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Background: One common mode of lead failure is insulation breach, which may result in myopotential noise and device malfunction. "Pseudo-unipolarization" of bipolar pacing stimuli, as observed from a routine 12-lead electrocardiogram (ECG) due to stimulus current leak, has been observed with insulation breaches., Objective: We sought to characterize this electrocardiographic finding to detect this type of lead malfunction., Methods: A total of 138 transvenous leads were analyzed, including 88 with known malfunction and 50 normal leads. The amplitude of a bipolar pacing stimulus on the ECG was recorded and compared with a control data set of newly implanted leads with bipolar stimuli normalized for output., Results: The malfunction group consisted of 61% right atrium and 39% right ventricle leads with mean pacing output of 2.74 V at 0.5 ms. There was a significant difference in ECG bipolar stimulus amplitudes at time of identification of failure (7.89 ± 7.56 mm/V; P < .001) compared with those of normal leads (0.86 ± 0.41 mm/V). Receiver operating characteristic curve for the prediction of lead malfunction based on absolute ECG amplitude displayed an area under the curve of 0.93 (95% CI, 0.891-0.969). When normalized for programmed stimulus output, a cutoff of 5 mm/V demonstrated a sensitivity of 91% and a specificity of 92% (area under the curve, 0.967; 95% CI, 0.938-0.996)., Conclusion: The maximum amplitude of a bipolar pacing stimulus on the ECG is significantly lower in normal functioning leads compared with those with known malfunction. This simply derived variable demonstrated good accuracy at identifying lead failure due to insulation breach., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Climate change is a severe global threat. Research on climate change and vulnerability to natural hazards has made significant progress over the last decades. Most of the research has been devoted to improving the quality of climate information and hazard data, including exposure to specific phenomena, such as flooding or sea-level rise. Less attention has been given to the assessment of vulnerability and embedded social, economic and historical conditions that foster vulnerability of societies. A number of global vulnerability assessments based on indicators have been developed over the past years. Yet an essential question remains how to validate those assessments at the global scale. This paper examines different options to validate global vulnerability assessments in terms of their internal and external validity, focusing on two global vulnerability indicator systems used in the WorldRiskIndex and the INFORM index. The paper reviews these global index systems as best practices and at the same time presents new analysis and global results that show linkages between the level of vulnerability and disaster outcomes. Both the review and new analysis support each other and help to communicate the validity and the uncertainty of vulnerability assessments. Next to statistical validation methods, we discuss the importance of the appropriate link between indicators, data and the indicandum. We found that mortality per hazard event from floods, drought and storms is 15 times higher for countries ranked as highly vulnerable compared to those classified as low vulnerable. These findings highlight the different starting points of countries in their move towards climate resilient development. Priority should be given not just to those regions that are likely to face more severe climate hazards in the future but also to those confronted with high vulnerability already., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The neuroendocrine hypothalamus regulates a spectrum of essential biological processes and underlies a range of diseases from growth failure to obesity. While the exploration of hypothalamic function has progressed well, knowledge of hypothalamic development is poor. In particular, very little is known about the processes underlying the genesis and specification of the neurons in the arcuate and ventromedial nuclei. Recent studies demonstrate that the proneural basic helix-loop-helix transcription factor Mash1 is required for neurogenesis and neuronal subtype specification in the ventral hypothalamus. We demonstrate here that Ngn3, another basic helix-loop-helix transcription factor, is expressed in mitotic progenitors in the arcuate and ventromedial hypothalamic regions of mouse embryos from embryonic days 9.5-17.5. Genetic fate mapping and loss of function studies in mice demonstrate that Ngn3+ progenitors contribute to subsets of POMC, NPY, TH and SF1 neurons and is required for the specification of these neuronal subtypes in the ventral hypothalamus. Interestingly, while Ngn3 promotes the development of arcuate POMC and ventromedial SF1 neurons, it inhibits the development of NPY and TH neurons in the arcuate nuclei. Given the opposing roles of POMC and NPY neurons in regulating food intake, these results indicate that Ngn3 plays a central role in the generation of neuronal populations controlling energy homeostasis in mice., (Copyright © 2010 Elsevier Inc. All rights reserved.)