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We consider the problem of detecting an elevated mean on an interval with unknown location and length in the univariate Gaussian sequence model. Recent results have shown that using scale-dependent critical values for the scan statistic allows to attain asymptotically optimal detection simultaneously for all signal lengths, thereby improving on the traditional scan, but this procedure has been criticised for losing too much power for short signals. We explain this discrepancy by showing that these asymptotic optimality results will necessarily be too imprecise to discern the performance of scan statistics in a practically relevant way, even in a large sample context. Instead, we propose to assess the performance with a new finite sample criterion. We then present three calibrations for scan statistics that perform well across a range of relevant signal lengths: The first calibration uses a particular adjustment to the critical values and is therefore tailored to the Gaussian case. The second calibration uses a scale-dependent adjustment to the significance levels rather than to the critical values and this adjustment is therefore applicable to arbitrary known null distributions. The third calibration restricts the scan to a particular sparse subset of the scan windows and then applies a weighted Bonferroni adjustment to the corresponding test statistics. This Bonferroni scan is also applicable to arbitrary null distributions and in addition is very simple to implement. We show how to apply these calibrations for scanning in a number of distributional settings: for normal observations with an unknown baseline and a known or unknown constant variance, for observations from a natural exponential family, for potentially heteroscadastic observations from a symmetric density by employing self-normalisation in a novel way, and for exchangeable observations using tests based on permutations, ranks or signs.

Proximal tibial valgus osteotomy is one of the treatment options for painful medial compartment osteoarthritis and varus deformity of the knee. The aim of our study was to determine and quantify how much osteotomy altered symptoms from medial compartment gonoarthrosis. In addition we aimed to establish whether the Tomofix plating system would permit early weight bearing and achieve union without the use of bone grafts. We prospectively analysed our experience with medial opening wedge high tibial osteotomy using the Tomofix plate. Thirty-five knees were included in the study. The mean age was 47 years (36-59 years). Mean duration of follow-up was 23 months (7-48 Months). All patients underwent medial opening wedge high tibial osteotomy using the Tomofix plating system. Data was recorded using the Oxford Knee score, the Knee Injury Osteoarthritis Outcome score and through review of pre and postoperative x-rays. Good outcomes were seen with statistically significant improvement of both scores. There were two delayed unions, the remainder united without requirement for graft. There was improvement, in Oxford and Knee injury osteoarthritis scores. Correction of mal-alignment was seen in all cases. Early weight bearing was found to be permissible without risk of adverse event. The Tomofix plate provided immediate stability and satisfactory healing of the osteotomy site without the need for bone graft. Good functional results were seen.

Social network analysis (SNA) consists of a broad set of frameworks and methods to assess how direct and indirect relationships influence individual functioning. Although interest in SNA has steadily increased in the psychological sciences, school psychology has not kept pace. This article provides a general overview of core SNA concepts, including how network data is typically collected in schools. Following this overview, we provide some caveats to considerations for school psychology researchers interested in collecting network data. Finally, we highlight the potential value of SNA to school psychologists by describing the networks of older adolescents as it pertains to aggression and the bystander effect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Political polarization and generational politics are important topics in contemporary political science classrooms. This article presents an approach to teaching political polarization in an introduction to politics course. Coauthored by two Generation Z students from the course and their Boomer Generation professor, the article provides conflicting views of young people and politics as found in the work of Robert Putnam and Russell Dalton. The article presents survey data on affective and issue political polarization from the course, including discussion by the two student coauthors of the survey results interpreting their generation’s political polarization. The course approaches the introductory politics course using cognitive psychology concepts including confirmative bias, motivated reasoning, and other cognitive biases. Teaching from this micro-level perspective helps students to reflect on their own political biases. The article provides concepts and readings for political science professors to use in replicating the course.

ObjectiveThe frequency and predictors of improvement in left ventricular ejection fraction (LVEF) in ischaemic cardiomyopathy and its association with mortality is poorly understood. We sought to assess the predictors of LVEF improvement ≥10% and its effect on mortality.MethodsWe compared characteristics of patients enrolled in The Surgical Treatment for Ischaemic Heart Failure (STICH) trial with and without improvement of LVEF ≥10% at 24 months. A logistic regression model was constructed to determine the independent predictors of LVEF improvement. A Cox proportional hazards model was created to assess the independent association of improvement in LVEF ≥10% with mortality.ResultsOf the 1212 patients enrolled in STICH, 618 underwent echocardiographic assessment of LVEF at baseline and 24 months. Of the patients randomised to medical therapy plus coronary artery bypass graft surgery (CABG), 58 (19%) had an improvement in LVEF >10% compared with 51 (16%) patients assigned to medical therapy alone (p=0.30). Independent predictors of LVEF improvement >10% included prior myocardial infarction (OR 0.44, 95% CI: 0.28 to 0.71, p=0.001) and lower baseline LVEF (OR 0.94, 95% CI: 0.91 to 0.97, p>10% (HR 0.61, 95% CI: 0.44 to 0.84, p=0.004) and randomisation to CABG (HR 0.72, 95% CI: 0.57 to 0.90, p=0.004) were independently associated with a reduced hazard of mortality.ConclusionsImprovement of LVEF ≥10% at 24 months was uncommon in patients with ischaemic cardiomyopathy, did not differ between patients assigned to CABG and medical therapy or medical therapy alone and was independently associated with reduced mortality.Trial registration numberNCT00023595.

751 Background: Pancreatic cancer carries a dismal prognosis and limited treatment options. Attempts to implement precision therapies have proved difficult to date, in part due to challenges obtaining high quality genetic material from pancreatic biopsies. Endoscopic ultrasound (EUS) is a common diagnostic procedure, but limited data is available on the clinical utility of these biopsies for comprehensive molecular profiling (CMP) to inform therapeutic choices. Methods: This study aimed to enrol up to 150 patients undergoing EUS biopsies for pancreatic cancer, in order to complete targeted DNA/RNA sequencing on 100. The primary outcome was to characterise the proportion of patients able to undergo CMP on their diagnostic EUS biopsies, with fresh-frozen biopsies preferred but FFPE specimens accepted if there was no alternative. Secondary endpoints included the proportion of patients with clinically relevant molecular findings as determined by Molecular Tumour Board (MTB) discussion, proportion of patients initiating targeted therapies, and quantitative/qualitative analysis on molecular material derived from fresh-frozen versus FFPE EUS biopsies. Results: 109 patients have been enrolled since May 2020, and molecular profiling has been completed for 102 patients. 2 patients (1.8%) were excluded due to having no available biopsies, and 5 biopsies (4.7%) were unable to be sequenced due to inadequate quality metrics. Common oncogenes were detected at roughly expected frequencies, with mutations in KRAS occurring in 91 (89.2%), TP53 in 67 (65.7%), SMAD4 in 11 (10.8%) and CDKN2A in 7 (6.8%). Median tumour mutation burden (TMB) in this cohort was low at 3.1Mut/Mb although 7 patients (6.9%) had a high TMB (defined as >10Mut/Mb), of which 3 (2.9%) had markedly hypermutated tumours (>200Mut/Mb). All processed samples were microsatellite stable. Therapeutically relevant mutations were detected in 21 (20.6%) including RNF43 in 7 patients (6.9%), KRAS G12C and BRCA in 3 patients each (2.9%), in addition to BRAF V600E in 2 (1.9%), and CHEK2 and BARD1 mutations in 1 each (0.9%). High TMB was observed in 7 patients (6.9%). To date, 5 patients (4.9%) have commenced on targeted therapies, with one patient notably experiencing a complete response to targeted therapy which has now been sustained for >12 months. Conclusions: This real-world study confirms the utility of endoscopic biopsies as a valuable and reliable source of genetic material for clinically relevant molecular tumour profiling. Secondary analyses are underway to further characterise treatment and survival implications in this cohort.

Introduction: Data are lacking on the natural history of heart failure with recovered ejection fraction (HFrecEF) with no available risk model for future heart failure events. This study aimed to understand the long-term outcomes of patients with HFrecEF, identify predictors of adverse events, and develop a risk stratification model. Methods: From an academic healthcare system we retrospectively identified patients who had an improvement in left ventricular ejection fraction (LVEF) from Results: 133 patients were included (median age 67, 39% female, 30% ischemic etiology). Kaplan-Meier survival was 70% at 5 years. Freedom from hospitalization was 58% at 1 year, and the risk of recurrent LVEF reduction to Conclusions: Patients with HFrecEF have significant heterogeneity in clinical outcomes ranging from persistent recovery to requiring advanced heart failure therapies or death. A risk model utilizing NYHA functional class, BNP and diuretic dose can accurately stratify mortality risk.

ObjectivePatients with non-ischaemic dilated cardiomyopathy (NICM) may experience a normalisation in left ventricular ejection fraction (LVEF). Although this correlates with improved prognosis, it does not correspond to a normalisation in the risk of death during follow-up. Currently, there are no tools to risk stratify this population. We tested the hypothesis that absolute global longitudinal strain (aGLS) is associated with mortality in patients with NICM and recovered ejection fraction (LVEF).MethodsWe designed a retrospective, international, longitudinal cohort study enrolling patients with NICM with LVEF 50%). We studied the relationship between aGLS measured at the time of the first recording of a normalised LVEF and all-cause mortality during follow-up. We considered aGLS >18% as normal and aGLS ≥16% as of potential prognostic value.Results206 patients met inclusion criteria. Median age was 53.5 years (IQR 44.3–62.8) and 56.6% were males. LVEF at diagnosis was 32.0% (IQR 24.0–38.8). LVEF at the time of recovery was 55.0% (IQR 51.7–60.0). aGLS at the time of LVEF recovery was 13.6%±3.9%. 166 (80%) and 141 (68%) patients had aGLS ≤18% and 18%). In unadjusted Kaplan-Meier survival analysis, aGLS ConclusionsIn patients with NICM and normalised LVEF, an impaired aGLS at the time of LVEF recovery is frequent and associated with worse outcomes.

Background The optimal threshold of left ventricular ejection fraction (LVEF) that should prompt aortic valve replacement (AVR) in asymptomatic patients with high‐gradient severe aortic stenosis (AS) is controversial. The aim of this study was to assess the relationship between LVEF and mortality benefit in comparing early AVR versus watchful waiting in asymptomatic patients with severe AS. Methods and Results MEDLINE, Embase, Web of Science, and Google Scholar were searched for observational studies and randomized controlled trials on adults with asymptomatic severe AS. Severe AS was defined by a peak aortic velocity ≥4 m/s and/or mean aortic valve gradient ≥40 mm Hg and/or calculated aortic valve area 2 or an indexed valve area 2 . Studies comparing AVR with conservative management were included and meta‐analysis on all‐cause mortality was performed. Ten eligible studies were identified with a total of 3332 patients. In 5 observational studies comparing early AVR versus watchful waiting, our meta‐analysis showed early AVR was associated with lower mortality with a hazard ratio (HR) of 0.41 (CI, 0.23–0.71; P P P =0.83). Conclusions Among asymptomatic patients with high‐gradient severe AS, AVR was associated with a mortality benefit across the spectrum of LVEF. Our study calls into question the need of an LVEF threshold for recommending AVR in this patient population.

Coronavirus Disease 2019 (COVID-19) has disrupted virtually every aspect of daily living, engendering forced isolation and social distance, economic hardship, fears of contracting a potentially lethal illness and feelings of helplessness and hopelessness. Unfortunately, there is no formula or operating manual for how to cope with the current global pandemic. Previous research has documented an array of responses to mass crises or disasters, including chronic anxiety and posttraumatic stress as well as resilience and recovery. Much can be learned from this research about how people have coped in the past in order to identify strategies that may be particularly effective in managing distress and cultivating resilience during these perilous times. We delineate multiple coping strategies (e.g., behavioral activation, acceptance-based coping, mindfulness practice, loving-kindness practices) geared to decrease stress and promote resilience and recovery. These strategies may be especially effective because they help individuals make meaning, build distress tolerance, increase social support, foster a view of our deep human interconnectedness, and take goal-directed value-driven actions in midst of the COVID-19 pandemic.

Given that economic growth is typically associated with ecological destruction and little improvement in human happiness, alternative indicators of progress have been developed to provide decision-makers with additional non-economic information that might better protect the environment and promote human well-being. However, to our knowledge, no experimental evidence exists which demonstrates that the use of such alternative indicators actually causes changes in behaviors. We therefore asked participants to pretend that they were the mayor of a small city that had the opportunity to develop natural land on its borders. Participants were randomly assigned to receive either standard indicators (consisting of only economic information) or alternative indicators (consisting of economic, ecological, and well-being information) as they made decisions over the course of their “term” as mayor. Participants who received alternative indicator feedback developed significantly fewer acres of the natural land than did those who received standard indicator feedback (Cohen’s d = .52). The effect of indicator type did not significantly interact with gender, ethnicity, or value orientation, but participants low in need for cognition were more sensitive to the type of indicator provided than were those high in need for cognition. The results provide the first experimental evidence supporting the claim that alternative indicators can cause decision-makers to focus less on economic outcomes and to prioritize well-being and ecological outcomes.

ObjectiveWe sought to describe front-of-package marketing strategies and nutritional quality of child-oriented beverages in Guatemala.DesignWe purchased all child-oriented ready-to-drink fruit drinks, milks and carbonated beverages in three convenience stores and one supermarket in Guatemala City. Front-of-package marketing was defined as the presence of spokes-characters, cartoons, celebrities, or health-related images, words, claims or endorsements on beverage packaging. We used the UK Nutrition Profiling Model (NPM) to classify beverages as healthy or less healthy.SettingGuatemala City, Guatemala.ResultsWe purchased eighty-nine beverages; most were fruit drinks (n52, 58 %), milk (15, 17 %), carbonated beverages (5, 17 %), rice/soya products (5, 6·0 %), water (1, 1 %) and energy drinks (1, 1 %). Two-thirds (57, 64 %) had health claims. Of those with a nutrition facts label (85, 96 %), nearly all (76, 89 %) were classified as less healthy. No association between the presence of health claims and NPM score (P=0·26) was found. Eight beverages had health-related endorsements. However, only one beverage was classified as healthy.ConclusionsIn this sample of beverages in Guatemala City, health claims and health-related endorsements are used to promote beverages with poor nutritional quality. Our data support evidence-based policies to regulate the use of front-of-package health claims and endorsements based on nutritional quality.

Richard Bauckham and N. T. Wright have proposed that in 1 Corinthians 8:6 Paul consciously expands upon the Shema, and would be understood to be doing so by his intended readers, and thus Paul includes Jesus within the unique divine identity. In this paper we question this proposal on several grounds. We argue that it is unlikely that 1 Corinthians 8:6 would be read as an expansion of the Shema. We demonstrate that κύριος in this context is unlikely to stand for Yhwh. We also raise doubts over the concept of “inclusion” within the divine identity. We conclude that 1 Corinthians 8:6 is better understood as an expression of monotheism simpliciter.

A malocclusion is a discrepancy of alignment in opposing dental arches or an abnormal relationship between teeth when the mouth is closed. These discrepancies may be congenital, developmental or acquired. This article discusses the development of malocclusions and their associated consequences, describes ideal occlusion and reviews classification of malocclusions. It also discusses the most common malocclusions seen in cats and dogs, and describes potential treatments.

Phyllodes breast tumours are fairly uncommon, and they can be benign, borderline or malignant. General surgeons usually encounter them following the surgical excision of a breast lump that had the appearance of a fibroepithelial lesion. The surgeon is then faced with the question of what to do to establish an acceptable treatment margin. In this discussion, we recommend a plan for the management of Phyllodes tumours based on a review of the recent literature, confirmed by a retrospective review of the results from our centre. A negative margin is acceptable treatment following a lumpectomy for Phyllodes tumours. Only patients with a positive margin should undergo a revision.

Introduction In patients with non-ischemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF), a normalization in LVEF portends improved outcomes. However, data on patients with ischemic cardiomyopathy and recovered LVEF is lacking. We therefore analyzed the STICH trial database to investigate the relationship between normalization of LVEF (>50%) and mortality in patients with ischemic cardiomyopathy. Methods Of the 1,212 patients with LVEF Results The 932 patients included in our analysis did not differ significantly from the STICH population not included in the analysis with respect to demographics, comorbidities and stratification to optimal medical therapy (OMT) plus CABG or OMT alone. Among them, 18 patients experienced normalization in LVEF at 30 days of follow-up and 35 patients experienced recovery in LVEF at two years. Recovery of LVEF at 30 days and recovery of LVEF at 2 years were not correlated. We therefore performed independent analysis to study the relationship between early (30 days) or late (2 years) recovery in LVEF and mortality. EF recovery at 30 days was not associated with improved all-cause mortality in unadjusted analysis (Kaplan-Meyer log-rank p=0.54, Figure 1A) or in multivariate analysis adjusting for comorbidities (HR 0.93; CI 0.48, 1.80; P=0.82). EF recovery at 2 years was associated with a reduction in all-cause mortality both in unadjusted analysis (Kaplan-Meyer log-rank p=0.004, Figure 1B) and in the multivariate Cox proportional hazard model (HR 0.41; CI 0.21, 0.80; P=0.009). Conclusion In patients with ischemic cardiomyopathy, delayed normalization of LVEF is associated with a mortality benefit, whereas early recovery in LVEF is not.

Pediatric kidney transplantation has become highly successful in the modern era and is the treatment of choice for children with end-stage renal disease (ESRD). Achieving successful surgical outcomes requires a methodical and multidisciplinary approach, beginning with a thorough preoperative evaluation. There are various anatomical and physiological considerations unique to children with chronic kidney disease that necessitates a nuanced surgical approach. In the preoperative phase, addressing underlying urological abnormalities and native kidney disease can be crucial to maximizing graft longevity and survival. Additionally, an individualized approach to surgical technique and fluid management during the operation is critical in preventing technical complications. Lastly, the risk of vascular and urologic complications is higher in the pediatric transplant population. A prompt diagnostic evaluation of early graft dysfunction is crucial to ensuring successful outcomes.

To evaluate factors associated with use of patient navigation in a prostate cancer population and identify whether navigation is associated with prolonged time to care. Cancer patient navigation has been shown to improve access to cancer screening, diagnosis, and treatment, but little is known about patient navigation in prostate cancer care. All men diagnosed with localized prostate cancer between 2009 and 2015 were abstracted from the MaineHealth multi-specialty tumor registry. Regression analyses controlling for patient-, disease-, and system-level factors evaluated characteristics associated with navigation utilization. The association between navigation utilization, barriers to care, and longer time to treatment was assessed with Cox proportional hazards regression. Of the patient population (n = 1587), 85% of men were navigated. Navigation use was associated with earlier year of diagnosis, treatment by a high-volume urologist, and lower risk disease (p

Background Quality of oncologic outcomes is of paramount importance in the care of patients with non–small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Commission on Cancer (CoC) accreditation. Methods The California Cancer Registry was queried from 2004 to 2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. Results A total of 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high-volume centers was associated with longer survival when compared with low- and medium-volume centers (hazard ratio 1.77, 1.474 to 2.141 and hazard ratio 1.23, 1.058 to 1.438). Conclusion These data suggest that surgical treatment in high-volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not.