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This research investigates medium‐scale disruptive events to understand how these events influence communication and coordination between two interdependent systems (i.e., the water system and the public health system). Medium‐scale events are events that are often overlooked as routine as they occur with more frequency than large‐scale events, yet they have the potential to provide important information about the state and vulnerability of systems, and, if not managed appropriately, can cascade into larger‐scale crises. A survey of US public drinking water systems (N = 471) shows that medium‐scale events promote coordination, especially when those events have a public dimension. Findings also reveal that several features of water systems including surface water sources, system size, and ownership types are associated with higher levels of interaction with the public health systems. Additionally, a network analysis identifies three distinct subnetworks that engage in emergency response activities. The strength of the working relationship was strongly associated with coordinated emergency responses, coordinated public responses, planning, and technical assistance. Findings have implications for both theory and crisis management. [ABSTRACT FROM AUTHOR]

Policy entrepreneurs have traditionally been recognized for their ability to influence policymakers by framing policy problems and pairing them with preferred solutions. Does their influence extend to the public? We examine this question in the context of the COVID‐19 pandemic in the United States. We analyze whether an individual's perception of a visible, national‐level policy entrepreneur, director of the National Institute of Allergy and Infectious Diseases (NIAID) Dr. Anthony Fauci, influences their perceived risk of contracting the virus and their uptake of recommended COVID‐19 risk mitigation behaviors. Findings indicate that approval of Dr. Fauci predicts individual risk perceptions and uptake of mask wearing practices, with his influence particularly strong among conservatives. However, Dr. Fauci's influence as a policy entrepreneur waned over time and was moderated by a host of factors such as an individual's worldview, perceptions of policy environment, and media consumption. [ABSTRACT FROM AUTHOR]

Copyright of Risk, Hazards & Crisis in Public Policy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Risk, Hazards & Crisis in Public Policy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As climate change continues to increase both the frequency and intensity of environmental hazards and disasters, the need for a cohesive national mitigation policy grows. As the environmental federalism scholarship indicates, the inherent tension in federal, state, and local policy implementation highlights that despite a national need, environmental quality is a local public good. To complicate matters, there is disagreement about the optimal level of decision‐making regarding the adoption and implementation of environmental policy. This study addresses this gap by considering the role of policy ambiguity and conflict in policy implementation. The analysis relies on primary qualitative data collected from open‐ended interviews with 22 local government officials in 12 municipalities following Hurricane Harvey. Through the lens of policy ambiguity and conflict, we find confirmatory support for the idea that policies with less ambiguous goals are more likely to be implemented. Furthermore, we find that policy conflict arises when local governments perceive there is little for the community to gain by implementing the federal program. Thus, the level of protection afforded to citizens varies greatly between communities and is influenced heavily by politics. This research supports the Ambiguity‐Conflict Model of policy implementation, an oft‐cited but rarely tested theoretical framework for assessing the intergovernmental politics of policy implementation. It also demonstrates the barriers to local implementation of federal environmental policy in a nested system of government. [ABSTRACT FROM AUTHOR]

Copyright of Review of Policy Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key Takeaways: Boil water notifications (BWNs) issued during 2021's Winter Storm Uri were typically followed, especially in households with children present and those with higher income. Cascading failure of interconnected systems (such as power and drinking water) inhibited some individuals from being able to follow boil water guidance. Of the people who boiled their water following BWNs, more than 92% reported boiling it for 2 minutes or more. [ABSTRACT FROM AUTHOR]

Objective: This study explores why state legislators think some issues are difficult and where they turn for help with these issues. Methods: We use content analysis of legislators' interview responses to identify sources of difficulty that arose during committee deliberations. Results: Many legislators say that issues are difficult because of committee and caucus politics, technical information, interest group pressure, jurisdictional competition, and budget constraints. We find few associations between sources of difficulty and legislator characteristics or institutional context. Mundane issues are often seen as difficult, with culture war issues rarely mentioned. Using cluster analysis, we identify five major categories of issue difficulty. We find that legislators grapple with these categories of difficulty by relying on interest groups, partisan staff, and committee members rather than on caucus leaders, the governor, or their voters. Conclusion: These findings contribute to our understanding of impediments to policy making that legislators navigate in legislative committees. [ABSTRACT FROM AUTHOR]

Copyright of Policy Studies Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Methionine aminopeptidase 2 (MetAP2) inhibition has been shown to result in significant weight loss and improved glucose control. This Phase 1 clinical trial assessed the safety and tolerability, pharmacokinetics and preliminary efficacy of a novel MetAP2 inhibitor, ZGN‐1061. Methods: This clinical trial included a single ascending dose (SAD) phase in healthy subjects (BMI, 23 to <30 kg/m2) and a multiple ascending dose (MAD) phase in otherwise healthy subjects (BMI, 27 to 40 kg/m2). SAD phase doses, administered subcutaneously (SC), were 0.2, 0.6, 1.2, 2.4, 3.6 and 4.8 mg and the MAD phase evaluated doses of 0.2, 0.6 and 1.8 mg twice weekly SC for 4 weeks. Results: The SAD phase included 39 subjects (ZGN‐1061, N = 28; placebo, N = 11); 90% were male and BMI was 26.4 kg/m2. ZGN‐1061 was well tolerated across all doses, with the most frequent adverse events being mild headache and procedural‐related irritation. There were no severe or serious adverse events. All doses of ZGN‐1061 were rapidly absorbed and cleared, resulting in short duration of exposure that is anticipated to minimize potential off‐drug target risks. The MAD phase included 29 subjects (ZGN‐1061, N = 22; placebo, N = 7); 76% were male and BMI was 33.5 kg/m2. Safety observations were consistent with SAD findings. Efficacy measures in the MAD phase indicated trends for weight change (−1.5 kg total ZGN‐1061 vs −0.2 kg placebo) and other biomarker changes. Conclusions: ZGN‐1061 was well tolerated with no safety signals in all doses tested. In addition, the desired pharmacokinetic profile and preliminary efficacy observations with ZGN‐1061 support evaluation in larger and longer clinical trials. [ABSTRACT FROM AUTHOR]

Training in evidence-based practices may better prepare providers to address the effect of behavioral health concerns on chronic homelessness. Through the Beck Initiative, a community-academic partnership, case managers ( n = 19) were selected to incorporate a cognitive-behavioral therapy (CBT) framework into services for chronic homelessness at seven sites in Philadelphia, PA. Details of the training components and development are presented. This training program demonstrated feasibility within these low-demand shelter settings (79% completed training, 10% left employment during training, 10% did not complete). Feedback measures indicated positive feedback regarding acceptability, usefulness, and quality of training. Planned discharges from the shelters were significantly more frequent in the 6 months posttraining compared with the 6 months before training. The CBT framework shows early promise for improving services for people experiencing chronic homelessness. This program also demonstrates the benefit of involving community stakeholders and academic partners to address one aspect of chronic homelessness. [ABSTRACT FROM AUTHOR]

Key content Gynaecological and breast cancers affect premenopausal and perimenopausal women at rates ranging 15-70% and treatment often causes the abrupt onset of menopause., Available studies do not show an increase in recurrence or decrease in survival among women with endometrial, ovarian or cervical cancer who use hormone replacement therapy (HRT)., Data regarding the risks of systemic HRT in survivors of breast cancer are varied, and an increase in breast cancer recurrence with the use of systemic HRT has been demonstrated in randomised controlled trials. Limited data exist regarding the use of vaginal estrogen, however, no effect on recurrence has been demonstrated., The decision regarding the use of HRT in women with cancer must be individualised and should take into account issues regarding quality of life., Learning objectives To review the evidence regarding the cancer-specific risks, that is, recurrence or death, of HRT in survivors of gynaecological and breast cancer., To provide recommendations for the use of HRT in survivors of gynaecological and breast cancer., Ethical issues How to balance the risks of HRT with quality of life concerns in survivors of gynaecological and breast cancer when evidence to guide our recommendations is limited? [ABSTRACT FROM AUTHOR]

Background The secretory form of acid sphingomyelinase (ASM) is postulated to play a key role in the retention and aggregation of lipoproteins in the subendothelial space of the arterial wall by converting sphingomyelin in lipoproteins into ceramide. The present study aimed to determine whether the level of circulating ASM activity affects lesion development in mouse model of atherosclerosis. Methods Apolipoprotein E deficient (ApoE [ABSTRACT FROM AUTHOR]

Exenatide is an incretin mimetic with potential gluco-regulatory activity in type 2 diabetes. This randomized, single-blind, placebo-controlled 6-way crossover study assessed exenatide’s effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at -1, 0, +1, +2, and +4 hours, relative to the 10 g exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC0-12 h values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the -1-hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption. [ABSTRACT FROM PUBLISHER]

Background Exenatide (exendin-4) exhibits dose-dependent glucoregulatory activity, but causes dose-limiting nausea and vomiting. This study was designed to formally assess the possibility of inducing tolerance to the side effects of nausea and vomiting at therapeutic doses of exenatide, using a dose-escalation methodology. Methods In this two-arm, triple-blind, multicenter study, 123 subjects with type 2 diabetes were enrolled and randomized; 99 (80.5%) of them completed the study. Subjects in the exenatide-primed arm received subcutaneous exenatide, starting at 0.02 µg/kg three times a day (TID) and increasing in 0.02 µg/kg per dose increments every 3 days for 35 days. Subjects in the exenatide-naive arm received placebo TID for 35 days. At the end of this 35-day regimen, subjects in both arms received the same highest dose of exenatide (0.24 µg/kg TID) for 3 days. Thus, the exenatide-naive arm received exenatide for the first time on Day 35. Results The exenatide-primed arm had a lower proportion of subjects experiencing nausea and vomiting in response to exposure to the highest dose of exenatide (27 vs 56% in the exenatide-naive arm; p = 0.0018). Kaplan-Meier estimates of cumulative incidence were 0.28 in the exenatide-primed arm, compared with 0.68 in the exenatide-naive arm ( p ≤ 0.001). As predicted by the study design, fewer subjects in the exenatide-primed arm reported severe nausea (29%) and vomiting (10%) than those in the exenatide-naive arm (48 and 31%, respectively). In the exenatide-primed arm, fasting serum glucose progressively declined over the first 35 days of dosing, but was unchanged in the exenatide-naive arm (placebo phase) during the same interval. Conclusion Gradual dose-escalation of exenatide successfully reduced the proportion of subjects experiencing dose-limiting nausea and vomiting, with no loss of glucoregulatory activity, thus demonstrating the value of gradual dose-escalation in mitigating the gastrointestinal side effects of exenatide. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib., Materials and Methods: Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151., Results: One-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo., Conclusions: MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity., (© 2017 John Wiley & Sons Ltd.)