Response to Comment on "Atlantic and Pacific multidecadal oscillations and Northern Hemisphere temperatures".

Kravtsov et al. claim that we incorrectly assess the statistical independence of simulated samples of internal climate variability and that we underestimate uncertainty in our calculations of observed internal variability. Their analysis is fundamentally flawed, owing to the use of model ensembles with too few realizations and the fact that no one model can adequately represent the forced signal.

Implications of temperature variation for malaria parasite development across Africa.

Temperature is an important determinant of malaria transmission. Recent work has shown that mosquito and parasite biology are influenced not only by average temperature, but also by the extent of the daily temperature variation. Here we examine how parasite development within the mosquito (Extrinsic Incubation Period) is expected to vary over time and space depending on the diurnal temperature range and baseline mean temperature in Kenya and across Africa. Our results show that under cool conditions, the typical approach of using mean monthly temperatures alone to characterize the transmission environment will underestimate parasite development. In contrast, under warmer conditions, the use of mean temperatures will overestimate development. Qualitatively similar patterns hold using both outdoor and indoor temperatures. These findings have important implications for defining malaria risk. Furthermore, understanding the influence of daily temperature dynamics could provide new insights into ectotherm ecology both now and in response to future climate change.

Solar forcing of regional climate change during the Maunder Minimum.

We examine the climate response to solar irradiance changes between the late 17th-century Maunder Minimum and the late 18th century. Global average temperature changes are small (about 0.3 degrees to 0.4 degrees C) in both a climate model and empirical reconstructions. However, regional temperature changes are quite large. In the model, these occur primarily through a forced shift toward the low index state of the Arctic Oscillation/North Atlantic Oscillation as solar irradiance decreases. This leads to colder temperatures over the Northern Hemisphere continents, especially in winter (1 degrees to 2 degrees C), in agreement with historical records and proxy data for surface temperatures.

CLIMATE CHANGE: Lessons for a New Millennium.

The climate changes believed to have occurred before this century have remained enigmatic, hampering our understanding of today's climatic changes. Reseachers trying to assess the human influence on the warming of the past century have commonly used complex ocean atmosphere models, but these models have their drawbacks. In his Perspective, Mann discusses a research article by Crowley, who has used a simple model driven by the most important natural and human-induced climate forcings to simulate climatic change over the last millennium. Comparing the model results with observations, Crowley makes what may be the most compelling case to date for the assertion that anthropogenic greenhouse gas increases are behind the dramatic continued warming of the globe.

Comparison of phenytoin with noncompetitive N-methyl-D-aspartate antagonists in a model of focal brain ischemia in rat.

Recent in vitro and in vivo experiments have suggested that excitatory amino acid antagonists, particularly those active at the N-methyl-D-aspartate receptor subtype, are effective in ameliorating ischemic injury due to their antiexcitotoxic activity. However, these drugs are also potent and effective in vivo anticonvulsants. The present experiments compared the noncompetitive N-methyl-D-aspartate antagonists phencyclidine and MK-801 with the anticonvulsant phenytoin in a model of focal brain ischemia. Fisher F-344 rats were subjected to tandem occlusion of the middle cerebral and ipsilateral common carotid arteries under halothane anesthesia. Compounds were administered intravenously 30 minutes and 24 hours after arterial occlusion; infarct size was assessed at 48 hours after occlusion. Phencyclidine had no effect on infarct volume at 1 mg/kg, significantly reduced (by 36%) infarct volume at 3 mg/kg, and produced a nonsignificant 26% decrease at 10 mg/kg. The more potent and selective noncompetitive antagonist MK-801 reduced (by 32%) infarct volume significantly at 0.1 mg/kg, produced a nonsignificant 23% decrease at 0.3 mg/kg, and had no effect at 0.5 mg/kg. Phenytoin, which is not a glutamate antagonist, reduced the infarct volume by 45% at 28 mg/kg. A single dose of phenytoin (28 mg/kg) administered 30 minutes after occlusion was neuroprotective, but delaying drug administration for more than 2 hours was ineffective. These data suggest that blockade of the N-methyl-D-aspartate receptor is effective in reducing the infarct size after focal cerebral ischemia. The neuroprotective activity of phenytoin suggests that this may be related to the common anticonvulsant action.

Forebrain contributions to one-kidney renal hypertension in the rabbit.

Electrolytic lesions were placed along the anteroventral wall of the third cerebral ventricle (AV3V region) in 10 albino rabbits (AV3V-X), and sham lesions were produced in 10 additional rabbits (SHAM). Two to 3 weeks later, all rabbits underwent unilateral nephrectomy and renal artery stenosis (clip I.D. = 0.508 mm). During a 1-week control period, and for 4 weeks after renal artery stenosis, measurements were made of mean arterial pressure (MAP), heart rate, body fluid compartment volumes, plasma electrolytes, and daily sodium, potassium, and water balances. Four weeks after renal artery stenosis (RAS), cardiovascular responses to norepinephrine (NE), angiotensin II (AII), saralasin, and autonomic blockade were obtained in the conscious animals. In SHAM rabbits, MAP rose from 77 to 117 mm Hg 4 weeks after RAS. In AV3V-X rabbits, MAP rose from 77 to only 92 mm Hg 4 weeks after RAS. Body fluid compartment volumes, plasma electrolytes, and fluid, sodium, and potassium balances showed similar modest changes in both groups of rabbits. Neither saralasin infusion nor autonomic blockade caused significantly different changes in MAP between SHAM and AV3V-X rabbits 4 weeks after RAS. However, pressor responses to both NE and AII were significantly less in AV3V-X rabbits at this time. It is concluded that one-kidney, one clip renal hypertension involves activation of neurohormonal pressor mechanisms originating in the forebrain, and that the expression of these pressor mechanisms in part includes an increase in cardiovascular reactivity.

Effect of forebrain lesions on response to chronic intraventricular angiotensin II.

We previously reported that chronic (10 days) intracerebroventricular (ivt) infusion of angiotensin II (ANG II) into conscious rabbits produced a significant rise in mean arterial pressure (MAP), water intake (WI), and urinary sodium excretion (UNaV), and a significant fall in plasma sodium (PNa) and potassium (PK) concentrations. Urinary potassium excretion (UKV) and body fluid volume were not changed significantly. In the present experiments, similar chronic infusions were carried out in intact rabbits and in rabbits with an electrolytic lesion placed in the anteroventral third cerebral ventricle (AV3V) region. Integrity of the AV3V area is essential for normal expression of a variety of acute physiological responses to ANG II injected into the brain. In rabbits with AV3V lesions, chronic ivt infusion of ANG II did not significantly alter MAP, but WI and fractional UNaV increased, and PNa decreased in a manner identical to that of sham-lesioned control rabbits. Plasma and extracellular fluid volumes increased, and body weight and food intake decreased in all rabbits during ANG II infusion, but to a slightly greater extent in the AV3V-lesioned rabbits. We conclude that an intact AV3V region is crucial for the hypertensive effect of chronic ivt fusions of ANG II in the rabbit but is not necessary for most of the fluid and electrolyte alterations associated with such infusions.

One-day fluorescent-antibody procedure for detecting salmonellae in frozen and dried foods.

The indirect fluorescent-antibody technique was used to examine 422 food samples for the presence of salmonellae. A cultural phase involving a 16-hr preenrichment in buffered nutrient broth-milk medium followed by a 4- to 5-hr subculture into fresh medium of the same composition was evaluated. This procedure yielded a sufficient population of salmonellae so that no false-negative results were obtained. Of the 31 false-positives obtained, 12 samples yielded positive cultural results upon extensive subculture of the original enrichment broths. Yeast cells and both vegetative and spore forms of bacilli were observed to fluoresce when stained with anti-Salmonella serum. Efforts to ascertain the cause of these cross-reactions and several alternate explanations are discussed.