À l’automne 1885 il

entre à la faculté de médecine de l’u

À l’automne 1885 il

entre à la faculté de médecine de l’université de Vienne, où il suivra l’enseignement de maîtres souvent prestigieux : Carl Toldt en anatomie, Otto Kahler en médecine interne, Theodor Billroth en chirurgie, Gustav Braun en obstétrique et gynécologie, Hermann Widerhofer en pédiatrie, Hanns Kundrat en histologie et anatomopathologie, Theodor Meynert en psychiatrie. Il est docteur en médecine (Doktor der gesamten Heilkunde) le 21 février 1891. Sa formation postdoctorale est originale, déjà caractéristique de sa carrière future, car elle comporte peu de stages cliniques mais de longs séjours dans des laboratoires de chimie renommés, à Würzburg, Munich et Zurich. À l’évidence, Landsteiner se détourne de la médecine clinique, qu’il n’exercera jamais, et affirme son intérêt pour la recherche en biologie humaine, qu’il Sirolimus entend pratiquer en chimiste. Landsteiner Pirfenidone solubility dmso reste à l’institut d’anatomopathologie jusqu’en 1907. Il y poursuit ses recherches sur l’agglutination des hématies humaines, dont il analyse les variations en fonction de divers facteurs tels que la température, la concentration en hématies, l’âge des individus. Il observe que les agglutinines « immunes » du groupe ABO sont plus résistantes à la chaleur que les agglutinines « normales », première avancée vers

la distinction maintenant classique entre anticorps antiérythrocytaires immuns et naturels. Par une analyse comparative du pouvoir agglutinant du sérum des mères et de leurs enfants nouveau-nés, il suggère

clairement la notion d’immaturité immunologique néonatale (« …l’organisme du nouveau-né, comparé à celui de l’adulte, doit être considéré comme incomplètement développé. ») [6]. Enfin, grâce au travail d’Adriano Sturli (1873–1966) et Alfred Decastello-Rechtwehr Sunitinib (1872–1960), deux jeunes collaborateurs de Landsteiner à l’institut d’anatomopathologie, s’impose progressivement l’existence du groupe AB [7]. En décembre 1907, Landsteiner quitte l’institut d’anatomopathologie. Il prend la direction, avec le titre de prosecteur, du service d’anatomopathologie du Wilhelminenspital, à Ottakring, dans l’ouest de Vienne. Il perd sa mère, tendrement aimée, en 1908. Il est nommé professeur adjoint d’anatomopathologie en 1911. En 1916, il épouse Léopoldine Hélène Wlasto (1880–1943), actrice de théâtre, d’origine grecque par son père, gestionnaire laïc de la paroisse orthodoxe grecque de Vienne. Leur fils Ernst, qui sera leur seul enfant, naît en 1917. En janvier 1920, chassé par la misère qui écrase l’Autriche après l’effondrement de l’Empire, Landsteiner quitte Vienne, avec sa famille, pour La Haye où il prend le poste de prosecteur à l’hôpital de la Croix Rouge (Rode Kruis Ziekenhuis).

The large catch increase of the 1960s and 1970s was largely due t

The large catch increase of the 1960s and 1970s was largely due the seaward and southward expansion of industrial (notably trawl) fisheries from waters along the coasts of developed countries

of the Northern Hemisphere. When this expansion ended – in Antarctic waters – catches could increase only by fishing in deeper waters [8] and [9]. Scientists with expertise on fishes, fisheries and Navitoclax research buy deep-sea biology question whether deep-sea fisheries can be sustainable [9], [10], [11], [12], [13], [14], [15], [16], [17], [18] and [19]. A sound answer depends on but transcends ecology, taking ocean policy makers into the realms of economics and law. Despite sharing an Ancient Greek root (oikos, meaning household), ecology and economics have diverged in their world views, often leading their practitioners to differing strategies for managing our collective household, the biosphere, including the Z-VAD-FMK clinical trial 99% of its volume that is ocean. But there are fundamental similarities between ecology and economics. In fisheries it is commonplace to call populations “stocks,” alluding to their similarity to capital stocks in economics. Central to this paper is the analogy

between (a) the biomass of fish stocks and the productivity they generate, with (b) capital stocks (principal) and the dividends (or interest) they generate. With deep-sea fisheries as our focus, this paper examines what the authors are calling Clark’s Law, the seminal connection between Exoribonuclease the ecological and economic determinants of sustainability as first explained in Clark [20] and [21]. Using comparable metrics and combining insights and the evidence from fisheries, ecology, economics and international ocean governance, this

paper examines whether deep-sea fisheries can be sustainable. Governments and international governing organizations need to know this because maintaining biodiversity in the deep sea is crucial to biogeochemistry on a global scale, and hence to humankind [22] and [23]. Commercial fishing is occurring at increasing depths around the globe. Based on readily available catch data series and fish life history parameters, Morato et al. [24] showed that marine fisheries worldwide have operated at increased depths since the 1970s. In the high seas (i.e. beyond countries’ exclusive economic zones, EEZs), the increasing depth of fishing was more dramatic, some 250 m. They based this inference on the relative increase in the global catch of species (or higher taxa) known to occur in deeper waters, which have increased 7-fold since the mid-1960s [25]. As fisheries operated farther offshore and deeper, exploiting increasing portions of the ranges of marine species [26] and [27], they also exploited the deeper part of these species’ ranges.

The proximal hair segment was chosen as it best correlates with t

The proximal hair segment was chosen as it best correlates with the one month time frame of the diet data. Models Etoposide in the candidate set included all combinations of the variables (e.g. Modelfish; Modelshellfish; Modelfish+shellfish; Modelfish*shellfish). [THg] was log transformed to improve normality. We examined the relationship between [THg] and δ15N and δ13C values using two separate simple linear regressions to test whether diet, as determined by δ15N and δ13C, affects mean [THg] (across segments; Proc REG; n = 73). Seventy three women had hair [THg], δ15N, and δ13C values determined. We log-transformed the data to

meet the assumption of homoscedasticity and examined for influential outliers. As we did not account for the negative sign associated with δ13C, a negative β-value indicates that [THg] decreased as δ13C is enriched (i.e. becomes less negative). Additionally, we ranked δ13C from 1 − 73 (from values of -18.52 to -12.19) and ran a regression on the ranks, selleck chemicals reducing the influence of an outlying individual (δ13C = -12.19). Lastly, we used general linear models (GLM) to evaluate the relationship

between the frequency of consumption of fish and shellfish as reported by the individual and δ13C and δ15N stable isotopes values (n = 61), using 2 separate a priori candidate model sets, each with 3 models. Cepharanthine Sixty one women had δ13C and δ15N measured and completed diet recalls. Models in the two candidate sets included all additive combinations of the variables (e.g. δ15N fish; δ15N fish+shellfish; δ13C fish; δ13C fish+shellfish). We added a constant (20) and square root-transformed δ13C to improve normality. Values are reported as

means ± SE unless otherwise indicated. Analyses were conducted using SAS (SAS Institute, Cary, NC). We considered results significant at α < 0.05. All statistical analyses were conducted with and without an individual with exceptionally high [THg] to ensure that this individual was not overly influential in our assessment. We used Akaike’s information criterion adjusted for small sample size (AICc) to select the best approximating models as it allowed us to evaluate a number of competing nested models without violating the rules of multiple comparisons and error rates (Burnham and Anderson, 2002). We used Tukey’s multiple comparison test to compare means. We measured [THg] in the proximal hair segments of 97 women. [THg] averaged 3.26 ± 0.97 μg g−1, ranging from 0.12 to 90.0 μg g−1 (750-fold range). When the individual with [THg] of 90.0 μg g−1 was excluded as an outlier, [THg] averaged 2.35 ± 0.38 μg g−1 and ranged from 0.12 to 24.20 μg g−1 (202-fold range).

Examples for this category are benzene and arsine – Non-standard

Examples for this category are benzene and arsine. – Non-standardized HBM analysis methods This category comprised well described HBM analysis methods, published in peer-reviewed journals. These methods have not yet been evaluated by scientific or governmental associations, institutions or agencies. The procedures have to be established at an expert laboratory and measurement results need to be reviewed by independent experts. Moreover, biological reference or threshold values are often not available to evaluate the results. Examples for this category are boron (in boron trichloride, boron trifluoride, diborane) and furane.

– HBM method not available This category contains chemical substances for which HBM analysis methods are

not yet available. A default sampling protocol is recommended and calls for the collection of urine spot samples of the potentially exposed selleck products persons and deep-frozen storage of the specimens (preferred temperature: −80 °C). Meanwhile HBM experts can evaluate, whether a new analysis method can be designed and evaluated to measure the stored samples in due time. Examples for this category are chloropicrine and perfluoroisobutene. To create a list of high quality standard HBM laboratories interested to support physicians in the collection and analysis of human specimens after a chemical incident the G-EQUAS was used as an information exchange platform. Accompanying the official invitation of the 44th G-EQUAS (fall 2009) a questionnaire in German was sent out to regional HBM laboratories. In addition, the members Talazoparib cell line of the “working-group on analyses of biological materials” of the Deutsche Forschungsgemeinschaft

were addressed. The registration form to be returned to the authors Ponatinib cost involved a declaration of consent, full address of the HBM laboratory (postal address, phone and fax number), contact person(s), office hours/availability, and analytical focus (organic chemicals/inorganic chemicals/both). The efforts resulted in a list of 13 HBM laboratories. Poison information centres may help on scene commanders and healthcare professionals to gain toxicological information on chemicals, to coordinate HBM campaigns and to get access to high quality standard HBM laboratories. Thus, a list of the poison information centres is included in the compendium (https://www.klinitox.de/index.php?id=3). In Germany a compendium was designed to introduce and facilitate the use of HBM and BRN measurement methods in a single approach following CBRN incidents. The compendium was published in 2012 as a guideline in the publication series “Forschung im Bevölkerungsschutz” of the German Federal Office of Civil Protection and Disaster Assistance (BBK) (Müller and Schmiechen, 2012). This paper briefly describes the main results of the research project. The concept of the compendium serves two major aims.

obliqua venom Nevertheless, biochemical markers of acute liver i

obliqua venom. Nevertheless, biochemical markers of acute liver injury (AST, ALT and γ-GT) were increased in the serum of animals after envenomation. As it is known that some of these enzymes are not specific to the liver, it is possible that they were derived from other sources, such as the red blood cells or skeletal muscle. For instance, increases in AST activity are also associated with damage

to cardiac and skeletal muscle and the kidneys ( Prado et al., 2010 and Shashidharamurthy et al., 2010). Despite these apparently conflicting observations, we cannot rule out the occurrence of liver injury, mainly because evidence of DNA damage was detected in liver cells using the comet assay. Probably, these findings indicate that the extent of acute hepatic injury in this model of envenomation was subtle and did not lead to gross histological alterations. As mentioned above, L. obliqua envenomation may have triggered an intense inflammatory response, selleck chemicals which may be involved in several of the clinical manifestations. The activation of the kallikrein-kinin system and the consequent release of vasoactive mediators (mainly bradykinin, histamine and prostaglandins) seems to play an essential role in the edematogenic, nociceptive and vascular effects ( Bohrer et al., 2007). Accordingly, we have shown that during envenomation the animals experienced neutrophilic leukocytosis, indicating that a systemic inflammatory response had occurred. Histological

sections also provided evidence of inflammatory cell infiltrates

in the heart, lungs and kidneys. Corroborating these results, a clear activation in the vascular bed that buy E7080 was characterized by an increase in leukocyte rolling and adhesion to the endothelium was observed in hamster cheek pouch venules that had previously been incubated with low doses of LOBE ( Nascimento-Silva et al., 2012). The up-regulated expression of genes from pro-inflammatory mediators and adhesion molecules, such as IL-8, IL-6, CCL2, CXCL1, E-selectin, VCAM-1 and ICAM-3, was also detected in endothelial cells and fibroblasts after incubation with LOBE. Once released, these mediators acted as chemoattractants, inducing inflammatory cell migration to the sites of injury http://www.selleck.co.jp/products/Decitabine.html ( Pinto et al., 2008 and Nascimento-Silva et al., 2012). Recently, classical methods of genetic toxicology have been applied to the identification of potential therapeutic agents in animal venoms (mainly for the treatment of some types of cancer) and have also provided a better understanding of the toxic mechanisms of action of these venoms in the human body (Marcussi et al., 2011 and Marcussi et al., 2013). During envenomation, genotoxic damage can occur directly due to the cytotoxic activity of the venom or indirectly through the production of cytotoxic mediators (such as free radicals, for example) in response to tissue injury. In both cases, the damage could lead to DNA fragmentation and eventually, cell death.

, 2011) Results are expressed as a percentage of fluorescence in

, 2011). Results are expressed as a percentage of fluorescence intensity with respect to the control. An oxidation system comprising 2,2′-azino-di (3-ethylbenzthiazoline-6-sulfonic

acid) (ABTS), myoglobin and hydrogen peroxide (H2O2) has been used for TAC assay to determine Trolox equivalent antioxidant capacity (Kambayashi et al., 2009 and Yu and Ong, 1999). We used this assay to assess the antioxidant capacity of PFT. Briefly, 90 μL of 10 mM phosphate buffered saline (pH 7.2), 50 μL of myoglobin solution, 20 μL of 3 mM ABTS solution, and 20 μL of PFT or Trolox solution were added to 96-well Avasimibe datasheet microplates. Reactions were started by addition of H2O2 (final concentration: 250 μM), and were followed at 600 nm with a microplate reader for 10 min. Cells were seeded into the Lab-Tek® 8-well chambered cover glass system (Thermo Fisher Scientific, Inc.) at densities of 2 × 104, and were incubated overnight under standard culture conditions. Cells

were pre-treated with or without PFT at 20 μM for 1 h, followed by incubation with DHA at 120 μM for the indicated times. Chambered slides were washed twice with phosphate buffered saline (PBS). For detection of protein 1 light chain 3 (LC3), cells were fixed in ice-cold 1:1 methanol:acetone for 30 min. Slides were immersed for 50 min in 1% goat serum and 0.1% Triton X-100 in PBS, and were then transferred to 10% goat serum/PBS for 20 min. Following the Venetoclax molecular weight PBS rinse, slides were Ergoloid incubated with primary antibody (anti-LC3; MBL, Nagoya, Japan) at 1:1000 in PBS for 1 h at room temperature, washed with PBS, and then incubated with fluorescein isothiocynate (FITC)-conjugated anti-rabbit secondary antibody (Beckman Coulter, Brea, CA) for 30 min. For detection of cytochrome c, after incubation with reagents, the medium was removed and cells were fixed in Mildform® (Wako, Osaka, Japan) for 10 min. Slides were immersed for 5 min in 0.1% Triton X-100 in PBS and were then transferred to 3% FBS/PBS for 30 min. After washing with PBS, slides were incubated with Alexa Fluor® 555 mouse anti-cytochrome c antibody (BD Pharmingen™, San Jose, CA)

at 1:40 in PBS for 1 h. After incubation with antibodies, rinsing with PBS and a drop of UltraCruz™ Mounting Medium with DAPI (Santa Cruz Biotechnology, Inc., Dallas, TX) was added to each well. Cells were observed under a confocal fluorescence microscope (C-1; Nikon, Tokyo, Japan) for blue fluorescence intensity (405 nm) indicating the nucleus, green fluorescence intensity (488 nm) indicating LC3-positive cells (indicative of autophagy), or red fluorescence intensity (562 nm) indicating expression of cytochrome c. In order to detect the effects of PFT and DHA on mitochondrial membrane potential (ΔΨM) in HepG2 cells, we used the Cell Meter JC-10 mitochondrial membrane potential assay kit (AAT Bioquest®, Inc., CA).

gaucho, and L laeta); these were the same antigens used in the i

gaucho, and L. laeta); these were the same antigens used in the immunization of the horses ( Fig. 1A). Taking into account that the in vivo neutralization tests were performed using only the L. intermedia venom, the ELISA plate coating was performed either with the L. intermedia crude venom ( Fig. 1B) or with the active recombinant component of L. intermedia venom (rLiD1) ( Fig. 1C). Regardless of the antigen or dilution used, there was no statistically significant difference between the sera with MS-275 solubility dmso low neutralizing potency (2#, 3#, and 4#) and the sera with high neutralizing potency (5–10). Because it was not possible to establish

a direct correlation between the ELISA reactivity and the neutralizing serum potency using crude venoms or recombinant protein Panobinostat nmr as antigens, we made the assumption

that some epitopes could be possibly associated with the neutralizing antibodies. Therefore, we carried out an epitope-localization in the major antigens of the three Loxosceles venoms using the Spot method. A set of overlapping peptides (15 residues, frame-shifted by three residues) corresponding to the amino acid sequences of SMase I (L. laeta), LiD1 (L. intermedia), and A1H-LoxGa (L. gaucho) was prepared. Fig. 2 shows the binding pattern of the different anti-Loxosceles antivenoms with overlapping peptides. Six high neutralizing potency anti-Loxosceles sera (5, 6, 7, 8, 9 and 10), dipyridamole three of low neutralizing potency (2#, 3# and 4#) and one pre-immune serum were evaluated. A limited number of these results were presented in Fig. 2 (pre-immune, 2#, 3#, 6, 8 and 9 sera). In general, peptides were recognized by antibodies from high neutralizing

potency sera. However, sera 3# and 8, which gave similar reactivities in ELISA ( Fig. 1), showed clearly different peptide reactivities, in accordance with our hypothesis. Sera reactivity against the LiD1 overlapping peptides indicated three immunodominant regions: one in the N-terminal, one in the center, and another in the C-terminus of the protein. A similar pattern was found with overlapping peptides from A1H-LoxGa. However, at least four regions were found to be strongly immunoreactive using sera against SMase I. Table 1 shows the peptides sequences, their position in the primary structure of the corresponding antigen, molecular weight, theoretical isoelectric point, hydrophobicity, and solvent accessibility. Frequency is the number of anti-Loxosceles sera with high neutralizing potency (HP) or low neutralizing potency (LP) (diluted at 1:5000 or 1:20 000) that were reactive against the peptides. Peptides 1, 2, and 3 did not react with the low neutralizing potency sera diluted 1:20 000. However, the peptides reacted consistently with the high neutralizing potency sera. Therefore, we selected the three peptides for further synthesis and characterization, namely peptides 1 and 3 from SMase I and peptide 2 from A1H-LoxGa and LiD1.

The substantial degree of familial clustering with ASD could be d

The substantial degree of familial clustering with ASD could be due predominantly to genetics, or shared genetic and environmental factors, but cannot be explained predominantly by environmental factors. Epidemiological studies of concordance of ASD in same-sex twins favor a predominantly genetic explanation, with heritability of at least 90% under a multi-factorial threshold model [6]. By contrast, a recent twin study [12•] estimated heritability to be 37% for strict autism and similar for ASD, albeit

with a wide confidence interval (8–84%). Selleckchem Ceritinib For various reasons, including the relatively low population prevalence of ASD and the relatively high frequency of de novo DNA alterations that can affect risk, interpretation of these twin studies is not straightforward. We expand on the issue of de novo variants in subsequent discussion. Concordance for a phenotype of either autism or milder cognitive and social deficits was 82% among monozygotic (MZ) twins, compared with ≈10% in DZ twin pairs [7, 9 and 13]. This finding suggests that the ASD phenotype extends beyond the traditional diagnostic boundaries to a subclinical realm: the so-called broader autism phenotype [14]. Family studies have similarly shown a marked increase in subclinical cognitive or behavioral features among the relatives of autistic individuals, compared with those of controls. Considering these data, and the striking similarity between autism

and the milder social deficits seen in some children, autism is now seen to

encompass a spectrum of similar, often genetically related disorders, and as a result the Diagnostic and Statistical Manual PI3K Inhibitor Library solubility dmso of Mental Disorders edition V (DSM-V) plans to group them under the single entity of ASD (Figure 1). As we shall discuss, Flucloronide various genes certainly have an important role in ASD, and there has been incremental progress toward their identification, enhancing clinical definition and diagnostic tools [3, 15, 16, 17 and 18]. Approximately 10% of individuals with ASD have an identifiable Mendelian condition or genetic syndrome. Fragile X syndrome (≈1–2% of ASD cases), tuberous sclerosis (≈1%), Rett syndrome (≈0.5%) and neurofibromatosis (NF1; <1%), are the most commonly cited. Other rare microdeletion or single gene defects have been associated with ASD including those found in Williams–Beuren, Sotos, Cowden, Moebius, Smith-Lemli-Opitz, and Timothy syndromes. ASD can also occur in some mitochondrial diseases and untreated phenylketonuria. A recent review [19] identified over 103 disease genes and 44 genomic loci among subjects with ASD or autistic behavior. These genes have all been causally implicated in intellectual disability, indicating that these two neurodevelopmental disorders often share a common genetic basis [20••]. High-resolution karyotyping reveals cytogenetically visible chromosome rearrangements in ∼5% of individuals with ASD. Our previous survey [21] found such abnormalities in 129/1749 ASD cases (7.4%).

Renal transplants were performed only when AHG-CDC CXMs were nega

Renal transplants were performed only when AHG-CDC CXMs were negative. The potential recipients considered HKI-272 mouse during the DD events were classified into 5 groups according to their % PRA: Group 1 (0%), group 2 (1–19%), group 3 (20–79%), group 4 (80–100%) and group 5 (unknown PRA). The patients in group 5 (unknown) were included in the

deceased donor waiting list in a time period when the % PRA assay was not part of the regular practice in our setting. In our institution, kidney allocation to patients on the waiting list has been based exclusively on a negative T and B cells AHG-CDC cross-match, the time on waiting list and blood group (equal ABO group with the donor). Patients without vascular and peritoneal access for dialysis are considered emergencies and always have had priority in our setting. All of the patients that undergo a DD KT at out institution receive some modality of induction therapy, whether anti-CD25 monoclonal antibodies or thymoglobulin, CH5424802 order and is mostly defined by the immunological patient risk. During this time period, the immunosuppression regimen for this group of patients consisted of tacrolimus, mycophenolate mofetil, and prednisone. Clinical information regarding 1-year post-KT graft function and/or the last graft function evaluation was

gathered from the corresponding patient records. Causes of graft loss and patient death were documented. The graft biopsy registry was analyzed to obtain the information regarding the total number of graft dysfunction

biopsies performed, and acute rejection events documented whether cellular, humoral or both. The histological analysis and diagnosis were performed using the current BANFF criteria at the time of the graft biopsy [11], [12], [13], [14], [15], [16] and [17]. Graft dysfunction was defined as SCr increase of ≥ 25% from baseline in the absence of an identified cause. The statistical analysis was performed using odds ratio with prior group stratification, logistic regression analysis, Kaplan Meier method and Log Rank. A p value < 0.05 was considered statistically significant with a confidence interval of 95%. For categorical variables, an analysis to determine frequencies, proportions, Chi2, and Spearman correlation coefficient was also performed. Fifty-eight DD events with a female to male ratio of 34:24 and a mean age of 35.4 ± 13.3 Vasopressin Receptor were identified. The ABO group distribution among these donors was of 35 donors for group “O”, 13 donors for group “A” and 10 donors for group “B”. A group of 179 potential kidney transplant recipients was included in the analysis all of whom were older than 18 years of age, with a female to male ratio of 98:81 and a ABO group distribution of 127 patients for group “O”, 33 patients for group “A” and 19 patients for group “B”. The mean PRA for all the potential recipients was 22 ± 32%, median [md] 0 (0–98). Males had a mean % PRA of 11.7 ± 26 md 0 (0–97) vs. females with a mean % PRA of 30.9 ± 35 md 13.

In the first case there is held to be a change in the individual’

In the first case there is held to be a change in the individual’s impairment. When the studies with methodological weaknesses were excluded, then 11 of the 44 people given phonological or orthographic information showed some generalisation to untreated items. Thus, around a quarter of participants in these studies improved on untreated as well as treated items. Findings from approaches involving ‘strategy’ and aimed at re-organising processes, such as orthographic self-cueing, were even more encouraging.

Thirteen of nineteen cases showed some selleck chemicals generalisation. Such approaches are, however, suitable for only some individuals with particular strengths (e.g., in retrieving orthographic knowledge). Interestingly, in a case series intervention using written cues, sixteen of eighteen participants improved on written naming, and four of these showed transfer to untreated items (Deloche et al., 1997; see also Carlomagno et al., 2001). This mirrors Nickels’ review in suggesting around one quarter may demonstrate generalisation in word production. There are several experimentally controlled single case studies with participants with deficits in post-lexical processing where intervention resulted in improvement on both treated and untreated items (Fisher et al., 2009; Franklin et al., 2002; Robson et al., 1998) For example,

Fisher et al. (2009) worked with a man with ‘mild phonological encoding impairment’. He showed significant generalisation to untreated items from an intervention which involved www.selleckchem.com/products/Adrucil(Fluorouracil).html attempting to name pictures with unrelated names or with shared phonology (magnet, mattress, macaroni). In contrast, Waldron et al. (2011) found no generalisation to untreated items, despite employing a previously successful intervention (Franklin et al.,

2002). The participants in Waldron’s study had a combination of lexical (stage 2) and post-lexical (stage 3) impairments. Raymer et al. (2012), in a study investigating errorless naming treatment and gestural facilitation of naming did not obtain generalisation to untrained items for the three participants with semantic anomia, but obtained some generalisation in naming for three of five participants with phonological anomia. Finally, studies using orthographic cueing aids demonstrate convincing generalisation to untreated Cyclooxygenase (COX) items (Best et al., 1997; Bruce and Howard, 1987; Howard and Harding, 1998). We aimed to explore the effects of a cueing hierarchy, especially generalisation to untreated items, and to relate the outcome to level of breakdown in naming. Specifically, we ask: (i) Can a cueing therapy improve word production (i.e., retrieval of meaning and form and phonological encoding) in participants with aphasia? From previous studies we predicted: (a) those with a post-semantic deficit, stage 2, with relative strengths in semantic and phonological output processing and a specific deficit in retrieving lexical forms will show item specific changes in naming (following e.g.