bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess all-cause mortality in the evaluation of a screening trial to account for selective participation
Authors: Kranse Ries , van Leeuwen Pim J , Hakulinen Timo , Hugosson Jonas , Tammela Teuvo L , Ciatto Stefano , Roobol Monique J , Zappa Marco , Aus Gunar , Bangma Chris H , Moss Sue M , Auvinen Anssi , Schröder Fritz H
Published: July 2013

Objective

In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial.

Methods

The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial.

Setting

The European prostate cancer screening trial (ERSPC).

Results

In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9–3.6 deaths per 1000 person-years.

Conclusions

Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.
A comparative study assessing the efficacy and acceptability of anorectal swabs for antenatal GBS screening
Authors: Law Kenneth S K , Parmar Priya , Gregora Michael , Abbott Jason
Published: July 2013

Objectives

To assess women's perception of pain and acceptability of low vaginal swab (LVS) and anorectal swab (ARS) for antenatal screening for Group B Streptococcus (GBS), and to compare the detection rate between these tests.

Methods

Separate LVS and ARS were collected at the 36-week antenatal visit, either by the patient herself or by her clinician. Acceptability and pain were evaluated on a Likert scale using a standardised questionnaire.

Results

A total of 278 women were recruited, with a median gestation of 36.3 weeks (IQR 36–37). Of these women, 96% undertook specimen self-collection. The overall prevalence of colonisation was 64/278 (23%); 52 women had positive LVS results (18.7%), and an additional 12 (5.5%; 95% CI 2.5–8.5) were negative on LVS but positive on ARS. Most women rated LVS (99%) and ARS (92%) to be either ‘pain-free’ or causing ‘mild discomfort’, and found the LVS (90%) and ARS (84%) to be either ‘totally acceptable’ or ‘somewhat acceptable’.

Conclusions

The addition of an ARS resulted in an enhanced GBS positive rate, and most women found the test acceptable.
Fragile X carrier screening in Korean women of reproductive age
Authors: Kim Mi Jin , Kim Do Jin , Kim Shin Young , Yang Jae Hyug , Kim Min Hyoung , Lee Si Won , Jeong Sin Ok , Park So Yeon , Ryu Hyun Mee
Published: July 2013

Objective

To estimate the distribution of the FMR1 alleles and the prevalence of the premutaion (PM) and full mutation (FM) of the FMR1 gene in Korean women of reproductive age.

Methods

Using polymerase chain reaction and Southern blot, 5829 women of reproductive age were screened (low-risk group n = 5470 and high-risk group n = 359) and 11 prenatal diagnoses were completed between September 2003 and December 2011.

Results

Of the 5829 women screened, normal FMR1 alleles (11,607) had a bimodal distribution with most alleles having 29 (37.87%) and 30 (31.87%) CGG repeats. Of the 5470 women in the low-risk group, 7 PM were identified, giving a PM carrier frequency of 1:781; none of the women had Fragile X syndrome. We also identified 38 intermediate alleles, with a reported incidence of 1:143. Of the 11 prenatal diagnoses, five were normal, five had a premutation, and one had a full mutation allele.

Conclusions

The carrier frequency is 1/781 (0.13%) in Korean women of reproductive age. This is lower than among Caucasians, but relatively higher than in other Asian populations. Although there may be a founder effect, these results might be valuable in understanding Fragile X syndrome in Koreans and Asians as a whole.
Media witnessing and the ‘crowd-sourced video revolution’
Authors: Andén-Papadopoulos Kari
Published: July 2013

Focusing on the critical case of the mobile phone footage of Gaddafi’s death in the context of Swedish television news and its audiences, this article considers how the nature of ‘media witnessing’ is being transformed through the employment of user-generated footage. On the basis of a combined text/audience analysis study, it shows that citizen video encodes an extraordinary sense of presence and participation. Critically, however, its facilitation of ‘pseudo-eyewitnessing’ is not enough in itself to sustain practices of bearing witness. Rather, the author shows that moral responsibility is fundamentally conditioned by the symbolic management of distance – which, audiences stress, is most efficiently provided by professional news packages. Importantly, then, this empirical study corroborates the so far mainly theoretical claim in literature on media witnessing which advocates that media representations need to maintain a ‘proper distance’ in order to construct scenes of suffering and violence as a moral cause to spectators.
The provocation of the humanitarian social imaginary
Authors: Wilkinson Iain
Published: July 2013

This article reviews recent attempts to analyse the visibility that is brought to human suffering within ‘social imaginaries’ committed to humanitarian concerns. It questions the conventions of critique that operate to cast the humanitarian social imaginary as a negative development within our political culture. It is designed to encourage a more critically reflexive and historically informed approach to the work of critique. It also argues that it is possible to trace a tradition in which humanitarian campaigners operate with the aim of appropriating the critical reaction to their work as part of their political strategy. In this regard, campaigners are more concerned to provoke moral controversy than to fashion ‘winning arguments’. Here the visualization of human suffering is valued more for its potential to generate value conflicts than for the extent to which it serves as an authentic or ideologically uncontaminated representation of social reality.
Assessment of patients with acute abdominal pain
Authors: Jandoo Rajan , Lawrence Matthew
Published: July 2013

Abdominal pain is a common presenting symptom to the GP surgery and can be particularly challenging when trying to decide whether the symptoms are severe enough to warrant a hospital admission. Patients with acute and severe abdominal pain often require urgent surgical intervention and being able to recognise these patients is extremely important. This article will revise the features in the history and examination pointing towards a more serious cause and help discriminate between those patients who can be managed entirely in primary care. It will provide a brief overview of the management of these patients in hospital and their care after discharge.
Initiating oral fingolimod treatment in patients with multiple sclerosis
Authors: Singer Barry A.
Published: July 2013

Fingolimod, the first oral disease-modifying therapy (DMT) approved for the treatment of multiple sclerosis (MS) and the only sphingosine 1-phosphate receptor modulator approved for any disease state, represents an important addition to the expanding DMT options for patients with MS. In three large phase III clinical trials, fingolimod 0.5 mg reduced relapses by approximately half compared with either placebo or weekly intramuscular interferon β1a. The risks associated with the use of fingolimod include first-dose bradycardia, macular edema, and elevation of liver enzymes; fingolimod may increase the risk of infections, some serious in nature, and potentially cause fetal harm. Breakthrough disease or intolerance of injectable medications may be factors that influence the initiation of fingolimod. Identification of potential patients suitable for fingolimod treatment requires a thorough understanding of the potential risks and the particular fingolimod indication of the national authority. To minimize risk, recommended baseline assessments that should be made prior to fingolimod initiation include complete blood count, liver transaminase levels, total bilirubin levels, electrocardiogram (ECG), ophthalmologic examination, varicella zoster infection status, and for women, childbearing potential. First-dose observation is required for all patients for at least 6 h, with hourly pulse and blood pressure measurements and ECG before and 6 h after the first dose. In the European Union, continuous telemetry monitoring is recommended. Healthcare providers should be aware of the potential for symptomatic bradycardia and the need for continuous overnight ECG monitoring for those at higher risk for bradycardia. With experience in over 63,000 patients and over 73,000 patient-years of exposure in clinical trials and postmarketing use, the benefits and full safety profile of fingolimod continue to become better elucidated. This information will enable healthcare providers to initiate fingolimod in appropriately selected and screened patients with MS.
Structural role of tellurium in the minerals of the pearceite-polybasite group
Authors: Bindi L. , Voudouris P. , Spry P. G.
Published: July 2013

The crystal structure of a Te-rich polybasite has been refined by means of X-ray diffraction data collected at room temperature (space group Pm1; R = 0.0505 for 964 observed reflections and 94 parameters; refined formula Ag14.46Cu1.54Sb1.58As0.42S9.67Te1.33). The structure comprises stacking of [(Ag, Cu)6(Sb, As)2(S, Te)7]2–A and [Ag9Cu(S, Te)2(S, Te)2]2+B layer modules in which Sb forms isolated SbS3 pyramids, as occurs typically in sulfosalts, Cu links two S atoms in a linear coordination and Ag occupies sites with coordination ranging from quasi linear to almost tetrahedral. The silver d10 ions are found in the B layer module along two-dimensional diffusion paths and their electron densities evidenced by means of a combination of a Gram-Charlier development of the atomic displacement factors and a split model. The Te-for-S substitution occurs at the same structural sites that Se substitutes for S in selenopolybasite and the Te occupancy at one of these sites is 0.49, thus suggesting the possibility that 'telluropolybasite' could be found in nature.
Aluminopyracmonite, (NH4)3Al(SO4)3, a new ammonium aluminium sulfate from La Fossa crater, Vulcano, Aeolian Islands, Italy
Authors: Demartin F. , Castellano C. , Campostrini I.
Published: July 2013

The new mineral aluminopyracmonite, ideally (NH4)3Al(SO4)3, was found in a medium-temperature (∼250°C) intracrater active fumarole at La Fossa crater, Vulcano, Aeolian Islands, Sicily, Italy. It occurs on a pyroclastic breccia as colourless to white prismatic crystals up to 0.2 mm long, in association with adranosite, mascagnite, alunite and salammoniac. The mineral is identical to the synthetic compound (NH4)3Al(SO4)3. It is trigonal, space group: R (no. 148) with a = 15.0324(8), c = 8.8776(5) 5, V = 1737.3(2) Å3 and Z = 6. The six strongest reflections in the X-ray powder diffraction pattern are: [dobs in Å (I)(hkl)] 3.336(100)(131), 7.469(62)(1 1 0), 3.288(60)(122), 4.289(45)(31), 2.824(29)(51), 4.187(27) (012). The empirical formula based on 12 anions is [(NH4)2.89K0.10]Σ 2.99(Al1.18Fe0.01)Σ 1.19S2.91O12, and the simplified formula (NH4,K)3Al(SO4)3. The measured density is 2.12(1) g/cm3, calculated density 2.143 g/cm3. The mineral is uniaxial(–) with ω = 1.545(3) and ε = 1.532(3) (λ = 589 nm). Using single-crystal diffraction data, the structure was refined to a final R(F) = 0.0258 for 998 independent observed reflections [I > 2σ(I)]. In spite of having unitcell parameters comparable with those of pyracmonite, the two minerals are not isostructural; the difference is related to a disordered conformation of the sulfate anions about the two independent Al3+ ions in aluminopyracmonite.
Camaronesite, [Fe3+(H2O)2(PO3OH)]2(SO4)·1–2H2O, a new phosphate-sulfate from the Camarones Valley, Chile, structurally related to taranakite
Authors: Kampf A. R. , Mills S. J. , Nash B. P. , Housley R. M. , Rossman G. R. , Dini M.
Published: July 2013

Camaronesite (IMA 2012-094), [Fe3+(H2O)2(PO3OH)]2(SO4)·1–2H2O, is a new mineral from near the village of Cuya in the Camarones Valley, Arica Province, Chile. The mineral is a low-temperature, secondary mineral occurring in a sulfate assemblage with anhydrite, botryogen, chalcanthite, copiapite, halotrichite, hexahydrite, hydroniumjarosite, pyrite, römerite, rozenite and szomolnokite. Lavender-coloured crystals up to several mm across form dense intergrowths. More rarely crystals occur as drusy aggregates of tablets up to 0.5 mm in diameter and 0.02 mm thick. Tablets are flattened on {001} and exhibit the forms {001}, {104}, {015} and {018}. The mineral is transparent with white streak and vitreous lustre. The Mohs hardness is 2½, the tenacity is brittle and the fracture is irregular, conchoidal and stepped. Camaronesite has one perfect cleavage on {001}. The measured and calculated densities are 2.43(1) and 2.383 g/cm3, respectively. The mineral is optically uniaxial (+) with ω = 1.612(1) and ε = 1.621(1) (white light). The pleochroism is O (pale lavender) > E (colourless). Electron-microprobe analyses provided Fe2O331.84, P2O529.22, SO315.74, H2O 23.94 (based on O analyses), total 100.74 wt.%. The empirical formula (based on 2 P a.p.f.u.) is: Fe1.94(PO3OH)2(S0.96O4)(H2O)4·1.46H2O. The mineral is slowly soluble in concentrated HCl and extremely slowly soluble in concentrated H2SO4. Camaronesite is trigonal, R32, with cell parameters:a = 9.0833(5), c = 42.944(3) Å, V = 3068.5(3) Å3 and Z = 9. The eight strongest lines in the X-ray powder diffraction pattern are [dobs Å (I)(hkl)]: 7.74(45)(101), 7.415(100)(012), 4.545(72)(110), 4.426(26)(018), 3.862(32)(021,202,116), 3.298(93)(027,119), 3.179(25)(208) and 2.818(25)(1·1·12,125). In the structure of camaronesite (R1 = 2.28% for 1138 Fo > 4σF), three types of Fe octahedra are linked by corner sharing with (PO3OH) tetrahedra to form polyhedral layers perpendicular to c with composition [Fe3+(H2O)2(PO3OH)]. Two such layers are joined through SO4 tetrahedra (in two half-occupied orientations) to form thick slabs of composition [Fe3+(H2O)2(PO3OH)]2(SO4). Between the slabs are partially occupied H2O groups. The only linkages between the slabs are hydrogen bonds. The most distinctive component in the structure consists of two Fe octahedra linked to one another by three PO4 tetrahedra yielding an [Fe2(PO4)3] unit. This unit is also the key component in the sodium super-ionic conductor (NASICON) structure and has been referred to as the lantern unit. The polyhedral layers in the structure of camaronesite are similar to those in the structure of taranakite. The Raman spectrum exhibits peaks consistent with sulfate, phosphate, water and OH groups.
A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia
Authors: Yang Guang , Zhou Yangsheng , Liu Xia , Xu Lian , Cao Yang , Manning Robert J. , Patterson Christopher J. , Buhrlage Sara J. , Gray Nathanael , Tai Yu-Tzu , Anderson Kenneth C. , Hunter Zachary R. , Treon Steven P.
Published: July 2013

Key Points

MYD88 L265P is a widely expressed somatic mutation in WM patients that supports NF-κB signaling through stimulation of BTK and IRAK 1/4. Combined suppression of BTK and IRAK in MYD88 L265P expressing WM cells promotes synergistic inhibition of NF-κB signaling and WM cell killing.
Phylogeny and evolutionary history of glycogen synthase kinase 3/SHAGGY-like kinase genes in land plants
Authors: Qi Xinshuai , Chanderbali André S , Wong Gane Ka-Shu , Soltis Douglas E , Soltis Pamela S
Published: July 2013

Background

GSK3 (glycogen synthase kinase 3) genes encode signal transduction proteins with roles in a variety of biological processes in eukaryotes. In contrast to the low copy numbers observed in animals, GSK3 genes have expanded into a multi-gene family in land plants (embryophytes), and have also evolved functions in diverse plant specific processes, including floral development in angiosperms. However, despite previous efforts, the phylogeny of land plant GSK3 genes is currently unclear. Here, we analyze genes from a representative sample of phylogenetically pivotal taxa, including basal angiosperms, gymnosperms, and monilophytes, to reconstruct the evolutionary history and functional diversification of the GSK3 gene family in land plants.

Results

Maximum Likelihood phylogenetic analyses resolve a gene tree with four major gene duplication events that coincide with the emergence of novel land plant clades. The single GSK3 gene inherited from the ancestor of land plants was first duplicated along the ancestral branch to extant vascular plants, and three subsequent duplications produced three GSK3 loci in the ancestor of euphyllophytes, four in the ancestor of seed plants, and at least five in the ancestor of angiosperms. A single gene in the Amborella trichopoda genome may be the sole survivor of a sixth GSK3 locus that originated in the ancestor of extant angiosperms. Homologs of two Arabidopsis GSK3 genes with genetically confirmed roles in floral development, AtSK11 and AtSK12, exhibit floral preferential expression in several basal angiosperms, suggesting evolutionary conservation of their floral functions. Members of other gene lineages appear to have independently evolved roles in plant reproductive tissues in individual taxa.

Conclusions

Our phylogenetic analyses provide the most detailed reconstruction of GSK3 gene evolution in land plants to date and offer new insights into the origins, relationships, and functions of family members. Notably, the diversity of this “green” branch of the gene family has increased in concert with the increasing morphological and physiological complexity of land plant life forms. Expression data for seed plants indicate that the functions of GSK3 genes have also diversified during evolutionary time.
Global Rsh-dependent transcription profile of Brucella suisduring stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses
Authors: Hanna Nabil , Ouahrani-Bettache Safia , Drake Kenneth L , Adams L Garry , Köhler Stephan , Occhialini Alessandra
Published: July 2013

Background

In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions.

Results

cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198 were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitrate reductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of the cbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis.

Conclusions

The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress.
Potential of bacteriophage ΦAB2 as an environmental biocontrol agent for the control of multidrug-resistant Acinetobacter baumannii
Authors: Chen Li-Kuang , Liu Yu-Lin , Hu Anren , Chang Kai-Chih , Lin Nien-Tsung , Lai Meng-Jiun , Tseng Chun-Chieh
Published: July 2013

Background

Multidrug-resistantAcinetobacter baumannii(MDRAB) is associated with nosocomial infections worldwide. To date, the use of a phage to prevent infections caused by MDRAB has not been demonstrated.

Results

The MDRAB-specific phage ϕAB2 was stable at 4°C and pH 7 in 0.5% chloroform solution, and showed a slight decrease in plaque-forming units (PFU)/ml of 0.3–0.9 log after 330 days of storage. The addition of ϕAB2 at a concentration of at least 105PFU/ml to anA. baumanniiM3237 suspension killed >99.9% ofA. baumanniiM3237 after 5 min, regardless ofA. baumanniiM3237 concentration (104, 105, or 106colony-forming units (CFU)/ml). The addition of ϕAB2 at a concentration of 108PFU/slide (>107PFU/cm2) to glass slides containingA. baumanniiM3237 at 104, 105, or 106CFU/slide, significantly reduced bacterial numbers by 93%, 97%, and 99%, respectively. Thus, this concentration is recommended for decontamination of glass surfaces. Moreover, infusion of ϕAB2 into 10% glycerol exhibited strong anti-MDRAB activity (99.9% reduction), even after 90 days of storage. Treatment of a 10% paraffin oil-based lotion with ϕAB2 significantly reduced (99%)A. baumanniiM3237 after 1 day of storage. However, ϕAB2 had no activity in the lotion after 1 month of storage.

Conclusions

Phages may be useful for reducing MDRAB contamination in liquid suspensions or on hard surfaces. Phages may also be inoculated into a solution to produce an antiseptic hand wash. However, the phage concentration and incubation time (the duration of phage contact with bacteria) should be carefully considered to reduce the risk of MDRAB contamination.
The association between oxcarbazepine-induced maculopapular eruption and HLA-B alleles in a Northern Han Chinese population
Authors: Lv Yu-Dan , Min Fu-Li , Liao Wei-Ping , He Na , Zeng Tao , Ma Di-Hui , Shi Yi-Wu
Published: July 2013

Background

We investigated the association between oxcarbazepine (OXC)-induced maculopapular eruption (MPE) and HLA-B alleles in a northern Han Chinese population, and conducted an analysis of clinical risk factors for OXC-MPE.

Methods

Forty-two northern Han Chinese patients who had been treated with OXC in Changchun, China were genotyped. Among them were 14 cases with OXC-induced MPE; the remaining 28 were OXC-tolerant. The HLA-B allele frequencies of the normal control group were found in the Allele Frequency Net Database. Polymerase chain reaction-sequence specific primer( PCR-SSP )was used for HLA-B*1502 testing and direct sequencing for four-digit genotype determination.

Results

Four-digit allele sequencing showed that there was no statistically significant difference in the frequency of the HLA-B*1502 allele between the OXC-MPE and OXC-tolerant controls (3.6% versus 7.5%, OR = 0.38, 95% CI = 0.04–3.40, P = 0.65), as well as between OXC-MPE and normal controls (3.6% versus 2.4%, OR = 1.54, 95% CI = 0.20–11.73, P = 0.49). However, a significant difference in the frequency of HLA-B*3802 alleles was found between the MPE group and normal controls (10.7% versus 1.9%, OR = 6.329, 95% CI = 1.783-22.460, P = 0.018). There was no significant difference in terms of age, gender, or final OXC dose between the OXC-MPE and OXC-tolerant groups.

Conclusions

There was no significant association between OXC-MPE and HLA-B*1502 in the northern Han Chinese population in our study. Instead, HLA-B*3802 was found to be a potential risk factor for OXC-MPE.
The cysteinyl leukotriene 2 receptor contributes to all-transretinoic acid-induced differentiation of colon cancer cells
Authors: Bengtsson Astrid M , Jönsson Gunilla , Magnusson Cecilia , Salim Tavga , Axelsson Cecilia , Sjölander Anita
Published: July 2013

Background

Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-transretinoic acid (ATRA).

Methods

To determine the effect of ATRA on CysLT2R promoter activation, mRNA level, and protein level, we performed luciferase gene reporter assays, real-time polymerase chain reactions, and Western blots in colon cancer cell lines under various conditions.

Results

ATRA treatment induces CysLT2R mRNA and protein expression without affecting CysLT1R levels. Experiments using siRNA and mutant cell lines indicate that the up-regulation is retinoic acid receptor (RAR) dependent. Interestingly, ATRA also up-regulates mRNA expression of leukotriene C4synthase, the enzyme responsible for the production of the ligand for CysLT2R. Importantly, ATRA-induced differentiation of colorectal cancer cells as shown by increased expression of MUC-2 and production of alkaline phosphatase, both of which could be reduced by a CysLT2R-specific inhibitor.

Conclusions

This study identifies a novel mechanism of action for ATRA in colorectal cancer cell differentiation and demonstrates that retinoids can have anti-tumorigenic effects through their action on the cysteinyl leukotriene pathway.
Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case–control study in Japan
Authors: Lin Yingsong , Ueda Junko , Yagyu Kiyoko , Ishii Hiroshi , Ueno Makoto , Egawa Naoto , Nakao Haruhisa , Mori Mitsuru , Matsuo Keitaro , Kikuchi Shogo
Published: July 2013

Background

It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk.

Methods

We conducted a hospital-based case–control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk.

Results

The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07–2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70–3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07–1.85). There were no significant interactions between TA/AA genotypes and body mass index.

Conclusions

Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples.
Influenza vaccination coverage rates among adults before and after the 2009 influenza pandemic and the reasons for non-vaccination in Beijing, China: A cross-sectional study
Authors: Wu Shuangsheng , Yang Peng , Li Haiyue , Ma Chunna , Zhang Yi , Wang Quanyi
Published: July 2013

Background

To optimize the vaccination coverage rates in the general population, the status of coverage rates and the reasons for non-vaccination need to be understood. Therefore, the objective of this study was to assess the changes in influenza vaccination coverage rates in the general population before and after the 2009 influenza pandemic (2008/2009, 2009/2010, and 2010/2011 seasons), and to determine the reasons for non-vaccination.

Methods

In January 2011 we conducted a multi-stage sampling, retrospective, cross-sectional survey of individuals in Beijing who were ≥ 18 years of age using self-administered, anonymous questionnaires. The questionnaire consisted of three sections: demographics (gender, age, educational level, and residential district name); history of influenza vaccination in the 2008/2009, 2009/2010, and 2010/2011 seasons; and reasons for non-vaccination in all three seasons. The main outcome was the vaccination coverage rate and vaccination frequency. Differences among the subgroups were tested using a Pearson’s chi-square test. Multivariate logistic regression was used to determine possible determinants of influenza vaccination uptake.

Results

A total of 13002 respondents completed the questionnaires. The vaccination coverage rates were 16.9% in 2008/2009, 21.8% in 2009/2010, and 16.7% in 2010/2011. Compared to 2008/2009 and 2010/2011, the higher rate in 2009/2010 was statistically significant (χ
2=138.96, p<0.001), and no significant difference existed between 2008/2009 and 2010/2011 (χ
2=1.296, p=0.255). Overall, 9.4% of the respondents received vaccinations in all three seasons, whereas 70% of the respondents did not get a vaccination during the same period. Based on multivariate analysis, older age and higher level of education were independently associated with increased odds of reporting vaccination in 2009/2010 and 2010/2011. Among participants who reported no influenza vaccinations over the previous three seasons, the most commonly reported reason for non-vaccination was ‘I don’t think I am very likely to catch the flu’ (49.3%).

Conclusions

Within the general population of Beijing the vaccination coverage rates were relatively low and did not change significantly after the influenza pandemic. The perception of not expecting to contract influenza was the predominant barrier to influenza vaccination. Further measures are needed to improve influenza vaccination coverage.
Abdominal cerebrospinal fluid pseudocyst occurring 21 years after ventriculoperitoneal shunt placement: a case report
Authors: Tamura Atsumi , Shida Dai , Tsutsumi Kyosuke
Published: July 2013

Background

Ventriculoperitoneal shunt (VPS) placement is an established procedure for the treatment of hydrocephalus of diverse etiologies in children and adults. Abdominal cerebrospinal fluid pseudocyst, which is potentially life threatening, is a rare complication and usually occurs during childhood. However, with increasing longevity following successful treatment, it can also occur in adults.

Case presentation

Here we describe a 22-year-old man who was admitted to our hospital because of diffuse abdominal distention. A VPS was placed 21 years earlier to treat hydrocephalus secondary to spina bifida. Abdominal computed tomography (CT) revealed a homogeneous low-density fluid collection adjacent to the VPS catheter tip, causing stomach obstruction. Thus a peritoneal pseudocyst around VPS was suspected and emergency laparotomy was performed. The large mass was localized in the left upper abdomen between the stomach and mesentery of the transverse colon, exactly at the omental bursa. The cystic mass was opened and 1500 ml of clear fluid was drained; the distal end of the VPS was repositioned outside the mass. Thus, an abdominal cerebrospinal fluid pseudocyst as a complication of VPS was diagnosed.

Conclusion

Gastroenterological surgeons should be aware of this possible complication, and this complication should be considered during differential diagnosis of an acute abdomen complaint.
Spatial cross-correlation modeling for propagation channels in indoor distributed antenna systems
Authors: Tian Li , Yin Xuefeng , Zhou Xu , Zuo Quan
Published: July 2013

In this contribution, the spatial cross-correlation of composite channels in a distributed antenna system (DAS) is studied for the case that a nine-antenna DAS is deployed in an indoor environment. As few measurement data of DAS propagation channels are available, the propagation graph modeling based on the electromagnetic wave reverberation theory is used to generate the synthetic impulse responses (IRs) for the composite channels induced by the different groups of antennas in the DAS. The simulations take into account the geographic parameters of the environment, the cluttering scatterers, the realistic visibility conditions, as well as the flexible locations for the antennas, and the user equipment. The uncorrelated scattering assumption is proved to be valid by using the real measurement data from the indoor environments. Based on this assumption, narrowband channel cross-correlation is computed by integrating the small-scale fading cross-correlation within the same delay bins in two channel IRs. The characteristics of the cross-correlation in four cases with different antenna grouping are investigated for the nine-antenna DAS. Part of the modeling results are shown to be consistent with the empirical counterparts for specific DAS constellations calculated using the real measurement data.
A decoding-based fusion rule for cooperative spectrum sensing with nonorthogonal transmission of local decisions
Authors: Bokharaiee Simin , Nguyen Ha H , Shwedyk Ed
Published: July 2013

Cooperative spectrum sensing in cognitive radio (CR) networks is studied in which each CR performs energy detection to obtain a binary decision on the absence/presence of the primary user. The problem of interest is how to efficiently report and combine the local decisions to/at the fusion center under fading channels. In order to reduce the required transmission bandwidth in the reporting phase, the paper examines nonorthogonal transmission of local decisions by means of on-off keying. Proposed and analyzed is a novel decoding-based fusion rule that essentially performs in three steps: (1) estimating minimum mean-square error of the transmitted information from cognitive radios, (2) making hard decisions of the transmitted bits based on the estimated information, and (3) combining the hard decisions in a linear manner. Simulation results support the theoretical analysis and show that the added complexity of the decoding-based fusion rule leads to a considerable performance gain over the simpler energy-based fusion rule when the reporting links are reasonably strong.
Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish
Authors: Flasse Lydie C , Pirson Justine L , Stern David G , Von Berg Virginie , Manfroid Isabelle , Peers Bernard , Voz Marianne L
Published: July 2013

Background

NEUROG3 is a key regulator of pancreatic endocrine cell differentiation in mouse, essential for the generation of all mature hormone producing cells. It is repressed by Notch signaling that prevents pancreatic cell differentiation by maintaining precursors in an undifferentiated state.

Results

We show that, in zebrafish, neurog3 is not expressed in the pancreas and null neurog3 mutant embryos do not display any apparent endocrine defects. The control of endocrine cell fate is instead fulfilled by two basic helix-loop-helix factors, Ascl1b and Neurod1, that are both repressed by Notch signaling. ascl1b is transiently expressed in the mid-trunk endoderm just after gastrulation and is required for the generation of the first pancreatic endocrine precursor cells. Neurod1 is expressed afterwards in the pancreatic anlagen and pursues the endocrine cell differentiation program initiated by Ascl1b. Their complementary role in endocrine differentiation of the dorsal bud is demonstrated by the loss of all hormone-secreting cells following their simultaneous inactivation. This defect is due to a blockage of the initiation of endocrine cell differentiation.

Conclusions

This study demonstrates that NEUROG3 is not the unique pancreatic endocrine cell fate determinant in vertebrates. A general survey of endocrine cell fate determinants in the whole digestive system among vertebrates indicates that they all belong to the ARP/ASCL family but not necessarily to the Neurog3 subfamily. The identity of the ARP/ASCL factor involved depends not only on the organ but also on the species. One could, therefore, consider differentiating stem cells into insulin-producing cells without the involvement of NEUROG3 but via another ARP/ASCL factor.
Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project
Authors: Mikosik Anna , Foerster Jerzy , Jasiulewicz Aleksandra , Frąckowiak Joanna , Colonna-Romano Giuseppina , Bulati Matteo , Buffa Silvio , Martorana Adriana , Caruso Calogero , Bryl Ewa , Witkowski Jacek M
Published: July 2013

Background

Ubiquitous system of regulatory, calcium-dependent, cytoplasmic proteases – calpains – and their endogenous inhibitor – calpastatin – is implicated in the proteolytic regulation of activation, proliferation, and apoptosis of many cell types. However, it has not been thoroughly studied in resting and activated human lymphocytes yet, especially in relation to the subjects’ ageing process. The CALPACENT project is an international (Polish-Italian) project aiming at verifying the hypothesis of the role of calpains in the function of peripheral blood immune cells of Polish (Pomeranian) and Italian (Sicilian) centenarians, apparently relatively preserved in comparison to the general elderly population. In this preliminary report we aimed at establishing and comparing the baseline levels of expression of μ- and m-calpain and calpastatin in various, phenotypically defined, populations of human peripheral blood lymphocytes for healthy elderly Sicilians and Poles, as compared to these values observed in young cohort.

Results

We have found significant differences in the expression of both μ- and m-calpain as well as calpastatin between various populations of peripheral blood lymphocytes (CD4+, CD8+ and CD19+), both between the age groups compared and within them. Interestingly, significantly higher amounts of μ- and m-calpains but not of calpastatin could be demonstrated in the CD4+CD28- and CD8+CD28-lymphocytes of old subjects (but not in the cells of young individuals), as compared to their CD28+counterparts. Finally, decreased expression of both calpains in the elderly T cells is not related to the accumulation of effector/memory (CD45RO+) cells in the latter, as the expression of both calpains does not differ significantly between the naïve and memory T cells, while is significantly lower for elderly lymphocytes if both populations are taken separately.

Conclusions

Observed differences in the amounts of CCS member proteins between various populations of lymphocytes of young and elderly subjects may participate in the impaired proliferative activity of these cells in the elderly.
Genome-wide Association Study of Sensory Disturbances in the Inferior Alveolar Nerve after Bilateral Sagittal Split Ramus Osteotomy
Authors: Kobayashi Daisuke , Nishizawa Daisuke , Takasaki Yoshito , Kasai Shinya , Kakizawa Takashi , Ikeda Kazutaka , Fukuda Ken-ichi
Published: July 2013

Background

Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed after BSSRO, even without distinct nerve injury. The mechanisms that underlie individual differences in the vulnerability to sensory disturbances have not yet been elucidated.

Methods

The present study investigated the relationships between genetic polymorphisms and the vulnerability to sensory disturbances after BSSRO in a genome-wide association study (GWAS). A total of 304 and 303 patients who underwent BSSRO were included in the analyses of hypoesthesia and dysesthesia, respectively. Hypoesthesia was evaluated using the tactile test 1 week after surgery. Dysesthesia was evaluated by interview 4 weeks after surgery. Whole-genome genotyping was conducted using Illumina BeadChips including approximately 300,000 polymorphism markers.

Results

Hypoesthesia and dysesthesia occurred in 51 (16.8%) and 149 (49.2%) subjects, respectively. Significant associations were not observed between the clinical data (i.e., age, sex, body weight, body height, loss of blood volume, migration length of bone fragments, nerve exposure, duration of anesthesia, and duration of surgery) and the frequencies of hypoesthesia and dysesthesia. Significant associations were found between hypoesthesia and the rs502281 polymorphism (recessive model: combined X2 = 24.72, nominal P = 6.633 × 10−7), between hypoesthesia and the rs2063640 polymorphism (recessive model: combined X2 = 23.07, nominal P = 1.563 × 10−6), and between dysesthesia and the nonsynonymous rs2677879 polymorphism (trend model: combined X2 = 16.56, nomina P = 4.722 × 10−5; dominant model: combined X2 = 16.31, nominal P = 5.369 × 10−5). The rs502281 and rs2063640 polymorphisms were located in the flanking region of the ARID1B and ZPLD1 genes on chromosomes 6 and 3, whose official names are “AT rich interactive domain 1B (SW11 -like)” and “zona pellucida-like domain containing 1”, respectively. The rs2677879 polymorphism is located in the METTL4 gene on chromosome 18, whose official name is “methyltransferase like 4”.

Conclusions

The GWAS of sensory disturbances after BSSRO revealed associations between genetic polymorphisms located in the flanking region of the ARID1B and ZPLD1 genes and hypoesthesia and between a nonsynonymous genetic polymorphism in the METTL4 gene and dysesthesia.
The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial
Authors: van der Hoeven Erik JRJ , Schonewille Wouter J , Vos Jan Albert , Algra Ale , Audebert Heinrich J , Berge Eivind , Ciccone Alfonso , Mazighi Mikael , Michel Patrik , Muir Keith W , Obach Víctor , Puetz Volker , Wijman Cristanne AC , Zini Andrea , Kappelle Jaap L
Published: July 2013

Background

Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials.

Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely.

Design

BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3.

Discussion

The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755).
A prostate-specific antigen doubling time of <6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy
Authors: Jackson William C , Johnson Skyler B , Li Darren , Foster Corey , Foster Benjamin , Song Yeohan , Schipper Matthew , Shilkrut Mark , Sandler Howard M , Morgan Todd M , Palapattu Ganesh S , Hamstra Daniel A , Feng Felix Y
Published: July 2013

Background

The ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. We sought to assess what PSADT threshold is most clinically prognostic in this setting.

Methods

575 patients who received SRT at a single institution for biochemical recurrence after radical prostatectomy were retrospectively reviewed. We assessed the impact of pre-SRT PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Kaplan-Meier methods, hazard ratio (HR) assessment, and Cox Proportional Hazard models were used to assess the discriminatory ability of various PSADT thresholds.

Results

Sufficient data to calculate PSADTs were available for 277 patients. PSADT was prognostic for BF, DM, PCSM, and OM on univariate analysis regardless of threshold. HR assessment identified 6 months as a strong threshold. No statistically significant difference was observed in BF, DM, PCSM, or OM between patients with PSADT <3 (n=40) and 3–6 months (n=61) or between 6–10 (n=62) and >10 months (n=114). However significant differences were seen in BF (HR:2.2, [95%CI: 1.4-3.5], p<0.01) and DM (HR:2.2, [95%CI: 1.2-4.3], p=0.02) between a PSADT of 3–6 and 6–10 months. On multivariate analysis a PSADT <6 months predicted BF (HR:2.0, [95%CI: 1.4-2.9], p=0.0001), DM (HR:2.0, [95%CI: 1.2-3.4], p=0.01), and PCSM (HR:2.6, [95%CI: 1.1-5.9], p=0.02).

Conclusions

A pre-SRT PSADT <6 months was a strong predictor of outcomes in our data set, including PCSM. The most common nomogram for SRT uses a 10-month PSADT threshold for assigning points used to assess BF following SRT. If validated, our findings suggest that a PSADT threshold of <6 months should be considered for stratification of patients in future clinical trials in this setting.