bluuebunny/crossref_metadata_2025 huggingface dataset:
Delphinidin Induces Autolysosome as well as Autophagosome Formation and Delphinidin‐Induced Autophagy Exerts a Cell Protective Role
Authors: Tsuyuki Satoshi , Fukui Sayuri , Watanabe Akari , Akune Satoshi , Tanabe Mizuki , Yoshida Kenichi
Published: November 2012

Anthocyanidins, which are polyphenols that are believed to be effective for preventing cancer, are composed of a basic structure of the plant pigment anthocyanin. In this study, we investigated the biological activity of anthocyanidins, including delphinidin, against HeLa cells. The cytotoxicity observed in the anthocyanidins‐treated cells was well correlated with the inhibitory effects of anthocyanidins on c‐Jun‐dependent transcriptional activity. Remarkably, anthocyanidin induced autophagosome formation but lacked the ability to induce apoptosis. Notably, delphinidin enhanced autolysosome formation as well as autophagosome formation. Delphinidin treatment resulted in the accumulation of the lipidated form of Map1lc3b protein in an Atg5‐dependent manner in mouse embryonic fibroblasts. Finally, we revealed that the cytotoxicity induced by delphinidin was more severe in Atg5‐deficient mouse embryonic fibroblasts than in wild‐type cells. Taken together, these results indicate that the cytotoxicity induced by delphinidin was accompanied by autophagy and delphinidin‐induced autophagy exerted a cell protective role. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:445‐453, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21443
Luteolin inhibition of V‐ATPase a3–d2 interaction decreases osteoclast resorptive activity
Authors: Crasto Gazelle J. , Kartner Norbert , Yao Yeqi , Li Keying , Bullock Liv , Datti Alessandro , Manolson Morris F.
Published: November 2012

V‐ATPase‐mediated acid secretion is required for osteoclast bone resorption. Osteoclasts are enriched in V‐ATPase a3 and d2 subunit isoforms, and disruption of either of their genes impairs bone resorption. Using purified fusion proteins of a3 N‐terminal domain (NTa3) and full‐length d subunits we determined in a solid‐phase binding assay that half‐maximal binding of d1 or d2 to immobilized NTa3 occurs at 3.1 ± 0.4 or 3.6 ± 0.6 nM, respectively, suggesting equally high‐affinity interactions. A high‐throughput modification of this assay was then used to screen chemical libraries for a3–d2 interaction inhibitors, and luteolin, a naturally occurring flavonoid, was identified, with half‐maximal inhibition at 2.4 ± 0.9 µM. Luteolin did not significantly affect NIH/3T3 or RAW 264.7 cell viability, nor did it affect cytokine‐induced osteoclastogenesis of RAW 264.7 cells or bone marrow mononuclear cells at concentrations ≤40 µM. Luteolin inhibited osteoclast bone resorption with an EC50 of approximately 2.5 µM, without affecting osteoclast actin ring formation. Luteolin‐treated osteoclasts produced deeper resorption pits, but with decreased surface area, resulting in overall decreased pit volume. Luteolin did not affect transcription, or protein levels, of V‐ATPase subunits a3, d2, and E, or V1V0 assembly. Previous work has shown that luteolin can be effective in reducing bone resorption, and our studies suggest that this effect of luteolin may be through disruption of osteoclast V‐ATPase a3–d2 interaction. We conclude that the V‐ATPase a3–d2 interaction is a viable target for novel anti‐resorptive therapeutics that potentially preserve osteoclast–osteoblast signaling important for bone remodeling. J. Cell. Biochem. 114: 929–941, 2013. © 2012 Wiley Periodicals, Inc.
Kallikrein‐binding protein inhibits LPS‐induced TNF‐α by upregulating SOCS3 expression
Authors: Dai Zhiyu , Lu Lei , Yang Zhonghan , Mao Yuling , Lu Juling , Li Cen , Qi Weiwei , Chen Yifei , Yao Yachao , Li Lei , Chen Shaobo , Zhang Yang , Cai Weibin , Yang Xia , Gao Guoquan
Published: November 2012

Kallikrein‐binding protein (KBP) was previously identified as a serpin family member with specific inhibitory effect on tissue kallikrein and angiogenesis, while there is little knowledge about the effects on inflammation. The aim of this study is to investigate whether KBP can suppress LPS‐induced inflammatory process. Our results showed that both recombinant KBP and KBP overexpression inhibited LPS‐stimulated TNF‐α transcription and translation in macrophage cell line RAW264.7 and primary macrophages. Furthermore, KBP treatment protected mice from endotoxin shock and repressed serum TNF‐α production, increasing survival rate of mice from 10% to 50% when compared to LPS alone. Moreover, qPCR and Western blot analysis demonstrated that both suppressor of cytokine signaling 3 (SOCS3) transcription and translation were induced by KBP treatment in the present of LPS. RNA interference assay and luciferase assay showed that SOCS3 was responsible for the down‐regulation of TNF‐α by KBP, rather than NF‐κB subunit p65 and β‐catenin. Therefore, we demonstrated that KBP suppressed LPS‐induced TNF‐α production via upregulating SOCS3 expression. These results present the protective effects of KBP on LPS‐induced inflammation and provide novel information for the anti‐inflammation mechanism. J. Cell. Biochem. 114: 1020–1028, 2013. © 2012 Wiley Periodicals, Inc.
Notch pathway is involved in high glucose‐induced apoptosis in podocytes via Bcl‐2 and p53 pathways
Authors: Gao Feng , Yao Min , Shi Yonghong , Hao Jun , Ren Yunzhuo , Liu Qingjuan , Wang Xiaomeng , Duan Huijun
Published: November 2012

Recent studies have shown that Notch pathway plays a key role in the pathogenesis of diabetic nephropathy (DN), however, the exact mechanisms remain elusive. Here we demonstrated that high glucose (HG) upregulated Notch pathway in podocytes accompanied with the alteration of Bcl‐2 and p53 pathways, subsequently leading to podocytes apoptosis. Inhibition of Notch pathway by chemical inhibitor or specific short hairpin RNA (shRNA) vector in podocytes prevented Bcl‐2‐ and p53‐dependent cell apoptosis. These findings suggest that Notch pathway mediates HG‐induced podocytes apoptosis via Bcl‐2 and p53 pathways. J. Cell. Biochem. 114: 1029–1038, 2013. © 2012 Wiley Periodicals, Inc.
Leptin modulates dose‐dependently the metabolic and cytolytic activities of NK‐92 cells
Authors: Lamas Bruno , Goncalves‐Mendes Nicolas , Nachat‐Kappes Rachida , Rossary Adrien , Caldefie‐Chezet Florence , Vasson Marie‐Paule , Farges Marie‐Chantal
Published: November 2012

Leptin, a hormone‐cytokine produced primarily in the adipose tissue, has pleiotropic effects on many biological systems and in several cell types, including immune cells. Hyperleptinemia is associated with immune dysfunction and carcinogenesis. Natural killer (NK) cells are critical mediators of anti‐tumor immunity, and leptin receptor deficiency in mice leads to impaired NK function. It was thus decided to explore the in vitro effects of leptin on human NK cell function. NK‐92 cells were cultured during 48 h with different leptin concentrations [absence, 10 (physiological), 100 (obesity), or 200 ng/ml (pharmacology)]. Their metabolic activity was assessed using the resazurin test. NK‐92 cell cytotoxicity and intracellular IFN‐γ production were analyzed by flow cytometry. NK‐92 cell mRNA and protein expression levels of cytotoxic effectors were determined by RT‐qPCR and Western blot. In our conditions, leptin exerted a dose‐dependent stimulatory effect on NK‐92 cell metabolic activity. In addition, high leptin concentrations enhanced NK‐92 cell cytotoxicity against K562‐EGFP and MDA‐MB‐231‐EGFP target cells and inversely reduced cytotoxicity against the MCF‐7‐EGFP target. At 100 ng/ml, leptin up‐regulated both NK cell granzyme B and TRAIL protein expressions and concomitantly down‐regulated perforin expression without affecting Fas‐L expression. In response to PMA/ionomycin stimulation, the proportion of IFN‐γ expressing NK‐92 cells increased with 100 and 200 ng/ml of leptin. In conclusion, leptin concentration, at obesity level, variably increased NK‐92 cell metabolic activity and modulated NK cell cytotoxicity according to the target cells. The underlying mechanisms are partly due to an up‐regulation of TRAIL and IFN‐γ expression and a down‐regulation of perforin. J. Cell. Physiol. 228: 1202–1209, 2013. © 2012 Wiley Periodicals, Inc.
Phosphorylation of Cdc6 at serine 74, but not at serine 106, drives translocation of Cdc6 to the cytoplasm
Authors: Yim Hyungshin , Park Ji‐Woong , Woo Sang Uk , Kim Seong‐Taek , Liu Linhua , Lee Chul‐Hoon , Lee Seung Ki
Published: November 2012

Phosphorylation‐dependent cytoplasmic translocation of human Cdc6 during S phase is sufficient to control its activity after origin firing. Export from the nucleus also serves as a mechanism for preventing re‐replication in mammalian cells. Phosphorylation of the CDK consensus serine residues 54, 74, and 106 has been suggested to be involved in the cytoplasmic translocation of Cdc6. To determine the relative importance of the three phosphorylation sites, we have generated Cdc6 variants by substituting one or more of the three serine residues with alanine or aspartic acid and have assessed their cytoplasmic translocation behavior. Phosphorylation of serine 74 mainly contributes to the cytoplasmic translocation of Cdc6, while serine 54 phosphorylation provides a minor contribution. In contrast, phosphorylation at serine 106 does not affect the nuclear export of Cdc6. Comparative results were found in cells coexpressing the phosphorylation defective mutants of Cdc6 and cyclin A as well as in non‐transfected cells synchronized by their release from a double thymidine block. We conclude that Cdk‐mediated phosphorylation of Cdc6 at serine 74 is required for the cytoplasmic translocalization of Cdc6 during the cell cycle. Phosphorylation of Cdc6 at serine 54 plays a minor role and phosphorylation of serine 106 plays no role in the cytoplasmic localization of Cdc6. The phosphorylation of S74 in Cdc6 could be important for binding to the nuclear export protein for translocalization. J. Cell. Physiol. 228: 1221–1228, 2013. © 2012 Wiley Periodicals, Inc.
Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer
Authors: Yu Xinhua , Lum Deirdre , Kiet Tuyen K. , Fuh Katherine C. , Orr James , Brooks Rebecca A. , Ueda Stefanie M. , Chen Lee‐may , Kapp Daniel S. , Chan John K.
Published: November 2012

Background and Objectives

To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients.

Methods

Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009.

Results

Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23–34%) over time.

Conclusions

In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures. J. Surg. Oncol. 2013;107:653–658. © 2012 Wiley Periodicals, Inc.
Increased PD‐1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer
Authors: Saito Hiroaki , Kuroda Hirohiko , Matsunaga Tomoyuki , Osaki Tomohiro , Ikeguchi Masahide
Published: November 2012

Background

Co‐signaling molecules play an important role in T cells. Programmed death‐1 (PD‐1) is an immunoinhibitory receptor and its overexpression on T cells appears to be involved in immune evasion in cancer patients. The present study was designed to investigate PD‐1 expression on T cells and its relationship with immune evasion in gastric cancer patients.

Methods

PD‐1 expression on CD4+ and CD8+ T cells obtained from peripheral blood mononuclear cells (PBMC), normal gastric mucosa, and gastric cancer tissue was evaluated by multicolor flow cytometry.

Results

PD‐1 expression on CD4+ and CD8+ T cells from gastric cancer patients was significantly higher than that from normal controls. PD‐1 expression on CD4+ and CD8+ T cells was related to disease progression. Furthermore, PD‐1 expression on CD4+ and CD8+ T cells from gastric cancer tissue was significantly higher than that from normal gastric mucosa and PBMC. PD‐1 positive CD4+ and CD8+ T cells produced significantly less IFN‐gamma than PD‐1 negative CD4+ and CD8+ T cells.

Conclusions

Upregulation of PD‐1 on both CD4+ and CD8+ T cells may be, in part, responsible for immune evasion in gastric cancer patients. J. Surg. Oncol. 2013;107:517–522. © 2012 Wiley Periodicals, Inc.
Salvage abdominoperineal resection for anal cancer following chemoradiation: A proposed scoring system for predicting postoperative survival
Authors: Correa Jose Humberto S. , Castro Leonaldson S. , Kesley Rubens , Dias Jurandir A. , Jesus Jose Paulo , Olivatto Luiz O. , Martins Ivanir O. , Lopasso Fabio P.
Published: November 2012

Background and Objectives

Anal carcinoma is treated primarily by chemoradiation. Failure of this treatment requires salvage surgery. The aims of this retrospective study were to assess the survival probability after rescue surgery and design a pathological risk score (PRS) to predict postoperative outcome.

Methods

From 1982 to 2011, the clinical and pathological data of 111 patients treated with chemoradiation or radiation alone and abdominoperineal resection were reviewed. The Kaplan–Meier method was used to assess overall survival and parametric modeling was applied to determine prognostic factors and design a PRS.

Results

The 2‐ and 5‐year overall survival rates were 60% and 24.5%, respectively. The multivariate analysis showed that nodal disease (P < 0.03), resection margin (P < 0.001), and perineural and/or lymphovascular invasion (P < 0.0001) were significantly associated with survival. Patients who presented negative values for these three variables were estimated to show a 5‐year survival rate of 55% compared with 0.03% for patients who presented positive values.

Conclusions

Positive surgical margin, the presence of perineural and/or lymphovascular invasion and positive nodal involvement were identified as significant independent predictors of mortality. The PRS was shown to be highly predictive of postoperative outcome. J. Surg. Oncol. 2013;107:486–492. © 2012 Wiley Periodicals, Inc.
Perioperative management of patients undergoing pancreatic resection: Implementation of a care plan in a tertiary‐care center
Authors: Salvia Roberto , Malleo Giuseppe , Butturini Giovanni , Dal Molin Marco , Esposito Alessandro , Marchegiani Giovanni , Paiella Salvatore , Malpaga Anna , Fontana Martina , Personi Beatrice , Bassi Claudio
Published: November 2012

Evidence‐based perioperative management is important for a successful outcome after pancreatic surgery. Use of protocolized pathways of care based on fast‐track concepts has been shown to reduce hospital stay and contain costs. These regimens include pain control, early device removal (nasogastric tube, abdominal drains), enforced early mobilization, and early oral feeding. In this article, current evidence on perioperative management of pancreatic resections was analyzed in the attempt to implement our institutional care plan. J. Surg. Oncol. 2013;107:51–57. © 2012 Wiley Periodicals, Inc.
Attachment and Mental Health Symptoms Among U.S. Afghanistan and Iraq Veterans Seeking Health Care Services
Authors: Currier Joseph M. , Holland Jason M. , Allen David
Published: November 2012

Attachment theory has become a primary framework for understanding adjustment to traumas. In a convenience sample of 157 U.S. service members from the Afghanistan and Iraq wars seeking health care services at a Veterans Administration (VA) hospital, this study examined (a) the impact of attachment characteristics on several key mental health symptoms in this new generation of veterans, (b) the relative frequencies of prominent attachment styles in the sample, and (c) how these higher order orientations related to study outcomes. First, with demographic and military background factors in the model, attachment‐related anxiety and avoidance were each uniquely associated with posttraumatic stress symptoms (PTSS), psychiatric distress, and alcohol misuse, βs = .25 to .60. Second, latent class analysis highlighted the underrepresentation of avoidant veterans of a dismissive type in the sample. Third, of the different possible types of attachment insecurities, veterans with a fearful disorganized orientation were also shown to be particularly vulnerable to PTSS and other problems, even when compared to preoccupied‐dependent persons. These findings yield further support for the protective benefit of attachment security, while also suggesting the importance of both attachment anxiety and avoidance in the context of postdeployment adjustment.
Blue LED inhibits the growth of Porphyromonas gingivalis by suppressing the expression of genes associated with DNA replication and cell division
Authors: Chui Chanthoeun , Hiratsuka Koichi , Aoki Akira , Takeuchi Yasuo , Abiko Yoshimitsu , Izumi Yuichi
Published: November 2012

Background and Objectives

Blue light has been employed or investigated in both the medical and dental fields. Many studies have so far been reported a bactericidal effect of blue light emitting diodes (LED). However, it is still unclear whether exposure to blue LED kills or inhibits the growth of bacteria. We therefore investigated the effect of blue LED irradiation on the growth of Porphyromonas gingivalis compared with the effects of red LED.

Materials and Methods

P. gingivalis cell suspensions were irradiated with blue or red LED (135 J/cm2) anaerobically, incubated for various lengths of time, and then the total RNAs were isolated. The RNA degradation and gene expression levels of stress‐related proteins in blue or red LED‐irradiated samples were examined using the RNA integrity number (RIN) and RT‐PCR, respectively. Quantitative RT‐PCR was done to investigate the gene expression profiles associated with chromosome replication and cell division.

Results

Exposure to blue LED delayed the growth of P. gingivalis, while red LED did not. The RIN value indicated no RNA degradation in either the blue or red LED‐irradiated samples. In addition, the gene expression levels of stress‐related molecules remained either constant or increased 15 minutes after the blue LED irradiation compared to that before irradiation, thus suggesting that blue LED may not kill P. gingivalis cells. However, the blue LED irradiation did lead to a remarkably decreased expression of genes associated with chromosomal DNA replication and cell division after 5 minutes; exposure to the red LED did not.

Conclusion

The inhibition of the growth of P. gingivalis by blue LED may therefore be induced not by a bactericidal effect, but instead due to a bacteriostatic effect mediated by the suppression of the genes associated with chromosomal DNA replication and cell division at the transcriptional level. Lasers Surg. Med. 44: 856–864, 2012. © 2012 Wiley Periodicals, Inc.
A case–control study on the association between rheumatoid arthritis and bladder pain syndrome/interstitial cystitis
Authors: Keller Joseph J. , Liu Shih‐Ping , Lin Herng‐Ching
Published: November 2012

Aim

While bladder pain syndrome/interstitial cystitis (BPS/IC) has been suggested by a number of studies to have autoimmune character, no population‐based study to date has been conducted investigating its association with rheumatoid arthritis (RA). This study aimed to examine the association between IC/BPS and having previously been diagnosed with RA.

Methods

We conducted this study by using administrative claims data sourced from the Taiwan National Health Insurance Database. Our study included 9,269 cases with BPS/IC and 46,345 randomly selected controls. Conditional logistic regression was performed to calculate the odds ratio (OR) for the association between previously diagnosed RA and IC/BPS.

Results

RA was found among 202 (2.2%) cases and 504 (1.12%) controls. Conditional logistic regression analysis suggested that when compared with controls, the OR for prior RA among cases was 1.66 (95% CI = 1.47–1.87, P < 0.001) after adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use disorder, and alcohol abuse. Additionally, BPS/IC was consistently and significantly associated with a previous diagnosis of RA regardless of prescription drug use; the OR for prior RA among groups prescribed ≤1 type of disease‐modifying antirheumatic drug (DMARD), two types of DMARDs, and ≥3 types of DMARDs or TNF‐alpha inhibitor when compared to controls were 1.49 (95% CI = 1.28–1.72), 1.91 (95% CI = 1.38–2.68), and 2.36 (95% CI = 1.77–3.17), respectively.

Conclusions

There is an association between RA and BPS/IC after adjusting for socio‐demographic characteristics and medical co‐morbidities. Neurourol. Urodynam. 32: 980–985, 2013. © 2012 Wiley Periodicals, Inc.
Biosimilars: Eine neue Gruppe rekombinanter Arzneimittel
Authors: Dingermann Theo , Zündorf Ilse
Published: November 2012

Seit Mitte 2006 ist mit den Biosimilars eine völlig neue Gruppe von Arzneimitteln verfügbar (Abb. 1). Biosimilars sind molekulare Kopien patentfrei gewordener Biologika, die sich über viele Jahre im klinischen Alltag als wirksame und sichere Wirkstoffe zur Behandlung teils sehr schwerer Krankheiten bewährt haben. Obwohl man die Entwicklung hin zur Realisierung und Akzeptanz des Biosimilar‐Konzeptes lange für undenkbar gehalten hat, hat sich dieses Konzept nicht zuletzt auch Dank einer souverän agierenden Zulassungsbehörde durchgesetzt.
Die klinische Entwicklung von Biosimilars
Authors: Brockmeyer Carsten
Published: November 2012

Biosimilare Arzneimittel (Biosimilars) sind Nachfolgeprodukte biomedizinischer Arzneimittel, die ihren Patentschutz verloren haben. Im Gegensatz zu “klassischen” Generika werden für Biosimilars in jedem Fall klinische Studien gefordert.
Patentrechtliche Aspekte bei der Herstellung von Biosimilars
Authors: Sommer Andrea
Published: November 2012

Biosimilars sind Nachfolgeprodukte biotechnologischer Arzneimittel (Biopharmazeutika), deren Patentschutz abgelaufen ist. In der EU‐Gesetzgebung wurde der Begriff “einem biologischen Referenzarzneimittel ähnliches biologisches Arzneimittel” (Biosimilar) geprägt, da ein biopharmazeutisches Nachahmerpräparat nur ähnlich (similar), aber nicht identisch mit dem Originalpräparat sein kann.
Kommt bald die Pille für den Mann?
Authors: Zündorf Ilse , Dingermann Theo
Published: November 2012

Seit den 1960er Jahren steht die Antibabypille zur oralen Kontrazeption für die Frau zur Verfügung. Dadurch wurde die Hauptverantwortung für die Familienplanung in die Hand der Frauen gelegt. Auch für den Mann wurde immer wieder – bisher mit wenig Erfolg – an einer “Pille” geforscht. Nun wurde eine Arbeit in Cell veröffentlicht, die einen wichtigen Schritt in die richtige Richtung aufzeigt.
Use of purified fibrinogen concentrate for dysfibrinogenemia and importance of laboratory fibrinogen activity measurement
Authors: Franzblau Emily B. , Punzalan Rowena C. , Friedman Kenneth D. , Roy Angshumoy , Bilen Ozlem , Flood Veronica H.
Published: November 2012

We report a patient with dysfibrinogenemia treated with purified fibrinogen concentrate who had discrepant post‐treatment laboratory values. The patient had mild bleeding symptoms and was diagnosed with dysfibrinogenemia based on fibrinogen activity of 51 mg/dl and antigen of 240 mg/dl. He was treated for an adenoidectomy with purified fibrinogen concentrate (RiaSTAP®) at a dose of 70 mg/kg. A discrepancy in post‐treatment fibrinogen activity was observed between the hospital and reference laboratories. Investigation revealed differences in laboratory assay and calibration methods. Fibrinogen concentrate may be a treatment option for patients with dysfibrinogenemia, but accurate laboratory technique is critical for fibrinogen measurement. Pediatr Blood Cancer 2013; 60: 500–502. © 2012 Wiley Periodicals, Inc.
Identifying periods of acceptable computer usage in primary care research databases
Authors: Horsfall Laura , Walters Kate , Petersen Irene
Published: November 2012

Purpose

To examine the effect of applying different data quality filters on the incidence of disease and prescribing trends over time in a primary care research database and validate a new method for defining periods of adequate computer usage.

Methods

Acceptable computer usage (ACU) was defined as the year in which a general practice was continuously entering on average at least two therapy records, one medical record and one additional health data record per patient per year. The effect of using this date on the incidence of a range of outcomes (antibiotic prescriptions, myocardial infarction, colon cancer, lung cancer) over time was compared with other methods for defining the start of patient follow‐up in The Health Improvement Network (THIN) primary care database containing UK patient records. Various combinations of the follow‐up start dates were applied to the data to calculate incidence rates: (i) registration date, (ii) practice computerization date, (iii) acceptable mortality recording (AMR) (iv) ACU.

Results

On average, the ACU date was 3.3 years after the AMR date. Applying the AMR or ACU dates separately or in combination produced trends in incidence rates more comparable with external data sources than using the year of practice registration or computerization. The estimated incidence rates were highly sensitive to different methods of defining start date in early time periods.

Conclusions

Using the latest of AMR and ACU dates is useful for improving the integrity of THIN data. Copyright © 2012 John Wiley & Sons, Ltd.
Controlling porous properties of polymer monoliths synthesized by photoinitiated polymerization
Authors: Yu Suzhu , Ma Khin Cho Cho , Mon Aye Aye , Ng Fern Lan , Ng Yen Yong
Published: November 2012

Porous monoliths have been successfully prepared by photoinitiated polymerization of hydroxyethyl methacrylate and ethylene glycol dimethacrylate monomers in a porogenic solvent. By varying the composition of the starting solutions such as initiator fraction, monomer ratio and pore generator (porogen) fraction and type, as well as UV intensity, monoliths have been obtained with narrow pore size distribution and median pore size from about a few nanometres to a few micrometres. © 2012 Society of Chemical Industry
Lauftiere: vom Spielzeug zum Roboter
Authors: Ucke Christian , Schlichting Hans Joachim
Published: November 2012

Lauftiere wackeln eine schiefe Ebene hinunter oder werden durch ein sich absenkendes Gewichtsstück gezogen. Schon Kleinkinder sind fasziniert von diesem über hundert Jahre alten Spielzeug. Ingenieure beschäftigen sich aktuell damit, da sich mit dem dahinter stehenden Prinzip überraschend energiesparende Konstruktionen von Laufrobotern realisieren lassen. Eine genaue Analyse ergibt interessante Parallelen zur Stick‐and‐Slip‐Bewegung des Pickspechts.
Die Suche nach dem Unsichtbaren
Authors: Kiefer Michael
Published: November 2012

Viele astronomische Beobachtungsergebnisse belegen die Existenz von Dunkler Materie. Nach derzeitiger Erkenntnis besteht sie aus nichtbaryonischen, schwach wechselwirkenden Elementarteilchen (WIMPs), die das Standardmodell der Teilchenphysik nicht enthält. Sie sollten extrem geringe Wechselwirkungsquerschnitte besitzen, aber in so großer Zahl am Ort der Erde vorhanden sein, dass ein direkter Nachweis möglich erscheint. Das Experiment CRESST hat in seinen aktuellen Messdaten mehrere Ereignisse gefunden, die von WIMPs herrühren könnten. Letztliche Klarheit können jedoch nur weitere Daten bringen.
Der Radar‐Ritter
Authors: Loos Andreas
Published: November 2012

Bei seinem Tod ging ein Rauschen durch den Blätterwald. Schließlich war ein echter Ritter gestorben, der nicht nur wegen seiner Verdienste in der Radioastronomie in diesen Ehrenstand gekommen war: Als Radar‐Experte hatte er im Kalten Krieg an vorderster Front gestanden.
Suprafluidität in zwei Dimensionen
Authors: Weitenberg Christof
Published: November 2012

Suprafluidität ist einer der verblüffendsten Effekte der Quantenmechanik. Dieser Zustand, bei dem sich eine Flüssigkeit ohne Reibung bewegt, wurde 1938 in flüssigem Helium entdeckt. Seit einigen Jahren studiert man ihn zudem intensiv an ultrakalten atomaren Quantengasen. Unserer Gruppe an der Ecole Normale Supérieure in Paris ist es kürzlich gelungen, die Supraflüssigkeit auch in einem zweidimensionalen Bose‐Gas direkt zu beobachten.
The Brush‐Shape Device Used to Generate Atmospheric and Homogeneous Plasmas for Biomedical Applications
Authors: Song Ying , Liu Dongping , Wang Wenchun , Ji Longfei , Zhang Qi , Ni Weiyuan , Niu Jinhai
Published: November 2012

The brush‐shape device mainly consisting of the well‐aligned and microns‐thick hollow quartz fibers can be used to generate an atmospheric and homogeneous cold plasma jet for biomedical applications. Addition of a trace amount of O2 into the feed gas greatly altered the electrical properties of the plasma jet, thus had an obvious effect on the sterilization efficiency. The uniformity of the brush‐shape plasma jet along its transverse direction was well consistent with the uniform distribution of sterilization efficiency. The atmospheric He plasma jet containing 1% O2 may kill all the Candida albicans cells with a population of 105 spores within an exposure time of 180 s. Analysis indicates that both O radicals and charged species can be an important contributor in this plasma inactivation.

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Bronchial artery–pulmonary artery malformation as a cause of cryptogenic hemoptysis
Authors: Nugent Zoe , Oliveira Vicente , MacLusky Ian , Amaral Joao , Connolly Bairbre , Yang Connie L.
Published: November 2012

A 12‐year‐old girl with two episodes of massive hemoptysis was found to have a localized pulmonary hemorrhage on bronchoscopy. Multiple investigations including a computed tomography (CT) angiogram failed to identify the cause. Catheterization of the pulmonary and bronchial vessels uncovered a bronchial artery to pulmonary artery fistula, which was embolized by interventional radiology. This is the first pediatric case of this type of anomaly and it illustrates the importance of angiography in the investigation of cryptogenic hemoptysis. Pediatr Pulmonol. 2013; 48:930–933. © 2012 Wiley Periodicals, Inc.
Adolescent asthma after rhinovirus and respiratory syncytial virus bronchiolitis
Authors: Ruotsalainen Marja , Hyvärinen Mari K. , Piippo‐Savolainen Eija , Korppi Matti
Published: November 2012

Background and Aims

Asthma risk is increased after bronchiolitis in infancy. Recent studies have suggested that the risk may be dependent on the causative virus. The aim of the study was to evaluate the asthma risk in adolescence in subjects hospitalized for rhinovirus or respiratory syncytial virus (RSV) bronchiolitis in infancy.

Subjects and Methods

At the median age of 16.5 years, a questionnaire was sent to 96 study subjects hospitalized for bronchiolitis at <24 months of age and since then prospectively followed‐up. Sixty‐seven (70%) returned the fulfilled questionnaire. RSV and rhinovirus etiology of bronchiolitis had been studied in serum and respiratory samples obtained on admission in infancy. The occurrence of asthma was compared between former bronchiolitis patients and population controls recruited for this study in adolescence.

Results

Doctor‐diagnosed asthma was present in 30% of former bronchiolitis patients and in 5% of controls (OR 7.9, 95% CI 3.3–19.3). The respective figures for self‐reported asthma were 64% and 11% (OR 14.7, 95% CI 7.2–30.0). Self‐reported asthma was more common in the former rhinovirus than RSV patients (83.3% vs. 47.6%, P = 0.023, mixed infections included; 81.3% vs. 50%, P = 0.067, mixed infections excluded).

Conclusions

Patients hospitalized for RSV and rhinovirus bronchiolitis at <24 months of age had an increased asthma risk at 15–18 years of age compared with population controls. Within the former bronchiolitis group, the risk of self‐reported asthma was higher after non‐RSV versus RSV and after rhinovirus versus non‐rhinovirus bronchiolitis. Pediatr Pulmonol. 2013; 48:633–639. © 2012 Wiley Periodicals, Inc.
Midkine is associated with neuroendocrine differentiation in castration‐resistant prostate cancer
Authors: Nordin Anna , Wang Wanzhong , Welén Karin , Damber Jan‐Erik
Published: November 2012

BACKGROUND

Castration‐resistant prostate cancer (CRPC) is an incurable disease and both androgen‐deprivation therapy (ADT) and neuroendocrine differentiation (NED) are closely related to CRPC transition. More knowledge concerning neuroendocrine (NE)‐transformed PC cells, the NED process and its association with CRPC, is needed. Expression of growth factor midkine (MDK) is correlated with poor clinical outcomes in various human cancers, including PC. In the present study, we have evaluated MDK expression and NED in two separate tumor groups: early and advanced PC.

METHODS

Immunohistochemical analysis of MDK, the neuronal marker tubulin‐beta III (TUBB3) and the NE‐marker chromogranin A (CGA) in a human archival material consisting of hormone naive (HN)/stage T1b (n = 29) and CRPC (n = 24) tumors. Triple immunofluorescent imaging was performed on a selection of specimens.

RESULTS

MDK, TUBB3, and CGA were upregulated in CRPC compared to HN tumors. MDK was highly associated to the expression of both CGA and TUBB3, and identified MDK‐positive NE‐like looking cells found to co‐express CGA or, more commonly, CGA together with TUBB3. CGA and TUBB3 staining displayed a partial expression overlap, an overlap almost exclusively displaying also MDK expression.

CONCLUSIONS

MDK upregulation in CRPC is associated with NED (shown by its relation to CGA and TUBB3). The results suggest that MDK represents an over‐bridging marker between different populations of NE‐like tumor cells, possibly as part of the NED process and associated CRPC transition, something that needs to be evaluated experimentally as does the applicability of MDK as a future target. Prostate 73: 657–667, 2013. © 2012 Wiley Periodicals, Inc.
Electrodeposition of In2O3 thin films from a dimethylsulfoxide based electrolytic solution
Authors: Henríquez R. , Muñoz E. , Dalchiele E. A. , Marotti R. E. , Martín F. , Leinen D. , Ramos‐Barrado J. R. , Gómez H.
Published: November 2012

Indium (III) oxide (In2O3) thin films have been obtained after heat treatment of In(OH)3 precursor layers grown by a potential cycling electrodeposition (PCED) method from a dimethylsulfoxide (DMSO) based electrolytic solution onto fluorine‐doped tin oxide (FTO) coated glass substrates. X‐ray diffraction (XRD) measurements indicate the formation of a polycrystalline In2O3 phase with a cubic structure. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed a smooth morphology of the In2O3 thin films after an optimized heat treatment had been developed. The surface composition and chemical state of the semiconductor films was established by X‐ray photoelectron spectroscopy analysis. The nature of the semiconductor material, flat band potential and donor density were determined from Mott–Schottky plots. This study reveals that the In2O3 films exhibited n‐type conductivity with an average donor density of 2.2 × 1017 cm−3. The optical characteristics were determined through transmittance spectra. The direct and indirect band gap values obtained are according to the accepted values for the In2O3 films of 2.83 and 3.54 eV for the indirect and direct band gap values.
Nitrogen and triple oxygen isotopes in near‐road air samples using chemical conversion and thermal decomposition
Authors: Smirnoff Anna , Savard Martine M. , Vet Robert , Simard Marie‐Christine
Published: November 2012

RATIONALE

The determination of triple oxygen (δ18O and δ17O) and nitrogen isotopes (δ15N) is important when investigating the sources and atmospheric paths of nitrate and nitrite. To fully understand the atmospheric contribution into the terrestrial nitrogen cycle, it is crucial to determine the δ15N values of oxidised and reduced nitrogen species in precipitation and dry deposition.

METHODS

In an attempt to further develop non‐biotic methods and avoid expensive modifications of the gas‐equilibration system, we have combined and modified sample preparation procedures and analytical setups used by other researchers. We first chemically converted NO3– and NH4+ into NO2– and then into N2O. Subsequently, the resulting gas was decomposed into N2 and O2 and analyzed by isotope ratio mass spectrometry (IRMS) using a pre‐concentration system equipped with a gold reduction furnace.

RESULTS

The δ17O, δ18O and δ15N values of nitrate and nitrite samples were acquired simultaneously in one run using a single analytical system. Most importantly, the entire spectrum of δ17O, δ18O and/or δ15N values was determined from atmospheric nitrate, nitric oxide, ammonia and ammonium. The obtained isotopic values for air and precipitation samples were in good agreement with those from previous studies.

CONCLUSIONS

We have further advanced chemical approaches to sample preparation and isotope analyses of nitrogen‐bearing compounds. The proposed methods are inexpensive and easily adaptable to a wide range of laboratory conditions. This will substantially contribute to further studies on sources and pathways of nitrate, nitrite and ammonium in terrestrial nitrogen cycling. Copyright © 2012 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Identifying implausible gestational ages in preterm babies with Bayesian mixture models
Authors: Zhang Guangyu , Schenker Nathaniel , Parker Jennifer D. , Liao Dan
Published: November 2012

Infant birth weight and gestational age are two important variables in obstetric research. The primary measure of gestational age used in US birth data is based on a mother's recall of her last menstrual period, which has been shown to introduce random or systematic errors. To mitigate some of those errors, Oja et al., Platt et al., and Tentoni et al. estimated the probabilities of gestational ages being misreported under the assumption that the distribution of infant birth weights for a true gestational age is approximately Gaussian. From this assumption, Oja et al. fitted a three‐component mixture model, and Tentoni et al. and Platt et al. fitted two‐component mixture models. We build on their methods and develop a Bayesian mixture model. We then extend our methods using reversible jump Markov chain Monte Carlo to incorporate the uncertainty in the number of components in the model. We conduct simulation studies and apply our methods to singleton births with reported gestational ages of 23–32 weeks using 2001–2008 US birth data. Results show that a three‐component mixture model fits the birth data better for gestational ages reported as 25 weeks or less; and a two‐component mixture model fits better for the higher gestational ages. Under the assumption that our Bayesian mixture models are appropriate for US birth data, our research provides useful statistical tools to identify records with implausible gestational ages, and the techniques can be used in part of a multiple‐imputation procedure for missing and implausible gestational ages. Published 2012. This article is a US Government work and is in the public domain in the USA.
Standard error of inverse prediction for dose–response relationship: approximate and exact statistical inference
Authors: Demidenko Eugene , Williams Benjamin B. , Flood Ann Barry , Swartz Harold M.
Published: November 2012

This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose–response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem whenxis predicted usingy‐value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentralt‐distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal‐to‐noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism. Copyright © 2012 John Wiley & Sons, Ltd.
Nowcasting influenza epidemics using non‐homogeneous hidden Markov models
Authors: Nunes Baltazar , Natário Isabel , Lucília Carvalho M.
Published: November 2012

Timeliness of a public health surveillance system is one of its most important characteristics. The process of predicting the present situation using available incomplete information from surveillance systems has received the term nowcasting and has high public health interest. Generally in Europe, general practitioners’ sentinel networks support the epidemiological surveillance of influenza activity, and each week's epidemiological bulletins are usually issued between Wednesday and Friday of the following week.

In this work, we have developed a non‐homogeneous hidden Markov model (HMM) that, on a weekly basis, uses as covariates an early observation of influenza‐like illness (ILI) incidence rate and the number of ILI cases tested positive to nowcast the current week ILI rate and the probability that the influenza activity is in an epidemic state.

We use Bayesian inference to find estimates of the model parameters and nowcasted quantities. The results obtained with data provided by the Portuguese influenza surveillance system show the additional value of using a non‐homogeneous HMM instead of a homogeneous one. The use of a non‐homogeneous HMM improves the surveillance system timeliness in 2 weeks. Copyright © 2012 John Wiley & Sons, Ltd.
Psychometric Evaluation of a Coping Questionnaire in Two Independent Samples of People with Diabetes
Authors: Persson Lars‐Olof , Erichsen Magdalena , Wändell Per , Gåfvels Catharina
Published: November 2012

The study examines internal item/scale structure and concurrent validity of a newly developed 48‐item questionnaire [General Coping Questionnaire (GCQ)] that measures 10 aspects of coping with chronic illness (self‐trust, problem‐reducing actions, change of values, social trust, minimization, fatalism, resignation, protest, isolation and intrusion). The tests were performed in two independent samples of persons with diabetes mellitus. The first sample consisted of 119 subjects with type I diabetes and the second sample of 184 subjects with type II diabetes. Concurrent validity was examined by comparisons with measures of health‐related quality of life (SF‐36), a measure of metabolic control (HbA1c) and incidence of diabetic complications. The item/scale structure was found to be similar and very good in both samples. The 10 dimensions correlated as expected with the measure of mental health, although the ‘negative’ dimensions of the GCQ correlated higher compared with the ‘positive’ dimensions. Weaker relations with metabolic control were also found in one of the samples. These tests provide further evidence that GCQ is a well‐structured, relevant and reliable instrument for assessing coping reactions in chronic somatic conditions. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of Optimism, Social Support, Fighting Spirit, Cancer Worry and Internal Health Locus of Control on Positive Affect in Cancer Survivors: A Path Analysis
Authors: Hodges Kayleigh , Winstanley Sue
Published: November 2012

The psychological impact of a cancer diagnosis can extend through treatment, well into cancer survivorship and can be influenced by a range of psychosocial resources. At different stages in this trajectory, optimism is known to affect well‐being directly. This study focusing upon the potential to flourish after cancer, investigates the relationship between optimism and positive affect during cancer survivorship together with four possible mediators: social support, fighting spirit, internal health locus of control and cancer worry, all of which have been shown to be important predictors of well‐being in cancer patients. Participants (n = 102) from online cancer forums completed standardized questionnaires, and path analysis confirmed that optimism had a direct effect on positive affect in cancer survivors. Social support and fighting spirit were also shown to be significant mediators of this relationship, accounting collectively for 50% of the variance in positive affect. Whilst cancer worry and internal health locus of control could be predicted from levels of optimism, they did not mediate the optimism–positive affect relationship. Efforts to promote optimism and thus encourage fighting spirit at diagnosis through treatment may be worthwhile interventions, as would ensuring appropriate social support through the trajectory. Copyright © 2012 John Wiley & Sons, Ltd.
Simulations of the Ladle Teeming Process and Verification With Pilot Experiment
Authors: Ni Peiyuan , Jonsson Lage T.I. , Jönsson Pär G.
Published: November 2012

The ladle teeming process was investigated by 2D axis‐symmetrical mathematical models and a pilot‐plant experiment. Different turbulence models, including the low Reynolds number k–ε model and the realizable k–ε model both with an enhanced wall treatment (EWT) and a standard wall function (SWF), were used to simulate this process. All of these turbulence model predictions generally agreed well with the experimental results. The velocity distributions in the nozzle were also predicted by these turbulence models. At the late stage of the teeming process, the drain sink flow phenomenon was studied. The combination of an inclined ladle bottom and a gradually expanding nozzle was found to be an effective way to alleviate a drain sink flow.