Abstract-Model-based design is a powerful design technique for cyber-physical systems, but too often literature assumes knowledge of a methodology without reference to an explicit design process, instead focusing on isolated steps such as simulation, software synthesis, or verification. We combine these steps into an explicit and holistic methodology for model-based design of cyber-physical systems from abstraction to architecture, and from concept to realization. We decompose model-based design into ten fundamental steps, describe and evaluate an iterative design methodology, and evaluate this methodology in the development of a cyber-physical system.

Chronic kidney disease (CKD) increasingly affects younger people, including adolescents and young adults. CKD among females is accompanied by unique reproductive and gynecologic health concerns; though to date, this area has not been well studied. Hormonal disruptions attributed to CKD may underlie the high prevalence of abnormal uterine bleeding and influence the age of menarche in adolescents. Period poverty as a socioeconomic barrier further exacerbates the female-specific burdens of CKD. Reduced fertility in CKD is likely multifactorial and may be related to a reduction in ovarian reserve, reproductive hormone disturbances, and gonadotoxic medication use in addition to low sexual function and activity. Fertility, sexual function and activity, and risk of sexually transmitted infections increase with transplantation. Pregnancy is possible at any stage of CKD, although often accompanied by high risks of maternal and fetal complications. Contraception is thus an important consideration in CKD, but use is low and the risks and benefits of different forms in the setting of CKD are not well characterized. Though patients with CKD report reproductive health as an important element of care, many nephrologists report lack of confidence and training in this area, highlighting the need for targeted research and education. The unique reproductive health care needs of the growing transgender youth population warrant attention in nephrology training with multidisciplinary input. This review will discuss female reproductive health and gynecologic considerations in adolescents and young adults with CKD while proposing clinical and research strategies to improve this understudied yet important aspect of kidney care.

Cardiovascular disease is the leading cause of death in women. Despite recognition of sex-specific differences in cardiovascular health, females are underrepresented across all aspects of cardiovascular research, playing a key role in reducing rigor and reproducibility in cardiovascular research and contributing to these poorer health outcomes. Therefore, we propose a framework to capture factors associated with female sex at the preclinical, recruitment, data collection, and data analysis stages. In preclinical cardiovascular research, female experimental models are commonly excluded despite similar variability in findings compared to males. To reduce this sex bias, inclusion of female models and incorporation of sex as a biological variable are critical to improve reproducibility and inform clinical research and care. While funding agencies have mandated the inclusion of women in clinical trials, greater efforts are needed to achieve an optimal participation to prevalence ratio to increase generalizability of results to real-world settings. Female participants face more stringent exclusion criteria in research compared to males owing to sex-specific factors. However, their routine exclusion from cardiovascular research is not only unethical, but limits generalizability and applicability to clinical practice. Identifying sex assigned at birth, collecting information on female sex-specific and -predominant factors associated with cardiovascular health and risk, and stratifying data by sex, including adverse events, are essential to ensure reproducibility and relevance of findings to target populations. Increasing female representation and the incorporation of female sex-specific cardiovascular risk factors in cardiovascular research will not only lead to enhanced rigor and reproducibility but improved cardiovascular health for all.