bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence of factor VIII inhibitors in severe haemophilia A following a major switch from full‐length to B‐domain‐deleted factor VIII: a prospective cohort comparison
Authors: Hay C. R. M. , Palmer B. P. , Chalmers E. A. , Hart D. P. , Liesner R. , Rangarajan S. , Talks K. , Williams M. , Collins P. W.
Published: November 2014

Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non‐switchers. Centres were requested to test all the patients for inhibitors prior to the switching date and 6‐monthly thereafter. Positive and negative inhibitor test data were also collected to analyse for testing bias. A total of 1198 patients with severe haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch were included in the analysis, of whom 516 switched to Refacto‐AF and 682 did not switch products. Five new inhibitors were reported amongst previously treated patients (>50 exposure days) with a median titre at the time of detection of 1.25 BU mL−1 (IQR 0.7–23.05). One inhibitor occurred in a non‐switcher using Kogenate, an incidence of 1.5 per 1000 treatment‐years (95% CI 0.2–10.5). Four inhibitors arose in patients who had switched from Kogenate (two) or Advate (two) to ReFacto‐AF, an incidence of 7.8 per 1000 treatment‐years (95% CI 2.9–20.8). These incidence rates did not differ significantly from one another (incidence rate ratio 5.3 (95% CI 0.5–260.3) or from the historical rate of 6.05 inhibitors/1000 treatment‐years (95% CI 5.18–7.06). Only one inhibitor (non‐switcher) persisted. Non‐switchers were significantly older (P = 0.03), and used significantly less FVIII per year (P = 0.005) prior to switching. Following switching, factor usage increased similarly (P = 0.53) in both groups. Switching from FLRFVIII to Refacto‐AF (BDDRFVIII) was not associated with an increased inhibitor development.
Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis
Authors: Carpenter S. L. , Soucie J. M. , Presley R. J. , Ragni M. V. , Wicklund B. M. , Silvey M. , Davidson H. ,   the Hemophilia Treatment Center Network Investigators
Published: November 2014

Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed were from an initial visit before 24 months of age, until time of hepatitis antibody titre testing. The SQ and IM study groups did not differ in demographics, haemophilia type or severity or bleeding history. The mean age at the time of HBV surface antibody (anti‐HBs) testing was 56.9 ± 20.3 months. Eighty‐five of 92 subjects (92.4%) who received vaccine SQ developed a positive antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P = 0.30). There was no statistically significant difference in distribution of titre values. The average age of the subjects at time of testing was 53 ± 20 months in the SQ group vs. 60 ± 20 months in the IM group (P = 0.02). The average time between the last dose of vaccine and anti‐HBs testing was 47.6 ± 18.5 months among SQ vaccinated subjects vs. 51.6 ± 20.5 months in the IM group (P = 0.2). Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.
The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease
Authors: Makris M. , Federici A. B. , Mannucci P. M. , Bolton‐Maggs P. H. B. , Yee T. T. , Abshire T. , Berntorp E.
Published: November 2014

Recurrent gastrointestinal bleeding is one of the most challenging complications encountered in the management of patients with von Willebrand disease (VWD). The commonest cause is angiodysplasia, but often no cause is identified due to the difficulty in making the diagnosis. The optimal treatment to prevent recurrences remains unknown. We performed a retrospective study of VWD patients with occult or angiodysplastic bleeding within the setting of the von Willebrand Disease Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies. Centres participating in the VWD PN recruited subjects under their care with a history of congenital VWD and gastrointestinal (GI) bleeding due to angiodysplasia, or cases in which the cause was not identified despite investigation. Patients with acquired von Willebrand syndrome or those for whom the GI bleeding was due to another cause were excluded. Forty‐eight patients from 18 centres in 10 countries were recruited. Seven individuals had a family history of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the most common methods of making the diagnosis. Recurrent GI bleeding in VWD is associated with significant morbidity and required hospital admission on up to 30 occasions. Patients were treated with multiple pharmacological agents with prophylactic von Willebrand factor concentrate being the most efficient in preventing recurrence of the GI bleeding. The diagnosis and treatment of recurrent GI bleeding in congenital VWD remains challenging and is associated with significant morbidity. Prophylactic treatment with von Willebrand factor concentrate was the most effective method of preventing recurrent bleeding but its efficacy remains to be confirmed in a prospective study.
Review: Clinical Management of Helicobacter pylori Infection in China
Authors: Xie Chuan , Lu Nong‐Hua
Published: November 2014

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.
Helicobacter cinaedi Induced Typhlocolitis in Rag‐2‐Deficient Mice
Authors: Shen Zeli , Feng Yan , Rickman Barry , Fox James G.
Published: November 2014

Background

Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase‐activating gene (Rag)‐2‐deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2−/− mouse model.

Materials and Methods

Sixty 129SvEv Rag2−/− mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice.

Results

H. cinaedi induced typhlocolitis in Rag2−/− mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon‐γ, tumor‐necrosis factor‐α, IL‐1β, IL‐10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL‐4, IL‐6, Cox‐2, and c‐myc mRNA expressions were not detected.

Conclusions

Our results indicated that the Rag2−/− mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS.
Low Prevalence and Incidence of Helicobacter pylori Infection in Children: A Population‐Based Study in Japan
Authors: Okuda Masumi , Osaki Takako , Lin Yingsong , Yonezawa Hideo , Maekawa Kohei , Kamiya Shigeru , Fukuda Yoshihiro , Kikuchi Shogo
Published: November 2014

Background

Infection of Helicobacter pylori mainly occurs in childhood. In Japan, incidence of gastric cancer is still high in the senior citizen population, but little is known about the current H. pylori infection status among children or their family members.

Methods

As a population‐based study, the prevalence of H. pylori infection and change in infection status over a 1‐year interval in children were determined. Family members of some participants were also invited to participate in the study to determine their infection status. All children of specific ages attending 16 schools in Sasayama, Hyogo Prefecture, were invited to participate. H. pylori infection was determined by the stool antigen test and diagnosis confirmed by polymerase chain reaction and the urea breath test.

Results

Helicobacter pylori prevalence was 1.9% among 689 children aged 0–8 years in 2010 and 1.8% among 835 children aged 0–11 in 2011. No feco‐conversion was observed in 430 children aged 0–8 years (170 were aged 0–4 years) who provided follow‐up stool samples after 1 year. The prevalence of infection was 6% (2 of 33) and 38% (6 of 16) in mothers of negative and positive probands (p = .04), respectively, and 12% (3 of 25) and 50% (8 of 16) (p = .01), respectively, in fathers.

Conclusion

Helicobacter pylori prevalence in Japanese children is approximately 1.8%, which is much lower than that reported in Japanese adults. New infection may be rare. Parent‐to‐child infection is thought to be the main infection route of the infrequent infection for children in Japan.
Helicobacter pylori Test‐and‐Treat Program Can Be Cost‐effective to Prevent Gastric Cancer in Taiwanese Adults: Referred to the Nationwide Reimbursement Database
Authors: Cheng Hsiu‐Chi , Wang Jung‐Der , Chen Wei‐Ying , Chen Chian‐Wei , Chang Shun‐Chiao , Sheu Bor‐Shyang
Published: November 2014

Background

Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare cost‐effectiveness ratios of H. pylori test‐and‐treat programs to prevent gastric cancer in Taiwan, referring to the nationwide reimbursement database and expected years of life lost.

Materials and Methods

During 1998–2009, there were 12,857 females and 24,945 males with gastric adenocarcinoma in Taiwan National Cancer Registry. They were followed up to 2010 and linked to the reimbursement database of National Health Insurance and the national mortality registry to determine lifetime health expenditures and expected years of life lost. Cost‐effectiveness ratios of H. pylori test‐and‐treat programs for prevention of gastric adenocarcinoma were compared between screenings with 13C‐urea breath test and with anti‐H. pylori IgG.

Results

The test‐and‐treat program with anti‐H. pylori IgG to prevent gastric adenocarcinoma had lower incremental cost‐effectiveness ratios than that with 13C‐urea breath test in both sexes (females: 244 vs 1071 US dollars/life‐year; males: 312 vs 1431 US dollars/life‐year). Cost saving would be achieved in an endemic area where H. pylori prevalence was >73.5%, or by selecting subpopulations with high absolute risk reduction rates of cancer after eradication. Moreover, expected years of life lost of gastric adenocarcinoma were higher and the incremental cost‐effectiveness ratios of test‐and‐treat programs were more cost‐effective in young adults (30–69 y/o) than in elders (≥70 y/o).

Conclusions

The test‐and‐treat program with anti‐H. pylori IgG shall be cost‐effective to prevent gastric adenocarcinoma in a high endemic area, especially beginning at 30 years of age when H. pylori prevalence rates become stabilized.
Helicobacter pylori Infection in Children. Antimicrobial Resistance and Treatment Response
Authors: Montes Milagrosa , Villalon Flor N. , Eizaguirre Francisco J. , Delgado Maider , Muñoz‐Seca Ignacio M. , Fernández‐Reyes María , Pérez‐Trallero Emilio
Published: November 2014

Background

The aim of this study was to determine the appropriateness of the recent recommendations for managing Helicobacter pylori infection in children in a university hospital in Southern Europe. Antimicrobial resistance and response to eradication therapy were also determined.

Materials and Methods

The presence of H. pylori was studied in 143 children: by gastric biopsy culture (GBC), 13C‐urea breath test (UBT) and stool antigen immunochromatography test (SAIT) in 56 children; by GBC and UBT in 20, by GBC and SAIT in 18, and by GBC alone in 49. Antimicrobial susceptibility was determined by E‐test. Infection was defined as a positive culture or positivity in both UBT and SAIT. Disease progression was studied in 118 patients. First evaluation of symptoms was carried out at 3–6 months after diagnosis and/or after treatment of the infection.

Results

H. pylori was detected in 74 from the 143 children analyzed (100% GBC positive, 98.1% UBT positive, and 58.1% SAIT positive). The main symptom was chronic abdominal pain (n = 121). Macroscopic antral nodularity was observed in 29.7% of infected patients and in 5.8% of uninfected patients, respectively. Resistance to clarithromycin and metronidazole was found in 34.7 and 16.7%, respectively. Eradication when susceptible antimicrobials were used occurred in 78.7% (48/61) versus 37.5% (3/8) when the treatment included a drug with resistance (p = .024). In patients with recurrent abdominal pain, symptoms resolved in 92.9% (39/42) patients with HP eradication versus 42.9% (6/14) without HP eradication (p < .001).

Conclusion

Treated patients often failed to meet the criteria established in the guidelines for H. pylori diagnostic screening and treatment because most of them had only recurrent abdominal pain, but remission of their symptoms was associated with H. pylori eradication.
Helicobacter pylori Infection Increase the Risk of Myocardial Infarction: A Meta‐Analysis of 26 Studies Involving more than 20,000 Participants
Authors: Liu Juan , Wang Feng , Shi Songli
Published: November 2014

Background

Myocardial infarction is a fatal cardiovascular disease and one of the most common death causes all around the world. The aim of the meta‐analysis was to quantify the risk of myocardial infarction associated with Helicobacter pylori infection.

Methods

A literature search was performed to identify studies published before 14 July, 2014, for relevant risk estimates. Fixed and random effect meta‐analytical techniques were conducted for myocardial infarction.

Results

Twenty‐six case–control studies involving 5829 myocardial infarction patients and more than 16,000 controls were included. Helicobacter pylori infection was associated with an increased risk of myocardial infarction (OR: 2.10, 95%CI: 1.75–2.53, p = .06). We also discovered a significant association between the bacteria and risk of myocardial infarction in young people (OR: 1.93, 95% CI: 1.41–2.66, p = .07), in elder people (OR: 2.02, 95% CI: 1.60–2.54, p = .29), in Caucasians (OR: 2.29, 95% CI: 1.99–2.63, p = .12), and in Asians (OR: 1.75, 95% CI: 1.12–2.73, p = .08).

Conclusion

Our meta‐analyses suggested a possible indication of relationship between Helicobacter pylori infection and the risk of myocardial infarction. The pathogenicity might not be affected by age and race. More researches should be conducted to explore the mechanisms involved.
Informational needs of gastrointestinal oncology patients
Authors: Papadakos Janet , Urowitz Sara , Olmstead Craig , Jusko Friedman Audrey , Zhu Jason , Catton Pamela
Published: November 2014

Objectives

In response to the dearth of consumer health information for patients with gastrointestinal cancers, this study examined the informational needs of these patients to build a plan for future resource development. Although studies have examined informational needs of some such cancers, no published literature has investigated the comprehensive informational needs across all sites of gastrointestinal cancer.

Methods

A cross‐sectional needs assessment comprising a self‐administered questionnaire was conducted at an ambulatory gastrointestinal oncology clinic in Toronto, Canada. Patient informational needs were measured, including importance of information, amount desired and preferred mode of delivery. Informational needs were grouped into six domains: medical, practical, physical, emotional, social and spiritual.

Results

Eighty‐two surveys were analysed. The majority of the respondents were male (53.8%), over the age of 50 (77.8%), and born outside of Canada (51.9%). While many did not speak English as a child (46.3%), and do not speak English at home (22.2%), nearly all indicated comfort with receiving health information in English (97.5%). The majority of respondents were college educated (79.3%) and married (73%). Multiple cancer types were reported; the most common being colorectal (39%), followed by pancreatic (12%) and cancers of the gallbladder or bile duct (12%). Overall, respondents placed highest importance on medical information (P < 0.001). Preferred education modalities were pamphlets, websites and one‐on‐one discussions with health‐care professionals.

Conclusions

This study highlights the principal informational needs of patients with gastrointestinal malignancies, along with preferred modality for information delivery. This information will guide the development of educational resources for future patients.
High‐grade encapsulated papillary carcinoma of the breast: an under‐recognized entity
Authors: Rakha Emad A , Varga Zsuzsanna , Elsheik Somaia , Ellis Ian O
Published: November 2014

Aims

Encapsulated papillary carcinoma (EPC) is a recognized special type of breast carcinoma. Despite compelling evidence indicating its invasive nature, although not of a conventional form, the current consensus is to manage EPC as an in‐situ disease, based on its indolent clinical behaviour. Although most EPCs are recognized to be of low and intermediate grade, a distinct proportion of these tumours do show high cytonuclear grade features. The existence and behaviour of these rare high‐grade variants remains to be defined. We aim to characterise these tumours and provide evidence to guide their management.

Methods and results

In this study, we have identified 12 high‐grade EPCs without associated conventional stromal invasion. To further characterize these high‐grade tumours, a series of invasive papillary carcinomas (n = 30) were assessed for the coexistence of EPC. The literature was also reviewed. Approximately 3% of pure EPCs showed high‐grade features as defined by nuclear pleomorphism and increased mitotic activity. These tumours not only showed histological features associated with aggressive behaviour, but were also often hormone receptor‐negative, tended to be of larger size, and were more frequently associated with stromal invasion. Of the 10 patients with follow‐up data, one with pure high‐grade EPC developed recurrence and died of her disease.

Conclusion

High‐grade EPC is rare, and its histological features and more aggressive clinical behaviour suggest that consideration should be given to managing it in a similar fashion to conventional forms of invasive breast carcinoma, based on established clinicopathological parameters.
Histology of microscopic colitis—review with a practical approach for pathologists
Authors: Langner Cord , Aust Daniela , Ensari Arzu , Villanacci Vincenzo , Becheanu Gabriel , Miehlke Stephan , Geboes Karel , Münch Andreas ,   the Working Group of Digestive Diseases of the European Society of Pathology (ESP) and the European Microscopic Colitis Group (EMCG)
Published: November 2014

Microscopic colitis has emerged as a major cause of chronic watery non‐bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathological phenotypes and no significant endoscopic abnormalities. Lymphocytic colitis is defined by an increased number of surface intraepithelial lymphocytes, and collagenous colitis by a thickened collagen band underneath the surface epithelium. There is increased inflammation in the lamina propria, but only little or no crypt architectural distortion. Incomplete and variant forms showing less characteristic features have been reported under different names. The differential diagnosis mainly includes resolving infectious colitis and changes related to the intake of drugs such as non‐steroidal anti‐inflammatory drugs. Substantial clinical and histological overlap between lymphocytic and collagenous colitis has been described, raising the suspicion that the conditions are two histological manifestations of the same entity, possibly representing different manifestations during the disease course or different stages of disease development. In this review, we provide a practical approach for pathologists, with a focus on diagnostic criteria and differential diagnosis, and discuss recent insights into the pathogenesis of disease and the relationship with classic chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative colitis.
Tumour budding is associated with hypoxia at the advancing front of colorectal cancer
Authors: Righi Alberto , Sarotto Ivana , Casorzo Laura , Cavalchini Silvia , Frangipane Elena , Risio Mauro
Published: November 2014

Aims

The tumour budding ability to predict cancer progression is felt to be worthy of investigation with regard to its biological properties. This study was aimed at evaluating the role of hypoxia and microvascularization in the morphogenesis of tumour budding in colorectal carcinoma.

Methods and results

The immunohistochemical expression of hypoxia‐inducible factor‐1α (HIF‐1α) and carbonic anhydrase IX in cancer cells and CD105 in carcinoma‐induced microvascularization were assessed in 479 colorectal cancers. Furthermore, MET proto‐oncogene, receptor tyrosine kinase (MET) gene amplification was searched using fluorescence in‐situ hybridization (FISH). Carbonic anhydrase IX and HIF‐1α overall scores differed significantly in low‐ compared to high‐grade tumour budding cancers (P < 0.001), both in pT1 and in pT2–4 tumours. Intratumour analysis of budding foci showed a striking absence of carbonic anhydrase IX immunostain in detaching cells with respect to the surrounding microsectors. The mean microvessel density values were significantly higher in the low‐ compared to the high‐grade tumour budding groups (P < 0.001). A similar copy number of MET gene was detected in the two groups.

Conclusions

Our study shows that tumour budding is associated with hypoxia induced by hypovascularization at the advancing front of colorectal cancer and that budding cells express a HIF‐1α‐mediated hypoxic tumour phenotype. MET gene amplification is not related to tumour budding morphogenesis.
Tyrosine kinase receptor B (TrkB) expression in colorectal cancers highlights anoikis resistance as a survival mechanism of tumour budding cells
Authors: Dawson Heather , Grundmann Sandra , Koelzer Viktor H , Galván José A , Kirsch Richard , Karamitopoulou Eva , Lugli Alessandro , Inderbitzin Daniel , Zlobec Inti
Published: November 2014

Aims

Tumour buds in colorectal cancer represent an aggressive subgroup of non‐proliferating and non‐apoptotic tumour cells. We hypothesize that the survival of tumour buds is dependent upon anoikis resistance. The role of tyrosine kinase receptor B (TrkB), a promoter of epithelial–mesenchymal transition and anoikis resistance, in facilitating budding was investigated.

Methods and results

Tyrosine kinase receptor B immunohistochemistry was performed on a multiple‐punch tissue microarray of 211 colorectal cancer resections. Membranous/cytoplasmic and nuclear expression was evaluated in tumour and buds. Tumour budding was assessed on corresponding whole tissue slides. Relationship to Ki‐67 and caspase‐3 was investigated. Analysis of Kirsten Ras (KRAS), proto‐oncogene B‐RAF (BRAF) and cytosine–phosphate–guanosine island methylator phenotype (CIMP) was performed. Membranous/cytoplasmic and nuclear TrkB were strongly, inversely correlated (P < 0.0001; r = −0.41). Membranous/cytoplasmic TrkB was overexpressed in buds compared to the main tumour body (P < 0.0001), associated with larger tumours (P = 0.0236), high‐grade budding (P = 0.0011) and KRAS mutation (P = 0.0008). Nuclear TrkB was absent in buds (P <0.0001) and in high‐grade budding cancers (P =0.0073). Among patients with membranous/cytoplasmic TrkB‐positive buds, high tumour membranous/cytoplasmic TrkB expression was a significant, independent adverse prognostic factor [P = 0.033; 1.79, 95% confidence interval (CI) 1.05–3.05]. Inverse correlations between membranous/cytoplasmic TrkB and Ki‐67 (r = −0.41; P < 0.0001) and caspase‐3 (r =−0.19; P < 0.05) were observed.

Conclusions

Membranous/cytoplasmic TrkB may promote an epithelial–mesenchymal transition (EMT)‐like phenotype with high‐grade budding and maintain viability of buds themselves.
Hyperplasia of the submucosal glands of the columnar‐lined oesophagus
Authors: Lörinc Ester , Öberg Stefan
Published: November 2014

Aim

To evaluate the presence of multi‐layered epithelium (ME) and to compare the distribution, size and morphology of the oesophageal submucosal glands (SMG) beneath reflux exposed metaplastic columnar mucosa with those of normal squamous epithelium in patients with columnar‐lined oesophagus (CLO).

Methods and results

In eight oesophageal resection specimens, the SMG of the metaplastic segments were significantly larger than those in the squamous segments of patients with CLO (0.81 versus 0.56 mm2, P = <0.001). There was an accumulation of SMG close to the neosquamocolumnar junction (NSCJ), as indicated by a higher median frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm) and metaplastic segments (0.031 SMG/mm) (P = 0.022). The frequency of ME was significantly higher in the metaplastic compared with the normal squamous segments (1/158 mm and 1/341 mm, respectively, P = 0.028) and ME was found almost exclusively (96%) in direct connection with the excretory ducts of SMG.

Conclusions

Hyperplasia of SMG in the metaplastic segment, accumulation of SMG near the NSCJ, the presence of ME in connection with the excretory ducts of SMG and metaplasia are all reflux‐induced morphological changes, possibly induced by stimulation of progenitors in the excretory ducts of the SMG.
Endodontic performance by Flemish dentists: have they evolved?
Authors: Neukermans M. , Vanobbergen J. , De Bruyne M. , Meire M. , De Moor R. J. G.
Published: November 2014

Aim

To gather information on aspects of endodontic practice and referral behaviour by Flemish (Dutch‐speaking Belgian) dentists and to compare the results with an earlier investigation.

Methodology

A postal questionnaire was distributed to 4468 active Flemish dentists. It consisted of multiple‐choice questions on endodontic practice and endodontic referral need. Basic information on age, gender, year of qualification and clinical specialty was also obtained. The questionnaire was free of charge to return. Data were imported in a database, subjected to descriptive and analytical statistics and compared to those of an earlier, comparable survey.

Results

The response rate was 18.5%. Of all respondents, 95% were general practitioners. More than half (56%) of the respondents never or seldom used rubber dam during endodontic treatment. The use of sodium hypochlorite as an irrigant was well established (80% of respondents using it), whereas the use of EDTA was limited. Female respondents were more likely to refer to an endodontist than male (70 versus 49%). Referrals for treatment of root canal obstruction (48%), perforations and root resorption (42%) and retreatment (39%) were rated ‘very important’. Younger respondents more frequently made use of magnification, rotary instruments and rubber dam. Activation of irrigants was incorporated by a small number of respondents (50% never, 12.6% seldom). Cold lateral condensation was used by most GDPs (35.3% always, 19.5% frequently).

Conclusions

Endodontic practice of general dentists in Flanders did not always comply with quality guidelines. However, when comparing the present data with those of a previous study, an obvious trend towards a more present‐day treatment protocol is noticeable, as well as an increased appeal for endodontic referral.
Process Parameters Development of Selective Laser Melting of Lunar Regolith for On‐Site Manufacturing Applications
Authors: Fateri Miranda , Gebhardt Andreas
Published: November 2014

Selective Laser Melting (SLM) is a candidate for on‐site manufacturing as its characteristics of energy source and powder‐based fabrication process are suitable for use with in situ material. The feasibility of using lunar regolith simulant to create objects with SLM process is investigated in this study. The process parameters are optimized and multiple objects are fabricated. A qualitative chemical analysis is carried out with scanning electron microscopy using energy‐dispersive X‐ray emission. Lastly, properties such as particle size distribution, particle shape, and crystal structure of the lunar simulant powder as well as the crystallinity and hardness of the fabricated objects are investigated.
Enhancement of CD8+ T‐cell memory by removal of a vaccinia virus nuclear factor‐κB inhibitor
Authors: Ren Hongwei , Ferguson Brian J. , de Motes Carlos Maluquer , Sumner Rebecca P. , Harman Laura E. R , Smith Geoffrey L.
Published: November 2014

Factors influencing T‐cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8+ T cells and this correlates with its inhibition of nuclear factor‐κB (NF‐κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF‐κB resulted in increased central and memory CD8+ T‐cell populations, increased CD8+ T‐cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8+ memory T‐cell function was increased following infection with vN1.I6E, with more interferon‐γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8+ T cells from mice infected with wild‐type virus (vN1.WT). This demonstrates the importance of NF‐κB activation within infected cells for long‐term CD8+ T‐cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8+ T‐cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety.
Use of A Bioreactor Consisting of Sequentially Aligned L‐Glutamate Dehydrogenase and L‐Glutamate Oxidase for the Determination of Ammonia by Chemiluminescence
Authors: Murachi T. , Tabata M.
Published: November 2014

A chemiluminometric method for the automated flow injection analysis of ammonia is described. The essence of the invention is the use of a bioreactor consisting of both immobilized L‐glutamate dehydrogenase (GLDH) and L‐glutamate oxidase (GLXD), which are sequentially aligned in this order in a minicolumn measuring 2.0 × 20 mm. The unidirectional constant flow of liquid through the column reactor minimizes the reversed diffusion of the solutes so that the following sequence of reactions is ensured. Thus, ammonia to be determined is first transformed by GLDH into L‐glutamate, which then produces hydrogen peroxide by GLXD. Hydrogen peroxide in the effluent from the column is then determined by its chemiluminescence upon admixing with luminol and potassium ferricyanide. The present method gives linearity of the standard curve for ammonia up to 1.0 mM. It is at least 100 times more sensitive than the conventional method for ammonia assay using ultraviolet absorption measurement.
Synthesis and Thermal, Structural, Dielectric, Magnetic and Magnetoelectric Studies of BiFeO3‐MgFe2O4 Nanocomposites
Authors: Singh Hemant , Yadav Kanhaiya Lal
Published: November 2014

Spinel–perovskite magnetoelectric (ME) nanocomposites xMgFe2O4–(1−x)BiFeO3, x = 0.1, 0.2, 0.3, and 0.4 were synthesized by sol‐gel method and characterized by differential thermal analysis, X‐ray diffraction analysis, dielectric and magnetic measurements. The samples were calcined at various temperatures and then the effect of annealing temperature on structural and magnetic properties was studied. From transmission electron microscopy, the average crystal size was found to be 30–50 nm. The magnetic behavior is found to be dependent on annealing temperature and magnesium ferrite content. The dielectric behavior with frequency and temperature has been modified with the induction of magnesium ferrite. The relative change of dielectric constant with magnetic field was observed in the nanocomposites. This relative change of magnetic field‐induced dielectric constant can also be expressed by Δε ~ γM2 (where γ is magnetoelectric coupling coefficient).
Glass‐Like Thermal Conductivity of (010)‐Textured Lanthanum‐Doped Strontium Niobate Synthesized with Wet Chemical Deposition
Authors: Foley Brian M. , Brown‐Shaklee Harlan J. , Campion Michael J. , Medlin Douglas L. , Clem Paul G. , Ihlefeld Jon F. , Hopkins Patrick E.
Published: November 2014

We have measured the cross‐plane thermal conductivity (κ) of (010)‐textured, undoped, and lanthanum‐doped strontium niobate (Sr2−xLaxNb2O7−δ) thin films via time‐domain thermoreflectance. The thin films were deposited on (001)‐oriented SrTiO3 substrates via the highly‐scalable technique of chemical solution deposition. We find that both film thickness and lanthanum doping have little effect on κ, suggesting that there is a more dominant phonon scattering mechanism present in the system; namely the weak interlayer‐bonding along the b‐axis in the Sr2Nb2O7 parent structure. Furthermore, we compare our experimental results with two variations of the minimum‐limit model for κ and discuss the nature of transport in material systems with weakly‐bonded layers. The low cross‐plane κ of these scalably‐fabricated films is comparable to that of similarly layered niobate structures grown epitaxially.
Rapid Bonding of Ti3SiC2 and Ti3AlC2 by Pulsed Electrical Current Heating
Authors: Shen Lu , Xue Jianming , Barsoum Michel W. , Huang Qing
Published: November 2014

Inspired by pressure resistance welding of metallic materials, herein we describe how two MAX phases—Ti3SiC2 and Ti3AlC2—were successfully joined by a rapid electric current heating method in a pulsed electric current sintering furnace. No welding agent was employed and the total processing time was less than 6 min. When the bulk temperature of the joint couple exceeded 1070°C, good joints, with shear strength above 50 MPa, were achieved in both homo‐ and heterojunction joints.
Flame‐Spray‐Processed CuO–WO3 Nanopowders as Photocatalysts
Authors: Lee Jusang , Gouma Pelagia I.
Published: November 2014

The scalable synthesis of Cu‐doped WO3 nanomaterials from molecular precursors is addressed here. A desktop flame spray pyrolysis process was used to synthesize of the oxide with 20 nm average diameter of the orthorhombic phase polymorph, which is the stable phase for WO3. The as‐sprayed nanoparticles exhibit superior photoelectrical response to visible light illumination compared with nanoparticles of the same system processed by other routes.
Experimental Variability in Kinetics of Moisture Expansion and Mass Gain in Ceramics
Authors: Le Goff Maxime , Gallet Yves
Published: November 2014

The rehydroxylation dating method of archeological fired‐clay artifacts relies on the reliability of the (time)1/4 power law model considered for long‐term moisture expansion and mass gain in ceramics. Here, we reanalyze different moisture expansion datasets that were previously used to verify this model. We show that these data obey an accurate (time)1/N power law, but they reveal a variability in the values of the exponent 1/N between ~1/2 and ~1/4. It is possible that this value is an intrinsic property of ceramics, naturally varying between a behavior governed by a Brownian process (t1/2 power law) and a behavior controlled by a one‐dimensional diffusion process (t1/4 power law).
Endoplasmic reticulum stress in adipose tissue augments lipolysis
Authors: Bogdanovic Elena , Kraus Nicole , Patsouris David , Diao Li , Wang Vivian , Abdullahi Abdikarim , Jeschke Marc G
Published: November 2014

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca2+ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24–48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.
Neuro‐cognitive performance of very preterm or very low birth weight adults at 26 years
Authors: Eryigit Madzwamuse Suna , Baumann Nicole , Jaekel Julia , Bartmann Peter , Wolke Dieter
Published: November 2014

Background

Children born very preterm (VP <32 weeks gestation) and/or with very low birth weight (VBLW <1500 g; subsequently VP/VLBW) have been previously reported to have more cognitive impairment and specific executive functioning problems than term children; however, it remains unclear whether these problems persist into adulthood. This study aimed to examine general intelligence (IQ) and executive functioning (EF) of adults born VP/VLBW in comparison to term controls. Additionally, the effects of smallness for gestational age (SGA) and family socioeconomic status (SES) at birth were investigated.

Methods

The Bavarian Longitudinal Study is a geographically defined prospective cohort study of neonatal at‐risk children born in 1985/86 in Southern Germany. A total of 217 VP/VLBW and 197 controls completed the battery of IQ and EF tests at 26 years of age.

Results

VP/VLBW adults scored significantly lower than controls in IQ and EF. There was a 1.16 standard deviation (SD) unit difference between the VP/VLBW and controls in Full‐Scale IQ. VP/VLBW adults were found to have general and multiple cognitive problems rather than specific deficits in EF. SGA was not a significant predictor of cognitive impairment. Family SES had a significant impact on general intelligence in both VP/VLBW and term controls. The SES effects amounted to 1.13 SD units between individuals born into high versus low SES.

Conclusions

No narrowing of cognitive deficits between VP/VLBW and term control adults to previous childhood assessments at 6 years of age was found. VP/VLBW adults do not outgrow their cognitive problems despite many receiving special educational support in childhood. Low family SES at birth has similar additive adverse effects on cognitive performance in VP/VLBW and term offspring.
Floral isolation is the major reproductive barrier between a pair of rewarding orchid sister species
Authors: Sun M. , Schlüter P. M. , Gross K. , Schiestl F. P.
Published: November 2014

The crucial role of reproductive isolation in speciation has long been recognized; however, a limited number of studies quantify different isolation barriers and embed reproductive isolation in a phylogenetic context. In this study, we investigate reproductive isolation between the often sympatrically occurring orchid species,Gymnadenia conopseaandG. odoratissima. We examine the phylogenetic relationship between the two species and analyse floral isolation, fruit set and seed viability from interspecies crosses, as well as the ploidy level. Additionally, we quantify interspecies differences in floral signals and morphology. The results suggest that the two species have a sister–species relationship. In terms of reproductive isolation, we found complete floral isolation between the two species, but little to no post‐pollination isolation; the species also mostly had the same ploidy level in the studied populations. We also show clear distinctions in floral signals, as well as in floral size and spur length. We propose that respective adaptation to short‐ vs. long‐tongued pollinators was the driver of speciation in the here studiedGymnadeniaspecies. Our study supports the key role of floral isolation in orchid speciation and shows that floral isolation is not restricted to highly specialized pollination systems, but can also occur between species with less specialized pollination.
The Food Web of Boiling Springs Lake Appears Dominated by the Heterolobosean Tetramitus thermacidophilus Strain BSL
Authors: Reeder William H.H. , Sanck Jessica , Hirst Marissa , Dawson Scott C. , Wolfe Gordon V.
Published: November 2014

We studied the protist grazers of Boiling Springs Lake (BSL), an acid geothermal feature in Lassen Volcanic National Park, using a combination of culture and genetic approaches. The major predator in BSL is a vahlkampfiid ameba closely related (95% 18S+ITS rRNA identity) to Tetramitus thermacidophilus, a heterolobose ameboflagellate recently isolated from volcanic geothermal acidic sites in Europe and Russia, as well as an uncultured heterolobosean from the nearby Iron Mountain acid mine drainage site. Tetramitus thermacidophilus strain BSL is capable of surviving the physical extremes of BSL, with optimal growth at 38–50 °C and pH 2–5. This bacterivore also ingested conidiospores of the ascomycete Phialophora sp., but ultrastructural observations reveal the latter may not be readily digested, and conidia were not separable from the ameoboflagellate culture, suggesting a possible symbiosis. DGGE fingerprint transects studies showed the organism is restricted to near‐lake environs, and we detected an average of ~500 viable cysts/cm3 sediment on the shoreline. Other grazing protists were isolated from lakeshore environments, including the lobose amebae Acanthamoeba sp. and Hartmannella sp., and the kinetoplastid flagellate Bodo sp., but none could tolerate both low pH and high temperature. These appear to be restricted to cooler near lake geothermal features, which also contain other potential grazer morphotypes observed but not successfully cultured, including ciliates, euglenids, testate amebae, and possible cercozoans. We compare the food web of BSL with other acidic or geothermal sites, and discuss the impact of protists in this unique environment.
Atlantic salmon, Salmo salar L. are broadly susceptible to isolates representing the North American genogroups of infectious hematopoietic necrosis virus
Authors: Kurath G , Winton J R , Dale O B , Purcell M K , Falk K , Busch R A
Published: November 2014

Beginning in 1992, three epidemic waves of infectious hematopoietic necrosis, often with high mortality, occurred in farmed Atlantic salmon Salmo salar L. on the west coast of North America. We compared the virulence of eleven strains of infectious hematopoietic necrosis virus (IHNV), representing the U, M and L genogroups, in experimental challenges of juvenile Atlantic salmon in freshwater. All strains caused mortality and there was wide variation within genogroups: cumulative mortality for five U‐group strains ranged from 20 to 100%, four M‐group strains ranged 30‐63% and two L‐group strains varied from 41 to 81%. Thus, unlike Pacific salmonids, there was no apparent correlation of virulence in a particular host species with virus genogroup. The mortality patterns indicated two different phenotypes in terms of kinetics of disease progression and final per cent mortality, with nine strains having moderate virulence and two strains (from the U and L genogroups) having high virulence. These phenotypes were investigated by histopathology and immunohistochemistry to describe the variation in the course of IHNV disease in Atlantic salmon. The results from this study demonstrate that IHNV may become a major threat to farmed Atlantic salmon in other regions of the world where the virus has been, or may be, introduced.