230 research outputs found

    Motivating Users to Build Heritage Collections Using Games on Social Networks

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    Efforts to motivate user participation and contribution towards digital libraries, such as heritage collections, are often unsuccessful, resulting in empty or underutilized collections. These collections have the potential to improve heritage preservation and education. However,without growth, they are of little use to society. Using a Facebook application, different techniques were compared for motivating user participation and contribution of content towards a heritage collection. It was found that direct competition outperformed a badge system and successfully motivated users to contribute. These results are particularly interesting since, in a developing country, such as where this research was carried out, community and collaboration are usually valued and favoured over competition

    Stercoral perforation proximal to the stapled anastomosis after low anterior resection with an intraluminal device

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    Stercoral perforation of the colon is a rare phenomenon and a potential life-threatening condition requiring acute intervention. A little more than 200 cases have been described to date. The mechanism is not completely understood. In this short communication, we present three patients with a colon perforation proximal to the anastomosis, similar to a stercoral perforation, following colorectal cancer resection with application of an intraluminal device, the C-seal

    Macropinocytotic uptake and infection of human epithelial cells with species B2 adenovirus type 35

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    The human adenovirus serotype 35 (HAdV-35, short Ad35) causes kidney and urinary tract infections, and infects respiratory organs of immunocompromised individuals. Unlike other adenoviruses, Ad35 has a low seroprevalence which makes Ad35-based vectors promising candidates for gene therapy. Ad35 utilizes CD46 and integrins as receptors for infection of epithelial and hematopoietic cells. Here, we show that infectious entry of Ad35 into HeLa, human kidney HK-2 cells and normal human lung fibroblasts strongly depended on CD46 and integrins but not heparan sulfate, and variably required the large GTPase dynamin. Ad35 infections were independent of expression of the carboxy-terminal domain of AP180 which effectively blocks clathrin-mediated uptake. Ad35 infections were inhibited by small chemicals against the serine/threonine kinase Pak1 (p21-activated kinase), protein kinase C (PKC), sodium-proton exchangers, actin and acidic organelles. Remarkably, the F-actin inhibitor jasplakinolide, the Pak1 inhibitor IPA-3 or the sodium-proton exchange inhibitor EIPA blocked the endocytic uptake of Ad35. Dominant-negative proteins or small interfering RNAs against factors driving macropinocytosis, including the small GTPase Rac1, Pak1 or the Pak1 effector C-terminal binding protein 1 (CtBP1) potently inhibited Ad35 infection. Confocal laser scanning microscopy, electron microscopy and live cell imaging showed that Ad35 colocalized with fluid phase markers in large endocytic structures that were positive for CD46, alpha v integrins and also CtBP1. Our results extend earlier observations with HAdV-3 (Ad3), and establish macropinocytosis as an infectious pathway for species B human adenoviruses in epithelial and hematopoietic cells

    Colorectal anastomotic leak:Transcriptomic profile analysis

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    BACKGROUND: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. METHODS: A set of human samples from the anastomotic site collected during stapled colorectal anastomosis were used in the study. Transcriptomic profiles were generated for patients who developing anastomotic leakage and case-matched controls with normal anastomotic healing to identify genes and biological processes associated with the development of anastomotic leakage. RESULTS: The analysis included 22 patients with and 69 without anastomotic leakage. Differential expression analysis showed that 44 genes had adjusted P < 0.050, consisting of two upregulated and 42 downregulated genes. Co-functionality analysis of the 150 most upregulated and 150 most downregulated genes using the GenetICA framework showed formation of clusters of genes with different enrichment for biological pathways. The enriched pathways for the downregulated genes are involved in immune response, angiogenesis, protein metabolism, and collagen cross-linking. The enriched pathways for upregulated genes are involved in cell division. CONCLUSION: These data indicate that patients who develop anastomotic leakage start the healing process with an error at the level of gene regulation at the time of surgery. Despite normal macroscopic appearance during surgery, the transcriptome data identified several differences in gene expression between patients who developed anastomotic leakage and those who did not. The expressed genes and enriched processes are involved in the different stages of wound healing. These provide therapeutic and diagnostic targets for patients at risk of anastomotic leakage

    Increased primary health care use in the fi rst year after colorectal cancer diagnosis

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    Abstract Objective. The view that the general practitioner (GP) should be more involved during the curative treatment of cancer is gaining support. This study aimed to assess the current role of the GP during treatment of patients with colorectal cancer (CRC). Design. Historical prospective study, using primary care data from two cohorts. Setting. Registration Network Groningen (RNG) consisting of 18 GPs in three group practices with a dynamic population of about 30 000 patients. Subjects. Patients who underwent curative treatment for CRC (n Ï­ 124) and matched primary care patients without CRC (reference population; n Ï­ 358). Main outcome measures. Primary healthcare use in the period 1998 -2009. Findings . Patients with CRC had higher primary healthcare use in the year after diagnosis compared with the reference population. After correction for age, gender, and consultation behaviour, CRC patients had 54% (range 23 -92%) more face-to-face contacts, 68% (range 36 -108%) more drug prescriptions, and 35% (range -4 -90%) more referrals compared with reference patients. Patients consulted their GP more often for reasons related to anaemia, abdominal pain, constipation, skin problems, and urinary infections. GPs also prescribed more acid refl ux drugs, laxatives, anti-anaemic preparations, analgesics, and psycholeptics for CRC patients. Conclusions. The GP plays a signifi cant role in the year after CRC diagnosis. This role may be associated with treatment-related side effects and psychological problems. Formal guidelines on the involvement of the GP during CRC treatment might ensure more effective allocation and communication of care between primary and secondary healthcare services

    Evaluation of the use of decision-support software in carcino-embryonic antigen (CEA)-based follow-up of patients with colorectal cancer

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    BACKGROUND: The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC) patients. This system gathers Carcino-Embryonic Antigen (CEA) values and automatically returns a recommendation based on the latest values. METHODS: Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. RESULTS: 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. CONCLUSION: CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians

    Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

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    &lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt

    The Detection of a Massive Chain of Dark H i Clouds in the GAMA G23 Field

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    We report on the detection of a large, extended H i cloud complex in the Galaxy and Mass Survey G23 field, located at a redshift of z ∼0.03, observed as part of the MeerKAT Habitat of Galaxies Survey campaign (a pilot survey to explore the mosaicing capabilities of the MeerKAT telescope). The cloud complex, with a total mass of 1010.0 M, lies in proximity to a large galaxy group with M dyn ∼1013.5 M. We identify seven H peak concentrations, interconnected as a tenuous chain structure, extending ∼400 kpc from east to west, with the largest (central) concentration containing 109.7 M in H gas distributed across 50 kpc. The main source is not detected in ultraviolet, optical, or infrared imaging. The implied gas mass-to-light ratio (M H I/L r) is extreme (>1000) even in comparison to other dark clouds. The complex has very little kinematic structure (110 km s-1), making it difficult to identify cloud rotation. Assuming pressure support, the total mass of the central concentration is > 1010.2 M, while a lower limit to the dynamical mass in the case of full rotational support is 1010.4 M. If the central concentration is a stable structure, it has to contain some amount of unseen matter, but potentially less than is observed for a typical galaxy. It is, however, not clear whether the structure has any gravitationally stable concentrations. We report a faint UV-optical-infrared source in proximity to one of the smaller concentrations in the gas complex, leading to a possible stellar association. The system nature and origins is enigmatic, potentially being the result of an interaction with or within the galaxy group it appears to be associated with

    Correspondence between primary and secondary care about patients with cancer:a Delphi consensus study

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    Introduction To provide optimal care for patients with cancer, timely and efficient communication between healthcare providers is essential. In this study, we aimed to achieve consensus regarding the desired content of communication between general practitioners (GPs) and oncology specialists before and during the initial treatment of cancer. Methods In a two-round Delphi procedure, three expert panels reviewed items recommended for inclusion on referral and specialist letters. Results The three panels comprised 39 GPs (42%), 42 oncology specialists (41%) (i.e. oncologists, radiotherapists, urologists and surgeons) and 18 patients or patient representatives (69%). Final agreement was by consensus, with 12 and 35 items included in the GP referral and the specialist letters, respectively. The key requirements of GP referral letters were that they should be limited to medical facts, a short summary of symptoms and abnormal findings, and the reason for referral. There was a similar requirement for letters from specialists to include these same medical facts, but detailed information was also required about the diagnosis, treatment options and chosen treatment. After two rounds, the overall content validity index (CVI) for both letters was 71%, indicating that a third round was not necessary. Discussion This is the first study to differentiate between essential and redundant information in GP referral and specialist letters, and the findings could be used to improve communication between primary and secondary care

    Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer:Long-Term Results of a Phase II Study

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    Background. In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. Methods. Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. Results. Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. Conclusions. Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years
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