Lymphocytes (5 × 105/well) were acutely treated (3 h) with 0.3 mM of the Selleckchem XAV 939 fatty acid mixture added or not by 2 μM of ASTA in the absence and presence of phorbol myristate acetate (PMA; 20 ng/well) used as a ROS inducer. After 3 h the absorbance was measured at 620 nm to evaluate H2O2 concentration (compared to a standard curve). Dihydroethidium (DHE) is a florescence probe and was used to measure the intracellular superoxide anion production. Once inside the cell, DHE is rapidly oxidized to ethidium (a red fluorescent compound) by superoxide with minor collaboration of other ROS. Lymphocytes (5 × 105/well)

were incubated with 5 μM DHE for 15 min at room temperature in the dark. At the beginning of the assay control cells were stimulated with PMA (20 ng/well) and 0.3 mM of the FA mixture added or not by 2 μM of ASTA. Cells were incubated in the dark at room temperature for additional 30 min. DPI (diphenylene iodonium 10 μM), an inhibitor of NADPH oxidase (Chen et al., 2007), was used to investigate if superoxide anion production occurred through NADPH-oxidase activation. Sodium

azide (SA – 400 μM) was used as a mitochondrial inhibitor. Afterwards, fluorescence was analyzed in a microplate reader (Tecan, Salzburg, Everolimus manufacturer Austria) (wavelengths of excitation and emission were 396 and 590 nm, respectively). The probe DCFH-DA was primarily used as an indicator of the production of H2O2 (Keston and Brandt, 1965) but is also described as being oxidized by other ROS such as HO , ROO , NO and peroxynitrite (Crow, 1997 and Wang and Joseph, 1999). The cells (5 × 105/well) were preloaded with DCFH-DA (5 μM) by incubation in culture medium for 30 min. DCFH-DA is cleaved intracellularly by non specific esterase and turns into high fluorescent 2,7-dichlorofluoroscein (DCF) upon oxidation by ROS. After the loading

period, cells were treated with FA with or without ASTA at 2 μM and cultured for 18 h. The experiments were conducted in the presence and absence of PMA (20 ng/well). After the culture period, cells were centrifuged and resuspended in 300 μL of Tyrode’s buffer and the fluorescence was monitored in spectrofluorimeter Tecan (Salzburg, Austria) with excitation at 485 nm and emission at 530 nm. The results of this why experiment were expressed as relative units of fluorescence. Nitric oxide production was performed according to Ding et al. (1988) through nitrite ( NO2-) determination. Nitric oxide (NO ) is rapidly converted into NO2- in aqueous solutions and, therefore, the total NO2- concentration can be used as a stoichometric indicator of NO production in culture. Lymphocytes (5 × 105/well) were cultured with 0.3 mM of the FA mixture with or without 2 μM of ASTA and LPS (10 μg/well) for 4 h. EGTA (ethylene glycol tetraacetic acid, 500 μM) was used as a calcium quelator and therefore to discard NO production by constitutive calcium-dependent NOS.

Strategic planning, on the other hand, is often subject to the values, policies, laws and institutions by which a set of issues are addressed. Governance in this context relates interests, stakeholder driven objectives as well as institutional processes and structures which are the basis for planning and decision-making. Governance therefore sets the stage within which management occurs (Olsen, 2003). While management

focuses on “tame” problems, strategic planning is often related to so-called “wicked” problems. “Wicked” problems are described as complex, tricky, unstructured, and difficult to define. They delineate from other and bigger problems BEZ235 research buy and involve normative judgments (Jentoft and Chuengpagdee, 2009). Therefore, in addition to technical information from natural sciences and economics, information and scientific advice referring to the political, societal and cultural context of decision making is needed. Solutions of such wicked problems require the recognition of conflicting values, beliefs and perceptions. Such planning produces winners and losers. Also the scientific support needs to be understood as a social process comprising interactions among actors, mediating between different stakeholders’

interest and respecting lobbying and existing power structures (Kannen, 2012). For a scientist to be a successful knowledge broker, the scientist needs to understand actors’ perceptions of particular problems and issues and how this is related to their attitudes and values (von Storch, 2009 and von Storch and Stehr, 2014). A tool for doing so is surveying stakeholders and regional and local residents. http://www.selleckchem.com/products/cb-839.html In one case, local residents from the North Sea coast of Schleswig-Holstein shared antagonistic views about wind farms emerged (Gee, 2010 and Ratter and Gee, 2012, see Fig. 2). One group saw wind farms as incompatible with their understanding of the sea as an open and wild natural area, mainly due to their esthetic impacts. medroxyprogesterone Others argue that wind farms as a renewable source for electricity production are favorable and visual aspects are less relevant. This

information may guide communication strategies of project developers and planners and help them to properly address particular groups of society. In general, social science analysis may support planning processes and (re-)shaping governance processes and actor interactions (e.g., Cormier et al., 2013 and Kannen et al., 2013). An example is the long-term vision for MSP in the Baltic Sea developed in the framework of the BalticSeaPlan project. Gee et al. (2011a) first identified a set of key transnational issues: a healthy marine environment, a coherent Pan-Baltic energy policy, safe, clean and efficient maritime transport and sustainable fisheries and aquaculture. Together with three key principles, namely Pan-Baltic thinking, spatial efficiency and spatial connectivity, these provide the core of a vision for transnational MSP (Gee et al., 2011b and Kannen, 2012).

We did observe, however, that Stat3 protein levels significantly increased in hepatocytes after 24 h of treatment with lansoprazole or vorinostat (Supplementary Fig. 1). It appears likely that the chemicals either potentiated or stabilized Smad or Stat3 binding to the Hepcidin promoter without increasing phosphorylation of the proteins, caused phosphorylation at a later time point, which would most likely be an indirect effect after other signal transduction cascades were activated, or acted via other pathways. The two most potent agonists, ipriflavone and vorinostat, active at 1 μM concentrations, were 10-fold more potent than genistein [18]. Interestingly,

ipriflavone, Raf inhibitor like genistein, is an isoflavone with estrogenic properties [38].

Ipriflavone is used to treat osteoporosis based on its ability to inhibit osteoclast activity, promote mineralization of osteoblasts [39], and increase bone mineral density in postmenopausal women [40]. However, our previous work indicated that estradiol does not increase Hepcidin GDC-0199 mouse expression and that blockade of the estrogen receptor fails to inhibit genistein’s effect on Hepcidin expression  [18], thus we think it is unlikely that ipriflavone is promoting Hepcidin expression in an estrogenic manner. Similar to our observation of genistein [18], ipriflavone increased expression of the BMP-dependent gene, ID3 ( Fig. 2B), however, unlike genistein, ipriflavone did not increase expression of the Stat3-dependent gene, SOCS3 ( Fig. 2C), or increase Stat3 phosphorylation ( Fig. 4B). Several of the hits that increased Hepcidin transcript levels were tyrosine kinase inhibitors affecting growth factor signaling ( Fig. 5), including SU6668, GTP 14564, and AG1296. SU6668 inhibits VEGF, FGF, and PDGF receptors [27]. We found that SU6668 exhibited the paradoxical effect of inhibiting Hepcidin-luciferase activity, but increasing Hepcidin transcript levels Dichloromethane dehalogenase in the quantitative realtime RT-PCR experiments. GTP 14564 and AG1296, however,

both increased Hepcidin-luciferase activity and Hepcidin transcript levels in quantitative realtime RT-PCR assays. GTP 14564 is a potent inhibitor of FLT3, c-Fms, c-Kit, and PDGFRβ [25], while AG1296 inhibits signaling by both PDGF-α and β receptors and by c-Kit, without affecting VEGF receptor signaling [26]. We demonstrated that AG1296 or GTP 14564′s stimulatory effects on the Hepcidin promoter can be significantly impaired by co-treating with EGF, FGF, or FLT3 (for AG1296 or GTP 14564) or PDGF or VEGF (for GTP 14564). Both PDGF-α and β receptors signal via PI3 Kinase, among other pathways, and can activate Src leading to transcription of c-Myc [41]. Two of the other Hepcidin stimulating agents that we identified in the screen, AS252424 and 10058-F4, affect pathways that can act downstream of PDGF receptor. AS252424 inhibits PI3 Kinase isoform γ [42], while 10058-F4 blocks c-Myc’s activity  [43] and [44].

Sukces wprowadzenia szczepionek koniugowanych przeciw meningokokom serogrupy C i czterowalentnych przeciw serogrupom A, C, W-135, Y, pozwala mieć nadzieję, że wprowadzenie szczepionki białkowej, skutecznej również w stosunku do meningokoków serogrupy B, pozwoli znacznie ograniczyć liczbę

zakażeń meningokokowych. Polskie doświadczenia w opanowaniu ognisk epidemicznych, które wystąpiły na terenie woj. opolskiego w roku 2007, wskazują na wysoką skuteczność szczepień interwencyjnych [19]. A. Skoczyńska – zasadniczy wkład w koncepcję i projekt pracy, zebranie, analiza signaling pathway i interpretacja danych, napisanie artykułu. A. Kuch – zasadniczy wkład w koncepcję i projekt pracy, zebranie C646 datasheet i analiza danych. I. Waśko, A. Gołębiewska, P. Ronkiewicz, M. Markowska, K. Wasiak – zebranie i analiza danych, Waleria Hryniewicz – krytyczne zrecenzowanie artykułu pod kątem istotnej zawartości intelektualnej oraz akceptacja ostatecznej wersji do opublikowania. Badanie zostało częściowo sfinansowane

przez Ministerstwo Zdrowia w ramach programu polityki zdrowotnej pn. „Monitorowanie zakażeń szpitalnych oraz inwazyjnych zakażeń bakteryjnych dla celów epidemiologicznych, terapeutycznych i profilaktycznych na lata 2009–2013” jako Modułu I programu pt. „Narodowy program ochrony antybiotyków w Polsce”, przez Ministerstwo Nauki i Szkolnictwa Wyższego w ramach specjalnego urządzenia badawczego pn. Mikrobank 2 oraz w ramach grantu badawczego firmy GlaxoSmithKline. Pomoc umożliwiająca udział w spotkaniach naukowych oraz honoraria z tytułu wygłoszonych wykładów finansowane przez firmy Pfizer (AS, AK, WH), GlaxoSmithKline (AS, WH), Baxter i Novartis (AS). Pozostali autorzy: nie występuje. Chlormezanone Autorzy dziękują wszystkim Uczestnikom programu BINet oraz wszystkim pozostałym lekarzom i mikrobiologom biorącym udział w monitorowaniu inwazyjnej choroby meningokokowej w Polsce poprzez przekazywanie izolatów wraz z danymi. “
“Antibody production defects

are the most common primary immunodeficiencies. The hallmark of this pathophysiologically, clinically, and genetically heterogeneous group of immunodeficiencies is a defect in mounting the antigen-specific antibody response that is an indispensable condition for the effective adaptive immunity to pathogens. A broad spectrum of diseases represents this group of immune disorders, ranging from often asymptomatic selective IgA deficiency (sIgAD) and IgG subclass deficiencies (IgGsD) to severe agammaglobulinemias in which the production of all immunoglobulin isotypes is severely impaired [1]. The onset of clinical manifestation falls predominatingly on the second half of the first year of life due to the protective effect of transplacentally obtained maternal IgG antibodies over the first 3–6 months.

11 Usually SENs are calcified and nonenhancing lesions, whereas SEGAs show avid enhancement after contrast; however, the radiologic appearance of both pathologies may overlap. Regardless, the most important difference between these two TSC brain lesions

see more is evidence of serial growth: SEGAs will grow, whereas SENs remain stable in size. Before the 2012 consensus conference, the diagnostic criteria developed for TSC during the 1998 consensus meeting were still in use.14 At the 2012 Washington Consensus Conference, it was decided by the invited expert panel to document the diagnostic criteria related to TSC brain lesions in the following manner:7 1. The presence of tubers (and other types of cortical dysplasia, such as cortical migration lines), SENs, or SEGAs will each individually be

defined as major criteria (two major criteria will suffice click here for the diagnosis of TSC as previously defined in 1998). Current evidence suggests, even though literature regarding the natural history of SEGAs is sparse, that new SEGAs very rarely arise after 20-25 years of age.6 Hence brain imaging, preferably magnetic resonance imaging with and without contrast, should be performed every 1 to 3 years until the age of 25 years. Because of a lack of knowledge of SEGA growth behavior beyond 25 years of age, follow-up magnetic resonance imaging may not be needed every 3 years but intervals may be prolonged in the presence of a

stable lesion and a stable patient. Screening and follow-up scans frequency should be tailored according to various clinical factors. New onset of symptoms such as headaches, visual complaints, nausea or vomiting, or increase in seizure activity should trigger an earlier scan. Similarly, a growing SEGA should prompt a more frequent clinical and radiological follow-up. Parents and patients should be educated regarding relevant symptoms that should Liothyronine Sodium prompt referral to medical evaluation. Treatment of SEGAs has been solely surgical because of a lack of responsiveness to other strategies such as chemotherapy or radiation. These modalities may also be associated with an increased risk of secondary malignancies.15 Many retrospective series have focused on surgical outcome, some of which include a heterogeneous group of patients with very different tumor anatomy and size as well as major differences in the number of patients treated; hence, there are different conclusions regarding risk of mortality, morbidities, and outcomes.16, 17, 18, 19, 20, 21 and 22 Generally, it is agreed that small tumors are usually less invasive, and that resecting noninvasive small tumors, diagnosed while still asymptomatic, is associated with excellent clinical outcomes, with low morbidity and mortality.

Then, two 7-Fr plastic stents were placed up to the right hepatic bile duct after endoscopic sphincterotomy to make the space for a magnet. One month later, a samarium cobalt rare-earth magnet was advanced in front of the papilla with a biopsy forceps using an oblique-viewing endoscope and the magnet was inserted up to the proximal right hepatic duct under fluoroscopic guidance. Another Raf inhibitor magnet was advanced to the distal right hepatic duct via the PTBD route and eventually two magnets were attracted towards each other. One month later, the fistula

was completed without any serious complications. This is the first report on successful MCA in a Billroth II gastrectomy patient. MCA may be beneficial for choledochocholedochostomy in selected patients. “
“After failed ERCP, other alternative biliary accesses such as PTBD, repeated ERCP, or surgical bypass could be considered. PTBD has a complication rate of 10% to 30% such as bile leak, bleeding, and peritonitis. Repeat ERCP could be as an alternative if immediate biliary drainage is not required. Surgical bypass is effective, but selleck chemicals llc is associated with considerable mortality and morbidity. EUS-guided transgastric imaging of dilated left intrahepatic duct is a useful technique to drain the left biliary system and an effective alternative for percutaneous transhepatic biliary drainage after failed ERCP. To date, EUS-guided biliary

drainage in isolated right hepatic

duct obstruction has not been attempted. In our center, 4 consecutive patients Low-density-lipoprotein receptor kinase were candidates for EUS-guided right hepatic duct approach within recent year with last case in October 2012. We performed three kinds of approaches to the right hepatic duct using EUS; (1) using a cholangiogram obtained by EUS-guided transduodenal puncture of the right hepatic duct as a “roadmap” to assist retrograde cannulation, (2) EUS-guided transduodenal puncture of the right hepatic duct and an antegrade balloon dilatation and stenting for bilioenteric anastomotic strictures in a patient with hepaticojejunostomy, and (3) transluminal stenting as an antegrade bypass stenting between the right hepatic duct and the duodenal wall under EUS-guidance. EUS-guided hepaticoduodenostomry (EUS-HD) of right hepatic duct by expert hands may be a relatively safe and feasible alternatives after failed ERCP. Moreover, an availability in the same session without dicontinuation of sedation after failed ERCP is another great advantage. In contrast, the other alternative accesses such as PTBD, repeated ERCP, and surgery almost need another session for further procedure on a different day. Further, large multicentered study may help enhance our results. “
“Bile Duct Injury after cholecystectomy remains a major problem in current surgical practice. BDI is associated with poor survival, increased morbidity and impaired quality of life.

Adjuvant cisplatin-based chemotherapy is recommended for patients with stage Selleck Proteasome inhibitor II–III NSCLC after radical resection according to the 7th TNM (Tumour, Nodes, Metastasis) classification [46]. Current guidelines for patients with stage III disease recommend the use of chemotherapy and radiotherapy, either sequentially or (preferably) concurrently [46]. However, treatment for stage III NSCLC is particularly challenging due

to patients’ comorbidities and tumour heterogeneity. Although treatment approaches for stage III NSCLC differ considerably between regions and centres, neoadjuvant (chemo-)radiotherapy followed by surgery remains a standard option in selected patients with resectable stage IIIA NSCLC. New drug development and research into the optimum chemo-radiation strategies for locally advanced NSCLC is also problematic due to the fact that patients are potentially curable and may not be willing to enrol in clinical trials. Novel approaches currently being investigated in stage III NSCLC include immunomodulatory strategies, agents acting on the cell cycle (e.g. aurora kinase inhibitors) and novel cytostatics [47] and [48]. ‘Window of opportunity’ trials undertaken before chemotherapy or chemo-radiotherapy may be a useful

means of testing new agents or strategies in this population. Such trials allow the efficacy of novel therapies to be investigated before the development of CB-839 supplier resistance arising from prior therapy [49]. Although this approach raises possible ethical concerns relating to the use of an agent of indeterminate efficacy when standard therapies are available, window trials, if carefully controlled, can provide valuable new information on the activity of new treatments for NSCLC [49] and [50]. The use of radiotherapy in lung cancer has seen a number of advances in recent years, with kinetics as well as

heterogeneity of tumours being taken into account [51], [52] and [53]. Uptake of radionuclides can also vary within tumours due to differing vascularisation. This presents the possibility of targeting different parts of the tumour with varying amounts of radiation to deliver higher doses with less toxicity [54]. Further possible future developments in radiotherapy are the combination of radiotherapy with targeted agents [55], and the use of proton-based technology, since such delivery improves target volume distribution and is more lung-sparing than photon-based delivery. Imaging biomarkers such as fluorodeoxyglucose (FDG)-positron emission tomography (PET) are also likely to be used increasingly in the future to predict an early response to radiotherapy, with changes in FDG uptake by the primary tumour found to be significantly predictive for 2-year survival in stage III NSCLC during the first week of (chemo-)radiotherapy [56]. Although cytotoxics like cisplatin have been used in the treatment of NSCLC for several decades, the mechanism(s) underlying resistance to these agents are poorly understood.

Since the horizontal numerical viscosity and diffusivity are extremely small in these simulations, this allows the effects of the explicit

model viscosity, diffusivity, and grid resolution to be isolated. Since SI can grow independent of the along-front direction (see Appendix A) and the goal here is not to model baroclinic mixed layer instability as in Boccaletti et al. (2007) or Fox-Kemper et al. (2008), it is sufficient to run the simulations in 2D, as in previous studies (e.g. Thorpe and Rotunno, 1989, Griffiths, 2003 and Taylor and Ferrari, 2009). Thus the models are run as 2D cross-channel spindown simulations of a symmetrically unstable front. Akin to Taylor and Ferrari, 2009, the initial state consists of a weakly stratified surface

layer Volasertib solubility dmso from -300-300 m GSK1120212 mouse density and velocity fields are decomposed into departures from a constant background state defined by equation(20) bT(x,z,t)=M2x+b(x,z,t),bT(x,z,t)=M2x+b(x,z,t), equation(21) uT(x,z,t)=VG(z)j+u(x,z,t),uT(x,z,t)=VG(z)j+u(x,z,t), equation(22) dVGdz=M2f,where the subscript T   indicates the total field. The model is set up to be horizontally periodic in the perturbation variables (no subscript), while the background state is assumed to be constant in time. The use of periodic boundary conditions allows the flow to freely evolve with no influence from lateral boundaries and no need to specify inflow/outflow conditions. The upper boundary is adiabatic with a rigid lid, and both vertical boundaries are set to be free-slip on the perturbation velocity uu. Throughout the rest

of this paper this model setup will be referred to as “frontal zone”. Finally, the initial density field is perturbed by a white noise with an amplitude of 10-410-4 kg m−3. Four sets of simulations only have been conducted in order to test the sensitivity of restratification by SI to different combinations of M2,N2M2,N2, and νhνh. The parameter choices for each set of simulations are listed in Table 1. The simulation parameters for each set are chosen such that the initial Richardson number in the surface layer is 0.25, which is neutral to KH instability (Stone, 1966) but still unstable to SI. The Richardson number in the thermocline is set at 12.5 so that it is stable to both types of instability. Each simulation set consists of seven individual simulations run at varying resolutions; individual simulations will henceforth be referred to by a numerical subscript (e.g. A1,B3A1,B3, etc.). The advantage of using a frontal zone 2D model is that f   and the domain-averaged M2M2 are constant in time, so that the time evolution of Ri   is governed only by the change in N2N2.

Examples of sophisticated language among animals include the bee dance, bird songs and the echo sounds of whales and dolphins, possibly not less complex than the language of original prehistoric humans. Where humans witnessed fire from lightening and other sources, Bortezomib purchase ignition was invented by percussion of flint stones or fast turning of wooden sticks associated

with tinder, the process being developed once or numerous times in one or many places (Table 1). Likely, as with other inventions, the mastery of fire was driven by necessity, under the acute environmental pressures associated with the descent from warm Pliocene climate to Pleistocene ice ages (Chandler et al., 2008 and de Menocal, 2004). Clear evidence for the use of fire by H.

erectus and Homo heidelbergensis has been uncovered in Africa and the Middle East. Evidence for fire in sites as old as 750 kyr in France and 1.4 Ma in Kenya are controversial ( Stevens, 1989 and Hovers and Kuhn, 2004). Possible records of a ∼1.7–1.5 Ma-old fire places were recovered in excavations at Swartkrans (South Africa), Chesowanja (Kenya), Xihoudu (Shanxi Province, China) and Yuanmou (Yunnan Province, China). These included black, grey, and learn more greyish-green discoloration of mammalian bones suggestive of burning. During the earliest Palaeolithic (∼2.6–0.01 Ma) mean global temperatures about 2 °C warmer than the Holocene allowed human migration through open vegetated savannah in the Sahara and Arabian Peninsula. The transition from the late Pliocene

to the Pleistocene, inherent in which was a decline in overall temperatures and thus a decrease in the energy of tropical storms, has in turn led to abrupt glacial-interglacial fluctuations, Dapagliflozin such as the Dansgaard-Oeschger cycles (Ganopolski and Rahmstorf, 2002), requiring rapid adaptation. Small human clans responded to extreme climate changes, including cold fronts, storms, droughts and sea level changes, through migration within and out of Africa. The development of larger brain size and cultural adaptations by the species H. sapiens likely signifies the strong adaptive change, or variability selection, induced by these climate changes prior to the 124,000 years-old (124 kyr) (1000 years to 1 kyr) Eemian interglacial, when temperatures rose by ∼5 °C to nearly +1 °C higher than the present and sea level was higher by 6–8 m than the present. Penetration of humans into central and northern Europe, including by H. heidelbergensis (600–400 kyr) and H. neanderthalensis (600–30 kyr) was facilitated by the use of fire for warmth, cooking and hunting. According to other versions ( Roebroeks and Villa, 2011), however, evidence for the use of fire, including rocks scarred by heat and burned bones, is absent in Europe until around 400 kyr, which implies humans were able to penetrate northern latitudes even prior to the mastery of fire, possibly during favourable climatic periods.

There is however a strong correspondence between AA and the development of open field systems in the mediaeval period, with 53% of AA units in the UK formed within the last 1000 years (Fig. 2). In Fig. 3 AA units are plotted by UK regions, with the first appearance of AA in southeast, central, southwest and northeast England, and in central and south Wales at c. 4400–4300 cal.

BP. AA in southeast, southwest, central England selleck kinase inhibitor as well as in Wales is associated with prehistoric farming. In southwest England and Wales there was significant AA formation during the mediaeval and post-mediaeval periods. AA in southern Scotland and northwest and northern England appears to be associated with mediaeval land-use change. In Fig. 4 AA units

are sub-divided according to catchment size where study sites are located. Most dated AA units fall either in catchments of <1 km2 Selleckchem trans-isomer or are found in ones with drainage areas that are >100–1000 km2. The smallest catchments (<1 km2) have no dated AA units before c. 2500 cal. BP and most occur after c.1000 cal. BP. It is also perhaps surprising how few 14C-dated anthropogenic colluvial deposits there are in the UK, making it difficult to reconstruct whole-catchment sediment budgets. AA units from the larger catchments (>100 km2) show a greater range of dates with the earliest units dating to c. 4400 cal. BP. Fig. 5 plots AA units according to sedimentary environment. Channel beds (Fig. 5A) record earlier-dated AA, whereas AA units in palaeochannels (Fig. 5B), on floodplains (Fig. 5C) and in floodbasins

(Fig. 5D) increase in frequency from c.4000 cal. BP, and especially in the mediaeval period. One possible explanation for the early channel bed AA units is that channel erosion BCKDHA or gullying was contributing more sediment than erosion of soil, and that this was a reflection of a hydrological rather than a sediment-supply response to human activities (cf. Robinson and Lambrick, 1984). The earliest coarse AA unit in the UK uplands is dated to c. 2600 cal. BP (Fig. 6) with 73% of gravel-rich AA formed in the last 1000 years, and a prominent peak at c. 800–900 cal. BP. Fine-grained AA units in upland catchments have a similar age distribution to their coarser counterparts, and 80% date to the last 1300 years. By contrast, AA units in lowland UK catchments, outside of the last glacial limits, are entirely fine-grained and were predominantly (69%) formed before 2000 cal. BP, especially in the Early Bronze Age and during the Late Bronze Age/Early Iron Age transition c. 2700–2900 cal. BP. Fig. 7 plots relative probability of UK AA classified according to their association with deforestation, cultivation and mining. The age distributions of AA units attributed to deforestation and cultivation are similar with peaks in the later Iron Age (c.2200 cal. BP).