand kilometres), with the purpose of investigating the respective roles of these two distinct characteristic fluid motions as functions of location, season and year. The emphasis is on studies of spectral slope variability, rather than absolute spectral magnitudes, giving a perspective not previously substantially presented. In particular, we have found a frequency band in which gravity‐wave Doppler shifting produces distinctly different spectral slopes than those predicted for 2‐D turbulence, and these differences are employed to distinguish the flow fields. The network used (excluding the Arctic site) covers an area of ∼106 km2 and includes a variety of different terrains. Radial velocities have been recorded on time scales of minutes for data lengths covering durations of up to 12 years. Altitude coverage is from 1 km to typically 14 km, at 500 m resolution. Results suggest a region from ∼2 to ∼5 km altitude (deeper for some radars) where waves are weaker and 2‐D turbulence appears to be generally more significant, but where occasional bursts of gravity‐wave activity can occur, while above typically 6–8 km, gravity waves increase in significance. There are distinct site‐to‐site variations. [ABSTRACT FROM AUTHOR]

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody‐negative post islet cell transplantation. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression (PPD) is the most common complication of childbearing. Understanding potential contributors, such as cesarean deliveries, is essential to improving maternal mental health. This study investigated the relationship between unplanned versus planned cesarean birth and postpartum depressive symptoms. Methods: We employed a sequential, mixed‐methods approach wherein the Edinburgh Postnatal Depression Scale (EPDS) was first administered to participants who had experienced a cesarean birth within the previous 12 months. EPDS scores among those in the unplanned vs. planned cesarean groups were compared by means of SPSS. Twenty‐five participants with EPDS scores >8 were then interviewed to provide subjective measures of maternal well‐being. Interview data were subjected to thematic qualitative analysis using a modified grounded theory approach. Results: The average EPDS score from 120 participants with unplanned cesareans was 10.7 ± 6.4, with 68.5% scoring >8. The average EPDS score from 93 participants with planned cesarean births was 8.96 ± 5.7, with 52.7% scoring >8. The difference in mean score was statistically significant (P < 0.05). Interview findings revealed several important themes including: support, medical interaction, stress, recovery, breastfeeding, and sleep. In several cases, participants were not properly screened, or screening tool responses were ignored. Numerous participants reported medical interactions where they felt ignored by practitioners, including one interviewee who stated, "I got my tubes tied because it was so traumatizing that I never wanted to give birth again." Discussion: Findings suggest that unplanned cesareans have a higher incidence and severity of postpartum depressive symptoms. Interview analyses highlight important areas for improvement and concern about the current state of postpartum mental health care and physician‐guided supports in this US sample. [ABSTRACT FROM AUTHOR]

Objective: Hyperemesis gravidarum is an illness that starts in early pregnancy and manifests itself with oral intake problems, electrolyte imbalance, ketonuria, and weight loss. Inflammation is closely associated with the hyperemesis gravidarum, and inflammatory indicators have been studied to understand its pathophysiology. This study investigates the relationship of ketonuria levels with inflammatory markers platelet‐to‐lymphocyte ratio (PLR), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) for hyperemesis gravidarum patients. Material and Methods: This retrospective case control study was conducted at Kütahya Medical Sciences University Tertiary Research and Training Hospital between December 2019 and December 2020. A total of 173 pregnancies, 82 of them with hyperemesis gravidarum and 91 of them low‐risk pregnancies were included in the study. The patients' demographic profiles and laboratory parameters were recorded. The patients were divided into hyperemesis gravidarum and control groups and the groups were compared for the levels of inflammation markers. For the hyperemesis gravidarum group, the relationship between ketonuria levels and the inflammation severity was investigated. Results: MLR, NLR, PLR levels were higher in the hyperemesis gravidarum group than the control group in a statistically significant way (p < 0.001 for all of the comparisons). The hyperemesis gravidarum group was subdivided into four groups based on their ketonuria levels, and their MLR, NLR, PLR levels were compared. The differences between the groups were statistically significant (p < 0.001) and the indicators increased with the ketonuria levels. Finally, ketonuria levels had a positive and significant correlation with MLR (rho =0.67, p < 0.001), PLR (rho =0.67, p < 0.001), and NLR (rho =0.8, p < 0.001). Conclusion: Hyperemesis gravidarum patients have higher levels of hematologic inflammation indicators than healthy pregnant patients. For these patients, the levels of the indicators increase with ketonuria levels. [ABSTRACT FROM AUTHOR]

This article presents a clustering approach that allows for rigorous statistical error control similar to a statistical test. We develop estimators for both the unknown number of clusters and the clusters themselves. The estimators depend on a tuning parameter α which is similar to the significance level of a statistical hypothesis test. By choosing α, one can control the probability of overestimating the true number of clusters, while the probability of underestimation is asymptotically negligible. In addition, the probability that the estimated clusters differ from the true ones is controlled. In the theoretical part of the article, formal versions of these statements on statistical error control are derived in a baseline model with convex clusters. A simulation study and two applications to temperature and gene expression microarray data complement the theoretical analysis. [ABSTRACT FROM AUTHOR]

We analyse seasonal and annual trends of extreme indices of air temperature and precipitation over Brazil during the period 1961–2018. The main goal is to investigate whether the climate is changing and if so, to explore if there is any marked seasonality in such changes. The daily observed datasets of maximum and minimum temperatures, and precipitation, are provided by the Brazilian National Institute of Meteorology and National Water Agency. We use the Sen Curvature and Mann‐Kendall statistical tests to compute the magnitudes and to evaluate the statistical significance of climate extremes trends, respectively. The results show that the warm extremes frequency of occurrence is increasing significantly while the opposite occurs for cold extremes, which reveals a very consistent and widespread warming over Brazil. The highest increases in warm extremes occur during austral spring and summer while for the cold extremes the greatest decreases are observed during austral winter. Unlike temperature, precipitation extremes show heterogeneous signals for most of the country. In Northeast Brazil, there are changes towards a drier climate, especially in summer and autumn. In the Southern region, the climate is becoming wetter, with a reduction in consecutive dry days, especially in spring. For the other regions, there is no strong clear change sign, but both positive and negative precipitation extreme trends, without statistical significance (mostly in Southeast Region). [ABSTRACT FROM AUTHOR]

Objective: Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most PRSs are constructed in European-ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late-onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH).Methods: We used a CH discovery (n = 4,312) and independent validation sample (n = 1,850) to construct an ancestry-specific PRS ("CH-PRS") and evaluated its performance alone and with other predictors using the area under curve (AUC) and logistic regression (strength of association with LOAD and statistical significance). We tested if CH-PRS predicted conversion to LOAD in a subsample with longitudinal data (n = 1,239). We also tested the CH-PRS in an independent replication CH cohort (n = 200) and brain autopsy cohort (n = 33). Finally, we tested the effect of ancestry on PRS by using European and African American discovery cohorts to construct alternative PRSs ("EUR-PRS", "AA-PRS").Results: The full model (LOAD ~ CH-PRS + sex + age + APOE-ɛ4), achieved an AUC = 74% (ORCH-PRS  = 1.51 95%CI = 1.36-1.68), raising to >75% in APOE-ɛ4 non-carriers. CH-PRS alone achieved an AUC = 72% in the autopsy cohort, raising to AUC = 83% in full model. Higher CH-PRS was significantly associated with clinical LOAD in the replication CH cohort (OR = 1.61, 95%CI = 1.19-2.17) and significantly predicted conversion to LOAD (HR = 1.93, CI = 1.70-2.20) in the longitudinal subsample. EUR-PRS and AA-PRS reached lower prediction accuracy (AUC = 58% and 53%, respectively).Interpretation: Enriching diversity in genetic studies is critical to provide an effective PRS in profiling LOAD risk across populations. ANN NEUROL 2021. [ABSTRACT FROM AUTHOR]

There is a large volume of published studies describing the positive role of Augmented Reality (AR) in educational settings. However, there is a paucity of empirical work that explores its role in supporting primary school pupil's motivation and creativity. Moreover, numerous studies have confirmed that pupils have difficulties in learning geometry and thinking geometrically. In this context, this paper explores the possibility of using AR software for low‐grade primary school pupils to enhance their creative thinking and increase their motivation during the informal geometry training course. A research‐based design process is adopted to replicate the primary school pupil's learning in this study, where pupils in the experimental group used mobile application to access AR virtual manipulatives, pupils in the control group used physical manipulatives. The applied AR technology allows pupils to handle 2D and 3D rounded corners and simple closed curves to find the most effective solutions for some learning challenges. Sixty‐two pupils from the first‐grade primary school in Egypt have participated in this study with the aim of investigating: (a) the primary school pupil's achievements and creative thinking in using AR techniques, and (b) the specific strategies that can increase their motivation and engagement. The most obvious finding to emerge from this study is that there was no statistically significant difference between the groups in geometry learning achievement, while statistically significant differences were found between the groups in the motivation and creative thinking skills in favour of the experimental group. Lay Description: What is already known about this topicAugmented Reality must have three characteristics: combining the real and virtual worlds, having real‐time interaction with the user and is being registered in a 3D environment.There is a growing body of literature that recognizes the importance of the 21st century skills in the new global economy.There has been significant interest in utilized AR in higher education. However, limited research has been conducted about integrating AR techniques to enhance young children's creative thinking skills and motivation in informal learning scenarios.To date, there are few studies that have investigated the association between augmented environment and learning theories. What this paper addsIntroduced an iterative methodology based on the cognitive theory of multimedia learning integrating the Universal Design for Learning (UDL) as the inclusive learning approach for creating Smart‐flashcard as a mobile AR applications for elementary school.Research studies on informal learning are particularly limited, so this study can fill a gap in the literature.This paper provides a conceptual approach for AR design, based on multimedia learning theory.AR Smart‐flashcard application represents a shift away from traditional textbooks, flashcards and other learning material where children are limited to viewing learning content passively towards a more dynamic and augmented one. Implications for practice and/or policyUsing AR applications, children interact with the 3D models, enhance creativity and collaboration in teams.The informal education can play a crucial role in developing some of the skills required for the 21st century.The study also highlights the need for new approaches combing the technical learning tools and pedagogical foundation. [ABSTRACT FROM AUTHOR]

Recent findings indicate that men with premature ejaculation report more frequent sexual problems associated with increased anxiety and interpersonal difficulties. Bearing this in mind, the neuroendocrine changes were examined in men with premature ejaculation and compared to other indicators of stressful experiences to see whether there can be any correlation which could indicate how these factors may contribute to the aetiology of premature ejaculation. Our study comprised 60 male outpatients diagnosed as having secondary premature ejaculation. Clinical examinations were focused on biochemical analysis of cortisol and psychometric scoring using a diagnostic tool for premature ejaculation, traumatic stress and somatoform dissociation. The control group consisted of a 60 healthy men. The results showed significant Spearman correlations of the Premature Ejaculation Diagnostic Tool score with Trauma Symptom Checklist score (R =.86), cortisol level (R =.47) and Somatoform Dissociation Questionnaire score (R =.61). In the control group, the results did not reach statistical significance. Spearman correlations of the Premature Ejaculation Diagnostic Tool score with Trauma symptoms checklist score was (R =.21), cortisol (R =.27) and with Somatoform dissociation questionnaire score (R =.25). These results represent the first reported findings documenting the relationship of traumatic stress indicators with the experience of secondary premature ejaculation and cortisol levels. [ABSTRACT FROM AUTHOR]

Background: The fragility index (FI) represents the number of participants whose status in a trial would have to change from a non‐event (not experiencing the primary endpoint) to an event (experiencing the primary endpoint) in order to turn a statistically significant result into a non‐significant result. We sought to evaluate the fragility indices of irritable bowel syndrome [IBS‐mixed (IBS‐M), IBS‐constipation (IBS‐C), & IBS‐diarrhea (IBS‐D)] trials. Methods: Irritable bowel syndrome trials published in high‐impact journals were identified from Medline. Trials had to be in adults, randomized, parallel‐armed, with at least one statistically significant binary outcome, and an achieved primary endpoint of therapeutic efficacy. FI and correlation coefficients were calculated, and regression modeling used to identify predictors of a high FI. Key Results: Twelve trials were analyzed with a median FI of 6 (range: 0–38). Median sample size in all trials was 366 (range: 44–856). Trial publication year (p = 0.71), journal impact factor (p = 0.52), duration of study (p = 0.12), and number need to treat [NNT] (p = 0.29) were not predictive of a high FI. While a lower p‐value correlated with a higher FI (p = 0.039), no correlation was noted between FI and impact factor (R = −0.20, p = 0.52), trial publication year (R = 0.12, p = 0.71), duration of trial (R = −0.46, p = 0.13), NNT (R = −0.34, p = 0.29), and sample size (R = 0.23, p = 0.5). The highest FI was in a Ramosetron trial (FI = 30) for IBS‐D. Conclusion & Inferences: A median of six participants is needed to nullify results in the included IBS trials suggesting how easily statistical significance based on a threshold p‐value may be overturned. [ABSTRACT FROM AUTHOR]

Conducting sensitivity analyses is an integral part of the systematic review process to explore the robustness of results derived from the primary analysis. When the primary analysis results can be sensitive to assumptions concerning a model's parameters (e.g., missingness mechanism to be missing at random), sensitivity analyses become necessary. However, what can be concluded from sensitivity analyses is not always clear. For instance, in a pairwise meta‐analysis (PMA) and network meta‐analysis (NMA), conducting sensitivity analyses usually boils down to examining how 'similar' the estimated treatment effects are from different re‐analyses to the primary analysis or placing undue emphasis on the statistical significance. To establish objective decision rules regarding the robustness of the primary analysis results, we propose an intuitive index, which uses the whole distribution of the estimated treatment effects under the primary and alternative re‐analyses. This novel index is compared to an objective threshold to infer the presence or lack of robustness. In the case of missing outcome data, we additionally propose a graph that contrasts the primary analysis results to those of alternative scenarios about the missingness mechanism in the compared arms. When robustness is questioned according to the proposed index, the suggested graph can demystify the scenarios responsible for producing inconsistent results to the primary analysis. The proposed decision framework is immediately applicable to a broad set of sensitivity analyses in PMA and NMA. We illustrate our framework in the context of missing outcome data in both PMA and NMA using published systematic reviews. [ABSTRACT FROM AUTHOR]

Purpose: Multiresolution hierarchical strategy is typically used in conventional optimization‐based image registration to capture varying magnitudes of deformations while avoiding undesirable local minima. A rough concept of the scale is captured in deep networks by the reception field of kernels, and it has been realized to be both desirable and challenging to capture convolutions of different scales simultaneously in registration networks. In this study, we propose a registration network that is conscious of and self‐adaptive to deformation of various scales to improve registration performance. Methods: Dilated inception modules (DIMs) are proposed to incorporate receptive fields of different sizes in a computationally efficient way. Scale adaptive modules (SAMs) are proposed to guide and adjust shallow features using convolutional kernels with spatially adaptive dilation rate learned from deep features. DIMs and SAMs are integrated into a registration network which takes a U‐net structure. The network is trained in an unsupervised setting and completes registration with a single evaluation run. Results: Experiment with two‐dimensional (2D) cardiac MRIs showed that the adaptive dilation rate in SAM corresponded well to the deformation scale. Evaluated with left ventricle segmentation, our method achieved a Dice coefficient of (0.93 ± 0.02), significantly better than SimpleElastix and networks without DIM or SAM. The average surface distance was less than 2 mm, comparable to SimpleElastix without statistical significance. Experiment with synthetic data demonstrated the effectiveness of DIMs and SAMs, which led to a significant reduction in target registration error (TRE) based on dense deformation field. The three‐dimensional (3D) version of the network achieved a 2.52 mm mean TRE on anatomical landmarks in DIR‐Lab thoracic 4DCTs, lower than SimpleElastix and networks without DIM or SAM with statistical significance. The average registration times were 0.002 s for 2D images with size 256 × 256 and 0.42 s for 3D images with size 256 × 256 × 96. Conclusions: The introduction and integration of DIMs and SAMs addressed the heterogeneous scale problem in an efficient and self‐adaptive way. The proposed method provides an alternative to the inefficient multiresolution registration setups. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the relationship between the empathic tendencies and altruistic behaviours of adolescents. Methods: This descriptive and correlational study was conducted with 323 high school students in the 2017–2018 academic year. Data were collected using a sociodemographic characteristics form, the altruism scale and the empathic tendency scale. Descriptive statistics were evaluated using the bivariate correlation test and the linear regression test. Results: The mean age of the participants was 16.06 ± 1.19 (min = 14, max = 20), and 50.8% of them were female. The adolescents' mean scores on the empathic tendency and altruism scales were 65.71 ± 9.08 and 67.84 ± 9.25, respectively. A statistically significant moderate positive relation was found between the adolescents' empathic tendencies and their altruistic behaviours (r = 0.369, p = 0.000). Conclusions: The empathic tendency skills and altruistic behaviours of adolescents who participated in this study were at a good level. It is important to plan and apply educational programmes that develop adolescents' empathic tendencies and altruistic behaviours and to teach them positive social behaviours such as altruism. [ABSTRACT FROM AUTHOR]

In this study, the problem of determining, with an adequate statistical significance, the relationship between teleconnection pattern indices and precipitation at climatological time scales has been addressed through a novel technique based on a rainfall zonation, by means of creating a regional precipitation database for a whole‐region correlation approach. Pearson correlation was performed to evaluate the mesoscale influence on precipitation in the Calabria region over the 1951–2010 time period, by means of a database of 79 rain gauges, divided in five Rainfall Zones (RZs) and seven teleconnection pattern indices relevant to the Mediterranean region, searching where results were significant (significance level < 0.05) and with an absolute correlation value higher than a prefixed threshold equal to 0.2. The Calabria region was chosen as it is located in the centre of the Mediterranean area, which constitutes a hot spot for climate change, and because it is equipped with a high‐density, long‐time series of precipitation gauge network, recently validated and homogenized. Correlation analysis between seasonal teleconnection indices and seasonal cumulated precipitation showed that the Western Mediterranean Oscillation and the East Atlantic/West Russian patterns were the most relevant teleconnections over all Calabria. Correlations of 3‐month averaged teleconnection indices versus monthly precipitation showed that the Mediterranean and Western Mediterranean Oscillations produce most significant results with correlation values higher than 0.2, with East Atlantic pattern a third close. Comparison between monthly teleconnection indices and monthly cumulated precipitation indicate that all modes of variability taken into account share a similarly weak correlation. Comparing the rainfall zone‐based study and the technique of averaging individual stations results post‐correlation, it was shown that on average only 43% of the stations would produce useful correlations, while the novel technique used all the valid and available station data, resulting in statistically more robust findings. [ABSTRACT FROM AUTHOR]

Researchers make hundreds of decisions about data collection, preparation, and analysis in their research. We use a many‐analysts approach to measure the extent and impact of these decisions. Two published causal empirical results are replicated by seven replicators each. We find large differences in data preparation and analysis decisions, many of which would not likely be reported in a publication. No two replicators reported the same sample size. Statistical significance varied across replications, and for one of the studies the effect's sign varied as well. The standard deviation of estimates across replications was 3–4 times the mean reported standard error. [ABSTRACT FROM AUTHOR]

Background: Transforaminal epidural steroid injection (TFESI) is widely practiced for the treatment of radicular pain. As its effectiveness is still subject to debate, a better patient selection for TFESI is necessary. We aimed to evaluate the potential of bedside‐suitable qualitative sensory testing (QualST) to determine the early effectiveness of TFESI for the treatment of chronic lumbosacral radiculopathy (LSR)‐related pain. Methods: Thirty‐six patients with chronic painful unilateral LSR were evaluated in a prospective observational study using five standardized sensory tests (10 g monofilament, 200 to 400 mN brush, Lindblom rollers with controlled 25 and 40°C temperature, and 40 g neurological pin). Quality of sensory perceptions on the painful leg was compared to the non‐painful leg and rated as normal sensitivity, hyposensitivity, or hypersensitivity. Pain and related characteristics were evaluated before TFESI, 1 week after and 4 weeks after intervention. Results: Seven sensory phenotypes were distinguished according to individual sets of sensory disturbances acquired with five sensory tests. Patients were grouped into four groups of allied phenotypes (normal sensitivity, hyposensitivity to 1 to 3 modalities, hyposensitivity to 4 to 5 modalities, and hypersensitivity). The whole study group showed significant improvement in most parameters of outcome measurements. Statistical analysis revealed some significant differences between sensory groups in patient‐reported treatment effect scales after 4 weeks. We also detected significant differences between sensory groups in repeated measures after 1 and 4 weeks in some pain intensity characteristics and patient‐reported treatment effect scales. Conclusion: QualST might be clinically applicable for detecting patient subgroups that could differ in the early treatment results of radicular pain by TFESI. [ABSTRACT FROM AUTHOR]

The insurance industry uses mathematical models to estimate the risks due to future natural catastrophes. For climate-related risks, historical climate data are a key ingredient used in making the models. Historical data for temperature and sea level often show clear and readily quantified climate change driven trends, and these trends would typically be accounted for when building risk models by adjusting earlier values to render the earlier data relevant to the future climate. For other climate variables, such as rainfall in many parts of the world, the questions of whether there are climate change driven trends in the historical data, and how to quantify them if there are, are less simple to answer. We investigate these questions in the context of European rainfall with a specific focus on how to deal with the uncertainty around trend estimates. We compare 10 empirical methodologies that one might use to model and predict trends, including traditional statistical testing and alternatives to statistical testing based on standard methods from model selection and model averaging. We emphasize prediction and risk assessment, rather than detection of trends, as our goal. Viewed in terms of this goal, the methods we consider each have qualitative and quantitative advantages and disadvantages. Understanding these advantages and disadvantages can help risk modellers make a choice as to which method to use, and based on the results we present, we believe that in many common situations model averaging methods, as opposed to statistical testing or model selection, are the most appropriate. [ABSTRACT FROM AUTHOR]

Background: To explore and analyze the influence of psychological nursing and health education on depression, anxiety and life quality of elderly patients with lung cancer. Methods: There were 84 elderly patients with lung cancer who were admitted and treated in our hospital since July 2018 till July 2019, serving as the objects of observation. The selected patients were divided into the control group (n = 42) and the observation group in principle of random allocation by computer numbers. Routine care was conducted to the control group, while psychological nursing and health education were implemented to the observation group, so as to compare the improvement effect of depression, anxiety, life quality and compliance on the two groups of patients before/after the two different nursing methods were adopted for intervention. Results: Hamilton Depression Scale and Hamilton Anxiety Scale scores in the observation group were lower than those in the control group, and the levels of various pulmonary function indicators including degree of blood oxygen saturation, forced expiratory volume in 1 second, forced vital capacity and maximum ventilatory capacity and quality of life scores were significantly improved; compared with the control group, the total compliance of the observation group was significantly increased, and the difference between the two groups was statistically significant (P < 0.05). Conclusion: The psychological nursing and health education implemented for elderly patients with lung cancer will improve patients' bad mood effectively, enhance life quality and perfect prognosis for patients, maintaining significant value in clinical application. [ABSTRACT FROM AUTHOR]

Despite growing awareness of the dangers of a dichotomous interpretation of trial results based on the 'statistical significance' of a treatment effect, the uptake of new approaches has been slow in diabetes medicine. We showcase a number of ways to interpret the evidence for a treatment effect applied to the cardiovascular outcome trials of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is): the P value function (or confidence curves), which depicts the treatment effect across the whole spectrum of confidence levels; the counternull value, which is the hazard ratio (i.e. treatment effect size) supported by the same amount of evidence as the null value (i.e. no treatment effect); and the S value, which quantifies the strength of the evidence against the null hypothesis in terms of the number of coin tosses yielding the same side. We show how this approach identifies potential treatment effects, highlights similarities among trials straddling the threshold of statistical significance, and quantifies differences in the strength of the evidence from trials reporting statistically significant results. For example, while REWIND, CANVAS and CREDENCE failed to reach statistical significance at the.05 level for all‐cause mortality, their counternull values indicate that reduced death rates by 19%, 24% and 31%, respectively, are supported by the same amount of evidence as that indicating no treatment effect. Moreover, similarities among results emerge in trials of GLP‐1RAs (REWIND, EXSCEL and LEADER) lying closely around the threshold of 'statistical significance'. Lastly, several S values, such as for the primary outcome in HARMONY Outcomes (S value 10.9) and all‐cause death in EMPAREG‐OUTCOME (S value 15.0), stand out compared with values for other outcomes and other trials, suggesting much larger differences in the evidence between these studies and several others that cluster around the.05 significance threshold. P value functions, counternull values and S values should complement the standard reporting of the treatment effect to help interpret clinical trials and make decisions among competing glucose‐lowering medications. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the percutaneous oblique osteotomy (POO) and the open chevron osteotomy technique for correction of hallux valgus deformity at a 2‐year follow‐up. Methods: This is a retrospective study of consecutive patients undergoing operative correction of hallux valgus using one of two techniques (POO vs open chevron osteotomy) from 2014 to 2018. Forty eight feet (41 patients) that underwent the POO was compared with 64 feet (58 patients) that underwent open chevron osteotomy. The hallux valgus angle (HVA), intermetatarsal angle (IMA) and American Orthopedic Foot & Ankle Society Hallux Metatarsophalangeal‐Interphalangeal scores (AOFAS‐HMI) were assessed preoperatively and postoperatively at the 1, 2‐year follow‐up. The Manchester–Oxford Foot Questionnaire (MOXFQ) were assessed preoperatively and postoperatively at the 2‐year follow‐up. The VAS score was collected preoperatively and on 2 weeks,1 year and 2‐year follow‐up. Results: Both groups achieved significant correction of the hallux deformity. The HVA in the POO group during the follow‐up period were 12.5 ± 2.22 and 17.9 ± 9.31, respectively, and in the open chevron group were 14.1 ± 6.78 and 14.8 ± 7.83, respectively. The IMA in the POO group during the follow‐up period were 7.61 ± 1.63 and 6.94 ± 1.53, respectively, and in the open chevron group were 6.89 ± 3.06 and 6.97 ± 2.95, respectively. Postoperative MOXFQ scores in all domains were significantly improved in both groups, however there was no significant difference in the improvement of any domain between POO and open groups at a 2‐year follow‐up. The AOFAS HMI scores in the POO group during the follow‐up period were 86.5 ± 10.7 and 85.2 ± 13.8, respectively, and in the open chevron group were 88.2 ± 10.8 and 79.5 ± 23.7, respectively. The VAS scores in the POO group during the follow‐up period were 2.00 ± 0.98, 2.00 ± 0.99 and 1.55 ± 1.11, respectively, and in the open chevron group were 5.51 ± 1.45, 2.56 ± 2.88 and 2.56 ± 2.88 respectively. The 1‐year and 2‐year follow‐up outcomes between POO and open groups showed no significant difference regarding AOFAS HMI scores and VAS scores, however the POO group showed statistically significant improvement of VAS scores in the postoperative 2 weeks (P < 0.001). There was no statistical significance between the POO and open group in terms of complications rates (8.3% vs 12.5%, P = 0.480). Conclusion: The POO technique is reliable and shows a comparable outcome to the open chevron osteotomy. However, the POO technique shows significantly less pain in the first 2 weeks after surgery. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic introduced unparalleled uncertainty into the lives of pregnant women, including concerns about where it is the safest to give birth, while preserving their rights and wishes. Reports on the increased interest in community births (at home or in birth centers) are emerging. The purpose of this project was to quantitatively investigate psychological factors related to this birth preference. Methods: This study included 3896 pregnant women from the COVID‐19 Pregnancy Experiences (COPE) Study who were anticipating a vaginal birth. COPE Study participants were recruited online between April 24 and May 15, 2020, and completed a questionnaire that included preference with respect to place of birth and psychological constructs: fear of childbirth, basic beliefs about birth, pandemic‐related preparedness stress, and pandemic‐related perinatal infection stress. Results: Women who preferred a community birth, on average, had less childbirth fear, had stronger beliefs that birth is a natural process, were less likely to see birth as a medical process, and were less stressed about being unprepared for birth and being infected with COVID‐19. In multivariate models, higher stress about perinatal COVID‐19 infection was associated with greater likelihood of preferring a community birth. The effect of perinatal infection stress on preference was stronger when preparedness stress was high. Discussion: Women's birth preferences during the COVID‐19 pandemic are associated with psychological processes related to risk perception. Community births are more appealing to women who view being in a hospital as hazardous because of the pandemic. Policies and prenatal care aimed to increase access to safe in‐hospital and out‐of‐hospital birth services should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Patient activation describes the knowledge, skills and confidence in managing one's own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes. Design: Cross‐sectional study. Setting and participants: Patients with non‐dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK. Outcome measures: Patient activation was measured using the PAM‐13. Demographic and health‐related variables, self‐reported symptom burden, health‐related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia. Results: 743 patients were included (eGFR: 32.3 (SD17.1) mL/min/1.73 m2, age 67.8 (SD13.9) years, 68% male). The mean PAM score was 55.1 (SD14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P =.004), greater number of comorbidities (P =.026) and lower haemoglobin (P =.025). Patients with low activation had a 17% greater number of CVD risk factors (P <.001). Risk factors in those with low activation were being older (P <.001) and having diabetes (P <.001). Conclusion: This study showed that only a minority of CKD patients are activated for self‐management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation. Patient or Public Contribution: Patients were involved in the design of main study. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol‐3‐kinase (PI3K) is important for cell proliferation, differentiation, and apoptosis, and the diverse physiological roles of different PI3K isoforms have highlighted the significance of the development of PI3Kδ inhibitors. A large number of PI3Kδ inhibitors have been reported after the FDA approval of Idelalisib, but the clinical use of Idelalisib was limited because of its serious side effects. Therefore, great efforts have been made on the development of PI3Kδ inhibitors with higher selectivity and lower toxicity, but there is no new PI3Kδ inhibitor coming into the market so far. Even so, as the first listed PI3K inhibitor, Idelalisib could be used as an effective tool to investigate the selective inhibition mechanism of PI3Kδ. Thus, in this study, a modeling strategy integrated 3D‐QSAR, pharmacophore model, and molecular dynamics simulation was employed to reveal the key chemical characteristics of Idelalisib analogs and the binding pattern between the inhibitors and PI3Kδ. First, the CoMFA model with high statistical significance was built to reveal the general structure–activity relationships. And then, a reliable pharmacophore model with a robust discrimination capability was constructed to expound the main chemical characteristics of the PI3Kδ inhibitors. Finally, molecular dynamics simulation was conducted to explore the binding modes and some key residues refer to δ‐selective binding were highlighted with binding‐free energy calculation. In summary, these models and results would provide some effective help for the discovery or the rational design of novel PI3Kδ inhibitors. [ABSTRACT FROM AUTHOR]

Abnormal eye movements are often associated with psychiatric disorders. Eye movements are sensorimotor functions of the brain, and aging and sex would affect their characteristics. A precise understanding of normal eye movements is required to distinguish disease‐related abnormalities from natural differences associated with aging or sex. To date, there is no multicohort study examining age‐related dependency and sex effects of eye movements in healthy, normal individuals using large samples to ensure the robustness and reproducibility of the results. In this study, we aimed to provide findings showing the impact of age and sex on eye movement measures. The present study used eye movement measures of more than seven hundred healthy individuals from three large independent cohorts. We herein evaluated eye movement measures quantified by using a set of standard eye movement tests that have been utilized for the examination of patients with schizophrenia. We assessed the statistical significance of the effects of age and sex and its reproducibility across cohorts. We found that 4‐18 out of 35 eye movement measures were significantly correlated with age, depending on the cohort, and that 10 of those, which are related to the fixation and motor control of smooth pursuit and saccades, showed high reproducibility. On the other hand, the effects of sex, if any, were less reproducible. The present results suggest that we should take age into account when we evaluate abnormalities in eye movements. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disasters cause significant human and monetary destruction and society as a whole is underprepared to address them. Disaster preparedness education is not covered extensively enough for health professionals or for the general public. METHODS: A disaster preparedness education intervention was performed using a non‐randomized controlled trial of a convenience sample with a pre‐ and post‐intervention survey. The adapted Emergency Preparedness Information Questionnaire (EPIQ), a validated survey tool, was utilized. Participants came from a health professions educational enrichment program for students from under‐resourced high schools in the Kansas City area. RESULTS: The experimental group shows statistically significant improvement in knowledge of disaster topics post‐intervention. Of 18 adapted EPIQ tool questions, 17 show statistically significant improvement in disaster knowledge post‐intervention for the experimental group with significance set at p <.05 (range of significant p values.000‐.017). CONCLUSIONS: The education intervention was effective and cost‐efficient. Disaster preparedness education should be included in THE secondary school curriculum. [ABSTRACT FROM AUTHOR]

Objective: People with severe mental illness often have difficulty sustaining employment. Work Behaviour Inventory and Work Environment Impact Scale are vocational assessments used by occupational therapists to evaluate the facilitators and barriers of work performance and work environment respectively. These factors may have an impact on job tenure and can inform occupational therapy practice. Methods: This study analysed retrospective data of 85 clients who attended a 3‐month Employment Internship Program from August 2016 to August 2017. Scores from Work Behaviour Inventory and Work Environment Impact Scale were analysed for associations with job tenure. Repeated measures were used to determine significant changes in Work Behaviour Inventory composite scores across the 3 months. Results: One‐month Work Behaviour Inventory composite scores, three Work Behaviour Inventory domains (cooperativeness, work habits, work quality), and three Work Environment Impact Scale domains (time demands, supervisor interaction, architecture) were significantly associated with job tenure. Significant differences in mean job tenure were also found between participants of different internship status. However, these factors did not predict job tenure in regression analysis. There were significant improvements in Work behaviour Inventory composite scores from the first to third month. Conclusions: Work behaviours such as cooperativeness, work habits, and work quality as well as work characteristics such as time demands, supervisor interaction, and workplace architecture may play a role in influencing job tenure. Occupational therapists may consider such factors and provide more targeted interventions to effectively sustain employment. [ABSTRACT FROM AUTHOR]

Background: The identification and treatment of psychiatric disorders in individuals with autism spectrum disorders (ASD) and ID presents many challenges. We describe the development of a professional network, together with a standardized protocol for clinical assessment, designed to promote clinical competence and professional development in eight clinical centers responsible for providing mental health services to autistic individuals with ID across all four health regions of Norway. Specific aims to describe: (1) patterns of psychiatric and behavior problems in patients treated by the network, (2) patterns of change over time, and (3) the relationship between psychiatric disorders and behavior problems. Method: A standardized protocol was used to assess individual progress in 132 patients (inpatients and outpatients) with autism and ID over 2 years (at referral (T1), after 1 year (T2), and after 2 years (T3)). Changes in psychiatric symptoms and behavior problems were assessed with the Psychopathology in Autism Checklist (PAC) and Aberrant Behavior Checklist (ABC). Results: Patients showed significant (p <.001) improvements from T1 to T2 on the psychosis, depression and anxiety subscales of the PAC, but no significant improvement on the obsessive compulsive disorder (OCD) subscale. Improvements were maintained from T2 to T3. Patients showed significant (p <.01) improvements on the ABC total score and on all ABC subscales except inappropriate speech from T1 to T2; these improvements were maintained from T2 to T3. Discussion The combination of a professional network and a standardized protocol for clinical assessment has promise as a strategy for improving professional competence and facilitating specialized mental health services for autistic individuals with ID and psychiatric disorders across an extensive geographical area. [ABSTRACT FROM AUTHOR]

Rationale: Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) is a preferred technique for analyzing complex organic mixtures. Currently, there is no consensus normalization approach, nor an objective method for selecting one, for quantitative analyses of FT‐ICR‐MS data. We investigate a method to evaluate and score the amount of bias various normalization approaches introduce into the data. Methods: We evaluate the ability of the Statistical Procedure for the Analysis of Normalization Strategies (SPANS) to guide the selection of appropriate normalization approaches for two different FT‐ICR‐MS data sets. Furthermore, we test the robustness of SPANS results to changes in SPANS parameter values and assess the impact of using various normalization approaches on downstream statistical analyses. Results: The normalization approach identified by SPANS differed for the two data sets. Normalization methods impacted the statistical significance of peaks differently, underscoring the importance of carefully evaluating potential methods. More consistent SPANS scores resulted when at least 120 significant peaks are used, where larger sets of peaks were obtained by increasing the p‐value threshold. Interestingly, we show that total sum scaling and highest peak normalization, used in previous studies, underperformed relative to SPANS‐recommended normalization approaches. Conclusions: Although there is no single, best normalization method for all data sets, SPANS provides a mechanism to identify an appropriate normalization method for analyzing FT‐ICR‐MS data quantitatively. The number of peaks used in the background distributions of SPANS contributes more significantly to the reproducibility of results than the p‐value thresholds used to obtain those peaks. [ABSTRACT FROM AUTHOR]

Background: Preterm infants have a higher risk of development disorders. Prematurity can be considered a source of stress, in both children and their parents, due to the high number of interventions that they require. Early intervention (EI) programmes have shown to have a positive influence on the neurodevelopment of children with neurological risk. On the other hand, parenting stress has a negative influence on the development of any child. This systematic review aimed to identify the effect of EI programmes on decreasing parenting stress suffered by parents of preterm babies. Methods: Systematic review and meta‐analysis of experimental studies in accordance with the PRISMA declaration guidelines were applied in this work. Results: Fifteen randomized clinical trials were included whose methodological quality was assessed using the PEDro scale. Stress data extraction was meta‐analysed using the inverse variance method in a random effects model. Statistical heterogeneity was assessed with the I2 heterogeneity statistic. The domains most commonly reported in the trials were the childcare‐related stress (Child Domain), personal discomfort (Parent Domain) and computation of both (Total Stress). The results showed significant (P < 0,05) and clinically relevant differences in favour of the EI programme group at 18 months and 5 years. Conclusions: This review found moderate to strong evidence of the impact of EI programmes on the reduction of parenting stress in parents of preterm babies. These findings offer useful insights regarding the delivery of current support and the development of future family interventions. Finally, recommendations are provided for future intervention evaluation studies in this area. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to predict myopia prevalence in urban Indian children and to describe the generational effect of myopia in different age groups over the next three decades from the year 2020. Methods: A systematic review of myopia prevalence in India was performed using the Preferred Reporting Items for the Systematic Reviews and Meta‐analysis (PRISMA) guidelines and included eight studies with 28 600 participants, which were published in the period 1 January 1999 to 31 December 2019. The best fit for the prediction model was assessed with the baseline prevalence data plotted against different years and fitted with multiple mathematical regressions (linear, second‐order polynomial, third order polynomial and exponential). Based on the quality of the fit assessed by the coefficient of determination (R2) values, the sum of squared residuals and statistical significance, final predictions for myopia prevalence in the 5 to 15‐year‐old urban Indian children was estimated using the aptly suited linear regression model. To describe the generational effect on myopia prevalence over the next three decades, the prevalence of myopia in both children and adults, based on the available literature (1999 to 2020) was plotted against age, as the baseline. Results: The prevalence of myopia in 5 to 15‐year‐old urban children increased from 4.44% in 1999 to 21.15% in 2019. Our predictions, based on the slope of 0.8% every year (4.05% for every 5 years) indicate that the prevalence of myopia will increase to 31.89% in 2030, 40.01% in 2040 and 48.14% in 2050. Due to the generational effect (caused by the nature of the condition lasting a lifetime once developed), there will be an overall increase in myopia prevalence across all age groups of 10.53% in the next three decades (2020 to 2050). Conclusion: The estimates of myopia prevalence across all age groups indicate the possible future epidemic of myopia in India within a few decades, similar to the situation in East Asian countries, unless active intervention to prevent myopia and changes in lifestyle are instigated to counteract myopia in India. Meticulously designed eye care services with focussed anti‐myopia strategies are needed to control the rising myopia prevalence in India. [ABSTRACT FROM AUTHOR]

There is a continuous need to find out the best treatment for old hypertrophic scars (OHSs). Thirty patients with OHSs were included. Each scar was divided into right half treated with PDL (handpiece with a 7‐mm spot, pulse duration of 1.5 ms and fluence of 6 J/cm2) and left half treated with FrCo2 laser (15 W, spacing 800 μm, dwelling time 600 μs and stack 3) once every month for three sessions. Scars were assessed before and after treatment clinically by Vancouver Scar Scale (VSS) and histologically using hematoxylin and eosin (H&E), Masson trichrome and orcein stains. Both halves showed statistically significant improvement after treatment. However, there was no statistically significant difference in VSS between them (P = 0.176). FrCo2 laser showed more significant improvement in pliability and height (Pp = 0.017, Ph = 0,011), while, PDL showed more significant improvement in vascularity (P = 0.039) of OHSs. Both PDL and ablative FrCo2 laser were effective in the treatment of OHSs, however, FrCo2 laser was more effective in improving OHSs pliability, and height which are the main concern in OHSs. [ABSTRACT FROM AUTHOR]