Ex vivo diagnosis of lung cancer using a Raman miniprobe.

Lung cancer is the most common cause of cancer death. The conventional method of confirming the diagnosis is bronchoscopy, inspecting the airways of the patient with a fiber optic endoscope. A number of studies have shown that Raman spectroscopy can diagnose lung cancer in vitro. In this study, Raman spectra were obtained from ex vivo normal and malignant lung tissue using a minifiber optic Raman probe suitable for insertion into the working channel of a bronchoscope. Shifted subtracted Raman spectroscopy was used to reduce the fluorescence from the lung tissue. Using principal component analysis with a leave-one-out analysis, the tissues were classified accurately. This novel technique has the potential to obtain Raman spectra from tumors from patients with lung cancer in vivo.

Imitation and 'theory of mind' competencies in discrimination of autism from other neurodevelopmental disorders

Several studies have reported imitative deficits in autism spectrum disorder (ASD). However, it is still debated if imitative deficits are specific to ASD or shared with clinical groups with similar mental impairment and motor difficulties. We investigated whether imitative tasks can be used to discriminate ASD children from typically developing children (TD) and children with general developmental delay (GDD). We applied discriminant function analyses to the performance of these groups on three imitation tasks and tests of dexterity, motor planning, verbal skills, theory of mind (ToM). Analyses revealed two significant dimensions. The first represented impairment of dexterity and verbal ability, and discriminated TD from GDD children. Once these differences were accounted for, differences in ToM and the three imitation tasks accounted for a significant proportion of the remaining intergroup variance and discriminated the ASD group from other groups. Further analyses revealed that inclusion of imitative tasks increased the specificity and sensitivity of ASD classification and that imitative tasks considered alone were able to reliably discriminate ASD, TD and GDD. The results suggest that imitation and theory of mind impairment in autism may stem from a common domain of origin separate from general cognitive and motor skill.

Microporation Techniques for Enhanced Delivery of Therapeutic Agents

Perhaps the greatest barrier to development of the field of transmembrane drug delivery is that only a limited number of drugs are amenable to administration by this route. The highly lipophilic nature and barrier function of the uppermost layer of the skin, the stratum corneum, for example, restricts the permeation of hydrophilic, high molecular weight and charged compounds into the systemic circulation. Other membranes in the human body can also present significant barriers to drug permeation. In order to successfully deliver hydrophilic drugs, and macromolecular agents of interest, including peptides, DNA and small interfering RNA, many research groups and pharmaceutical companies Worldwide are focusing on the use of microporation methods and devices. Whilst there are a variety of microporation techniques, including the use of laser, thermal ablation, electroporation, radiofrequency, ultrasound, high pressure jets, and microneedle technology, they share the common goal of enhancing the permeability of a biological membrane through the creation of transient aqueous transport pathways of micron dimensions across that membrane. Once created, these micropores are orders of magnitude larger than molecular dimensions and, therefore, should readily permit the transport of hydrophilic macromolecules. Additionally, microporation devices also enable minimally-invasive sampling and monitoring of biological fluids. This review deals with the innovations relating to microporation-based methods and devices for drug delivery and minimally invasive monitoring, as disclosed in recent patent literature. © 2010 Bentham Science Publishers Ltd.

Delivery of Methylene Blue and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: A potential means of photodynamic therapy of infected wounds

Poly(vinyl alcohol)-borate complexes were evaluated as a potentially novel drug delivery platform suitable for in vivo use in photodynamic antimicrobial chemotherapy (PACT) of wound infections. An optimised formulation (8.0%w/w PVA, 2.0% w/w borax) was loaded with 1.0 mg ml(-1) of the photosensitisers Methylene Blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Both drugs were released to yield receiver compartment concentrations (>5.0 mu g ml(-1)) found to be phototoxic to both planktonic and bicifilm-grown methicillin-resistant Staphylococcus aureus (MRSA), a common cause of wound infections in hospitals. Newborn calf serum, used to simulate the conditions prevalent in an exuding wound, did not adversely affect the properties of the hydrogels and had no significant effect on the rate of TMP-mediated photodynamic kill of MRSA, despite appreciably reducing the fluence rate of incident light. However, MB-mediated photodynamic kill of MRSA was significantly reduced in the presence of calf serum and when the clinical isolate was grown in a biofilm. Results support the contention that delivery of MB or TMP using gel-type vehicles as part of PACT could make a contribution to the photodynamic eradication of MRSA from infected wounds. (C) 2009 Elsevier B.V. All rights reserved.

Discovery of multiple neuropeptide families in the phylum Platyhelminthes

Available evidence shows that short amidated neuropeptides are widespread and have important functions within the nervous systems of all flatworms (phylum Platyhelminthes) examined, and could therefore represent a starting point for new lead drug compounds with which to combat parasitic helminth infections. However, only a handful of these peptides have been characterised, the rigorous exploration of the flatworm peptide signalling repertoire having been hindered by the dearth of flatworm genomic data. Through searches of both expressed sequence tags and genomic resources using the basic local alignment search tool (BLAST), we describe 96 neuropeptides on 60 precursors from 10 flatworm species. Most of these (51 predicted peptides on 14 precursors) are novel and are apparently restricted to flatworms; the remainder comprise nine recognised peptide families including FMRFamide-like (FLPs), neuropeptide F (NPF)-like, myomodulin-like, buccalin-like and neuropeptide FF (NPFF)-like peptides; notably, the latter have only previously been reported in vertebrates. Selected peptides were localised immunocytochemically to the Schistosoma mansoni nervous system. We also describe several novel flatworm NPFs with structural features characteristic of the vertebrate neuropeptide Y (NPY) superfamily, previously unreported characteristics which support the common ancestry of flatworm NPFs with the NPY-superfamily. Our dataset provides a springboard for investigation of the functional biology and therapeutic potential of neuropeptides in flatworms, simultaneously launching flatworm neurobiology into the post-genomic era. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Experimental observations of the stress regime in unsaturated compacted clay when laterally confined

Construction processes often involve reformation of the landscape, which will inevitably encompass compaction of artificially placed soils. A common application of fill materials is their use as backfill in many engineering applications, for example behind a retaining wall. The post-construction behaviour of clay fills is complex with respect to stresses and deformation when the fills become saturated over time. Heavily compacted fills swells significantly more than the lightly compacted fills. This will produce enhanced lateral stresses if the fill is laterally restrained. The work presented in this paper examines how the stress regime in unsaturated clay fills changes with wetting under laterally restrained conditions. Specimens of compacted kaolin, with different initial conditions, were wetted to various values of suction under zero lateral strain at constant net overburden pressure which allowed the concept of K _{0 (the ratio between the net horizontal stress and the net vertical stress) to be examined. Tests were also carried out to examine the traditional concept of the earth pressure coefficient ‘at rest' under loading and unloading and its likely effects on the stress–strain properties. The results have shown that the stress regime (i.e. the lateral stress) changes significantly during wetting under laterally restrained conditions. The magnitude of the change is affected by the initial condition of the soil. The results have also indicated that the earth pressure coefficient ‘at rest' during loading (under the normally consolidated condition) is unaffected by suction and such loading conditions inevitably lead to the development of anisotropic stress–strain properties}

Dublin docklands. The urban fabric as cultural heritage

Introduction

Since the 1980s there have been major policies and projects for the redevelopment of Dublin Docklands. These projects were mainly aimed at profitable development of office, commercial and residential space, without a sound plan that would preserve the identity or community of the area. The recent shift in policies and urban design principles in the Dublin Docklands Area Master Plan 2008 shows that policy makers have acknowledged that mistakes were made in the last decades of the 20th century. The current map of the Dublin Docklands Area Master Plan 2008 gives us useful information about these changes. The Ringsend/ Irishtown area, which has kept a great part of its urban form and community identity throughout centuries, is described as an ‘area of protection of residential and services amenities’ (DDDA, 2008, map A). Meanwhile, the area of the Grand Canal Docks, recently developed, is described with the objective ‘to seek the social, economic and physical development or rejuvenation
within an area of mixed use of which residential and enterprise facilities would be the predominant uses’ (DDDA, 2008, map A). This classification shows that recent development has been unable to achieve the cohesion and complexity of existing neighbourhoods, revealing flaws not only in policy, but also in the built environment and approaches to urban design.

The shift towards the consideration of more community participation reveals a need to understand the tradition and past of these communities, while the urban fabric of small plots in the existing neighbourhoods, therefore, seems to have a very important role in the conservation of identity of place and providing the opportunity for difference within regularity. On the other hand, the new fabric of residential block developments in the docklands denies the possibility of developing a sense of community, and by providing only regularity, does not leave space for difference.

This paper will address questions related to urban morphology and town analysis in the case of Ringsend and Irishtown. This will provide a tool to learn from the past and perhaps find new models of development that might be less detrimental for the heritage of cities and urban communities. One of the ideas of this paper is to adhere to the new tendency in conservation policies to provide a broader analysis of urban areas, not only considering individual monuments in cities, but also analysing the significance of urban morphology and intangible heritage. It forms part of an OPW Post- Doctoral Fellowship in Conservation Studies and Environmental History.1 Research has been carried out in different areas of urban history of Dublin’s southern waterfront, including infrastructure history and a thorough analysis of the letters of the Pembroke Estate of the 19th century, which included the areas of Ringsend and Irishtown. However, this paper focuses on the study of urban form of the area and its significance to Dublin’s heritage.

Binding and degradation of fibrinogen by Bacteroides fragilis and characterization of a 54 kDa fibrinogen-binding protein

Bacteroides fragilis is a bacterium that resides in the normal human gastro-intestinal tract; however, it is also the most commonly isolated Gram-negative obligate anaerobe from human clinical infections, such as intra-abdominal abscesses, and the most common cause of anaerobic bacteraemia. Abscess formation is important in bacterial containment, limiting dissemination of infection and bacteraemia. In this study, we investigated B. fragilis binding and degradation of human fibrinogen, the major structural component involved in fibrin abscess formation. We have shown that B. fragilis NCTC9343 binds human fibrinogen. A putative Bacteroides fragilis fibrinogen-binding protein, designated BF-FBP, identified in the genome sequence of NCTC9343, was cloned and expressed in Escherichia coli. The purified recombinant BF-FBP bound primarily to the human fibrinogen Bß-chain. In addition, we have identified fibrinogenolytic activity in B. fragilis exponential phase culture supernatants, associated with fibrinogenolytic metalloproteases in NCTC9343 and 638R, and cysteine protease activity in YCH46. All nine clinical isolates of B. fragilis examined degraded human fibrinogen; with eight isolates, initial A-chain degradation was observed, with varying Bß-chain and -chain degradation. With one blood culture isolate, Bß-chain and -chain degradation occurred first, followed by subsequent A-chain degradation. Our data raise the possibility that the fibrinogen-binding protein of B. fragilis, along with a variety of fibrinogenolytic proteases, may be an important virulence factor that facilitates dissemination of infection via reduction or inhibition of abscess formation.

The growing visibility of creationism in Northern Ireland: are new science teachers equipped to deal with the issues?

The growing visibility of various forms of creationism in Northern Ireland raises issues for science education. Attempts have been made at political levels to have such “alternatives” to evolution taught in the science classroom, and the issue has received coverage in local press and media. A sample of 112 pre-service science teachers answered a survey on attitudes toward evolution. Preliminary analysis revealed many of these new teachers held views contrary to scientific consensus—over one fifth doubt the evidence for human evolution, and over one quarter dispute the common ancestry of life. Over two thirds indicated a preference for teaching a “range of theories” regarding these issues in science. In addition, 49 pre-service biology teachers viewed a DVD resource promoting “intelligent design” and completed an evaluation of it. The biology teachers also took part in either focus groups or additional questionnaires. A majority took the resource at face value and made positive comments regarding its utility. Many articulated views contrary to the stated positions of science academies, professional associations, and the UK government teaching directives regarding creationism. Most indicated a perception that intelligent design is legitimate science and that there is a scientific “controversy” regarding the legitimacy of evolution. Concern is raised over the ability of these new teachers to distinguish between scientific and non-scientific theories. The suggestion is made that the issue should be addressed directly with pre-service science teachers to make clear the status of such “alternatives.” The paper raises implications for science education and questions for further research.

A Population-Based Study of IGF Axis Polymorphisms and the Esophageal Inflammation, Metaplasia, Adenocarcinoma Sequence

BACKGROUND & AIMS: Insulin-like growth factor (IGF) axis plays a key role in cell development, proliferation, and survival and is implicated in the etiology of several cancers. Few studies have examined the relationship between genetic variation of this axis and esophageal adenocarcinoma (EAC) or its precursors. METHODS: In a population-based case-control study, we investigated the association of common polymorphisms of IGF-1, IGF-2, IGF-1 receptor, IGF binding protein -3, growth hormones (GH) 1 and GH2, and GH receptor with reflux esophagitis (RE), Barrett esophagus (BE), and EAC. Two hundred and thirty RE, 224 BE, 227 EAC cases, and 260 controls were studied. Gene polymorphisms were identified using publicly available online resources; 102 IGF axis tag and putatively functional single-nucleotide polymorphisms (SNPs) were analyzed using MassARRAY iPLEX and Taqman assays. Results were analyzed using Haploview.
RESULTS: Three polymorphisms were disease-associated. IGF1 SNP rs6214 was associated with BE (adjusted P = .039). Using GG genotype as reference, odds ratio for BE in AA (wild-type) was 0.43 (95% confidence interval [CI], 0.24-0.75). GH receptor SNP rs6898743 was associated with EAC (adjusted P = .0112). With GG as reference, odds ratio for EAC in CC (wildtype) genotype was 0.42 (95% CI, 0.23-0.76). IGF1 (CA)(17) 185-bp allele was associated with RE (adjusted P = .0116). Using IGF1(non17) as reference, odds ratio for RE in IGF1(17) carriers was 7.29 (95% CI, 1.57-46.7).
CONCLUSIONS: In this study, 3 polymorphisms of IGF genes were associated with EAC or its precursors. These polymorphisms may be markers of disease risk; independent validation of our findings is required. These results suggest the IGF pathway is involved in EAC development.

Playing with the ‘Erbe’: The Legacy of the Songs of the 1848 Revolution in the GDR

After the twelve-year rupture caused by the Nazis, in the Soviet zone after 1945 attempts were made to reconnect with the traditions of workers’ songs and critical folk songs that were viewed as the cultural heritage of the communist movement. One of these ‘repertoires’ of song was that of the 1848 Revolution. In the 1950s GDR researchers such as the Germanist Bruno Kaiser, the musicologist Inge Lammel and in particular the folklorist Wolfgang Steinitz made substantial contributions to the collecting and publication of the 1848 songs. Their work provided an important reference point for the singers of the German folk song revival in the GDR from the late 1970s onwards. As the cases of groups such as Folkländer and Wacholder showed, theirs was a particularly creative appropriation of the revolutionary Erbe that involved performing protest songs of the past as if they were criticising the present.

A fish bradykinin (Arg0; Trp5; Leu8-bradykinin) from the defensive skin secretion of the European edible frog; Pelophylax kl. esculentus: structural characterization; molecular cloning of skin kininogen cDNA and pharmacological effects on mammalian smooth muscle

Extensive studies on bradykinin-related peptides (BRPs) generated from plasma kininogens in representative species of various vertebrate taxa, have confirmed that many amphibian skin BRPs reflect those present in putative vertebrate predators. For example, the (Val1, Thr6)-bradykinin, present in the defensive skin secretions of many ranids and phyllomedusines, can be generated from plasma kininogens in colubrid snakes - common predators of these frogs. Here, we report the presence of (Arg0, Trp5, Leu8)-bradykinin in the skin secretion of the European edible frog, Pelophylax kl. esculentus, and have found it to be encoded in single copy by a kininogen with an open-reading frame of 68 amino acid residues. This peptide is the archetypal bony fish bradykinin that has been generated from plasma kininogens of the bowfin (Amia calva), the long-nosed gar (Lepisosteus oseus) and the rainbow trout (Onchorhynchus mykiss). More recently, this peptide has been shown to be encoded within cloned kininogens of the Atlantic cod (Gadus morhua) spotted wolf-fish (Anarichas minor), zebrafish (Danio rerio), pufferfish (Tetraodon nigroviridis) and Northern pike (Esox lucius). The latter species is regarded as a major predator of P. kl. esculentus. Synthetic (Arg0, Trp5, Leu8)-bradykinin was previously reported as having multiphasic effects on arterial blood pressure in conscious trout and here we have demonstrated that it can antagonize the relaxation in rat arterial smooth muscle induced by canonical mammalian bradykinin. The discovery of (Arg0, Trp5, Leu8)-bradykinin in the defensive skin secretion of this amphibian completes the spectrum of vertebrate taxon-specific BRPs identified from this source.

The Perils of Moviegoing in America, 1896-1950

The Perils of Moviegoing in America is a film history that examines the various physical and (perceived) moral dangers facing audiences during the first fifty years of film exhibition.

Chapter 1: “Conflagration”
As early as 1897, a major fire broke out at a film exhibition in San Francisco, with flames burning the projectionist and nearby audience members. From that point until the widespread adoption of safety stock in 1950, fires were a very common movie-going experience. Hundreds of audience members lost their lives in literally thousands of theatre fires, ranging from early nickelodeons to the movie palaces of the thirties and forties.

Chapter 2: “Thieves Among Us”
Bandits robbed movie theatres on hundreds of occasions from the early days of film exhibition through the end of the Great Depression. They held up ticket booths, and they dynamited theatre safes. They also shot theatre managers, ushers, and audience members, as a great many of the robberies occurred while movies were playing on the screens inside.

Chapter 3: “Bombs Away”
Bombings at movie theatres became common in small towns and large cities on literally hundreds of occasions from 1914 to the start of World War II. Some were incendiary bombs, and some were stench bombs; both could be fatal, whether due to explosions or to the trampling of panicked moviegoers

Chapter 4: “It’s Catching”
Widespread movie-going in the early 20th century provoked an outcry from numerous doctors and optometrists who believed that viewing films could do irreparable harm to the vision of audience members. Medical publications (including the Journal of the American Medical Association) published major studies on this perceived problem, which then filtered into popular-audience magazines and newspapers.

Chapter 5: “The Devil’s Apothecary Shops”
Sitting in the dark with complete strangers proved worrisome for many early filmgoers, who had good reason to be concerned. Darkness meant that prostitutes could easily work in the balconies of some movie theatres, as could “mashers” who molested female patrons (and sometimes children) after the lights were dimmed. That was all in addition to the various murderers who used the cover of darkness to commit their crimes at movie theatres.

Chapter 6: “Blue Sundays”
Blue laws were those regulations that prohibited businesses from operating on Sundays. Most communities across the US had such legislation on their books, which by the nickelodeon era were at odds with the thousands of filmgoers who went to the movies every Sunday. Theatre managers were often arrested, making newspaper headlines over and over again. Police sometimes even arrested entire film audiences as accomplices in the Blue Law violations.

Chapter 7: “Something for Nothing”
In an effort to bolster ticket sales, many movie theatres in the 1910s began to hold lotteries in which lucky audience members won cash prizes; by the time of the Great Depression, lotteries like “Bank Night” became a common aspect of the theatre-going enterprise. However, reception studies have generally overlooked the intense (and sometimes coordinated) efforts by police, politicians, and preachers to end this practice, which they viewed as illegal and immoral gambling.

The needs of children and young people with cerebral palsy.

Because cerebral palsy (CP) is a sufficiently common condition of childhood and adolescence, the number and needs of these children and young people with cerebral palsy are monitored by centres across the UK () and Europe (). This article describes the epidemiology of CP in childhood using data derived from the Northern Ireland Cerebral Palsy Register, which is one of the longest running CP registers in Europe. The findings presented here are similar to, and representative of, the epidemiology of CP in the western world ().