A study of HER2 gene amplification and protein expression in gastric cancer

Background Gastric cancer is a leading cause of cancer-related mortality, and current treatment outcomes for advanced disease remain poor. HER2 has been identified as a potential candidate for targeted therapy in gastric cancers displaying HER2 gene amplification and protein overexpression.

Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet

We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first-and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

A 60 GHz wide tuning range SiGe bipolar VCO for HDMI and wireless docking applications

A wide tuning range voltage controlled oscillator (VCO) with novel architecture is proposed in this work. The entire circuit consists of a VCO core, a summing circuit, a single-ended to differential (STD) converter and a buffer amplifier. The VCO core oscillates at half the desired frequency and the second harmonic of the VCO core is extracted by the summing circuit, which is then converted to a differential pair by the STD. The entire VCO circuit operates from 58.85 to 70.85 GHz with 20% frequency tuning range. The measured VCO gain is less than 1.6 GHz/V. The measured phase noise at 3 MHz offset is less than -78 dBc/Hz across the entire tuning range. The differential phase error of the output signals is measured by down converting the VCO output signals to low gigahertz frequency using an on-chip mixer. The measured differential phase error is less than 8°. The VCO circuit, which is constructed using 0.35 µm SiGe technology, occupies 770 × 550 µm2 die area and consumes 62 mA under 3.5 V supply.

Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans

Survival is reportedly worse in patients with cancer concurrently diagnosed with deep venous thrombosis. However, information on specific malignancies is limited. From a cohort study of male US veterans we identified incident cancer cases (n aEuroS== aEuroS412 008) and compared survival patterns among those with versus without a history of deep venous thrombosis. Using Cox proportional hazard models, we estimated hazard ratios (HRs) and 95%% confidence intervals as measures of the relative risk of dying. Individuals with (versus without) a concomitant deep venous thrombosis and cancer diagnosis had a higher risk of dying (HR aEuroS== aEuroS1.38; 1.28--1.49). The most prominent excess mortality (HR aEuroS== aEuroS1.29--2.55) was observed among patients diagnosed with deep venous thrombosis at the time of diagnosis of lung, gastric, prostate, bladder, or kidney cancer. Increased risk of dying was also found among cancer patients diagnosed with deep venous thrombosis 1 year (HR aEuroS== aEuroS1.14; 1.07--1.22), 1--5 years (HR aEuroS== aEuroS1.14; 1.10--1.19), and > 5 years (HR aEuroS== aEuroS1.27; 1.23--1.31) before cancer; this was true for most cancer sites (HR aEuroS== aEuroS1.17--1.64). In summary, antecedent deep venous thrombosis confers a worse prognosis upon cancer patients. Advanced stage at diagnosis, treatment effects, lifestyle factors, and comorbidity could explain differences by cancer site and time frame between a prior deep venous thrombosis diagnosis and cancer outcome.

Motor skill deficits in children with partial hearing

AIM:
We examined the effect of partial hearing, including cochlear implantation, on the development of motor skills in children (aged 6-12y).

METHOD:
Three independent groups of children were selected: a partial hearing group (n=25 [14 males, 11 females]; mean age 8y 8mo, SD 1y 10mo), a nonverbal IQ-matched group (n=27 [15 males, 12 females]; mean age 9y, SD 1y 6mo), and an age-matched group (n=26 [8 males, 18 females]; mean age 8y 8mo, SD 1y 7mo) from three schools with special units for children with partial hearing. All children with partial hearing had a bilateral hearing loss >60 decibels. Motor and balance skills were assessed using the Movement Assessment Battery for Children (MABC) and two protocols from the NeuroCom Balance Master clinical procedures.

RESULTS:
The mean standardized total MABC score of the children with partial hearing (95% confidence interval [CI] 71.8-88.7) was significantly lower than both the age-matched (95% CI 95.8-111.4; p<0.01) and the IQ-matched (95% CI 87.6-103.0; p=0.03) comparison groups. The children with partial hearing had particular difficulties with balance, most notably during tests of intersensory demand. However, subgroup analyses revealed that the effect of cochlear implantation was clearly dependent on the nature of the task.

INTERPRETATION:
Children with partial hearing are at high risk of clinical levels of motor deficit, with balance difficulties providing support for conventional vestibular deficit theory. However, the effect of cochlear implantation suggests that other sensory systems may be involved. A broader ecological perspective, which takes into account factors external to the child, may prove a useful framework for future research.

Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood

Background: The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues.

A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation

Background:

Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis.

Methods:

We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV1).

Results:

The change from baseline through week 24 in the percent of predicted FEV1 was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P < 0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P < 0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Questionnaire-revised instrument (a 100-point scale, with higher numbers indicating a lower effect of symptoms on the patient's quality of life) (P < 0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P < 0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was -48.1 mmol per liter (P < 0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%).

Conclusions:

Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.

Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent

Previous studies have shown that following whole-body irradiation bone marrow (BM)-derived cells can migrate into the central nervous system, including the retina, to give rise to microglia-like cells. The detailed mechanism, however, remains elusive. We show in this study that a single-dose whole-body ?-ray irradiation (8 Gy) induced subclinical damage (i.e., DNA damage) in the neuronal retina, which is accompanied by a low-grade chronic inflammation, para-inflammation, characterized by upregulated expression of chemokines (CCL2, CXCL12, and CX3CL1) and complement components (C4 and CFH), and microglial activation. The upregulation of chemokines CCL2 and CXCL12 and complement C4 lasted for more than 160 days, whereas the expression of CX3CL1 and CFH was upregulated for 2 weeks. Both resident microglia and BM-derived phagocytes displayed mild activation in the neuronal retina following irradiation. When BM cells from CX3CR1gfp/+ mice or CX3CR1gfp/gfp mice were transplanted to wild-type C57BL/6 mice, more than 90% of resident CD11b+ cells were replaced by donor-derived GFP+ cells after 6 months. However, when transplanting CX3CR1gfp/+ BM cells into CCL2-deficient mice, only 20% of retinal CD11b+ cells were replaced by donor-derived cells at 6 month. Our results suggest that the neuronal retina suffers from a chronic stress following whole-body irradiation, and a para-inflammatory response is initiated, presumably to rectify the insults and maintain homeostasis. The recruitment of BM-derived myeloid cells is a part of the para-inflammatory response and is CCL2 but not CX3CL1 dependent. © 2012 Wiley Periodicals, Inc.

Production of a monoclonal antibody and its application in an optical biosensor based assay for the quantitative measurement of Pantothenic Acid (Vitamin B5) in foodstuffs

Pantothenicacid (PA), vitamin B5, is an essential B vitamin that may be fortified in food and as such requires robust and accurate methods of detection to meet compliance legislation. This study reports the production and characterisation of the first monoclonalantibody (MAb) specific for PA and the subsequent development of a surface plasmon resonance (SPR) biosensorassay for the quantification of PA. The developed assay was compared with an SPR based commercial kit which utilised a polyclonal antibody (PAb). Foodstuffs, including cereals (n = 43), infant formulas and baby food (n = 10) and fruit juices (n = 48) were analysed by both the MAb and PAb biosensorassays and comparison plots showed good correlation (R2 0.77–0.99). The results indicate that the MAb basedbiosensorassay is suitable for the measurement of PA in foodstuffs and has the added advantage of facilitating a constant, long term supply of identical antibody. Preliminary matrix studies suggest the MAb basedassay is an excellent candidate for further validation studies and routine quality assurance based analysis.

The personality of “aggressive” and “non-aggressive” dog owners

The relationship between pet-keeping and owner personality has attracted considerable attention. Little focus, however, has been directed towards the personality of pet owners in relation to the type of pet owned. This study therefore explored the personality of pet owners in relation to the type of dog breed owned, focusing specifically on owners of breeds widely considered to be “aggressive” versus those more generally perceived as “non-aggressive”. One hundred and forty seven owners of “aggressive” (German shepherd dogs, Rottweilers) or “non-aggressive” (Labrador retrievers, Golden retrievers) dog breeds completed the Eysenck Personality Questionnaire short scale. Breed of dog owned was significantly related to owners’ psychoticism scores, with people who kept “aggressive” dogs having significantly higher scores on this trait than owners of “non-aggressive” dogs. Dog breed ownership was not significantly related to neuroticism, extraversion or lie scale scores, although male owners of “aggressive” dogs were found to be significantly less neurotic than women who kept “aggressive” or “non-aggressive” dogs. Overall, findings suggest that there is a significant relationship between dog breed ownership and specific personality traits, with owners of breeds widely considered to be “aggressive” harbouring more psychotic tendencies than people who choose to keep dogs with a reputedly less aggressive temperament.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Social Identity and Youth Aggressive and Delinquent Behaviors in a Context of Political Violence

The goal of the current study was to examine the moderating role of in-group social identity on relations between youth exposure to sectarian antisocial behavior in the community and aggressive behaviors. Participants included 770 mother-child dyads living in interfaced neighborhoods of Belfast. Youth answered questions about aggressive and delinquent behaviors as well as the extent to which they targeted their behaviors toward members of the other group. Structural equation modeling results show that youth exposure to sectarian antisocial behavior is linked with increases in both general and sectarian aggression and delinquency over one year. Reflecting the positive and negative effects of social identity, in-group social identity moderated this link, strengthening the relationship between exposure to sectarian antisocial behavior in the community and aggression and delinquency towards the out-group. However, social identity weakened the effect for exposure to sectarian antisocial behavior in the community on general aggressive behaviors. Gender differences also emerged; the relation between exposure to sectarian antisocial behavior and sectarian aggression was stronger for boys. The results have implications for understanding the complex role of social identity in intergroup relations for youth in post-accord societies.

Adolescents' educational outcomes in a social ecology of parenting, family, and community risks in Northern Ireland

This study examines the influence of social ecological risks within the domains of parenting, family environment, and community in the prediction of educational outcomes for 770 adolescents (49% boys, 51% girls, M = 13.6 years, SD = 2.0) living in a setting of protracted political conflict, specifically working class areas of Belfast, Northern Ireland. Controlling for religious community, age, and gender, youths' lower academic achievement was associated with family environments characterized by high conflict and low cohesion. School behaviour problems were related to greater exposure to community violence, or sectarian and nonsectarian antisocial behaviour. Youths' expectations about educational attainment were undermined by conflict in the family environment and antisocial behaviour in the community, as well as parenting low in warmth and behavioural control. Findings underscore the importance of considering family and community contributions to youths' educational outcomes. Suggestions regarding targeted interventions toward promoting resilience are discussed, such as assessing both child and family functioning, developing multidimensional interventions for parents, and building community partnerships, among others.