Obfuscating transparency?

Several recent and prominent articles in Science and Nature deliberately mischaracterized the nature of genuine scientific evidence. Those articles take issue with the United States Environmental Protection Agency's recent proposal to structure its policies and rules only from studies with transparently published raw data. The articles claim it is an effort to obfuscate with transparency, by eliminating a host of studies not offering raw data. A remarkable declaration by a Science editorial is that properly trained experts can verify the scientific evidence of studies without access to raw data, We assert the Agency's proposal must be sustained. Transparency in reporting is a fundamental ethical imperative of objective scientific research justifying massive official regulations and policies. Putative hazards bereft of independent scientific evidence will continue to stoke public anxieties, calling for precautionary regulations and policies. These should rely not on spurious science but on transparent tradeoffs between the smallest exposures compatible with utility and with social perceptions of affordable precaution.

Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding.

Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)-an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0-8 mmol/l) in control but not MLP liver, indicating that GK is flux-generating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.

Toxicologic and epidemiologic clues from the characterization of the 1952 London smog fine particulate matter in archival autopsy lung tissues.

Exposure to atmospheric fine particulate matter (PM), even at low ambient concentrations, has clearly been linked to increases in mortality and morbidity. A 10- micro g m(-3) increase in PM10 (PM < 10 micro m) has been found to produce a 0.5% increase in daily mortality. The mechanism of action is a source of debate, although recent attention has focused on the cardiac effects of PM exposures. Likewise, several possible etiologic agents have been implicated, including ultrafine PM (PM

Relativism, regulation and the dangers of indifferent science: the Sir Roy Cameron lecture of the Royal College of Pathologists.

The evaluation of data obtained from scientific investigations is not easy and the process often seems counterintuitive to the uninformed. Some commentators hold the conviction that ideological motives colour all deliberations-this makes it easy to suggest that in any scientific debate an opponent's reason for holding a particular viewpoint or belief depends on his or her motives, rather than their knowledge base. This position may be useful in providing the grounds on which to mount a polemic against any perceived threat (drugs in modern medicine, pesticides in intensive agriculture or genetically modified organisms). However, its existence is not a reason to ignore the fact that the data obtained by use of the scientific method may be of a different kind from that which depends on opinions, honed by prejudices. Here I use prejudice to mean a bias that may be favourable or unfavourable to a particular viewpoint, rather than to a willful disregard of fact or an unreasoning predilection to arrive at a particular answer--the Precautionary Principle is a good example of only considering results that fit a preconceived viewpoint. The conviction that opinions cannot be based on independent thought has led to a disregard of professionalism and the development of the view that who pays you determines your opinion--not your science. This is relativism, which embodies the assertion that knowledge is relative and that ethical truths depend on the individuals and groups holding them-there are no absolutes. This compounds the problems of regulatory toxicology which is always beset by unavoidable uncertainties and suffers from being based on the use of the results of testing procedures many decades old which have themselves failed to incorporate new knowledge about the processes we investigate (see Hartung, 2009). A more vigorous assertion of the particular values of the scientific viewpoint and a willingness to incorporate new knowledge into regulatory decision making is necessary.

Vascular smooth muscle cells cultured on elastin membranes

Smooth muscle cells from thoracic aortas of 12-week-old rats were cultured on elastin membranes for up to 21 days. The cell cultures were examined using light microscopy, trasmission and scanning electron microscopy. The contractile phenotype characteristic for resident arterial wall muscle cell changed to the synthetic phenotype. In the synthetic state, the muscle cells contain few filaments, but a substantial amount of orgenelles are involved with synthesis. The cells grown on elastin substrates showed a multilayered pattern with the formation of nodules. Cell degeneration was present from dayeight and increased with time. At the end of the experiment, the center of the multilayered areas showed degenerative changes with numerous foam cells of smooth muscle origin, areas of necrosis and a considerable amount of calcium deposit. Our experimental model would be valuable in the investigation of the pathological changes associated with smooth muscle cell proliferation in vessels

Cell to stroma contacts in the tunica media of the hypertensive rat thoracic aorta

The variation in mechanical stress to which the aortic wall is subjected requires that forces be transmited between its components by means of relatively strong but compliant attachments. We have used transmission electron microscopy in order to study the cell to stroma contacts (smooth muscle cell-elastic fiber contact) in the tunica media of normotensive and hypertensive aortas of Sprague-Dawley rats. Hypertension was produced with a silver clip positioned around the left renal artery and the vessels were fexed by intravital perfusion at normal and elevated pressure. In ultrathin sections, the density of cell to stroma contacts per 100 µm cell perimeter and per 100 cell profiles were determined using an image analysis computer. In the hypertensive group the density of cell to stroma contacts fell considerably when compared with the control group. This research provides insights into the conditions under which high blood pressure may produce medial injuries and, perhaps, be a factor in the precipitation of dissections