Anti-angiogenesis therapies: their potential in cancer management

Angiogenesis plays an important role in normal animal growth and development. This process is also vital for the growth of tumors. Angiogenesis inhibitors have a different mechanism of action to traditional chemotherapy agents and radiation therapy. The angiogenesis inhibitors can act synergistically with conventional treatments and tend to have non-overlapping toxicities. There are four drugs which have a proven role in treating cancer patients. Bevacizumab is a humanized monoclonal antibody that binds to and neutralizes vascular endothelial growth factor (VEGF). Sunitinib and sorafenib inhibit multiple tyrosine kinase receptors that are important for angiogenesis. Thalidomide inhibits the activity of basic fibroblast growth factor-2 (bFGF). The licensed indications and the supporting evidence are discussed. Other drugs are currently being tested in clinical trials and the most promising of these drugs are discussed. Aflibercept, also known as VEGF-trap, is a recombinant fusion protein that binds to circulating VEGF. The vascular disrupting agents act by targeting established blood vessels. These exciting new treatments have the potential to transform the management of cancer

PartiGeneDB—collating partial genomes

Owing to the high costs involved, only 28 eukaryotic genomes have been fully sequenced to date. On the other hand, an increasing number of projects have been initiated to generate survey sequence data for a large number of other eukaryotic organisms. For the most part, these data are poorly organized and difficult to analyse. Here, we present PartiGeneDB (http://www.partigenedb.org), a publicly available database resource, which collates and processes these sequence datasets on a species-specific basis to form non-redundant sets of gene objects—which we term partial genomes. Users may query the database to identify particular genes of interest either on the basis of sequence similarity or via the use of simple text searches for specific patterns of BLAST annotation. Alternatively, users can examine entire partial genome datasets on the basis of relative expression of gene objects or by the use of an interactive Java-based tool (SimiTri), which displays sequence similarity relationships for a large number of sequence objects in a single graphic. PartiGeneDB facilitates regular incremental updates of new sequence datasets associated with both new and exisitng species. PartiGeneDB currently contains the assembled partial genomes derived from 1.83 million sequences associated with 247 different eukaryotes

Artificial intelligence surgery: how do we get to autonomous actions in surgery?

Most surgeons are skeptical as to the feasibility of autonomous actions in surgery. Interestingly, many examples of autonomous actions already exist and have been around for years. Since the beginning of this millennium, the field of artificial intelligence (AI) has grown exponentially with the development of machine learning (ML), deep learning (DL), computer vision (CV) and natural language processing (NLP). All of these facets of AI will be fundamental to the development of more autonomous actions in surgery, unfortunately, only a limited number of surgeons have or seek expertise in this rapidly evolving field. As opposed to AI in medicine, AI surgery (AIS) involves autonomous movements. Fortuitously, as the field of robotics in surgery has improved, more surgeons are becoming interested in technology and the potential of autonomous actions in procedures such as interventional radiology, endoscopy and surgery. The lack of haptics, or the sensation of touch, has hindered the wider adoption of robotics by many surgeons; however, now that the true potential of robotics can be comprehended, the embracing of AI by the surgical community is more important than ever before. Although current complete surgical systems are mainly only examples of tele-manipulation, for surgeons to get to more autonomously functioning robots, haptics is perhaps not the most important aspect. If the goal is for robots to ultimately become more and more independent, perhaps research should not focus on the concept of haptics as it is perceived by humans, and the focus should be on haptics as it is perceived by robots/computers. This article will discuss aspects of ML, DL, CV and NLP as they pertain to the modern practice of surgery, with a focus on current AI issues and advances that will enable us to get to more autonomous actions in surgery. Ultimately, there may be a paradigm shift that needs to occur in the surgical community as more surgeons with expertise in AI may be needed to fully unlock the potential of AIS in a safe, efficacious and timely manner

Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A Mutations

OBJECTIVE: Despite the clinical importance of an accurate diagnosis in individuals with monogenic forms of diabetes, restricted access to genetic testing leaves many patients with undiagnosed diabetes. Recently, common variation near the HNF1 homeobox A (HNF1A) gene was shown to influence C-reactive protein levels in healthy adults. We hypothesized that serum levels of high-sensitivity C-reactive protein (hs-CRP) could represent a clinically useful biomarker for the identification of HNF1A mutations causing maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Serum hs-CRP was measured in subjects with HNF1A-MODY (n = 31), autoimmune diabetes (n = 316), type 2 diabetes (n = 240), and glucokinase (GCK) MODY (n = 24) and in nondiabetic individuals (n = 198). The discriminative accuracy of hs-CRP was evaluated through receiver operating characteristic (ROC) curve analysis, and performance was compared with standard diagnostic criteria. Our primary analyses excluded approximately 11% of subjects in whom the single available hs-CRP measurement was >10 mg/l. RESULTS: Geometric mean (SD range) hs-CRP levels were significantly lower (

The qualification of collective absolutes and the individuality of persons and events in mid-nineteenth-century Spain

This article argues, on the basis of intellectual, literary, and art history, against the view that mid-nineteenth-century notions of individuality in Spain were products of a social structure based around a bourgeoisie, or, in other accounts, based around a failed effort to establish a bourgeoisie. Instead, it argues that an emphasis on individuality could take radically different forms, that there was no core shared idea of 'individuality'. The article argues that the key motivating factor in these varying notions of individuality was a conflict between and concerning different factions within an oligarchic elite over the future of that elite

A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

Objective: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration: ClinicalTrials.gov NCT01232803

Some cultural consequences in Spain of the Spanish Invasion of Morocco 1859-60

This article argues is a contribution to the study of interrelationships between colonialism, art, and literature in the nineteenth century. The article argues that the Spanish invasion of Morocco in 1859 led to contradictions and tensions within liberal nationalism, not least because of concerns about the tensions between the need for military reassertion of Spain and the respect for the independence of nations. This led to some reconfiguration of Spanish intellectuals' already complex relationship with North Africa and Islam. A major, perhaps surprising consequence of this reconfiguration, was some equation of Moroccan identity with a monotonous surface that was resistant to the gaze. In consequence, the Catalan painter Fortuny's crucial experience of Morocco led him to value near blank surfaces, and thus to make a major contribution to the origins of modern art

Randomised, open-label, phase II study of Gemcitabine with and without IMM-101 for advanced pancreatic cancer

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspectiv