Evolutionary fallacies of Nazi psychiatry. Implications for current research

Evolutionary theory has had a major impact on psychiatry since the middle of the 19th century. During the Nazi regime psychiatry supported compulsory sterilization and euthanasia of physically and mentally ill and subsequently the killing of "inferior" races by borrowing scientifically invalid conclusions from evolutionary biology. The present paper deals with some of the flaws and shortcomings of the scientific paradigms of evolutionary theory adopted by psychiatry during the Nazi regime and discusses possible implications for modern research in evolutionary psychology and psychiatry.     

The effects of neutrons in Hiroshima. Implications for the risk estimates

Risk estimates for radiation-induced late effects are relevant to various considerations in radiation protection. Most of these considerations relate to small doses for which no excess risk can be seen even in extensive epidemiological studies. Risk coefficients for radiation protection must, therefore, be based on uncertain extrapolation of observations obtained at moderate or high doses. The extrapolation can not be replaced, as yet, by new, more direct information on processes such as radiation-induced genetic instability or adaptive response. While the new findings indicate complexities that may be highly relevant to the effectiveness- or lack of effectiveness- of radiation at low doses, they remain insufficiently understood to permit a decision as to whether dose-effect relations are linear, curvilinear, or have a threshold in dose. In view of these uncertainties radiation-protection regulations are, today, based on the conservative assumption of a linear dose dependence without threshold. This approach assures a sufficient degree of protection, but it may become unreasonably over-conservative, when the cautious hypothesis is treated as proven fact, and when-in addition-the assumed initial slope of the dose relation is not critically evaluated. A reliable evaluation needs to be based on the follow-up of the atom-bomb bomb survivors, and several major aspects of current interest are discussed here. a) Mortality from solid tumours in Hiroshima shows a statistically significant excess at a colon dose of 50 mGy; however, it is likely that this is the result of a bias in assigning causes of death. b) The solid cancer mortality data of the atom-bomb survivors are consistent with linearity in dose, but they can be shown to be equally consistent with a considerable degree of curvature. c) Even with the present dosimetry system, DS86, a substantial part of the effect at small doses in Hiroshima could be due to neutrons. If this is the case, the risk estimates for gamma-rays need to be accordingly decreased. d) Numerous neutron-activation measurements in Hiroshima indicate that the DS86 underestimates the neutron doses. The evidence is, up to now, based only on activation products of low energy neutrons, but efforts are currently underway to determine activation products of high energy neutrons. If these measurements should substantiate the present trend, the cancer data in Hiroshima would cease to be reliable proof of an effect of gamma-rays at low doses. Instead the dose dependence for gamma-rays could be purely quadratic, and any initial slope in the linear-quadratic dependence might well be attributable to neutrons only.     

Catheter related bloodstream infection (CR-BSI) in ICU patients: making the decision to remove or not to remove the central venous catheter

Background

Approximately 150 million central venous catheters (CVC) are used each year in the United States. Catheter-related bloodstream infections (CR-BSI) are one of the most important complications of the central venous catheters (CVCs). Our objective was to compare the in-hospital mortality when the catheter is removed or not removed in patients with CR-BSI.

Methods

We reviewed all episodes of CR-BSI that occurred in our intensive care unit (ICU) from January 2000 to December 2008. The standard method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and a positive semi quantitative (>15 CFU) culture of a catheter segment from where the same organism was isolated. The conservative method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and one of the following: (1) differential time period of CVC culture versus peripheral culture positivity of more than 2 hours, or (2) simultaneous quantitative blood culture with 5∶1 ratio (CVC versus peripheral).

Results

53 CR-BSI (37 diagnosed by the standard method and 16 by the conservative method) were diagnosed during the study period. There was a no statistically significant difference in the in-hospital mortality for the standard versus the conservative method (57% vs. 75%, p = 0.208) in ICU patients.

Conclusion

In our study there was a no statistically significant difference between the standard and conservative methods in-hospital mortality.     

Nitrogen application is required to realize wheat yield stimulation by elevated CO2 but will not remove the CO2‐induced reduction in grain protein concentration

Elevated CO₂ (eCO₂) generally promotes increased grain yield (GY) and decreased grain protein concentration (GPC), but the extent to which these effects depend on the magnitude of fertilization remains unclear. We collected data on the eCO₂ responses of GY, GPC and grain protein yield and their relationships with nitrogen (N) application rates across experimental data covering 11 field grown wheat (Triticum aestivum) cultivars studied in eight countries on four continents. The eCO₂‐induced stimulation of GY increased with N application rates up to ~200 kg/ha. At higher N application, stimulation of GY by eCO₂ stagnated or even declined. This was valid both when the yield stimulation was expressed as the total effect and using per ppm CO₂ scaling. GPC was decreased by on average 7% under eCO₂ and the magnitude of this effect did not depend on N application rate. The net effect of responses on GY and protein concentration was that eCO₂ typically increased and decreased grain protein yield at N application rates below and above ~100 kg/ha respectively. We conclude that a negative effect on wheat GPC seems inevitable under eCO₂ and that substantial N application rates may be required to sustain wheat protein yields in a world with rising CO₂.     

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.     

Being on the track of thimerosal. Review

The common preservative thimerosal is one of the most important organic mercury compounds human populations are exposed to. It has toxic effect on several cell lines, and it also induces programmed cell death in in vitro experiments. Association is suggested between application of thimerosal-containing vaccines and the occurrence of neurodevelopmental disorders, like autism. While specific recommendations were made to eliminate thimerosal from vaccines, consistent evidence is still lacking for an association of exposure and disease. Unfortunately, it is very hard to study the molecular background of complex human diseases directly; however, investigations on more simple model organisms may lead to a better understanding of thimerosal as a possible disease inducing factor.     

Why modification of the LD50 test will not be enough

During the last 10 years, the 'Three Rs' (reduction, refinement and replacement) concept of alternatives has come to be widely accepted, and new national and international laws require that non-animal procedures should replace animal experimentation wherever possible. Some reduction and refinement of animal use in toxicity testing has been achieved, and non-animal methods are becoming widely used as prescreens. However, even replacing the LD50 test by a modified and validated animal test, the Fixed Dose Procedure, will be a major achievement. In this paper it is argued that this is not good enough, and that more effort must be put into the development, validation, acceptance and use of genuine replacement alternative tests.