Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Evidence of marine ice-cliff instability in Pine Island Bay from iceberg-keel plough marks.

Marine ice-cliff instability (MICI) processes could accelerate future retreat of the Antarctic Ice Sheet if ice shelves that buttress grounding lines more than 800 metres below sea level are lost. The present-day grounding zones of the Pine Island and Thwaites glaciers in West Antarctica need to retreat only short distances before they reach extensive retrograde slopes. When grounding zones of glaciers retreat onto such slopes, theoretical considerations and modelling results indicate that the retreat becomes unstable (marine ice-sheet instability) and thus accelerates. It is thought that MICI is triggered when this retreat produces ice cliffs above the water line with heights approaching about 90 metres. However, observational evidence confirming the action of MICI has not previously been reported. Here we present observational evidence that rapid deglacial ice-sheet retreat into Pine Island Bay proceeded in a similar manner to that simulated in a recent modelling study, driven by MICI. Iceberg-keel plough marks on the sea-floor provide geological evidence of past and present iceberg morphology, keel depth and drift direction. From the planform shape and cross-sectional morphologies of iceberg-keel plough marks, we find that iceberg calving during the most recent deglaciation was not characterized by small numbers of large, tabular icebergs as is observed today, which would produce wide, flat-based plough marks or toothcomb-like multi-keeled plough marks. Instead, it was characterized by large numbers of smaller icebergs with V-shaped keels. Geological evidence of the form and water-depth distribution of the plough marks indicates calving-margin thicknesses equivalent to the threshold that is predicted to trigger ice-cliff structural collapse as a result of MICI. We infer rapid and sustained ice-sheet retreat driven by MICI, commencing around 12,300 years ago and terminating before about 11,200 years ago, which produced large numbers of icebergs smaller than the typical tabular icebergs produced today. Our findings demonstrate the effective operation of MICI in the past, and highlight its potential contribution to accelerated future retreat of the Antarctic Ice Sheet

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Factors Affecting Frequency Discrimination of Vibrotactile Stimuli: Implications for Cortical Encoding

BACKGROUND: Measuring perceptual judgments about stimuli while manipulating their physical characteristics can uncover the neural algorithms underlying sensory processing. We carried out psychophysical experiments to examine how humans discriminate vibrotactile stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Subjects compared the frequencies of two sinusoidal vibrations applied sequentially to one fingertip. Performance was reduced when (1) the root mean square velocity (or energy) of the vibrations was equated by adjusting their amplitudes, and (2) the vibrations were noisy (their temporal structure was irregular). These effects were super-additive when subjects compared noisy vibrations that had equal velocity, indicating that frequency judgments became more dependent on the vibrations' temporal structure when differential information about velocity was eliminated. To investigate which areas of the somatosensory system use information about velocity and temporal structure, we required subjects to compare vibrations applied sequentially to opposite hands. This paradigm exploits the fact that tactile input to neurons at early levels (e.g., the primary somatosensory cortex, SI) is largely confined to the contralateral side of the body, so these neurons are less able to contribute to vibration comparisons between hands. The subjects' performance was still sensitive to differences in vibration velocity, but became less sensitive to noise. CONCLUSIONS/SIGNIFICANCE: We conclude that vibration frequency is represented in different ways by different mechanisms distributed across multiple cortical regions. Which mechanisms support the “readout” of frequency varies according to the information present in the vibration. Overall, the present findings are consistent with a model in which information about vibration velocity is coded in regions beyond SI. While adaptive processes within SI also contribute to the representation of frequency, this adaptation is influenced by the temporal regularity of the vibration

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Chromosome identification in the Andean common bean accession G19833 (Phaseolus vulgaris L., Fabaceae)

Characterization of all chromosomes of the Andean G19833 bean genotype was carried out by fluorescent in situ hybridization. Eleven single-copy genomic sequences, one for each chromosome, two BACs containing subtelomeric and pericentromeric repeats and the 5S and 45S ribosomal DNA (rDNA) were used as probes. Comparison to the Mesoamerican accession BAT93 showed little divergence, except for additional 45S rDNA sites in four chromosome pairs. Altogether, the results indicated a relative karyotypic stability during the evolution of the Andean and Mesoamerican gene pools of P. vulgaris

A Quantitative, Non-Destructive Methodology for Habitat Characterisation and Benthic Monitoring at Offshore Renewable Energy Developments

Following governments' policies to tackle global climate change, the development of offshore renewable energy sites is likely to increase substantially over coming years. All such developments interact with the seabed to some degree and so a key need exists for suitable methodology to monitor the impacts of large-scale Marine Renewable Energy Installations (MREIs). Many of these will be situated on mixed or rocky substrata, where conventional methods to characterise the habitat are unsuitable. Traditional destructive sampling is also inappropriate in conservation terms, particularly as safety zones around (MREIs) could function as Marine Protected Areas, with positive benefits for biodiversity. Here we describe a technique developed to effectively monitor the impact of MREIs and report the results of its field testing, enabling large areas to be surveyed accurately and cost-effectively. The methodology is based on a high-definition video camera, plus LED lights and laser scale markers, mounted on a “flying array” that maintains itself above the seabed grounded by a length of chain, thus causing minimal damage. Samples are taken by slow-speed tows of the gear behind a boat (200 m transects). The HD video and randomly selected frame grabs are analysed to quantify species distribution. The equipment was tested over two years in Lyme Bay, UK (25 m depth), then subsequently successfully deployed in demanding conditions at the deep (>50 m) high-energy Wave Hub site off Cornwall, UK, and a potential tidal stream energy site in Guernsey, Channel Islands (1.5 ms−1 current), the first time remote samples from such a habitat have been achieved. The next stage in the monitoring development process is described, involving the use of Remote Operated Vehicles to survey the seabed post-deployment of MREI devices. The complete methodology provides the first quantitative, relatively non-destructive method for monitoring mixed-substrate benthic communities beneath MPAs and MREIs pre- and post-device deployment

Immunoregulation of bovine macrophages by factors in the salivary glands of Rhipicephalus microplus

<p>Abstract</p> <p>Background</p> <p>Alternative strategies are required to control the southern cattle tick, <it>Rhipicephalus microplus</it>, due to evolving resistance to commercially available acaricides. This invasive ectoparasite is a vector of economically important diseases of cattle such as bovine babesiosis and anaplasmosis. An understanding of the biological intricacies underlying vector-host-pathogen interactions is required to innovate sustainable tick management strategies that can ultimately mitigate the impact of animal and zoonotic tick-borne diseases. Tick saliva contains molecules evolved to impair host innate and adaptive immune responses, which facilitates blood feeding and pathogen transmission. Antigen presenting cells are central to the development of robust T cell responses including Th1 and Th2 determination. In this study we examined changes in co-stimulatory molecule expression and cytokine response of bovine macrophages exposed to salivary gland extracts (SGE) obtained from 2-3 day fed, pathogen-free adult <it>R. microplus</it>.</p> <p>Methods</p> <p>Peripheral blood-derived macrophages were treated for 1 hr with 1, 5, or 10 μg/mL of SGE followed by 1, 6, 24 hr of 1 μg/mL of lipopolysaccharide (LPS). Real-time PCR and cytokine ELISA were used to measure changes in co-stimulatory molecule expression and cytokine response.</p> <p>Results</p> <p>Changes were observed in co-stimulatory molecule expression of bovine macrophages in response to <it>R</it>. <it>microplus </it>SGE exposure. After 6 hrs, CD86, but not CD80, was preferentially up-regulated on bovine macrophages when treated with 1 μg/ml SGE and then LPS, but not SGE alone. At 24 hrs CD80, CD86, and CD69 expression was increased with LPS, but was inhibited by the addition of SGE. SGE also inhibited LPS induced upregulation of TNFα, IFNγ and IL-12 cytokines, but did not alter IL-4 or CD40 mRNA expression.</p> <p>Conclusions</p> <p>Molecules from the salivary glands of adult <it>R. microplus </it>showed bimodal concentration-, and time-dependent effects on differential up-regulation of CD86 in bovine macrophages activated by the TLR4-ligand, LPS. Up regulation of proinflammatory cytokines and IL-12, a Th1 promoting cytokine, were inhibited in a dose-dependent manner. The co-stimulatory molecules CD80, as well as the cell activation marker, CD69, were also suppressed in macrophages exposed to SGE. Continued investigation of the immunomodulatory factors will provide the knowledge base to research and develop therapeutic or prophylactic interventions targeting <it>R. microplus</it>-cattle interactions at the blood-feeding interface.</p

Skills training in minimally invasive surgery in Dutch obstetrics and gynecology residency curriculum

The complexity of acquiring minimally invasive surgical (MIS) skills, combined with smaller case volumes for residents have pushed the development of skills training facilities on simulators outside the operating room (OR). Medico-legal and financial constraints have stimulated this development even more. However, the implementation of simulator training into a residency curriculum is shown to be troublesome. MIS skills training is organized in a uniform and easily applicable way in the Dutch obstetrics and gynecology residency curriculum. Every resident is obliged to attend the same basic surgical skills course, named Cobra-alpha course, intentionally during postgraduate year (PGY) 1 or 2. Furthermore, surgical skills are trained, evaluated and expanded on simulators in teaching hospitals. Additional to the Cobra-alpha course, residents may attend advanced training courses and congresses focusing on laparoscopy and hysteroscopy. This organization guarantees a uniform introduction to MIS skills training for every resident. However, preconditions for continuous training and evaluation after this introduction have to be optimized