Testing Parameter Stability: A Wild Bootstrap Approach

Unknown-breakpoint tests for possible structural change have become standard in recent years, with the most popular being the so-called Sup-F tests, whose asymptotic distribution was derived by Andrews (1993). We highlight two problems that lead to poor performance when testing for structural breaks in dynamic time series models using the Andrews critical values: High persistence of explanatory variables and heteroskedasticity. We propose a so-called ``wild bootstrap'' approach to generating critical values for the Sup-F statistic and report that this approach performs well across a wide variety of possible data generating processes, including those with large coefficients on lagged dependent variables and heteroskedasticity.

Has euro-area inflation persistence changed over time?

This paper analyzes the stability over time of the econometric process for Euro-area inflation since 1970, focusing in particular on the behaviour of the so-called persistence parameter (the sum of the coefficients on the lagged dependent variables). Perhaps surprisingly, in light of the Lucas critique, our principal finding is that there appears to be relatively little instability in the parameters of the Euro-area inflation process. Full-sample estimates of the persistence parameter are generally close to one, and we fail to reject the hypothesis that this parameter has been stable over time. We discuss how these results provide some indirect evidence against rational expectations models with strong forward-looking elements, such as the New-Keynesian Phillips curve. JEL Classification: E31, E52euro area, Inflation persistence, Lucas Critique

Has Euro-Area Inflation Persistence Changed Over Time?

This paper analyzes the stability over time of the econometric process for Euro-area inflation since 1970, focusing in particular on the behaviour of the so-called persistence parameter (the sum of the coefficients on the lagged dependent variables). Perhaps surprisingly, in light of the Lucas critique, our principal finding is that there appears to be relatively little instability in the parameters of the Euro-area inflation process. Full-sample estimates of the persistence parameter are generally close to one, and we fail to reject the hypothesis that this parameter has been stable over time. We discuss how these results provide some indirect evidence against rational expectations models with strong forward-looking elements, such as the New-Keynesian Phillips curve.

Dip(ping) into Foreign Waters…Irish Paramedics’ Royal College Experience.

The Diploma in Immediate Medical Care awarded by the Royal College of Surgeons of Edinburgh is an internationally recognised award specifically aimed at the area of pre-hospital emergency medical care. The study syllabus is based on phase 1 of the UK Pre-Hospital Emergency Medicine curriculum. Award examinations are inter-professional with a set standard regardless of candidates’ clinical level or back-round. The Dip IMC has a reputation for being difficult to pass and, equally, for attracting medical professionals of the highest standard at all grades.To date in Ireland, it has mostly been doctors specialising in emergency medicine that have attempted the award. With the introduction of advanced paramedic practice, the range of practitioners eligible to attempt it has increased. At the time of writing, three Irish advanced paramedics have successfully achieved the award.While it is a difficult award to achieve, and much content is outside current Irish paramedic scope of practice, a motivated, well prepared advanced paramedic can be successful. This article outlines the processes and preparations that two such paramedics followed to successfully achieve the Dip IMC RCSEd

A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics. Methods: The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population. Results: A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles. Conclusions: The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice

11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome

Abstract Context: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS. Methods: One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four–hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded. Results: As expected, serum concentrations of the classic androgens testosterone (P &amp;lt; 0.001), androstenedione (P &amp;lt; 0.001), and dehydroepiandrosterone (P &amp;lt; 0.01) were significantly increased in PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P &amp;lt; 0.0001]. Obese (n = 51) and nonobese (n = 63) patients with PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance. Conclusions: We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk. </jats:sec

Materialities and imaginaries of home: geographies of British returnees in later life

This article explores home materialities and home imaginaries in later life, to provide insight into the dialectical relation between the spatial processes of ageing and migration. The article draws on empirical research with British return migrants in older age. The analysis purposively selects four participants from among a wider sample of interviewees to highlight some of the diversity among British returnees and their varied experiences of remaking home upon return. The article explores both the privilege and vulnerabilities of all British returnees as the meaning of home transforms in later life

Search for a strongly decaying neutral charmed pentaquark

We present a search for a charmed pentaquark decaying strongly to $D^{(*)-}p$. Finding no evidence for such a state, we set limits on the cross section times branching ratio relative to $D^{*-}$ and $D^-$ under particular assumptions about the production mechanism.Comment: To be published in Physics Letters

Dual targeting of CD19 and CD22 with Bicistronic CAR-T cells in Patients with Relapsed/Refractory Large B Cell Lymphoma

Relapse following CD19-directed chimeric antigen receptor T-cells (CAR-T) for relapsed/refractory large B-cell lymphoma (r/r LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multi-antigen targeting and PD-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in r/r LBCL as inpatient or outpatient therapy (NCT03289455, https://clinicaltrials.gov/ct2/show/NCT03289455). Endpoints include toxicity (primary) and response rates (secondary). AUTO3 was manufactured for 62 patients using autologous leukapheresis, modified with a bicistronic transgene. 52 patients received AUTO3 (7/52,50x106; 45/52,150-450x106) and 48/52 received pembrolizumab. Median age was 59 years (range,27-83) and 46/52 had stage III/IV disease. Median follow-up was 21.6 months (range,15.1-51.3) at last data cut (Feb 28, 2022). AUTO3 was safe: grade 1-2 and grade 3 CRS affected 18/52 (34.6%) and 1/52 (1.9%) patients, neurotoxicity arose in 4 patients (2/4, grade 3-4), HLH affected 2 patients, and no Pembrolizumab-associated autoimmune sequalae were observed. On this basis, outpatient administration was tested in 20 patients, saving a median of 14 hospital days/patient. AUTO3 was effective: overall response rates were 66% (48.9%, CR; 17%, PR). For patients with CR, median DOR was not reached, with 54.4% (CI: 32.8, 71.7) projected to remain progression-free beyond 12 months after onset of remission. DOR for all responding patients was 8.3 months (95% CI: 3.0, NE) with 42.6% projected to remain progression-free beyond 12 months after onset of remission. Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities

ARTP statement on pulmonary function testing 2020.

The Association for Respiratory Technology & Physiology (ARTP) last produced a statement on the performance of lung function testing in 1994. At that time the focus was on a practical statement for people working in lung function laboratories. Since that time there have been many technological advances and alterations to best practice in the measurement and interpretation of lung function assessments. In light of these advances an update was warranted. ARTP, therefore, have provided within this document, where available, the most up-to-date and evidence-based recommendations for the most common lung function assessments performed in laboratories across the UK. These recommendations set out the requirements and considerations that need to be made in terms of environmental and patient factors that may influence both the performance and interpretation of lung function tests. They also incorporate procedures to ensure quality assured diagnostic investigations that include those associated with equipment, the healthcare professional conducting the assessments and the results achieved by the subject. Each section aims to outline the common parameters provided for each investigation, a brief principle behind the measurements (where applicable), and suggested acceptability and reproducibility criteria