Efficacy and survival of biologic agents in psoriasis: a practical real-life 12-year experience in a French dermatology department.

Background: Drug survival in a real-life setting is critical to long-term use of biologics for psoriasis. Objective: We describe our 12-year experience with biologics in psoriasis patients. Patients and Methods: All patients treated with biologics including infliximab, adalimumab (ADA), etanercept (ETA), and ustekinumab (UST) for psoriasis vulgaris between January 2005 and December 2016 were retrospectively analyzed. Results: In total, 545 treatment series were administered to 269 patients, including 211 treatment series with ADA, 135 with ETA, 77 with infliximab, and 122 with UST. ADA and ETA were initiated most often as first-line therapy; 65.3% of treatment sequences were discontinued. UST had the highest drug survival. The major reason for treatment termination was a loss of efficacy (44.9%). Definitive discontinuation increased with the number of biologic therapy sequences. Limitations: Subjects were not randomized to the different treatments. Conclusions: In a long-term real-life setting, drug survival of UST is better than that of TNF-a inhibitors for both biologic-naive and biologic-experienced patients with psoriasis.

A Pleistocene palaeovegetation record from plant wax biomarkers from the Nachukui Formation, West Turkana, Kenya.

Reconstructing vegetation at hominin fossil sites provides us critical information about hominin palaeoenvironments and the potential role of climate in their evolution. Here we reconstruct vegetation from carbon isotopes of plant wax biomarkers in sediments of the Nachukui Formation in the Turkana Basin. Plant wax biomarkers were extracted from samples from a wide range of lithologies that include fluvial-lacustrine sediments and palaeosols, and therefore provide a record of vegetation from diverse depositional environments. Carbon isotope ratios from biomarkers indicate a highly dynamic vegetation structure (ca 5-100% C4 vegetation) from 2.3 to 1.7 Ma, with an overall shift towards more C4 vegetation on the landscape after about 2.1 Ma. The biomarker isotope data indicate ca 25-30% more C4 vegetation on the landscape than carbon isotope data of pedogenic carbonates from the same sequence. Our data show that the environments of early Paranthropus and Homo in this part of the Turkana Basin were primarily mixed C3-C4 to C4-dominated ecosystems. The proportion of C4-based foods in the diet of Paranthropus increases through time, broadly paralleling the increase in C4 vegetation on the landscape, whereas the diet of Homo remains unchanged. Biomarker isotope data associated with the Kokiselei archaeological site complex, which includes the site where the oldest Acheulean stone tools to date were recovered, indicate 61-97% C4 vegetation on the landscape.This article is part of the themed issue 'Major transitions in human evolution'.

On the occurrence of a widespread contamination by herbicides of coral reef biota in French Polynesia.

Research has been conducted within the framework of the French Initiative for Coral Reefs (IFRECOR) to assess pesticide pollution levels in the coral reef trophic webs in French Polynesia. Unexpected widespread contamination by herbicides was found in algae, fishes and macro-invertebrates located at various levels of the reef trophic web. Concentrations in organisms investigated were for the majority below the lowest observable effect level and do not pose a dietary risk to native population who subsist on these fish. However, the widespread contamination may affect the reef ecosystem in the future as coral symbiotic algae, Symbidinium sp. (Dinophyta) are particularly sensitive to photosystem II herbicides, particularly the substituted urea and triazine derivatives.

3.3-million-year-old stone tools from Lomekwi 3, West Turkana, Kenya.

Human evolutionary scholars have long supposed that the earliest stone tools were made by the genus Homo and that this technological development was directly linked to climate change and the spread of savannah grasslands. New fieldwork in West Turkana, Kenya, has identified evidence of much earlier hominin technological behaviour. We report the discovery of Lomekwi 3, a 3.3-million-year-old archaeological site where in situ stone artefacts occur in spatiotemporal association with Pliocene hominin fossils in a wooded palaeoenvironment. The Lomekwi 3 knappers, with a developing understanding of stone's fracture properties, combined core reduction with battering activities. Given the implications of the Lomekwi 3 assemblage for models aiming to converge environmental change, hominin evolution and technological origins, we propose for it the name 'Lomekwian', which predates the Oldowan by 700,000 years and marks a new beginning to the known archaeological record.

Stable isotope-based diet reconstructions of Turkana Basin hominins.

Hominin fossil evidence in the Turkana Basin in Kenya from ca. 4.1 to 1.4 Ma samples two archaic early hominin genera and records some of the early evolutionary history of Paranthropus and Homo. Stable carbon isotopes in fossil tooth enamel are used to estimate the fraction of diet derived from C3 or C4 resources in these hominin taxa. The earliest hominin species in the Turkana Basin, Australopithecus anamensis, derived nearly all of its diet from C3 resources. Subsequently, by ca. 3.3 Ma, the later Kenyanthropus platyops had a very wide dietary range--from virtually a purely C3 resource-based diet to one dominated by C4 resources. By ca. 2 Ma, hominins in the Turkana Basin had split into two distinct groups: specimens attributable to the genus Homo provide evidence for a diet with a ca. 65/35 ratio of C3- to C4-based resources, whereas P. boisei had a higher fraction of C4-based diet (ca. 25/75 ratio). Homo sp. increased the fraction of C4-based resources in the diet through ca. 1.5 Ma, whereas P. boisei maintained its high dependency on C4-derived resources.

Pedogenic carbonate stable isotopic evidence for wooded habitat preference of early Pleistocene tool makers in the Turkana Basin.

The origin and evolution of early Pleistocene hominin lithic technologies in Africa occurred within the context of savanna grassland ecosystems. The Nachukui Formation of the Turkana Basin in northern Kenya, containing Oldowan and Acheulean tool assemblages and fossil evidence for early members of Homo and Paranthropus, provides an extensive spatial and temporal paleosol record of early Pleistocene savanna flora. Here we present new carbon isotopic (δ(13)CVPDB) values of pedogenic carbonates (68 nodules, 193 analyses) from the Nachukui Formation in order to characterize past vegetation structure and change through time. We compared three members (Kalochoro, Kaitio, and Natoo) at five locations spanning 2.4-1.4Ma and sampled in proximity to hominin archaeological and paleontological sites. Our results indicate diverse habitats showing a mosaic pattern of vegetation cover at each location yet demonstrate grassland expansion through time influenced by paleogeography. Kalochoro floodplains occurred adjacent to large river systems, and paleosols show evidence of C3 woodlands averaging 46-50% woody cover. Kaitio habitats were located along smaller rivers and lake margins. Paleosols yielded evidence for reduced portions of woody vegetation averaging 34-37% woody cover. Natoo environments had the highest percentage of grasslands averaging 21% woody cover near a diminishing Lake Turkana precursor. We also compared paleosol δ(13)CVPDB values of lithic archaeological sites with paleosol δ(13)CVPDB values of all environments available to hominins at 2.4-1.4Ma in the Nachukui and Koobi Fora Formations. Grassy environments became more widespread during this interval; woody canopy cover mean percentages steadily decreased by 12%. However, significantly more wooded savanna habitats were present in the vicinity of lithic archaeological sites and did not mirror the basin-wide trend of grassland spread. Hominin lithic archaeological sites consistently demonstrated woody cover circa 40% throughout our study interval and were 4-12% more woody than coeval basin environs. We propose that Turkana Basin early tool makers may have preferred a more wooded portion of the savanna ecosystem to reduce heat stress and to gain differential access to potable water, raw materials, animal carcasses, and edible plants.

An earlier origin for the Acheulian.

The Acheulian is one of the first defined prehistoric techno-complexes and is characterized by shaped bifacial stone tools. It probably originated in Africa, spreading to Europe and Asia perhaps as early as ∼1 million years (Myr) ago. The origin of the Acheulian is thought to have closely coincided with major changes in human brain evolution, allowing for further technological developments. Nonetheless, the emergence of the Acheulian remains unclear because well-dated sites older than 1.4 Myr ago are scarce. Here we report on the lithic assemblage and geological context for the Kokiselei 4 archaeological site from the Nachukui formation (West Turkana, Kenya) that bears characteristic early Acheulian tools and pushes the first appearance datum for this stone-age technology back to 1.76 Myr ago. Moreover, co-occurrence of Oldowan and Acheulian artefacts at the Kokiselei site complex indicates that the two technologies are not mutually exclusive time-successive components of an evolving cultural lineage, and suggests that the Acheulian was either imported from another location yet to be identified or originated from Oldowan hominins at this vicinity. In either case, the Acheulian did not accompany the first human dispersal from Africa despite being available at the time. This may indicate that multiple groups of hominins distinguished by separate stone-tool-making behaviours and dispersal strategies coexisted in Africa at 1.76 Myr ago.

Primate archaeology.

All modern humans use tools to overcome limitations of our anatomy and to make difficult tasks easier. However, if tool use is such an advantage, we may ask why it is not evolved to the same degree in other species. To answer this question, we need to bring a long-term perspective to the material record of other members of our own order, the Primates.

First ecotoxicological assessment assay in a hydroelectric reservoir: the Lake Taabo (Côte d'Ivoire).

Organochlorine pesticides (OCPs) contamination was assessed in marketable species, two fishes (tilapia and catfish) and a prawn from the Lake Taabo (Côte d'Ivoire). Lindane and endosulfan were the main contaminants, suggesting their current use. DDT, endrin, heptachlor plus traces of chlordane, aldrin and fipronil were also detected. In fishes and in prawns, enzymatic biomarkers exhibited significant correlations with OCPs levels, showing the feasibility of a biomonitoring. The transfer of OCPs along the aquatic food web and their immunosuppressive effects in human are discussed. This preliminary study highlights that the pesticide contamination was concomitant with the increase in infectious diseases in the bordering population of this African lake.

Kaletepe Deresi 3 (Turkey): archaeological evidence for early human settlement in Central Anatolia.

Located in the Central Anatolian Volcanic Province, Kaletepe Deresi 3 was discovered in the summer of 2000 and has been under investigation since that time. Volcanic activity in the region generated a number of obsidian intrusions that have attracted humans to the area throughout prehistory. The stratigraphic sequence at Kaletepe Deresi 3, more than 7 m in depth, presents a series of archaeological horizons representing the Lower and Middle Paleolithic. The site contains the longest open-air Paleolithic sequence excavated in Turkey, as well as the first in situ Acheulean industry documented in Anatolia. Tephras in the upper Middle Paleolithic horizons and the rhyolithic bedrock bracket the timespan represented at Kaletepe Deresi 3. The lithic industry at the site illustrates a wide range of technological behaviors and documents changes in raw-material exploitation and artifact manufacture through the Lower and Middle Paleolithic.

Stable isotope variability in tissues of the Eurasian perch Perca fluviatilis.

Stable isotope analysis is frequently used as a complementary method of dietary analysis, to describe trophic relationships and assess food-web structure. These studies allow a precise determination, based on the calculation of a diet-tissue fractionation factor. The fractionation factor, determined for whole organisms or specific tissues, may vary substantially in natura. In the present study, delta13C and delta15N were assessed in lipid-free tissues (spleen, liver, viscera, scales, gills, spine, white muscle, brain) and in available energy reserves (proteins, glycogen, lipids) of Eurasian perch (Perca fluviatilis) reared under controlled conditions and fed for 4 months with the same artificial diet. Some discrepancies in delta15N and delta13C data were observed among tissues, respectively up to 3.43 per thousand and 2.54 per thousand for delta15N and delta13C. The 15N signature in organs depends on their metabolic activity. Despite a significant delta13C enrichment from feed to tissues, the lipids in spine, liver and viscera exhibit a certain stability.

Biomarker responses in European eel (Anguilla anguilla) exposed to persistent organic pollutants. A field study in the Vaccarès lagoon (Camargue, France).

A screening of relevant biomarkers was carried out in order to evaluate metabolic and cellular damages in European eels exposed to a non-point source contamination by persistent organic pollutants (POP) such as polycyclic aromatic hydrocarbons (PAH) and organochlorine compounds (OC) in a protected area, the Nature Reserve of Camargue (France). Investigations were focused on metabolic responses including detoxification mechanisms (biotransformation, antioxidant process), energy requirements and enzymatic membrane markers either involved in neuronal conduction (acetylcholinesterase, AChE) or in osmoregulation and energy metabolism (ATPases). The hepatic and muscular glycogen rates seemed to be suitable biomarkers as well as three hepatic activities involved in the protection against oxyradicals: catalase, glutathione peroxidase (SeGPx) and superoxide dismutases (SOD). The muscle and gill ATPases as well as the muscle and brain AChE showed more significant relevance in terms of biomarkers than the biotransformation enzymes: ethoxyresorufine-O-deethylase (EROD) and uridine diphospho-glucuronyl transferase (UDPGT). However, most of these enzymatic activities depend on numerous abiotic factors, which must be taken into account in such a biomarker assessment approach. Our study provides some conclusive elements to approve the use in situ of biomarkers developed from laboratory studies. It also raises a question regarding the location of contaminant impregnation in fish organ, in relation with age, development status or mode of contamination, and its influence on biomarker response. If the relevance of membrane indicators is confirmed, this study provides an original statement of the extent of the ecotoxicological threat for the aquatic species in a protected area, due to the occurrence of POP in the cell membranes.

First occurrence of early Homo in the Nachukui Formation (West Turkana, Kenya) at 2.3-2.4 Myr.

Cognitive abilities and techno-economic behaviours of hominids in the time period between 2.6-2.3 Myr have become increasingly well-documented. This time period corresponds to the oldest evidence for stone tools at Gona (Kada Gona, West Gona, EG 10-12, OGS 6-7), Hadar (AL 666), lower Omo valley (Ftji1, 2 & 5, Omo 57, Omo 123) in Ethiopia, and West Turkana (Lokalalei sites -LA1 & LA2C-) in Kenya. In 2002 a new palaeoanthropological site (LA1alpha), 100 meters south of the LA1 archaeological site, produced a first right lower molar of a juvenile hominid (KNM-WT 42718). The relative small size of the crown, its marked MD elongation and BL reduction, the relative position of the cusps, the lack of a C6 and the mild expression of a protostylid, reinforced by metrical analyses, demonstrate the distinctiveness of this tooth compared with Australopithecus afarensis, A. anamensis, A. africanus and Paranthropus boisei, and its similarity to early Homo. The LA1alpha site lies 2.2 m above the Ekalalei Tuff which is slightly younger than Tuff F dated to 2.34+/-0.04 Myr. This juvenile specimen represents the oldest occurrence of the genus Homo in West Turkana.

Late Pliocene hominid knapping skills: the case of Lokalalei 2C, West Turkana, Kenya.

Relatively few remains of Late Pliocene hominids' knapping activities have been recovered to date, and these have seldom been studied in terms of manual dexterity and technical achievements. With regard to early hominid technological development, the evidence provided by the data from 2.34 Myr site of Lokalalei 2C (Kenya) questions both the prior assumption of a continuous and linear evolutionary trend in lithic production and the idea that it long remained static. The level of elaboration evinced by the lithic assemblage is quite unexpected in view of its age, and seemingly more advanced that what can be surmised for other Late Pliocene East-African sites, including the nearby site of Lokalalei 1. Analysis relies mainly on the dynamic reconstruction of entire cobble reduction sequences from particularly informative refitting groups. The Lokalalei 2C knappers had already internalised the notion of planning and foresight in raw material procurement and management. Beyond simple mastery of the basic technical constraints peculiar to stone knapping, they conducted a highly controlled debitage of flakes following constant technical rules and resulting in high productivity. The data suggest that early hominids displayed distinct technical competencies and techno-economic patterns of behavior, thus pointing to an intrasite complexity and intersite diversity which are not accounted for by the existing chrono-cultural classifications.

Effect of potassium dichromate and fenitrothion on hemoglobins of Chironomus riparius Mg. (Diptera, Chironomidae) larvae: potential biomarker of environmental monitoring.

In an attempt to identify Chironomus hemoglobins as biomarkers for environmental monitoring, alterations in the hemoglobins in Chironomus riparius Mg. (Diptera: Chironomidae) larvae, exposed to potassium dichromate and fenitrothion, were investigated under laboratory conditions. The hemoglobins were evaluated in terms of their total contents by a cyanomethemoglobin procedure, individual components by electrophoresis of isoelectric focusing, and their oxidation by multi wavelength rapid-scanning spectrophotometry. The total hemoglobin contents increased at the high level of fenitrothion exposure. No variations in the individual hemoglobin component levels were found, by exposure to either fenitrothion or potassium dichromate. Whereas, the absorption spectra of the hemoglobins showed decreases in the peaks corresponding to the oxyhemoglobins by exposure to both compounds, but more sensitively by the chromium, which probably reflects the increase of the autoxidation of the oxyhemoglobins to methemoglobins by these compounds. These results suggest that autoxidation of the hemoglobins in Chironomus riparius seems to be a sensitive parameter in response to redox-active chemical exposure, and this biochemical parameter could be developed as a biomarker in environmental monitoring.

Multilevel effects of sublethal fenitrothion exposure in Chironomus riparius Mg. (Diptera, Chironomidae) larvae.

The effects of fenitrothion exposure on fourth-instar Chimnomus riparius larvae were investigated on biochemical, physiological, and population-level parameters. Biochemical effects were investigated through measurements of acetylcholinesterase and cytosolic superoxide dismutase activities. Water content and dry weight of the larvae were used as physiological parameters, and the emergence rate of adults was used as a descriptor of population-level effects. Results showed that the response of most parameters exhibited a concentration-dependent relationship. Although biochemical parameters proved to be very sensitive, no direct relation was observed with effects at a higher level of biological organization. Perturbations of osmoregulation, as reflected by changes in water content of the larvae, were more directly related with emergence failure. This study demonstrates that the use of several biological parameters can provide complementary information about the effects of chemical exposure. Therefore, use of a multilevel approach in C. riparius seems to be a promising way to diagnose environmental quality.

Relationships between persistent organic chemicals residues and biochemical constituents in fish from a protected area: the French National Nature Reserve of Camargue.

The Reserve of Biosphere of Camargue [French National Nature Reserve of Camargue (NNRC)] is a protected area frequently exposed to natural and anthropogenic environmental alterations. To evaluate potential contamination of fish with lipophilic chemicals-organochlorines (OCs) and polycyclic aromatic hydrocarbons (PAHs)-a biological monitoring survey was carried out. Metabolic reserve levels were evaluated to select appropriate biological indicators able to be significant biomarkers. In addition, the incorporation of xenobiotic molecules in the lipid compartments was investigated. The contents of glycogen, total lipids, proteins and lipidic phosphorus were analyzed in liver and skeletal muscles of three teleostean: the European eel (Anguilla anguilla); the crucian carp (Carassius auratus); and the catfish (Ictalurus melas). The atmospheric origin of the PAH detected in any season in the biomass and the OCs compounds contamination by derive from agricultural treatments are established. In contradiction with some laboratory acute intoxication studies, we observe a positive correlation between tissue concentrations of contaminants and the muscular glycogen amount, a sensitive energy reserve marker. Moreover, it seems likely that the incorporation of these xenobiotics is located preferentially in the membrane structures.

Accumulation of lipophilic microcontaminants and biochemical responses in eels from the Camargue Biosphere Reserve.

We assessed the impacts of persistent organic micropollutants on aquatic trophic webs in brackish and freshwater communities in the Camargue National Nature Reserve (NNR). We found that organochlorine compounds affect fish communities, particularly those of the common eel (Anguilla anguilla). The aims of this study were (1) to determine the amount of lipophilic xenobiotics such as polycyclic aromatic hydrocarbons (PAHs), which are probably of atmospheric origin, and two organochlorines (OC), lindane and dieldrin, which are from irrigation waters, in liver and muscle (2) to define in situ biomarkers and (3) to identify the mode by which fish from 'unpolluted' areas become contaminated. All of the species were contaminated with low, but fluctuating quantities of PAHs and OCs, regardless of the sampling season. Lindane and dieldrin were always detected and naphtalene was the most abundant hydrocarbon. The OC and PAH content was rarely correlated with the lipid content in storage tissues and their concentrations in the lipidic fractions (neutral and polar) varied greatly. We found a number of correlations between persistent organic pollutant (POP) tissue concentrations and the activities of enzymatic membrane markers. For example, there is a relationship between the concentrations of the most volatile PAHs and the activity of muscle acetylcholinesterase (AChE) and between the concentration of benzo-PAH and the activities of ATPases in the gills and/or muscle.