BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

Shepherdson [14] showed that for a discrete ordered ring I, I is a model of IOpen iff I is an integer part of a real closed ordered field. In this paper, we consider integer parts satisfying PA. We show that if a real closed ordered field R has an integer part I that is a nonstandard model of PA (or even IΣ₄), then R must be recursively saturated. In particular, the real closure of I, RC (I), is recursively saturated. We (...) also show that if R is a countable recursively saturated real closed ordered field, then there is an integer part I such that R = RC(I) and I is a nonstandard model of PA. (shrink)

The accurate pricing of securities in the capital markets depends upon the markets being both efficient and fair. In management buyout transactions (MBOs), the price bid by inside managers enhances the efficient pricing of securities but raises a reasonable doubt about the fairness to existing shareholders. This study addresses this fairness question in MBOs and offers short-term and long-term legal alternatives which allow both the efficiency and fairness criteria to be met. In the short-term the case law established in the (...) Basic v. Levinson decision for merger negotiation disclosures should be applied to MBO transactions. Over the longer horizon, legislative changes should be made to existing securities laws. Applying the investor protection principles of the 1933 and 1934 securities acts to MBO transactions will suppress the temptation of managers to extract shareholder wealth for their personal gain. (shrink)

Soil is fragile and nonrenewable but the most basic of natural resources. It has a capacity to tolerate continuous use but only with proper management. Improper soil management and indiscriminate use of chemicals have contributed to some severe global environmental issues, e.g., volatilization losses and contamination of natural waters by sediments and agricultural fertilizers and pesticides. The increasing substitution of energy for labor and other cultural inputs in agriculture is another issue. Fertilizers and chemicals account for about 25% of the (...) production energy investment in agriculture. An additional 60% is accounted for by machinery, gasoline, electricity, and power-related inputs. Fertilizer additions to cropland are not utilized fully and significant amounts, depending on conditions, are either lost in surface runoff or leached into the ground water. The annual discharge of dissolved solids from agricultural lands to the waterways in the USA is substantial. The increasing use of herbicides in agriculture is a threat to the quality of surface and ground water, although this threat is dependent upon both the chemistry of the compound and the ecosystem in which it is used. Especially within the Third World, development of an environmental ethic and environmental laws have not kept pace with the increase in pesticide use. Above all is the severe and global problem of soil degradation currently occurring at the rate of five to seven million hectares per year. The policy and moral aspects of these issues are discussed. (shrink)

Substrate cycles are ubiquitous structures of the cellular metabolism (e.g. Krebs cycle, fatty acids -oxydation cycles, etc... ). Moiety-conserved cycles (e.g. adenine nucleotides and NADH/NAD, etc...) are also important.The role played by such cycles in the metabolism and its regulation is not clearly understood so far. However, it was shown that these cycles can generate multistationarity (bistability), irreversible transitions, enhancement of sensitivity, temporal oscillations and chaotic motions (Hervagault & Canu, 1987; Hervagault & Cimino, 1989; Reich & Sel'kov, 1981; Ricard & (...) Soulié, 1982). Fig. 1: Scheme of the open binary substrate cycle under study. The substrate S is converted into P with a net rate v2. Substrate P is converted in turn into S with a net rate v3. Step v2 is inhibited by excess of the substrate, S. In addition, the cycle operates under open conditions, that is zero-order input of S at rates \ga0(v1) and first order outputs of S and P at rates \gaS and \gaP(v4), respectively. (shrink)

The evolution equations for grain growth and coarsening have been derived in the open literature mainly based on phenomenological considerations. Applying a thermodynamic extremal principle, the evolution equations are derived in a rigorous way. All kinetic parameters are provided directly. Existing relations are proved and generalized.

Objective To evaluate the modes of death and treatment offered in the last 24 h of life to patients dying in 10 Brazilian intensive care units (ICUs) over a period of 2 years. Design and setting Cross-sectional, multicentre, retrospective study based on medical chart review. The medical records of all patients that died in seven paediatric and three adult ICUs belonging to university and tertiary hospitals over a period of 2 years were included. Deaths in the first 24 h of (...) admission to the ICU and brain death were excluded. Intervention Two intensive care fellows of each ICU were trained in fulfilling a standard protocol (κ=0.9) to record demographic data and all medical management provided in the last 48 h of life. The Student t test, Mann–Whitney U test, χ2 test and RR were used for data comparison. Measurements and main results 1053 medical charts were included (59.4% adult patients). Life support limitation was more frequent in the adult group (86% vs 43.5%; p<0.001). A ‘do not resuscitate’ order was the most common life support limitation in both groups (75% and 66%), whereas withholding/withdrawing were more frequent in the paediatric group (33.9% vs 24.9%; p=0.02). The life support limitation was rarely reported in the medical chart in both groups (52.6% and 33.7%) with scarce family involvement in the decision making process (23.0% vs 8.7%; p<0.001). Conclusion Life support limitation decision making in Brazilian ICUs is predominantly centred on the medical perspective with scarce participation of the family, and consequently several non-coherent medical interventions are observed in patients with life support limitation. (shrink)

This paper discusses some engineering considerations that should be taken into account when building a knowledge based system, and recommends isomorphism, the well defined correspondence of the knowledge base to the source texts, as a basic principle of system construction in the legal domain. Isomorphism, as it has been used in the field of legal knowledge based systems, is characterised and the benefits which stem from its use are described. Some objections to and limitations of the approach are discussed. The (...) paper concludes with a case study giving a detailed example of the use of the isomorphic approach in a particular application. (shrink)

The temporal behaviour of the nonlinear compartmental model we have developed for rat calcium metabolism is discussed with respect to the theoretical properties of the self-oscillating autocatalytic subunit around which the model is constructed. Depending on the approximations made, this subunit is described by a minimal two-variable model, SU2, or by a three-variable one, SU3. The diversity of the theoretical dynamic behaviours possible with SU2 is greatly increased with SU3. But the identification of SU3 parameter values in three different experimental (...) situations reveals that biological constraints efficiently preserve a simple circadian rhythm for bone metabolism. This analysis indicates the significant contribution of the available bone crystal pool to the dynamic organization of this tissue, and hence to extracellular calcium homeostasis. (shrink)