Fluid electrolyte changes in trained subjects after water loading and during restriction of muscular activity and chronic hyperhydration

The objective of this investigation was to determine fluid electrolyte changes after water-loading tests and during hypokinesia (decreased number of km taken per day) and daily intake of fluid and salt supplementation (FSS). The studies during hypokinesia (HK) were performed for 364 d on 30 endurance-trained male volunteers in the age range of 23–26 yr, with an average peak oxygen uptake, POU, of 64 mL/kg/min. All volunteers were divided into three equal groups: 10 volunteers were placed on a continuous regime of exercise of 14.4 km/d and served as control subjects (CS); 10 volunteers were submitted to continuous HK without FSS and were considered as the unsupplemented hypokinetic subjects (UHS); and 10 volunteers were under continuous HK and FSS and were considered as the supplemented hypokinetic subjects (SHS). For the simulation of the hypokinetic effect, the UHS and SHS groups were kept continuously under an average of 2.7 km/d for the duration of the study. Prior to exposure to HK, the two groups of volunteers were on the same exercise regime as the control group. During a 60-d preexperimental period and during the remainder of the study, water-loading tests with a water load of 20 mL/kg body wt/min were performed, and urinary and plasma electrolytes (sodium, potassium, calcium, and magnesium) were measured. In the SHS group, urinary excretion of electrolytes and plasma electrolyte content decreased, while in the UHS these values increased after water loading tests and during HK. Based on the obtained data, it is concluded that chronic hyperhydration may be used to prevent or minimize urinary and plasma electrolyte changes in endurance-trained volunteers after water-loading tests and during prolonged restriction of muscular activity.     

Rainfall,groundwater and refuges: Predicting extinctions of Australian tropical mammal species

Abstract A general decline in populations of some savanna mammal species has occurred since the mid-1980s in a fairly pristine national park environment in the Australian wet-dry tropics. Terrestrial native rodents have exhibited the greatest decline and marsupials the least. During the same period, waterholes have dried up and the previous strong association of mammals with riparian vegetation has diminished. A regional index of the level of groundwater was developed from 16 unexploited bores from across the northern half of the Northern Territory. Predicted mean groundwater values over 28 years showed a strong increase throughout the 1970s and a similar decrease throughout the 1980s. Using data since 1986, strong correlations between mammal numbers and groundwater levels for the preceding two years, and much weaker relationships with rainfall, were obtained. In turn, the groundwater levels were best correlated with an eight-year running mean of rainfall for both Darwin and Alice Springs and an eleven-year running mean for the Southern Oscillation Index. Extrapolating backward in time, cumulative pressure variation at Darwin showed two extended periods of predicted low ground-water values, 1900s–1920s and 1940s. Both periods were preceded by the last records of a number of now-extinct mammals from central Australia. A third trough in the early 1960s suggests another period of extinction in central Australia, previously unappreciated due to the lack of survey work in the 1950s. Further, by this analysis, the past 20 years has been the best period for mammals since weather records commenced. Analysis of continental-scale distributions of mammals showed evidence of fluctuations suggesting rocky areas are important refuges for some species during periods of low groundwater levels. In contrast to those in savanna habitats, the mammals of the extensive wetland areas fluctuated in harmony with rainfall on a short-term basis except where habitat is flooded. It is the species which occur only in savanna but not also in rocky or wetland habitats which are most at risk. A number of other species-vulnerability characteristics were identified: riparian vegetation specificity; the degree to which they fall within the critical size range (35 g-5. 5 kg); degree of semelparity; smallness of population size; and smallness of geographic range. Those savanna species with annual life histories strongly associated with riparian areas are likely to be in greatest jeopardy. The species which appear to be most vulnerable in northwestern Australia are Conilurus penicillatus, Mesembriomys gouldii, Mesembriomys macrurus, Antechinus bellus, Phascogale tapoatafa and Rattus tunneyi. Our recent benign climatic history has coincided with the great public environmental awakening and upsurge in environmental research and management efforts. This historical accident has probably led us to overstate the negative effects of human impact and also our ability to change the course of biological history by ameliorating human impact. Our distorted view of these factors has further led us to over-emphasize research of a spatial nature to the detriment of temporal studies. We must redress this balance.     

WHICH BENEFITS OF RESEARCH PARTICIPATION COUNT AS ‘DIRECT’?

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research.     

ON THE NEED FOR IMPROVED PROTECTIONS OF INCAPACITATED AND NON‐BENEFITING RESEARCH SUBJECTS

In this article, it is claimed that the protective provisions for adults with impaired decision‐making capacity are misguided, insofar as they do not conclusively state whether research on this group should be permitted only as an exception, and as they arbitrarily allow for some groups to benefit from such research while others will not. Moreover, the presumed or former will of the subject is given insufficient weight, and the minimal risk standard does not make sense in this context. Because of these problems, the present guidelines allow for the possibility of vulnerable people being exploited, something that is hidden behind a guise of solidarity. Instead we need to address the real issues at stake by rewriting the present statutes. It is suggested that new guidelines should be in some continuity with earlier efforts. However, in order to protect these subjects there is additional need for appointed representatives who monitor research and for legal obligations to compensate for any injuries suffered. Without these or similar measures we won't have an adequate system in place for the protection of non‐benefiting persons who are unable to consent to research.     

Einstein’ssons for energy accounting in LCA

The role and meaning of accounting for energy, including feedstock energy, is reviewed in connection to Einstein’s special theory of relativity. It is argued that there is only one unambiguous interpretation of the term energy-content: The one that corresponds tome The implications for life cycle inventories is that all discussions concerning upper heating value, lower heating value, feedstock energy, etc. are pointless as long as the motivation for choosing one or the other is not specified in relation to the safeguard subjects defined for a particular analysis (LCA or energy analysis). The subjective aspects of energy accounting schemes, even though based on mere thermodynamics, are highlighted. In inventory analysis, it is recommended that energy carriers should be accounted separately and in mass terms. For illustrative purposes, energy statistics and energy assessment are discussed in view of the safeguard subjects underlying the accounting procedures. Based on a set of theses, one possible energy accounting scheme as an indicator of the “consumption of non-renewable energy resources” within the impact assessment of LCA is sketched. It is emphasised that energy accounting schemes do not reflect environmental impacts caused by the energy sources, and the characteristics of the indicator “consumption of non-renewable energy resources” introduced here are highlighted. An erratum to this article is available at .     

Cardiovascular and Renal Outcomes With Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors Combination Therapy: A Meta-Analysis of Randomized Cardiovascular Outcome Trials

ObjectiveThe cardiovascular (CV) and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in people with type 2 diabetes are well known. However, similar beneficial effects of SGLT2i in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) are unknown. It is of interest to explore a trial-level meta-analysis to fill this knowledge gap.MethodsA literature search was conducted in the PubMed and Embase databases until January 31, 2023. All CV outcome trials (CVOTs) reporting the CV and renal outcomes of SGLT2i with or without background DPP4i therapy against the placebo were retrieved. A meta-analysis was subsequently conducted by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio using primarily random-effects analysis.ResultsThis meta-analysis showed that the beneficial 3-point major adverse cardiovascular events composite (3 CVOTs; N = 32 418), the composite of CV death or heart failure hospitalization (hHF) (4 CVOTs; N = 37 687), hHF (3 CVOTs; N = 27 545), CV death (4 CVOTs; N = 34 565), and renal outcomes (2 CVOTs; N = 25 406) with SGLT2i were similar with or without background DPP4i therapy against the placebo (P_{heterogeneity} = .71, .07, .87, .72, and .25; respectively). However, against the placebo, the summary estimates for the 3-point major adverse cardiovascular events composite, hHF, and renal outcomes were stronger with SGLT2i alone, whereas the summary estimates for CV death or hHF composite were larger with SGLT2i with background DPP4i therapy.ConclusionBeneficial CV and renal effects of SGLT2i are similar against the placebo regardless of background DPP4i therapy.     

RESEARCH ON PRISONERS – A COMPARISON BETWEEN THE IOM COMMITTEE RECOMMENDATIONS (2006) AND EUROPEAN REGULATIONS

The Institute of Medicine (IOM) Committee on Ethical Considerations for Revisions to DHHS Regulations for Protection of Prisoners Involved in Research published its report in 2006. It was charged with developing an ethical framework for the conduct of research with prisoners and identifying the safeguards and conditions necessary to ensure that research with prisoners is conducted ethically. The recommendations contained in the IOM report differ from current European regulations in several ways, some being more restrictive and some less so. For example, the IOM report suggests limiting the percentage of prisoners that should be involved in a biomedical study to 50%, a limit that does not exist in Europe. However, the report does not specifically advise against research without a direct benefit to an individual prisoner: the European regulations are more restrictive than the IOM committee recommendations in this respect. The definition of minimal risk varies, as well as the proposed role of the minimal risk requirement and of the principle of subsidiarity (research that can only be done effectively in prisons). The IOM report proposes a number of thoughtful suggestions, which it would be beneficial to implement everywhere, such as registers of research on prisoners. The European regulations offer pragmatic solutions to several thorny issues. In summary, the IOM committee report represents an admirable effort to tackle the present inconsistencies and deficiencies of federal regulations in the US on research on prisoners (45 CFR 46 Subpart C). Nonetheless, before acting on the recommendations, US regulators might consider revisiting international guidelines such as those published by the Council for International Organizations of Medical Science (CIOMS) and the Declaration of Helsinki.     

Reciprocity‐Based Reasons for Benefiting Research Participants: Most Fail,the Most Plausible is Problematic

A common reason for giving research participants post‐trial access (PTA) to the trial intervention appeals to reciprocity, the principle, stated most generally, that if one person benefits a second, the second should reciprocate: benefit the first in return. Many authors consider it obvious that reciprocity supports PTA. Yet their reciprocity principles differ, with many authors apparently unaware of alternative versions. This article is the first to gather the range of reciprocity principles. It finds that: (1) most are false. (2) The most plausible principle, which is also problematic, applies only when participants experience significant net risks or burdens. (3) Seldom does reciprocity support PTA for participants or give researchers stronger reason to benefit participants than equally needy non‐participants. (4) Reciprocity fails to explain the common view that it is bad when participants in a successful trial have benefited from the trial intervention but lack PTA to it.