Response to Comment on "U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art".

Slimak et al challenge the reliability of our oldest (>65,000 years) U-Th dates on carbonates associated with cave paintings in Spain. They cite a supposed lack of parietal art for the 25,000 years following this date, along with potential methodological issues relating to open-system behavior and corrections to detrital or source water 230Th. We show that their criticisms are unfounded.

U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art.

The extent and nature of symbolic behavior among Neandertals are obscure. Although evidence for Neandertal body ornamentation has been proposed, all cave painting has been attributed to modern humans. Here we present dating results for three sites in Spain that show that cave art emerged in Iberia substantially earlier than previously thought. Uranium-thorium (U-Th) dates on carbonate crusts overlying paintings provide minimum ages for a red linear motif in La Pasiega (Cantabria), a hand stencil in Maltravieso (Extremadura), and red-painted speleothems in Ardales (Andalucía). Collectively, these results show that cave art in Iberia is older than 64.8 thousand years (ka). This cave art is the earliest dated so far and predates, by at least 20 ka, the arrival of modern humans in Europe, which implies Neandertal authorship.

An early modern human presence in Sumatra 73,000-63,000 years ago.

Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence. AMH evidence from this period is rare and lacks robust chronologies owing to a lack of direct dating applications, poor preservation and/or excavation strategies and questionable taxonomic identifications. Lida Ajer is a Sumatran Pleistocene cave with a rich rainforest fauna associated with fossil human teeth. The importance of the site is unclear owing to unsupported taxonomic identification of these fossils and uncertainties regarding the age of the deposit, therefore it is rarely considered in models of human dispersal. Here we reinvestigate Lida Ajer to identify the teeth confidently and establish a robust chronology using an integrated dating approach. Using enamel-dentine junction morphology, enamel thickness and comparative morphology, we show that the teeth are unequivocally AMH. Luminescence and uranium-series techniques applied to bone-bearing sediments and speleothems, and coupled uranium-series and electron spin resonance dating of mammalian teeth, place modern humans in Sumatra between 73 and 63 ka. This age is consistent with biostratigraphic estimations, palaeoclimate and sea-level reconstructions, and genetic evidence for a pre-60 ka arrival of AMH into ISEA. Lida Ajer represents, to our knowledge, the earliest evidence of rainforest occupation by AMH, and underscores the importance of reassessing the timing and environmental context of the dispersal of modern humans out of Africa.

U-series dating of Paleolithic art in 11 caves in Spain.

Paleolithic cave art is an exceptional archive of early human symbolic behavior, but because obtaining reliable dates has been difficult, its chronology is still poorly understood after more than a century of study. We present uranium-series disequilibrium dates of calcite deposits overlying or underlying art found in 11 caves, including the United Nations Educational, Scientific, and Cultural Organization (UNESCO) World Heritage sites of Altamira, El Castillo, and Tito Bustillo, Spain. The results demonstrate that the tradition of decorating caves extends back at least to the Early Aurignacian period, with minimum ages of 40.8 thousand years for a red disk, 37.3 thousand years for a hand stencil, and 35.6 thousand years for a claviform-like symbol. These minimum ages reveal either that cave art was a part of the cultural repertoire of the first anatomically modern humans in Europe or that perhaps Neandertals also engaged in painting caves.

Stratigraphic context and direct dating of the Neandertal mandible from Cova del Gegant (Sitges, Barcelona).

Stratigraphic study of the Cova del Gegant's sedimentary fill revealed different cycles of accumulation of typical interior cave and delta facies. A precise chronology for these deposits, the faunal remains and stone tools contained therein was obtained by radiocarbon, U-Th and OSL. Our results indicate that the Upper Pleistocene archaeological sequence dates between 49.3 +/- 1.8 ka BP, the U-Th age of the overlying flowstone, and 60.0 +/- 3.9 ka BP, the OSL age of the basal deposits. We have also directly dated the site's Neandertal mandible to 52.3 +/- 2.3 ka by U-Th.

Hovk 1 and the Middle and Upper Paleolithic of Armenia: a preliminary framework.

The territory of present day Armenia is a geographic contact zone between the Near East and the northern Caucasus. Armenian Middle and Upper Paleolithic records are both few and patchy as a result of the historical paucity of systematic archaeological research in the country. Consequently, it is currently difficult to correlate the Armenian Middle and Upper Paleolithic records with those from other neighboring regions. We present new archaeological and chronometric data (luminescence, U-Th, and 14C) from our ongoing research at Hovk 1 Cave in northeast Armenia. We discuss in particular two activity phases in Hovk 1 Cave for which we have outline chronometric data: (1) an early Middle Paleolithic occupational phase, dated by optically stimulated luminescence (OSL) to 104+/-9.8 ka BP(OSL); and (2) a Paleolithic occupational phase characterized by microlithic flakes dated by AMS 14C to 39,109+/-1,324 calibrated years BP(Hulu). The two phases are separated by a hiatus in hominin occupation corresponding to MIS 4 and an episode in early MIS 3. These chronometric data, taken together with the preliminary paleoenvironmental reconstruction of the Hovk 1 Cave and environment, suggest that these activity phases represent short-lived and seasonal use of the cave presumably by small groups of hunters during episodes of mild climate. Neither tool manufacture nor butchery appears to have taken place within the cave, and consequently, the archaeological record included, for the most part, finished tools and blanks. We address the chronology and techno-typological aspects of Hovk 1 lithics in relation to: (1) the Paleolithic records of Armenia, and (2) the broader interregional context of early Middle Paleolithic hominin occupation and the Middle-Upper Paleolithic transition in the Caucasus.

Late Pleistocene human skull from Hofmeyr, South Africa, and modern human origins.

The lack of Late Pleistocene human fossils from sub-Saharan Africa has limited paleontological testing of competing models of recent human evolution. We have dated a skull from Hofmeyr, South Africa, to 36.2 +/- 3.3 thousand years ago through a combination of optically stimulated luminescence and uranium-series dating methods. The skull is morphologically modern overall but displays some archaic features. Its strongest morphometric affinities are with Upper Paleolithic (UP) Eurasians rather than recent, geographically proximate people. The Hofmeyr cranium is consistent with the hypothesis that UP Eurasians descended from a population that emigrated from sub-Saharan Africa in the Late Pleistocene.

A multiple infusion start time (MIST) protocol for stable isotope studies of fetal blood.

A new approach utilizing multiple infusion start times for two stable isotopes of leucine was applied to seven pregnancies in order to assess equilibration times for isotopic studies when a single fetal blood sample is available. Two infusates, one containing l -[1-(13)C]-leucine and the other l -[5,5,5-D3]-leucine, were given as a primed constant infusion in the maternal circulation at fetal blood sampling (FBS). In five patients l -[1-(13)C]-leucine infusion was started at time zero (T(0)) whereas l -[5,5,5-D3]-leucine infusion began 30 min later, and both were continued until the umbilical sample was obtained at 149.7+/-8.8 min. In order to assure non-steady state conditions, in two patients the first infusion started at T(0)and the second 17 and 6 min before FBS was performed at 115 and 154 min, respectively. The fetal/maternal ratio for l -[5,5,5-D3]-leucine over the fetal/maternal ratio for l -[1-(13)C]-leucine was 0.98+/-0.03, indicating steady state conditions for both infusions for the first six patients. In the last patient the ratio was 0.51, indicative of non-steady state conditions for the shortest infusion time. Our results show that a single fetal sample can provide data for fetal amino acid enrichments reflecting multiple time points. Leucine steady state is achieved 20 min after a primed continuous infusion both in the maternal and fetal circulations.

An in vivo study of ovine placental transport of essential amino acids.

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes. Measurements of concentration and molar enrichment in maternal and fetal plasma and of umbilical plasma flow were used to calculate the ratio of transplacental pulse flux to maternal concentration (clearance) for each EA. Five EA (Met, Phe, Leu, Ile, and Val) had relatively high and similar clearances and were followed, in order of decreasing clearance, by Trp, Thr, His, and Lys. The five high-clearance EA showed strong correlation (r(2) = 0.98) between the pulse flux and maternal concentration. The study suggests that five of the nine EA have similar affinity for a rate-limiting placental transport system that mediates rapid flux from mother to fetus, and that differences in transport rates within this group of EA are determined primarily by differences in maternal plasma concentration.

Sealice on salmonids: their biology and control.

Lepeophtheirus salmonis and Caligus elongatus are the two common species of sealice responsible for serious disease problems in salmonid aquaculture. L. salmonis in particular is the most serious parasitic infection on Atlantic salmon farms in the Northern Hemisphere and is the best-known species. This review examines the voluminous literature on the biology and control of sealice and brings together ideas for developing our knowledge of these organisms. Research on the distribution, host range, structure, life cycle, epidemiology, laboratory maintenance, reproductive biology, physiology and pathogenesis is reviewed in depth. The control strategy and economic cost to the industry is discussed. The interactions between wild and cultured salmonids are examined.

Changes in physiological parameters and feeding behaviour of Atlantic salmon Salmo salar infected with sea lice Lepeophtheirus salmonis.

Atlantic salmon Salmo salar L. artificially infected with salmon lice Lepeophtheirus salmonis (Krøyer 1837) recovered from detrimental physiological changes and skin damage induced by preadult lice as the parasites matured. Growth rates of Atlantic salmon remained unaffected by lice infection, but food consumption decreased with increasing feeding and movement of the lice prior to and post-mating, correlating with the appearance of head erosions and detrimental changes in physiological integrity. Food consumption of the fish increased as the lice moulted to the adult stage and gravid female lice settled in a posterior location on the fish, subsequently reducing the impact of infection and allowing recovery of the skin damage. However, the impact of preadults was limited, as the decrease in food consumption of fish at 21 d post-infection had no effect on either the specific growth rate or condition factor of the fish. Furthermore, the intensity of lice infections at each of the sample days was not correlated with food consumption, specific growth rate or any of the haematological or physiological parameters measured, either before or after infection, indicating that lice intensity was independent of social dominance/subordinance. This work has provided the first evidence that infected fish can recover from the detrimental changes caused by lice infection, even when they are still infected with lice. If fish can survive the preadult stage of lice, then the mortal impact of lice infections is greatly reduced.

Effects of salmon lice Lepeophtheirus salmonis on sea trout Salmo trutta at different times after seawater transfer.

The physiological and behavioural effects and skin damage caused by salmon lice Lepeophtheirus salmonis (Krøyer) infections on sea trout Salmo trutta L. smolts were greater in fish infected with lice 2 wk after seawater transfer than in fish infected 6 wk after seawater transfer. The initial prevalence of infection was 100% for both groups and the intensity of infection decreased significantly with time over 5 wk. Significantly fewer of the fish infected 2 wk after seawater transfer had resumed feeding by the end of the experiment, leading to a loss of body condition. Furthermore, these fish suffered more severe damage to the skin and detrimental changes in physiological integrity than fish infected 6 wk after seawater transfer as a direct consequence of feeding preadult lice, leading to osmoregulatory failure and death. Although this study was carried out in laboratory conditions, results indicate that lice infections may potentially have a detrimental impact on the survival of wild smolts after seawater transfer.

Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury.

Reperfusion injury, which occurs upon the reintroduction of blood flow to an ischemic organ, is responsible for considerable damage in heart attacks and strokes. However, no treatment for reperfusion injury is currently available. A major cause of reperfusion injury is the iron-mediated generation of hydroxyl radical (.OH). In this study we have explored the capacity of novel iron chelators called "exochelins" to prevent reperfusion injury. Exochelins, siderophores of Mycobacterium tuberculosis, are unique iron chelators because they are lipid soluble, and hence able to enter cells rapidly. In the iron-free state, exochelins prevented .OH formation. Desferri-exochelins prevented oxidative injury to cultured cardiac myocytes, and did so more rapidly and effectively than the nonlipid soluble iron chelator deferoxamine. The capacity of various desferri-exochelins to protect myocytes from oxidative injury varied directly with their solubility in lipid. Infused into isolated rabbit hearts during reperfusion after a period of ischemia, desferri-exochelins dramatically improved systolic and diastolic left ventricular function, preserved coronary flow, reduced release of the cardiac enzyme lactic dehydrogenase, and reduced myocardial concentrations of .OH metabolites. Thus, highly diffusible desferri-exochelins block injury caused by .OH production and have potential for the treatment of reperfusion injury.

Leucine metabolism in chronically hypoglycemic hypoinsulinemic growth-restricted fetal sheep.

We measured leucine flux rates during infusions of L-[1-14C]- and L-[1-1C]leucine in fetal sheep exposed to maternal insulin-induced hypoglycemia over the last 8 wk (40%) of gestation to determine effects of chronic glucose deficiency and hypoglycemia on fetal leucine metabolism. Compared with control fetuses (C, n = 5), hypoglycemic fetuses (HG, n = 8) weighed less (C, 3.43 +/- 0.07 kg; HG, 2.32 +/- 0.24 kg), had lower plasma glucose (C, 1.04 +/- 0.02 mM; HG, 0.59 +/- 0.01 mM), insulin (C, 48 +/- 6 pM; HG, 12 +/- 6 pM), and leucine concentrations (C, 195.6 +/- 8.3 microM; HG, 140.8 +/- 15.0 microM), lower rates of net leucine uptake (C, 4.2 +/- 0.6 mumol.min-1.kg-1; HG, 2.1 +/- 0.4 mumol.min-1.kg-1) and leucine flux into protein accretion (C, 2.8 +/- 0.2 mumol.min-1.kg-1; HG, 0.6 +/- 0.1 mumol.min-1.kg-1), and an increased rate of leucine release from protein breakdown (C, 1.1 +/- 0.1 mumol.min-1.kg-1; HG, 3.3 +/- 0.2 mumol.min-1.kg-1) (P < 0.05 for all). Plasma leucine disposal, flux into protein synthesis, and oxidation were not different between groups. We conclude that adaptations of fetal leucine metabolism to long-term hypoglycemia and decreased glucose apply represent diminished leucine uptake and increased leucine release from protein breakdown, which are associated with decreased incorporation of leucine into protein accretion and a slower rate of fetal growth.

7 Gryzmish: toward an understanding of collaboration.

Nurses and physicians have a long history of conflicted relationships. The conflict is multifaceted and deeply rooted in a mesh of social, economic, and professional issues. This legacy makes collaboration very difficult, but not impossible, to achieve. The barriers imposed by history must be dismantled for nurses and physicians to forge a new relationship. This new relationship will not just happen. It requires a vision, an unswerving commitment, and a leap of faith that collaboration will dramatically improve patient care and provider satisfaction. Collaborative relationships, although positive and progressive, are not easily forged. People must examine and work on their inner feelings. Physicians and nurses need to communicate openly and address conflict directly. Role realignment causes anxiety, uncertainty, and frustration. Often it may seem easier to revert to former patterns of behavior. Dysfunctional as those may be, they offer role familiarity. Collaboration is a conscious, learned behavior that must be constantly nurtured, reinforced, and reflected on, for it holds great promise for both patients and providers.

Sequential development of the immune response in rainbow trout [Oncorhynchus mykiss (Walbaum, 1792)] to experimental plerocercoid infections of Diphyllobothrium dendriticum (Nitzsch, 1824).

Development of the inflammatory response of rainbow trout to experimental infections with Diphyllobothrium dendriticum plerocercoids is described using light and electron microscopy. The cellular response to plerocercoids occurred within 2 weeks post-infection (p.i.). This was followed by an increase in leucocyte numbers during weeks 3-6 p.i., with full encapsulation of plerocercoids by week 6 p.i. Neutrophils were the first leucocytes to engage the developing plerocercoid, followed by large influxes of macrophages which transformed into epithelioid cells. With longer times p.i. the accumulation of different leucocyte types increased, and a blood vascular network developed. Full development of the composite cyst was characterized by fibroplasia, particularly at the periphery of the cyst, and the subsequent deposition of a collagenous tissue matrix. Enzyme-linked immunosorbent assay (ELISA) examination of serum samples taken over the 20 week period showed that specific anti-D. dendriticum antibody titres were first detected at 5 weeks p.i. and increased to a maximum by 11 weeks p.i.

Moral outrage and moral discourse in nurse-physician collaboration.

True collaboration between clinical nurses and physicians in acute care settings can be difficult to achieve. The author describes a patient care unit dedicated to the study and development of such collaborative relationships. She reports an unexpected favorable outcome of such collaboration: the decline in incidents of moral outrage among nurses faced with moral dilemmas. This decline is attributed to such factors as mutual trust and respect between nurses and physicians, an appreciation that the two practice areas are interdependent, and the development of a synergistic alliance between the two that enhances patient care.