Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Outcomes of synchronous and metachronous bilateral small renal masses (< 4 cm):a population‑based cohort study

Objectives: To report longitudinal outcomes of a population based cohort of patients diagnosed with bilateral small renal masses from a period of over 11 years.Patients and Methods: Consecutive patients diagnosed with bilateral small renal masses (synchronous or metachronous) of a defined geographical area were recorded in a large database (TUCAN database) between January 2005 and December 2016. Patients had a unique identifier number and followed during this period using an agreed upon protocol. Clinicopathological characteristics and outcomes of bilateral small renal masses on active surveillance were analysed and compared to propensity score matched sporadic unilateral small renal masses. Data were analysed for renal mass growth rate, rate of intervention and development of metastatic disease and patient survival.Results: A total of 1060 patients were diagnosed with renal cancer, of which bilateral small renal masses accounted for 70 (6.6%) cases. Synchronous SRMs were observed in 63 patients, whereas metachronous lesions were found in seven patients during the study period. Metachronous lesion mean time to appearance was 62 ± 41 months (range, 9 to 149 months). While most cases were sporadic, four were found to be hereditary. Growth rate of bilateral small renal masses did not differ from that of unilateral sporadic small renal masses. Similarly, there were no differences between the groups for rate of interventions and survival.Conclusion: Progression, rate of metastases and survival for patients diagnosed with bilateral small renal masses is similar to those diagnosed with unilateral disease

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Erosion characteristics and floc strenght of Athabasca river cohesive sediments: towards managing sediment-related issues

Purpose: Most of Canada’s tar sands exploitations are located in the Athabasca river basin. Deposited cohesive sediments in Athabasca river and tributaries are a potential source of PAHs in the basin. Erosional behavior of cohesive sediments depends not only of fluid turbulence but on sediments structure and particularly the influence of organic content. This research tries to describe this behavior in Athabasca river sediments. Methods: An experimental study of cohesive sediments dynamics in one of the tributaries, the Muskeg river, was developed in a rotating annular flume. Variation of the shear stress allowed the determination of erosional strength for beds with different consolidation periods. Particle size measurements were made with a laser diffraction device operated in a continuous flow through mode. Optical analyses of flocs (ESEM and TEM) were performed with samples taken at the end of the experiments. Results: An inverse relationship between suspended sediment concentration (SS) and the consolidation period was found. The differences are related in this research to the increasing organic content of the sediments with consolidation period. The particle size measurements during the experiments showed differences on floc strength that are also related to changing organic content during different consolidation periods. ESEM and TEM observations confirm the structural differences for beds with different consolidation periods. The effects of SFGL on floc structure and in biostabilization of the bed are discussed. Conclusions: It is recommended in this paper that consolidation period should be taken into account for the modeling of erosion of cohesive sediments in the Athabasca river. Relating to transport models of pollutants (PAHs) it is highly recommended to consider flocs organic content, particularly algae, in the resuspension module.Environment Canada, CONACY

Psychosocial issues of women with type 1 diabetes transitioning to motherhood: a structured literature review

BACKGROUND: Life transitions often involve complex decisions, challenges and changes that affect diabetes management. Transition to motherhood is a major life event accompanied by increased risk that the pregnancy will lead to or accelerate existing diabetes-related complications, as well as risk of adverse pregnancy outcomes, all of which inevitably increase anxiety. The frequency of hyperglycaemia and hypoglycaemia often increases during pregnancy, which causes concern for the health and physical well-being of the mother and unborn child. This review aimed to examine the experiences of women with T1DM focusing on the pregnancy and postnatal phases of their transition to motherhood. METHODS: The structured literature review comprised a comprehensive search strategy identifying primary studies published in English between 1990-2012. Standard literature databases were searched along with the contents of diabetes-specific journals. Reference lists of included studies were checked. Search terms included: 'diabetes', 'type 1', 'pregnancy', 'motherhood', 'transition', 'social support', 'quality of life' and 'psychological well-being'. RESULT: Of 112 abstracts returned, 62 articles were reviewed in full-text, and 16 met the inclusion criteria. There was a high level of diversity among these studies but three common key themes were identified. They related to physical (maternal and fetal) well-being, psychological well-being and social environment. The results were synthesized narratively. CONCLUSION: Women with type 1 diabetes experience a variety of psychosocial issues in their transition to motherhood: increased levels of anxiety, diabetes-related distress, guilt, a sense of disconnectedness from health professionals, and a focus on medicalisation of pregnancy rather than the positive transition to motherhood. A trusting relationship with health professionals, sharing experiences with other women with diabetes, active social support, shared decision and responsibilities for diabetes management assisted the women to make a positive transition. Health professionals can promote a positive transition to motherhood by proactively supporting women with T1DM in informed decision-making, by facilitating communication within the healthcare team and co-ordinating care for women with type 1 diabetes transitioning to motherhood

What Affects Social Attention? Social Presence, Eye Contact and Autistic Traits

Social understanding is facilitated by effectively attending to other people and the subtle social cues they generate. In order to more fully appreciate the nature of social attention and what drives people to attend to social aspects of the world, one must investigate the factors that influence social attention. This is especially important when attempting to create models of disordered social attention, e.g. a model of social attention in autism. Here we analysed participants' viewing behaviour during one-to-one social interactions with an experimenter. Interactions were conducted either live or via video (social presence manipulation). The participant was asked and then required to answer questions. Experimenter eye-contact was either direct or averted. Additionally, the influence of participant self-reported autistic traits was also investigated. We found that regardless of whether the interaction was conducted live or via a video, participants frequently looked at the experimenter's face, and they did this more often when being asked a question than when answering. Critical differences in social attention between the live and video interactions were also observed. Modifications of experimenter eye contact influenced participants' eye movements in the live interaction only; and increased autistic traits were associated with less looking at the experimenter for video interactions only. We conclude that analysing patterns of eye-movements in response to strictly controlled video stimuli and natural real-world stimuli furthers the field's understanding of the factors that influence social attention

Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0–29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative β-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak