The Transformational Effects of Public-Private Partnerships in Cleveland: An Inside View of Good Government under Mayors Voinovich and Jackson

This article focuses on two mayoral-led public-private partnerships designed to renew good government in Cleveland — Mayor George Voinovich’s Operations Improvement Task Force (OITF) (1979-1982) and Mayor Frank Jackson’s Operations Efficiency Task Force (OETF) (2006-2009). The Voinovich OITF public-private partnership enabled Cleveland to “come back” after the city’s 1978 default. The Jackson OETF public-private partnership successfully rightsized Cleveland in relationship to its much smaller population needs during challenging economic times without disruptions in service. The authors use three data sources, including interviews with both mayors and their key partnership managers, to gain a complete inside picture of each mayoral-led public-private partnership. The article concludes with the lessons learned and the governance implications of a mayoral-led public-private partnership in fostering long-term (transformative) administrative change. This article shows how both mayoral-led public-private partnerships quietly transformed Cleveland’s government to meet the demands of fewer resources, greater complexity, more transparency, and more timely decisions in the delivery of public services to citizens

The Transformative Effects of Public-Private Partnerships in Cleveland: An Inside View of Good Government under Mayors Voinovich and Jackson

This article focuses on two mayoral-led public-private partnerships designed to renew good government in Cleveland — Mayor George Voinovich’s Operations Improvement Task Force (OITF) (1979-1982) and Mayor Frank Jackson’s Operations Efficiency Task Force (OETF) (2006-2009). The Voinovich OITF public-private partnership enabled Cleveland to “come back” after the city’s 1978 default. The Jackson OETF public-private partnership successfully rightsized Cleveland in relationship to its much smaller population needs during challenging economic times without disruptions in service. The authors use three data sources, including interviews with both mayors and their key partnership managers, to gain a complete inside picture of each mayoral-led public-private partnership. The article concludes with the lessons learned and the governance implications of a mayoral-led public-private partnership in fostering long-term (transformative) administrative change. This article shows how both mayoral-led public-private partnerships quietly transformed Cleveland’s government to meet the demands of fewer resources, greater complexity, more transparency, and more timely decisions in the delivery of public services to citizens

Targeted Immunotherapy with Rituximab Leads to a Transient Alteration of the IgG Autoantibody Profile in Pemphigus Vulgaris

In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of keratinocyteadhesion. The aim of the present study was to study the effect of the B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients who were followed up clinically and serologically by Dsg3 ELISA over 12-24 months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3 (Dsc3EC1-5). Specifically, 14/22 showed IgG reactivity against the Dsg3EC1 subdomain, 5/22 patients against Dsg3EC2, 7/22 against Dsg3EC3, 11/22 against Dsg3EC4, and 2/22 against Dsg3EC5. Within 6 months after rituximab, all the patients showed significant clinical improvement and reduced IgG against Dsg3 (5/22) and the various subdomains, that is, Dsg3EC1 (7/22), Dsg3EC2 (3/22), Dsg3EC3 (2/22), sg3EC4 (2/22), and Dsg3EC5 (0/22). During the entire observation period, 6/22 PV patients experienced a clinical relapse which was associated with the reappearance of IgG against previously recognized Dsg3 subdomains, particularly against the Dsg3EC1. Thus, in PV, rituximab only temporarily depletes pathogenic B cell responses against distinct subdomains of Dsg3 which reappear upon clinical relapse

MRI-TRUS fusion for electrode positioning during irreversible electroporation for treatment of prostate cancer

We aimed to introduce an approach for image-guided positioning of electrodes for irreversible electroporation (IRE) in patients with prostate cancer using a magnetic resonance imaging-transrectal ultrasonography (MRI-TRUS) fusion technique. In 10 consecutive patients with biopsy-proven Gleason score ≤3+4 prostate cancer, 19 G electrodes were inserted into the prostate using a transperineal access. Magnetic resonance images of the prostate acquired before IRE were fused with transrectal ultrasound images acquired during IRE. The position of the ultrasound probe was tracked via a sensor and corresponding magnetic resonance images were calculated in real-time. While MRI allowed delineation of the target volume, the position of the electrodes could be visualized on ultrasound images; the distance between individual electrode pairs was measured. Based on these measurements the software installed on the IRE unit was able to calculate the voltage necessary to generate the electric field for ablation. Using contrast-enhanced ultrasound, changes in perfusion within the ablation zone after IRE were documented. This technique allowed positioning of the electrodes around the target volume under image guidance in all patients treated with IRE. The target lesion and a safety margin were covered within the estimated ablation zone. MRI-TRUS guidance for IRE combines the advantages of good visualization of the target lesion on MRI with the ability of ultrasound to acquire imaging in real-time with a mobile device

Estrogen Receptor Alpha as a Key Target of Red Wine Polyphenols Action on the Endothelium

BACKGROUND: A greater reduction in cardiovascular risk and vascular protection associated with diet rich in polyphenols are generally accepted; however, the molecular targets for polyphenols effects remain unknown. Meanwhile evidences in the literature have enlightened, not only structural similarities between estrogens and polyphenols known as phytoestrogens, but also in their vascular effects. We hypothesized that alpha isoform of estrogen receptor (ERalpha) could be involved in the transduction of the vascular benefits of polyphenols. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used ERalpha deficient mice to show that endothelium-dependent vasorelaxation induced either by red wine polyphenol extract, Provinols, or delphinidin, an anthocyanin that possesses similar pharmacological profile, is mediated by ERalpha. Indeed, Provinols, delphinidin and ERalpha agonists, 17-beta-estradiol and PPT, are able to induce endothelial vasodilatation in aorta from ERalpha Wild-Type but not from Knock-Out mice, by activation of nitric oxide (NO) pathway in endothelial cells. Besides, silencing the effects of ERalpha completely prevented the effects of Provinols and delphinidin to activate NO pathway (Src, ERK 1/2, eNOS, caveolin-1) leading to NO production. Furthermore, direct interaction between delphinidin and ERalpha activator site is demonstrated using both binding assay and docking. Most interestingly, the ability of short term oral administration of Provinols to decrease response to serotonin and to enhance sensitivity of the endothelium-dependent relaxation to acetylcholine, associated with concomitant increased NO production and decreased superoxide anions, was completely blunted in ERalpha deficient mice. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that red wine polyphenols, especially delphinidin, exert their endothelial benefits via ERalpha activation. It is a major breakthrough bringing new insights of the potential therapeutic of polyphenols against cardiovascular pathologies

Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol.

INTRODUCTION: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020177408

Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity.

INTRODUCTION: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER: CRD42020177408

The Higgs Working Group: Summary Report 2003

Theoretical progress in Higgs boson production and background processes is discussed with particular emphasis on QCD corrections at and beyond next-to-leading order as well as next-to-leading order electroweak corrections. The residual theoretical uncertainties of the investigated processes are estimated in detail. Moreover, recent investigations of the MSSM Higgs sector and other extensions of the SM Higgs sector are presented. The potential of the LHC and a high-energy linear e+e- collider for the measurement of Higgs couplings is analyzed.Comment: 169 pages, Proceedings 3rd Les Houches Workshop: Physics at TeV Colliders, Les Houches, France, 26 May - 6 Jun 200

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community