As a result of this investigation Bayer chose a recombinant B-dom

As a result of this investigation Bayer chose a recombinant B-domain-deleted FVIII molecule with a single site modification to which a 60 kDa PEG molecule was attached for further development. A Phase 1 study in 14 patients showed that this molecule had an extended half-life of 19 h compared to 13 h in controls [107]. This therefore represented an approximately 1.5-fold increase in half-life and was achieved without any adverse events or inhibitor development. Notwithstanding the limitations

described above, Baxter have pursued a chemical modification method to modify FVIII. Careful control of the reaction DNA Synthesis inhibitor conditions resulted in a full length FVIII molecule PEGylated in a 2:1 molar ratio using a 20 kDa PEG molecule. Further analysis showed that 60% of the PEG was attached to the B domain, which may be advantageous as this will be removed during FVIII activation. A Phase 1 study in 10 patients showed a half-life extension of approximately Selleckchem OTX015 1.5-fold, again with no significant adverse events [108]. A third approach to PEG modification of FVIII has

been followed by Novo Nordisk. They noted that their B-domain-deleted FVIII molecule retained a single O-linked glycan in the residual B domain. Following desialylation of the FVIII, a specific transferase was used to transfer a sialic acid-modified PEG molecule onto the remaining O-linked glycan chain, following which the remaining N-linked glycans were resialylated. The FVIII molecule therefore contained a single 40 kDa PEG addition which resulted in a half-life extension of approximately 1.6-fold in a Phase 1 study [109, 110]. Thus, all three PEG modification strategies have received similar modest prolongations of FVIII half-life. The addition of the immunoglobulin Fc fragment to molecules results in their attachment to the neonatal Fc receptor after

cellular uptake and protects them from breakdown in endosomes, eventually resulting in their return to circulation. This technique has been successfully used to prolong the half-life of other therapeutic molecules and Powell et al. Acetophenone reported on the effect of modifying FVIII in this way in a Phase 1 study of patients with haemophilia A. In 16 previously treated patients (PTPs), the half-life of FVIII was prolonged from 11 h to 18.8 h, representing a mean 1.7-fold increase in half-life. There were no adverse events and no antibody production, but again the prolongation is relatively modest [111]. Overall, it is clear from the studies reported so far that none of the modified molecules have been able to exceed the twofold extension in half-life produced by LRP knockout. It is worth noting that this modest prolongation of half-life is in contrast to the threefold or greater increase in half-life achieved using similar techniques to modify factor IX [112].

45% after one year [20] On the other hand, in Latin America, a h

45% after one year [20]. On the other hand, in Latin America, a higher recurrence of H. pylori infection has been observed. A large trial

involving 7 countries in which more than 1000 subjects were followed up for 1 year after a successful eradication therapy, confirmed by a negative UBT result, reported an H.  pylori recurrence in 11.5% of cases [34]. Data from recent studies show that the prevalence of H. pylori infection is still high in most countries worldwide. RG-7388 price H. pylori seems to be less frequent in northern European and North American populations; however, about one-third of the adults seem to still be infected. In these countries, H. pylori remains highly prevalent in immigrants coming from countries with a high prevalence of H. pylori. Moreover, the lower prevalence of infection in the younger generations would suggest a further GSK126 research buy decline in H. pylori prevalence in the community over the coming decades. Competing interests: The authors have no competing interests. “
“Background and Aims: Helicobacter pylori infection appears to be a protective factor for gastroesophageal reflux disease (GERD). However, H. pylori is associated with the subtype of esophageal carcinoma, and long-term proton-pump inhibition usage would cause gastric atrophy in patients with persistent

H. pylori infection, which is a precancerous lesion. The relationship between H. pylori infection and GERD is still unclear. We aimed to confirm whether the eradication of H. pylori would worsen or improve symptomatic or endoscopic GERD. Methods:  A systematic review of the published data was undertaken, and a

meta-analysis was performed to determine the effect of H. pylori eradication on the occurrence of symptomatic (heartburn, acid regurgitation) and endoscopically proven erosive (esophagitis) GERD in patients with or Aurora Kinase without pre-existing GERD. Results:  A total of 11 articles met the inclusion criteria and thus were included in the meta-analysis. There was no significant difference in the frequency of symptomatic or endoscopically proven erosive GERD after the eradication between patients with H. pylori eradicated and those with persistent infection, regardless of follow-up period, location, or the baseline disease. Conclusion: H. pylori eradication does not aggravate the clinical outcomes in terms of short-term and long-term posteradication occurrence of GERD. There is no association between H. pylori eradication and the development of GERD in the patients with different diseases, even those with GERD. “
“Several studies have reported that the application of ecabet sodium during the eradication of Helicobacter pylori can improve the eradication rate and reduce therapy-associated side effects. However, the efficacy and safety of this therapy are controversial. To determine whether ecabet sodium improves the eradication rate of H. pylori and examine treatment safety by conducting a meta-analysis based on randomized controlled trials (RCTs).

”16–18 Myofibroblasts have similarly been given different names w

”16–18 Myofibroblasts have similarly been given different names when associated with the portal tract. Cassiman and colleagues10, 19 identified three myofibroblast populations in cirrhotic rat and human livers: myofibroblasts clearly derived from HSCs, portal/septal myofibroblasts postulated to be derived from PFs, click here and interface myofibroblasts, with an intermediate

phenotype and unclear origin. For clarity, we refer here to all fibroblasts in the portal region (whether periductal or not) as PFs and to all non–HSC-derived myofibroblasts in the portal region as portal myofibroblasts, acknowledging that the cells in each category are heterogeneous. Portal myofibroblasts in particular may originate from different precursor cell populations, potentially

buy Palbociclib including vascular smooth muscle cells from the walls of the hepatic artery and portal vein. Isolated PFs in culture, which undergo myofibroblastic differentiation, are a useful new tool for studying mechanisms of biliary fibrosis. Unfortunately, isolation techniques, nomenclature, and identification of these presumably heterogeneous cells vary. PFs clearly distinct from HSCs by marker analysis have been isolated by outgrowth from dissected bile duct segments and express α-SMA and type I collagen after undergoing growth in culture.17, 20 We have isolated PFs from rat liver by way of sequential protease perfusion, bile duct dissection, and size selection and have observed that they undergo progressive myofibroblastic differentiation Cediranib (AZD2171) over 10 to 14 days.21, 22 In no case, however, is it understood how well isolated PFs and portal myofibroblasts reflect the corresponding cell populations in vivo. A variety of markers have been used to identify PFs, although the findings of different groups have not always coincided. Markers considered specific for PFs

include fibulin-2, interleukin-6 (IL-6), elastin, and the ecto-ATPase nucleoside triphosphate diphosphohydrolase-2 (NTPD2) (Fig. 1). Expression of P100, α2-macroglobulin, and neuronal proteins (including neuronal cell adhesion marker and synaptophysin) and the absence of lipid droplets have also been used to differentiate PFs from HSCs (for review, see Cassiman et al.,10 Ramadori and Saile,18 and Guyot et al.23). As research on PFs increases, the application of a uniform set of markers by different investigators would undoubtedly clarify many published results. α-SMA, α-smooth muscle actin; BDE, bile duct epithelia; BDL, bile duct ligation; HSC, hepatic stellate cell; IL-6, interleukin-6; MCP-1, monocyte chemotactic protein-1; NTPD2, nucleoside triphosphate diphosphohydrolase-2; p75NTR, p75 neurotrophin receptor; PDGF, platelet-derived growth factor; PF, portal fibroblast; TGF-β, transforming growth factor-β. The embryologic origins of PFs are not known, and definitive lineage tracing has not been performed.

There were three additional categories—inflammatory response, cel

There were three additional categories—inflammatory response, cell cycle, and nucleic acid metabolism—in which genes from at least one but not all three assays were overrepresented. The most notable difference between the PBM2 search from the other assays was an enrichment of genes involved in developmental processes. This is consistent with the known role of HNF4α in early development,34 and could be explained

by the fact that the cells used in the ChIP-chip and RNAi assays are from adult stages, not embryonic stages. In general, the ChIP assay yielded more significant GO terms in all categories, which is most likely a reflection of the more specific nature BMS-777607 cost of this assay and the stringent cutoff values used. In order to more closely compare the three methods of identifying potential target genes, we cross-referenced the PBM2 search results with the HNF4α RNAi and ChIP-chip results. We identified 198 genes that

were positive in all three categories, i.e., bound by HNF4α in ChIP-chip, down-regulated by HNF4α in HepG2 RNAi, and containing one or more verified HNF4α-binding sites in the −2 kb to +1 kb region of the promoter (Fig. 7A). A similar analysis with the SVM2 search yielded 135 genes (Fig. 7B). Among these two categories, there were ∼260 nonredundant genes, PD0332991 order of which ∼240 were not in the original list of HNF4α target genes from the literature (Supporting Table 1A). Several of these genes are new targets within known categories of HNF4α targets Aldol condensation (e.g., homeostasis = solute carrier proteins, SLC genes; lipid metabolism = e.g., ABCC6, DGAT2, hydroxysteroid dehydrogenase

[HSDs] genes), or more recently identified targets of HNF4α (e.g., CREB3L3, NR1I2, NR1H4, DO1).35–38 There were also many genes that, like NINJ1, are in completely new categories of genes not typically associated with HNF4α (e.g., signal transduction, immune response, stress response, apoptosis, cancer related, and cell structure) (Fig. 7C), several of which are reminiscent of the new functional categories identified by GO (Fig. 6). In order to determine whether the ChIP signal overlapped with the PBM or SVM sites in these new targets, all three datasets were visualized using Integrated Genome Browser. Although not all ChIP signals aligned exactly with the PBM or SVM sites, a very large number did; a sampling of these are shown in Fig. 8. Identification of TF binding sites and target genes can be a laborious process. Recent genome-scale technologies such as expression profiling and genome-wide location analysis can greatly expand the repertoire of potential targets with relative ease, although the question remains as to which are direct targets that contain bona fide binding sites. PBMs allow for a high-throughput identification of DNA binding sequences that can then be integrated with the other techniques, and can also be used to predict potential new targets in additional tissues or developmental stages.

One other study looking at the effect of pretreatment with PPI on

One other study looking at the effect of pretreatment with PPI on eradication rates did not find a benefit [11]. In addition to trials focussing on certain specific regimens, there were a number of studies that focussed on the processes of second- and third-line therapies over the last year. Regarding second-line therapy, one study from Japan revealed very high second-line eradication BMN673 rates with PPI, amoxicillin, and metronidazole for 1 week after failure of first-line eradication therapy with a PPI, amoxicillin, and clarithromycin and that the trend was stable over 5 years

with a reported overall second-line eradication rate of 92.4% [12]. Another group reported a prospective study of patients with antibiotic resistance and found excellent eradication selleck rates of 88.6% in this population when culture-based selection for second-line therapy was employed [13]. When treatment failure occurred, the interval between first-line H. pylori eradication treatment and second-line treatment may be critical to the second-line

therapeutic effect. A Japanese study reported an 88.6% ITT eradication rate for those treated with PPI, amoxicillin (1500 mg/day), and metronidazole (500 mg/day) for 1 week within 6 months of initial treatment failure compared with 68.8% when the second-line therapy was commenced after more than 180 days [14]. On the issue of third-line therapy, a multicenter study also from Japan compared several options for rescue treatment and found triple therapy with PPI, amoxicillin, and sitafloxacin as the best option with 70% eradication and only 7.7% resistance [15]. A very comprehensive review article this year suggested that in general clinical practice, levofloxacin–amoxicillin–PPI given twice daily, unless regional or new data show high quinolone resistance, is a good second-line combination [16]. In one other study, doxycycline was seen to have no efficacy against H. pylori in a series of 16 patients with multiresistant strains when used see more with PPI and amoxicillin [17]. There have been several studies again this year examining sequential and concomitant (non-bismuth quadruple) therapy, both in comparison with

standard triple therapy and each other. Sequential therapy consists of 5 days of PPI therapy plus amoxicillin, followed by a further 5 days of PPI with two other antibiotics, usually clarithromycin and metronidazole. By contrast, concomitant therapy involves maintaining three antibiotics along with the PPI for the duration of therapy. A very large and comprehensive meta-analysis and systematic review of studies looking at 5666 patients receiving sequential therapy compared with 7866 receiving other regimens concluded that the overall eradication rate of sequential therapy was suboptimal at 84.3% [18]. It was, however, superior to 7-day triple therapy (risk ratio (RR) 1.21, number needed to treat (NNT) of 6), and marginally superior to 10-day triple therapy (RR 1.

Liver necrosis and neutrophil infiltration were assessed with H&E

Liver necrosis and neutrophil infiltration were assessed with H&E and immunohistochemical staining, respectively. Serum and

hepatic bile acid levels were measured as well. RESULTS: Compared with wild-type, NHERF-1-/mice had more than 50% reduction in hepatic radixin expression (P<0.001). NHERF-1-/- BDL mice showed significantly lower scores of hepatic necrosis (P<0.01) as well as reduced neutrophil accumulation in the liver compared to the wild-type BDL group. Western blotting demonstrated that ICAM-1was reduced to about 70% of the wild-type in both sham and BDL NHERF-1-/- mouse liver (P<0.05). No significant difference in hepatic bile acid levels was detected between WT and NHERF1-/- mice in both the sham and BDL groups, but serum bile acid levels tended to be decreased in NHERF-1-/- BDL mice. CONCLUSIONS: These findings indicate that NHERF-1 is an important determinant of the expression of hepatic radixin as well as ICAM-1, an essential HIF cancer molecule involved in liver injury associated

with neutrophil-dependent inflammation after BDL. While changes in the expression of these proteins can have protective effects in cholestatic liver injury, the protection seems independent of hepatic bile acid concentrations. This study indicates that adhesion molecules are potential therapeutic targets in cholestasis. Disclosures: The following people have nothing to disclose: Man Li, Albert Mennone, Carol J. Soroka, Kathy M. Harry, Edward J. Weinman, James L. Boyer Sustained cholestasis results in injury to the biliary epithelium with subsequent ductular reaction, pericholangitis, stellate cell activation, and Barasertib fibrogenesis. Such pathologies are commonly associated with diseases such as primary biliary cirrhosis and primary sclersoing cholangitis. The Wnt/p-catenin pathway has been shown to play an important role during bile duct development, but its role in adult bile duct injury and repair remains

undetermined. Mice lacking p-catenin in hepatocytes and biliary epithelial cells (Kし)and littermate wild-type (WT) control mice were subjected to bile duct ligation (BDL), a short-term model of acute intrahepatic cholestasis. learn more Intriguingly, while bilirubin levels were comparably enhanced, hepatocyte injury, intrahepatic cholestasis and fibrosis were notably decreased in the KO after BDL. Further analysis yielded a significant decrease in total hepatic bile acids (BA) in the KO, which was associated with suppression of BA synthesis and an increase in apical BA transporter expression. Further, expression of Shp-1 mRNA was dramatically increased in KO after BDL. Hep3B cells transfected with Shp-1 reporter demonstrated a significant increase in activity when treated with p-catenin siRNA in the presence of FXR agonist GW4064. Finally, coprecipitation studies demonstrate a physical association of p-catenin and FXR in the WT that increases after BDL, suggesting an inhibitory function for pcatenin in FXR activation.

” Systematic “protocol” evaluations at each visit, liver tissue e

” Systematic “protocol” evaluations at each visit, liver tissue examinations at 6 month intervals, uniform treatment schedules, predefined responses to disease behavior, regular surveillance schedules using mailed serum specimens,

GSK3 inhibitor serum and liver tissue banks, and commitment to indefinite patient follow-up were the manifestations of this “tenacity.” I remain convinced that rigid adherence to protocol and compulsive follow-up are essential components of successful clinical investigation (Table 1). Bill Summerskill died suddenly in March 1977, and I was abruptly launched solo into the realm of CALD. Life-saving therapy had now been established by three controlled clinical trials; the disease was rare; funding sources were limited or uninterested,

and my principal initial concern was that there was nothing more to study.21,39,40 The practical clinical problems that required answers became obvious quickly through routine patient care, and they generated a compelling urgency for further clinical studies. Remarkable work from Meyer zum Buschenfelde’s group in Mainz, Germany,41-44 and Roger Williams’ group in London, England,45-49 invigorated the concept of autoimmune hepatitis, and I suddenly realized anew that I was in an exciting place at an exciting time. The first objective was to describe the clinical phenotype of autoimmune hepatitis and to distinguish it from other diseases. This was done by describing its autoantibodies,50 Quisqualic acid histological manifestations,51,52 clinical presentations,53-55 and response to corticosteroid treatment.56-58 The ITF2357 price disease had to be distinguished from systemic lupus

erythematosus59 and chronic viral hepatitis60; it had to be released from the early restrictive requirement for 6 months of disease activity61; subtypes based on mutually exclusive serological markers had to be explored62-64; and it had to accommodate patients with nonclassical manifestations.65 This was the era of serological exploration, and collaborations with Mikio Nishioka,66-70 Francesco Bianchi,71,72 Michael Manns62-64 and their coworkers were essential to understand the nature and clinical significance of antinuclear reactivities, including antibodies to ribonucleoproteins, histones, single-stranded DNA and doubled-stranded DNA, antibodies to actin, antibodies to liver kidney microsome type 1 (anti-LKM1), antibodies to soluble liver antigen (anti-SLA), and antimitochondrial antibodies in autoimmune hepatitis. These efforts complemented studies performed elsewhere, and they supported concepts of an acute autoimmune hepatitis,54 two serologically distinct forms of the disease,73 variant syndromes characterized by antimitochondrial antibodies,74 bile duct changes,75-79 or concurrent viral infection,80-82 and a seronegative state frequently misclassified as cryptogenic chronic hepatitis.

Methods:  Between May 2009 and November 2010, 164 consecutive pat

Methods:  Between May 2009 and November 2010, 164 consecutive patients with HBV-related HCC who underwent hepatic resection were prospectively enrolled in the study. Among these, 126 patients received antiviral treatment before the operation (the antiviral group) and 38 patients did not receive any antiviral treatment (the non-antiviral group). Results:  Ten patients (6.1%) developed HBV reactivation perioperatively (within 1 month after hepatectomy). The incidence of HBV reactivation in the antiviral group and non-antiviral group were 1.6% KU-60019 clinical trial (2/126) and 21.1% (8/38), respectively (P < 0.001). On univariate analysis, preoperative HBV DNA < 1.0 × 103 copies/mL

and non-antiviral therapy were significantly correlated with the occurrence of HBV reactivation (P = 0.044 and P < 0.001, respectively). Aloxistatin in vitro Only non-antiviral therapy remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95% confidence interval, 2.80–85.46, P = 0.002). The recovery of liver function (defined as a decrease of alanine aminotransferase back to normal) was achieved in 86.8% (132/152) patients without HBV

reactivation and in 37.5% (3/8) patients with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001). Conclusion:  Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given. "
“Chemokine receptors mediate migration of immune cells into the liver, thereby promoting liver inflammation. C-C motif chemokine receptor (CCR) 9+ macrophages are crucial in the pathogenesis of acute liver inflammation, but the role and underlying mechanisms of this macrophage subset in chronic liver injury and subsequent liver

fibrosis are not fully understood. We confirmed that tumor necrosis factor alpha (TNF-α)-producing CCR9+ macrophages accumulated during the initiation of carbon tetrachloride (CCl4)-induced liver injury, and CCR9 deficiency attenuated the degree of liver damage. Accumulation Immune system of CCR9+ macrophages persisted prominently during the process of liver fibrosis induced by repetitive CCl4 or thioacetamide (TAA)/leptin administration. Increased CCR9 expression was also found on activated hepatic stellate cells (HSCs). Importantly, experimental liver fibrosis was significantly ameliorated in CCR9−/− mice compared with wild-type (WT) mice, assessed by α-smooth muscle actin (α-SMA) immunostain, Sirius red staining, and messenger RNA (mRNA) expression levels of α-SMA, collagen 1α1, transforming growth factor (TGF)-β1, and tissue inhibitor of metalloproteinase (TIMP)-1. Accumulated CD11b+ macrophages in CCl4-treated WT mice showed marked increases in TNF, NO synthase-2, and TGF-β1 mRNA expression compared with CCR9−/− mice, implying proinflammatory and profibrogenic properties.

Key Word(s): 1 colon capsule; 2 CT-colonography; 3 incomplete;

Key Word(s): 1. colon capsule; 2. CT-colonography; 3. incomplete; 4. optical colonoscopy; Presenting Author: TIING LEONG ANG Additional Deforolimus chemical structure Authors: RAPAT PITTAYANON, SHIAW HOOI HO, RUNGSUN RERKNIMITR, KHEAN LEE GOH, ENG KIONG TEO Corresponding Author: TIING LEONG ANG Affiliations: Changi General Hospital; Chulalongkorn Hospital; University of Malaya Objective: White light endoscopy (WLE) may miss intestinal metaplasia (IM), dysplasia and early gastric cancer. Narrow band imaging (NBI) during endoscopy improves mucosal surface contrast. The current NBI system is limited by a dark endoscopic view and is only useful for characterization

of lesions. The new EXERA III NBI system (Olympus, Tokyo, Japan) with bright illumination and high

definition resolution may increase detection rate. The study aim to determine whether there was a difference in the detection rate of focal gastric lesions between WLE and NBI using the EXERA III NBI system. Methods: Three study sites were involved (Singapore, Thailand and Malaysia). Inclusion criteria: 1) subjects aged >50 years BIBW2992 clinical trial undergoing diagnostic UGI endoscopy. Exclusion criteria: 1) active gastrointestinal bleeding; 2) coagulopathy; 3) previous partial gastrectomy. Patients were randomized to either WLE or NBI. The presence of focal gastric lesions and the morphology based on the Paris classification were recorded. Lesions were biopsied and endoscopic diagnoses were confirmed by histology. The difference in the detection rate of focal lesions was analysed. Results: From January to February 2013, 421 patients were recruited (WLE: 211; NBI: 210). NBI detected

significantly more focal gastric lesions compared Pyruvate dehydrogenase to WLE (41% vs. 26.5%, p = 0.002). NBI detected significantly more cases of IM compared to WLE (20.5% vs. 5.7%; p < 0.001). These cases of IM presented as subtle mucosal abnormalities (morphology: 0_Is: 3.6%; 0_IIa: 65.5%; 0_IIb: 25.5%; 0_IIc: 5.5%). NBI detected significantly more cases of erosions or ulcers (8.6% vs. 3.8%, p = 0.45). There was no difference in the detection rate of fundic gland polyps. As only 6 cases of gastric cancer were detected, no meaningful analysis concerning its detection rate could be performed. Conclusion: NBI was useful for the detection of subtle focal gastric lesions. NBI increased the detection rate of IM compared to WLE. Key Word(s): 1. high definition; 2. narrow band imaging; 3. intestinal; 4. metaplasia; Presenting Author: JIEFU LU Additional Authors: HAIXING JIANG Corresponding Author: HAIXING JIANG Affiliations: 1st Affiliated hospital of Guangxi medical university Objective: Explore the safety and feasibility of percutaneous endoscopic gastrostomy, and the superiority compared with traditional nasogastric tube nutrition. Evaluate the effect of percutaneous endoscopic gastrostomy clinical application.

Based on our dataset of 147 sequences, including 67 new sequences

Based on our dataset of 147 sequences, including 67 new sequences, we recovered four well-supported

deep clades within Buthus scorpions from the Maghreb and Southern Europe. This further strengthens the support for cryptic diversity in the Maghreb region. The broader sampling of the Maghreb permitted a better understanding of the phylogeographic structure in this area. Three clades were restricted to Morocco and appear to have originated at the Atlantic Coast of this country, while the fourth was found throughout the region. We propose a model with two colonizing events to explain the distribution patterns across the Strait selleck inhibitor of Gibraltar, with an initial colonization from North Africa to Iberia followed by a reinvasion of the Rif Mountains region in Morocco. “
“Dental enamel hypoplasia is a developmental defect in enamel caused by physiological stress during dental development. Previous analysis of enamel hypoplasia in sheep has demonstrated that variation in its frequency can be linked to nutrition levels, with animals suffering from malnutrition more susceptible

to enamel hypoplasia formation. Variation in enamel hypoplasia frequency has also been linked to climatic and ecological factors, leading to variation in the availability of fodder supplies and, consequently, variation in nutritional intake. In this paper, the occurrence of enamel hypoplasia in two modern sheep populations is, for the first time, correlated with known seasonal physiological and nutritional stress events. Using known age-at-death Epigenetics inhibitor data, the dental development rates for sheep are reconstructed, allowing the position of enamel hypoplasia on the tooth crown to be linked to known periods of malnutrition and physiological stress. Both populations live under identical climatic conditions but with very different diets.

Clear differences are observed between the two populations, with peaks of enamel Astemizole hypoplasia correlating with different seasonal periods of malnutrition as well as common physiological stressors linked to birth and weaning. This is the first time that a clear correlation has been made between seasonal variation in nutrition and the occurrence of hypoplastic enamel defects in caprine populations. As such, this study provides a baseline from which the nutritional impact of caprine foddering and husbandry practices can be determined in future archaeological studies. “
“Tigers are globally endangered and continue to decline due to poaching, prey depletion and habitat loss. In Nepal, tiger populations are fragmented and found mainly in four protected areas (PAs). To establish the use of standard methods, to assess the importance of prey availability and human disturbance on tiger presence and to assess tiger occupancy both inside and outside PAs, we conducted a tiger occupancy survey throughout the Terai Arc Landscape of Nepal.