A New Class of Non-Linear Stability Preserving Operators

We extend Br\"and\'en's recent proof of a conjecture of Stanley and describe a new class of non-linear operators that preserve weak Hurwitz stability and the Laguerre-P\'olya class.Comment: Fixed typos, spelling, and updated links in reference

How should implementation of the human right to health be assessed? A scoping review of the public health literature from 2000 to 2021.

The human right to health is a critical legal tool to achieve health justice, and universal health coverage is included among the Sustainable Development Goals. However, the content and meaning of the right to health may not be used adequately in public health research. We conducted a scoping review of the literature to discover the extent to which the legal principles underlying the right to health are used in public health. We mapped the various attempts to assess implementation of this right since its legal content was clarified in 2000.The first studies emerged in 2006, with an increase and a wider variety of investigations since 2015. We observe that some key principles do form the basis of right-to-health assessments, but some concepts remain unfamiliar. Critically, public health academics may have limited access to human rights research on health, which creates a gap in knowledge between the two disciplines

Anxiety, emotional processing and depression in people with multiple sclerosis.

BACKGROUND: Despite the high comorbidity of anxiety and depression in people with multiple sclerosis (MS), little is known about their inter-relationships. Both involve emotional perturbations and the way in which emotions are processed is likely central to both. The aim of the current study was to explore relationships between the domains of mood, emotional processing and coping and to analyse how anxiety affects coping, emotional processing, emotional balance and depression in people with MS. METHODS: A cross-sectional questionnaire study involving 189 people with MS with a confirmed diagnosis of MS recruited from three French hospitals. Study participants completed a battery of questionnaires encompassing the following domains: i. anxiety and depression (Hospital Anxiety and Depression Scale (HADS)); ii. emotional processing (Emotional Processing Scale (EPS-25)); iii. positive and negative emotions (Positive and Negative Emotionality Scale (EPN-31)); iv. alexithymia (Bermond-Vorst Alexithymia Questionnaire) and v. coping (Coping with Health Injuries and Problems-Neuro (CHIP-Neuro) questionnaire. Relationships between these domains were explored using path analysis. RESULTS: Anxiety was a strong predictor of depression, in both a direct and indirect way, and our model explained 48% of the variance of depression. Gender and functional status (measured by the Expanded Disability Status Scale) played a modest role. Non-depressed people with MS reported high levels of negative emotions and low levels of positive emotions. Anxiety also had an indirect impact on depression via one of the subscales of the Emotional Processing Scale ("Unregulated Emotion") and via negative emotions (EPN-31). CONCLUSIONS: This research confirms that anxiety is a vulnerability factor for depression via both direct and indirect pathways. Anxiety symptoms should therefore be assessed systematically and treated in order to lessen the likelihood of depression symptoms

Whole systems approaches to obesity and other complex public health challenges: a systematic review

Background: Increasing awareness of the complexity of public health problems, including obesity, has led to growing interest in whole systems approaches (WSAs), defined as those that consider the multifactorial drivers of overweight and obesity, involve transformative co-ordinated action across a broad range of disciplines and stakeholders, operate across all levels of governance and throughout the life course. This paper reports a systematic review of WSAs targeting obesity and other complex public health and societal issues, such as healthy lifestyles for prevention of non-communicable disease. Methods: Seven electronic databases were searched from 1995 to 2018. Studies were included if there had been an effort to implement a WSA. Study selection was conducted by one reviewer with a random 20% double checked. Data extraction and validity assessment were undertaken by one reviewer and checked by a second reviewer. Narrative synthesis was undertaken. Results: 65 articles were included; 33 about obesity. Most examined multicomponent community approaches, and there was substantial clinical and methodological heterogeneity. Nevertheless, a range of positive health outcomes were reported, with some evidence of whole systems thinking. Positive effects were seen on health behaviours, body mass index (BMI), parental and community awareness, community capacity building, nutrition and physical activity environments, underage drinking behaviour and health, safety and wellbeing of community members, self-efficacy, smoking and tobacco-related disease outcomes. Features of successful approaches reported in process evaluations included: full engagement of relevant partners and community; time to build relationships, trust and capacity; good governance; embedding within a broader policy context; local evaluation; finance. Conclusions: Systems approaches to tackle obesity can have some benefit, but evidence of how to operationalise a WSA to address public health problems is still in its infancy. Future research should: (a) develop an agreed definition of a WSA in relation to obesity, (b) look across multiple sectors to ensure consistency of language and definition, (c) include detailed descriptions of the approaches, and (d) include process and economic evaluations

Formative Research on Perceptions of Biobanking: What Community Members Think

Preparing healthy community members with timely communications prior to engaging them in a request to donate biospecimens promises to improve the experience of biobanking participation. To this end, a qualitative study was conducted to assess community member knowledge, attitudes, beliefs, and informational needs about cancer-related biospecimen collection in a large metropolitan area in southwest Florida. The study utilized purposive sampling techniques to recruit a total of 95 participants to participate in 12 focus groups, segmented by race/ethnicity and language preference (mixed race, African American only, and Spanish speaking) and age (18–29, 30–54, and 55 and older). Focus group interviews were analyzed using content analysis to identify emergent themes. Overall, participants in the 30 years and older groups were favorable toward participating in biobanking if their concerns were addressed, such as confidentiality and consent issues, in contrast to participants aged 18–29 who were more skeptical. For all participants, the desire to participate in research that seeks new cancer treatments outweighed mistrust. Moreover, many cited the potential scientific benefit for future generations as a primary motivator. Finally, in some groups a therapeutic misconception was expressed, where participants expressed a willingness to forego confidentiality of their health status in exchange for therapeutic benefit. This study contributes to the literature on community perceptions of the benefits and barriers of biobanking and adds to the development of meaningful education communication priming tools to advance understandings about biobanking

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471