Principle Of States Research Articles

Motivational Kantianism: Cassirer's late shift towards a regulative conception of the apriori

Cassirer often pointed out that the physics of his time had progressively become a ‘physics of principles’ rather than a ‘physics of models'. Until the 1920s, Cassirer regarded these principles (the energy principle, the relativity principle etc.) as a constitutive but provisional form of the a priori, imposing specific limitations on the form of the allowable laws of nature. This paper argues that Cassirer shifted the role of the a priori to a deeper level in the 1930s. The a priori acquires a regulative meaning, motivating the search for the laws of nature without providing any particular insight into their form. The paper contends that, in this way, Cassirer embraced what might be called a ‘motivational Kantianism’. It can be argued whether this stance still deserves to be called a form of ‘neo-Kantianism’. However, depriving the a priori of any specific content allowed Cassirer to attribute a constitutive role to ‘statements of principle’ without granting them a priori status. This paper concludes that this attitude towards the role of ‘principles’ in physics sets Cassirer's philosophy apart from its positivist and post-positivist counterparts.

Harmonising terminology with MedDRA for plain language summaries.

Human volunteers are key stakeholders in any clinical research. For inclusiveness it is ethically imperative to ensure data transparency even after the completion of clinical trials. This is also supported by the Declaration of Helsinki, which in a statement of ethical principles, provides guidance to physicians and other participants in medical research involving human volunteers, suggesting that they have the full right to the results of a trial (1).

The Nature of Social Work: An Ecocentered Analysis of Key Social Work Statements.

This article addresses references to people's natural environments in some of the central declarative statements that shape social work worldwide. Four types of documents were analyzed, including statements associated with the Global Definition of Social Work, the Global Standards for Social Work Education and Training, the Global Social Work Statement of Ethical Principles, and the Grand Challenges for Social Work initiative. The analysis was driven by a critical-interpretive approach, seeking explicit and possibly implied references to nature and the environment across documents, with special attention to themes concerning the relationship between micro and macro perspectives, disciplinarity and inter- or transdisciplinarity, and relations between humankind and nature. In general, direct references to social work's possible intersections with issues related to nature and the natural environment were scarce in the materials examined. That having been said, our analysis did find that ecocentered interpretations enable locating prospective "bridges" for the incorporation of deeper ecological perceptions of social work into statements. Such findings constitute a call to action, and the possible implications of continuing to broadly disregard ecological aspects of social work in core materials published by influential professional institutions are discussed.

Little Lewis and Latin Folk in Chaucer's Prologue to the Treatise on the Astrolabe

Little Lewis and Latin Folk in Chaucer's Prologue to the <i>Treatise on the Astrolabe</i>

Comparing the Literatures: Literary Studies in a Global Age

Comparing the Literatures: Literary Studies in a Global Age

Establishing a statement of principles for community engagement with civil engineering

Community engagement with civil engineering is essential to deliver the UN Sustainable Development Goals and to address ‘wicked’ problems such as climate change. This paper explains how the Institution of Civil Engineers developed its statement of Principles for Community Engagement with Engineering to underpin best practice across the infrastructure project life cycle. The principles are intended to be adaptable to suit a range of contexts, sectors and scales of project, and to support civil engineers at different stages of their career and levels of influence. They provide a foundation for further development of best-practice case studies and guidance, to be shared through civil engineering education and professional development.

Fentanyl‐Induced Sleep Disruption in C57BL/6J (B6) Mice is not Secondary to Increased Motor Activity or Hypothermia

Studies of mice have enhanced the understanding of opioid‐induced respiratory depression (10.1152/jn.00017.2021) and opioid abuse (10.1016/j.neuropharm.2013.08.028). The potential that mechanistic insights gained from studies of mice may be relevant for humans is consistent with the close genetic homology between these two species. Features of mouse biology, however, may limit the extent to which studies of opioid effects can be generalized. Fentanyl administered to mice can increase motor activity (10.1152/jn.00711.2020), cause hypothermia (10.1124/jpet.102.037655), alter cortical electroencephalogram (EEG) power, and disrupt the temporal organization of sleep (10.1152/jn.00266.2021). Our recent finding that fentanyl causes dose‐dependent sleep disruption in B6 mice (10.1096/fasebj.2021.35.S1.01706) led us to test the hypothesis that fentanyl‐induced increases in wakefulness are not caused by changes in motor activity or body temperature. The FASEB Statement of Principles for the use of Animals in Research and Education was followed. Adult males (n=8) were housed in a temperature‐ and humidity‐controlled room with a 12:12h light:dark cycle. Mice were implanted with electrodes and subcutaneous telemeters (DSI HD‐X02) to record EEG, electromyogram, motor activity, and body temperature. Seven to 10 days after recovery from surgery each mouse received a series of subcutaneous injections (0.3 mL) of saline (vehicle) and increasing half‐log doses of fentanyl (0.001 to 3 mg/kg). All injections were made within 60 min of light onset and mice were recorded for 4 h. Injections in the same mouse were separated by 3 or 4 days. Repeated measures mixed model ANCOVAs were performed to evaluate percent time awake between fentanyl dose while accounting for the effects of motor activity and body temperature. Each ANCOVA model was evaluated to determine if the motor activity and body temperature slopes at each level of fentanyl were equal to zero by including the fentanyl main effect and the fentanyl by motor activity (p = 0.11) or fentanyl by body temperature (p = 0.19) interaction. This established the lack of dependence between fentanyl dose and motor activity or body temperature when explaining differences in percent of time in wakefulness. Subsequent common slope models were performed including the main effects for fentanyl with body temperature and fentanyl with motor activity to confirm no effects of either covariate on percent time awake. Motor activity (p = 0.611) and body temperature (p = 0.614) were not found to be significant predictors of increased wakefulness. This finding supports the interpretation that fentanyl causes sleep disruption that is not secondary to enhanced motor activity or hypothermia.

Sexually dimorphic role of smooth muscle cell estrogen receptor alpha in aging‐associated arterial stiffness

BackgroundAging is associated with rising arterial stiffness (AS), an independent risk factor for cardiovascular disease. The development of aging‐associated AS follows a sexually dimorphic pattern with women developing AS later in life. Estrogen and estrogen receptor alpha (ERα) are protective in the premenopausal state, potentially due to the regulation of the vasoprotective angiotensin II type 2 receptor (AT2R), however, the role of estrogen/ERα in aging‐associated AS has not been defined and the mechanisms of the sexually‐dimorphic development of aging‐associated AS are unknown.Methods/ResultsAll studies were conducted in accordance with the FASEB Statement of Principles for the use of Animals in Research and Education. We generated novel smooth muscle cell‐specific ERα‐KO mice and measured aortic pulse wave velocity (PWV), an index of AS, in 3, 12, and 18 month old male and female intact and KO mice. Male mice develop increases in AS from 3 to 12 months compared to 3 to 18 months in females (p&lt;0.05). SMC‐ERα‐KO protected females from the aging‐associated increase in AS (p&lt;0.05). Circulating estrogens also declined in 18 month old females vs. 3 mo. (p&lt;0.05), suggesting a role for unliganded SMC‐ERα in aging‐associated AS. SMC‐ERα‐KO females were also protected from the aging‐associated decline in aortic AT2R expression observed in intact females (p&lt;0.05). To further investigate the potential role of unliganded SMC‐ERα in AS, we performed ovariectomy (OVX) or sham surgeries in young female SMC‐ERα‐Intact and KO mice and measured PWV. Results demonstrated an OVX‐driven increase in AS that was prevented by SMC‐ERα‐KO (p&lt;0.05). This was also associated with an OVX‐mediated decrease in aortic expression of the AT2R, which was prevented by SMC‐ERα‐KO. To determine the in vivo role of AT2R in the vascular protection observed in 12 month old female mice, we treated 12 month old male and female mice with AT2R antagonist PD‐123319 (3mg/kg/day) or vehicle via osmotic minipumps for 4 weeks. Chronic inhibition of the AT2R increased AS in 12 month old females (p&lt;0.05), but not males, suggesting that AT2R‐mediated protection contributes to the delay in aging‐associated AS in female mice. In vitro studies also demonstrated that estrogen upregulates AT2R mRNA and protein in female mouse aortic SMC, supporting an estrogen‐mediated mechanism of AT2R driven vascular protection in females.ConclusionThese data indicate sex differences in the time course of the development of aging‐associated arterial stiffness and suggest the presence of unliganded SMC‐ERα contributes specifically to aging‐associated arterial stiffness in females via reductions in vascular AT2R. Further, these results implicate that AT2R agonist therapy may improve cardiovascular outcomes in aging women to retain the beneficial downstream effects of estrogen signaling, without the potential detrimental effects of hormone replacement therapy.

Opioid‐Induced Respiratory Depression (OIRD) in C57BL/6J (B6) Mice is Mitigated by Prefrontal Cortex Neostigmine Administration

Opioids diminish the wakefulness stimulus for breathing in humans (10.1152/physiol.00043.2020) and mice (10.1152/jn.00017.2021). The neuronal networks underlying the wakefulness stimulus remain poorly understood. Cholinergic transmission in the prefrontal cortex (PFC) promotes cortical EEG activation (10.1152/jn.2002.87.6.2817), increases wakefulness (10.3389/fnins.2020.567849), and stimulates breathing (10.1096/fasebj.2021.35.S1.01735). This study is using whole‐body plethysmography (WBP) to test the hypothesis that microinjection of the acetylcholinesterase inhibitor neostigmine (Neo) into the PFC attenuates OIRD caused by systemic fentanyl administration in male B6 mice. All procedures followed the FASEB Statement of Principles for the use of Animals in Research and Education. Previous studies of the dose‐dependent effects of fentanyl in B6 mice used CO2 to stimulate breathing (10.1038/npp.2015.201). Therefore, we first quantified the dose‐dependent effects of systemic fentanyl administration on B6 mice breathing room air. Mice (n=12) received a 0.3 mL intraperitoneal (IP) injection of saline (control) and 8 increasing doses of fentanyl (0.001 to 3 mg/kg), each separated by one half‐log unit. Repeated measures one‐way ANOVA showed that fentanyl caused a dose‐dependent decrease (F(2.47; 27.12)= 20.30, p&lt;0.0001) in minute ventilation (V̇E) quantified as mL/min/g body weight. Additional mice (n=4) were implanted with a 26‐gauge guide cannula aimed for the PFC at coordinates (mm) A/P = 1.94; M/L = 0.3; D/V = 2.5 relative to bregma (histology pending). Seven to ten days after surgery, WBP was used to evaluate the respiratory effects of 0.1 mg/kg IP fentanyl in combination with unilateral PFC microinjection of saline (control) or 0.016 nmol/50nL Neo (4.8 ng). Breathing was compared among three conditions: 1=(IP saline+PFC saline), 2=(IP fentanyl+PFC saline), and 3=(IP fentanyl+PFC Neo). Centrally administered drugs rapidly diffuse away from a microinjection site. Accordingly, V̇E was quantified during the initial 10 min after PFC microinjection. Comparison between conditions 1 and 2 showed that IP fentanyl caused a 19.7% decrease in V̇E. Comparing conditions 2 and 3 showed that IP fentanyl+PFC Neo caused a 44.3% increase in V̇E. Regression analyses revealed that PFC Neo delayed the onset of OIRD. During the initial 5 min after PFC Neo, time accounted for 84% of the variance in V̇E compared to 60% of the variance after PFC saline. During the 6 to 10 min after PFC injection, time explained only 27% of the variance in V̇E, likely due to Neo diffusing away from the PFC. The slope of the minute ventilation line (V̇E=(0.03)(min)+3.2) increased after IP fentanyl + PFC Neo and decreased (V̇E=(‐0.12)(min)+3.8) after IP fentanyl + PFC saline. The slopes of these two functions were significantly different (p&lt;0.01). For up to 8 min, 4.8 ng of Neo delivered into the PFC diminished OIRD caused by 0.1 mg/kg IP fentanyl. These findings support our working hypothesis that enhancing cholinergic transmission in the PFC promotes to the wakefulness stimulus for breathing and mitigates OIRD.

Institutional logics and the multiorganizational governance arrangements of humanitarian INGOs

AbstractGovernance within the growing number of multiorganizational international nongovernmental organization (INGO) families in the humanitarian sector is challenging. Ideas are evolving about what the objectives of humanitarian INGOs should be, what the most appropriate means of achieving these objectives are, and how best to demonstrate effectiveness and integrity to others. Within this context, scholars observe that choices in governance approaches are driven largely by internal politics within the bounds of legitimacy, leading some to refer to INGOs as principled‐instrumentalists. However, we know little about the principles bounding these instrumental choices. Drawing from an institutional logics perspective, this paper compares the multiorganizational governance arrangements of 40 humanitarian INGO families with the values they espouse in their statements of values, principles, or beliefs. The idea being that these statements of values can serve as a window into the logics guiding organizational decision‐making and provide the basis for how power is enacted and strategies chosen within these social settings. These findings have the potential to help leaders of multisite nonprofits make sense of the ways changing values, beliefs, and logics are prompting their organizations to reconsider how they balance inherent management tensions.

Fraud and Deceit in Medical Research

Fraud and Deceit in Medical Research

How to appear fully committed to doing nothing at all about structural and systemic racism: A modest proposal for health and higher education services.

How to appear fully committed to doing nothing at all about structural and systemic racism: A modest proposal for health and higher education services.

Ethics in Psychiatric Research.

Ethics in Psychiatric Research.

Prisoners During the Pandemic

Abstract In connection with the COVID-19 pandemic, all countries of the world are taking actions to minimize the spread of the virus. These actions interfere with civil rights and liberties. They particularly affect convicts who serve prison sentences, as such sentences deprive them many of their rights or significantly restrict them. Recognizing the situation of prisoners at this difficult time, in March 2020, the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment (CPT) issued the Statement of principles relating to the treatment of persons deprived of their liberty in the context of the coronavirus disease (COVID-19)1, while the Subcommittee on Prevention of Torture and other Cruel, Inhuman, or Degrading Treatment or Punishment prepared Advice to States parties and national preventive mechanisms to the coronavirus disease (COVID-19) pandemic. The purpose of this paper is to determine whether our country, while taking certain actions, takes into account the recommendations contained in both aforementioned documents.

Harmonising terminology with MedDRA for plain language summaries.

Human volunteers are key stakeholders in any clinical research. For inclusiveness it is ethically imperative to ensure data transparency even after the completion of clinical trials. This is also supported by the Declaration of Helsinki, which in a statement of ethical principles, provides guidance to physicians and other participants in medical research involving human volunteers, suggesting that they have the full right to the results of a trial (1).

Putting AI ethics to work: are the tools fit for purpose?

Bias, unfairness and lack of transparency and accountability in Artificial Intelligence (AI) systems, and the potential for the misuse of predictive models for decision-making have raised concerns about the ethical impact and unintended consequences of new technologies for society across every sector where data-driven innovation is taking place. This paper reviews the landscape of suggested ethical frameworks with a focus on those which go beyond high-level statements of principles and offer practical tools for application of these principles in the production and deployment of systems. This work provides an assessment of these practical frameworks with the lens of known best practices for impact assessment and audit of technology. We review other historical uses of risk assessments and audits and create a typology that allows us to compare current AI ethics tools to Best Practices found in previous methodologies from technology, environment, privacy, finance and engineering. We analyse current AI ethics tools and their support for diverse stakeholders and components of the AI development and deployment lifecycle as well as the types of tools used to facilitate use. From this, we identify gaps in current AI ethics tools in auditing and risk assessment that should be considered going forward.

Moral consideration of nonhumans in the ethics of artificial intelligence

This paper argues that the field of artificial intelligence (AI) ethics needs to give more attention to the values and interests of nonhumans such as other biological species and the AI itself. It documents the extent of current attention to nonhumans in AI ethics as found in academic research, statements of ethics principles, and select projects to design, build, apply, and govern AI. It finds that the field of AI ethics gives limited and inconsistent attention to nonhumans, with the main activity being a line of research on the moral status of AI. The paper argues that nonhumans merit moral consideration, meaning that they should be actively valued for their own sake and not ignored or valued just for how they might benefit humans. Finally, it explains implications of moral consideration of nonhumans for AI ethics research and practice, including for the content of AI ethics principles, the selection of AI projects, the accounting of inadvertent effects of AI systems such as via their resource and energy consumption and potentially certain algorithmic biases, and the research challenge of incorporating nonhuman interests and values into AI system design. The paper does not take positions on which nonhumans to morally consider or how to balance the interests and values of humans vs. nonhumans. Instead, the paper makes the more basic argument that the field of AI ethics should move from its current state of affairs, in which nonhumans are usually ignored, to a state in which nonhumans are given more consistent and extensive moral consideration.

ACTRIMS Forum 2021 – Invited Program

Background: After an historical absence of data, studies on MS epidemiology in Latin America (LATAM) have consistently increased since the foundation of LACTRIMS in 1999. The socioeconomic and political health impact of MS in the region remains to be established. Objectives: To assess the presence of MS frequencies in the different regions of LATAM and its reflection in local health policies and neurological care and education on the disease. Methods: Thematic presentations from 10 biennial LACTRIMS meetings (2000-2019) and recent publications on Latin American epidemiology cited in PubMed (2012-2020) assessing content for societal effects and policy provided the framework for this study. Official statement of principles (SOP) from 16 MS organizations representing 14 different countries from the Latin American MS organizations Network (LATEM) were included. Since 2018, LATEM's positions derive from input led by ASOGEM (Guatemala);APEMED (Paraguay);ALEM (Colombia) and ABEM (Brazil). Other groups explored for SOP) were 'Renacer' (Dominican Republic), ESMUP (Peru), ALCEM and EMA (Argentina), EMUR (Uruguay), FEMMEX (Mexico) and FUCACEM (MS Central American and Caribbean Foundation). Determination of societal impact was assessed by the development of registered local neurological MS study groups, or events of significance including legal accomplishments or governmental determinations improving education and care of MS. Results: The MS International Federation and the WHO place the prevalence of disease for the majority of countries in LATAM from very low (0-5/100,000) to low-to-moderate (5.5-20/100,000). Two areas, a Monterrey's suburb in northeast Mexico (25° N), and Buenos Aires, Argentina (34° S) show moderate frequencies (30/100,000), while the highest prevalence in LATAM is noted in Puerto Rico (77.7/100,000). Countries with a large geographic extensions show zonal differences. Prevalence data from 15 countries is available. Only four national incidence studies: Panama, Uruguay, Chile and Argentina, exist. A study from the six Central American countries and three Spanish-speaking Caribbean country islands (Cuba, Puerto Rico and Dominican Republic) show high index of EDSS disability > 3.5 (37%) among the subjects included in these series, hence potentially reflecting into additional socioeconomic burden to the local communities. Eight CTRIMS national associations have developed in the region, all functioning as LACTRIMS' chapters. Another multinational study group from Central America and the Caribbean emerged recently as a forum (FOCEM). Recent virtual discussions emphasized every effort to avoid the COVID-19 pandemic to disrupt access to MS therapies in the region. The organizations play a determining role in preventing the indiscriminate approval by uninformed local health agencies of medications lacking safety and efficacy evidence, i.e. biosimilar products (ASOGEM). Conclusions: The emergence of MS in the Americas, despite its reportedly low epidemiologic frequencies, has affected importantly the socioeconomic health regional systems. Initiatives to integrate the neurological community with MS organizations and stakeholders to improve MS education, its management, and access to quality therapy in LATAM appear thus far to be a regionwide unifying tendency.

International standards for the prevention of the ill-treatment of persons deprived of their liberty in the context of the coronavirus disease (COVID-19) pandemic

The paper examines international standards for the prevention of ill-treatment of persons deprived of their liberty in the context of the COVID-19 pandemic in the member states of the Council of Europe. The Committee's Statement of principles relating to the treatment of persons deprived of their liberty in the context of the coronavirus disease (Covid-19) pandemic has been analyzed. The paper identifies the positive obligations of the state in the field of guaranteeing human rights, namely legal, practical and derivative means. The responses of Member States to a number of questions that have been the subject of CPT recommendations for many years have been examined. The absolute nature of the prohibition of torture and inhuman or degrading treatment or punishment, which is an imperative of international law, is revealed. The basic principle must be to take all possible action to protect the health and safety of all persons deprived of their liberty. The paper defines the following principles: 1. WHO guidelines on fighting the pandemic as well as national health and clinical guidelines consistent with international standards must be respected and implemented fully in all places of deprivation of liberty. 2. Staff availability should be reinforced, and health and safety protection as well as training necessary in order to be able to continue to fulfil their tasks in places of deprivation of liberty. 3. Any restrictive measure taken vis-à-vis persons deprived of their liberty to prevent the spread of Covid-19 should have a legal basis and be necessary, proportionate, respectful of human dignity and restricted in time. 4. Alternatives to deprivation of liberty. 5. Special attention will be required to the specific needs of detained persons with particular regard to vulnerable groups and/or at-risk groups, such as older persons and persons with pre-existing medical conditions. 6. Restrictions on contact with the outside world, including visits, should be compensated for by increased access to alternative means of communication (such as telephone or Voice-overInternet-Protocol communication). 7. Respect of the right to maintain adequate personal hygiene (including access to hot water and soap) and the right of daily access to the open air (of at least one hour). 8. Fundamental safeguards against the ill-treatment of persons in the custody of law enforcement officials (access to a lawyer, access to a doctor, notification of custody) must be fully respected in all circumstances and at all times.

Neostigmine Microinjected into Prefrontal Cortex of C57BL/6J (B6) Mice Stimulates Breathing

The prefrontal cortex modulates breathing (Neuroscience 123: 17, 2004; J Physiol 591: 6069, 2013) via neurochemical mechanisms that remain to be fully characterized. This study is testing the hypothesis that microinjection of neostigmine bromide, an acetylcholinesterase inhibitor, into the prefrontal cortex of freely behaving mice alters breathing. All procedures involving mice were conducted in accordance with the FASEB Statement of Principles for the use of Animals in Research and Education. Adult male mice (n = 8) were anesthetized and implanted with a 26-gauge guide cannula aimed at the medial prefrontal cortex. One week after recovering from surgery, mice were microinjected (50 nL) with saline (vehicle control) and two concentrations of neostigmine (0.005 and 0.016 nmol/50 nL; 1.5 and 4.8 ng/50 nL). Each mouse received saline and neostigmine in a repeated measures within-subjects design. Respiratory rate (RR) expressed as breaths/min was quantified using whole-body plethysmography. Repeated measures one-way ANOVA showed neostigmine significantly (F(1.9,13.9) = 6.3, p = 0.0116) altered RR. Relative to saline, RR was increased 11.9% by 0.005 nmol and 18.2% by 0.016 nmol neostigmine. Dunnett's post hoc comparisons test revealed that 0.016 nmol significantly (p < 0.05) increased RRwhen compared to saline. Cohen's d = 1.34 for saline vs. 0.016 nmol neostigmine. Histological analyses of microinjection sites confirmed drug delivery into the prelimbic region of the prefrontal cortex. Mean ± S.D. coordinates of the injection sites were 1.8 ± 0.4 mm anterior, 0.3 ± 0.1 mm lateral, and 2.6 ± 0.6 mm ventral relative to bregma (Paxinos and Franklin, 2008). The mechanism by which cholinergic transmission in the prefrontal cortex stimulates breathing remains to be identified. We speculate that the neostigmine-induced increase in RR evoked from the prefrontal cortex may be modulated by projections from the prefrontal cortex to arousal promoting regions of the nucleus pontis oralis (PnO) (J. Neurosci. 29: 871, 2009). Neuroanatomical studies show that the PnO shares reciprocal connections with respiratory neurons in the ponto-medullary brainstem (Lung Cell. Mol. Physiol. 2: L251, 1995). These anatomical data are consistent with functional studies showing that respiratory rate in B6 mice significantly increased in tandem with increases in prefrontal cortex ACh release (Neuroscience 123: 17, 2004). Considered together, the present results support the interpretation that cholinergic neurotransmission in the prefrontal cortex stimulates the drive to breathe. Ongoing studies are further characterizing the site-dependent and concentration-dependent stimulation of breathing by cholinergic transmission in the prefrontal cortex.