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Coronary artery disease is associated with impaired clot structure. The aim of this study was to investigate acute phase myocardial infarction (AMI) and provide detailed quantitative analysis of clot ultrastructure. Clot formation and breakdown, pore size, fiber density, fiber radius and protofibril packing were investigated in plasma clots from AMI patients. These data were compared to those from healthy controls. Analysis on clot formation using turbidity showed increased lag time, suggesting changes in protofibril packing and increased fiber size for AMI patients compared to healthy controls. Additionally, increased average rate of clotting and decreased time to maximum absorbance in AMI patients suggest that clots formed more quickly. Moreover, we observed increased time from max OD to max rate of lysis. Increased fibrinogen and decreased plasminogen in AMI patients were accounted for in represented significant differences. AMI samples showed increased time to 25% and 50% lysis, but no change in 75% lysis, representative of delayed lysis onset, but expediated lysis once initiated. These data suggest that AMI patients formed less porous clots made from more densely packed fibers with decreased numbers of protofibrils, which was confirmed using decreased permeation and increased fiber density, and decreased turbidimetry. AMI plasma formed clots that were denser, less permeable, and lysed more slowly than healthy controls. These findings were confirmed by detailed analysis of clot ultrastructure, fiber size, and protofibril packing. Dense clot structures that are resistant to lysis may contribute to a prothrombotic milieu in AMI. [ABSTRACT FROM AUTHOR]

Background: The human gut microbiome harbours diverse species of archaea, bacteria, fungi, protists and viruses. To date, most gut microbiome studies have focused on bacteria, neglecting other microbial communities. Consequently, less is known about the diversity and abundance of the latter. Here, we aimed to characterise the diversity and composition of protists in the gut of preschoolaged children (PSAC) in rural Zimbabwe relative to host age, sex, and schistosome infection status. Methods: The gut protist of 113 PSAC (1-5 years) was examined via shotgun metagenomic sequencing and analysed for diversity. Variation in protist abundance with host and environmental factors was analysed by permutational multivariate analysis of variance (PERMANOVA). To investigate how the composition of specific taxa varies across age, sex, nutritional measures and Schistosoma hematobium infection status, analysis of the composition of microbiomes (ANCOM) was used. Results: Eighty protist genera were identified, and the most abundant genera detected was Blastocystis. The prevalence of pathogenic protists was comparatively low, with 12.4% and 3.4% of the participants' gut colonised by E. histolytica and Cryptosporidium, respectively. Of all the independent variables only S. haematobium infection showed significant relationship with the structure of the gut protist, being associated with increases in Peronospora, Pseudoperonospora, Plasmopara and Blastocystis (FDR= 0.009). Summary: This study provides data on the prevalence and diversity of the gut protists in young Zimbabwean children with an emphasis on the host factors; age, sex and schistosome infection status. Our results showed no association between the host factors investigated, including anthropometric measures adjusted for age and the intestinal protist composition and structure, but S. haematobium infection status was associated with composition of specific taxa. There is a need for more studies determining how pathogenic protist interact with non-pathogenic protist in people exhibiting clinical symptoms to inform therapy and nutraceuticals. [ABSTRACT FROM AUTHOR]

Enteric (typhoid) fever remains a problem in low- and middle-income countries that lack the infrastructure to maintain sanitation and where inadequate diagnostic methods have restricted our ability to identify and control the disease more effectively. As we move into a period of potential disease elimination through the introduction of typhoid conjugate vaccine (TCV), we again need to reconsider the role of typhoid diagnostics in how they can aid in facilitating disease control. Recent technological advances, including serology, transcriptomics, and metabolomics, have provided new insights into how we can detect signatures of invasive Salmonella organisms interacting with the host during infection. Many of these new techniques exhibit potential that could be further explored with the aim of creating a new enteric fever diagnostic to work in conjunction with TCV. We need a sustained effort within the enteric fever field to accelerate, validate, and ultimately introduce 1 (or more) of these methods to facilitate the disease control initiative. The window of opportunity is still open, but we need to recognize the need for communication with other research areas and commercial organizations to assist in the progression of these diagnostic approaches. The elimination of enteric fever is now becoming a real possibility, but new diagnostics need to be part of the equation and factored into future calculations for disease control. [ABSTRACT FROM AUTHOR]

This article looks at media representations of the projected regeneration of Northern Ireland, paying particular attention to a recent promotional film made to elicit support for the redevelopment of a part of Belfast's city centre. Commissioned by Castlebrooke Investments, 'Tribeca Belfast' offers a future prospectus of the city that is as superficial as it is bland. It is, however, illustrative of two influential ideas and strategies that took flight at the end of the Cold War and the 'triumph of capitalism'. One seeks peace through the application of neo-liberal nostrums; the other combines brand theory with state-craft in pursuit of global competitiveness. Both propose models of citizenship that are politically benign, either preferring middle class solipsism or demanding brand loyalty. In Castlebrooke's projection of a future Belfast, this translates into a city peopled by a mobile professional class, waited upon and entertained by servile locals. But such a sterile vision is inimical to building peace and political progress because it underestimates and downplays the significance of marginalized groups who through their activism and expressions of solidarity can lay better claim to the 'heart and soul' of Belfast evoked by Castlebrooke. [ABSTRACT FROM AUTHOR]

Background Robust household sampling, commonly applied for population-based investigations, requires sampling frames or household lists to minimize selection bias. We have applied Google Earth Pro satellite imagery to constitute structure-based sampling frames at sites in Pikine, Senegal; Pietermaritzburg, South Africa; and Wad-Medani, Sudan. Here we present our experiences in using this approach and findings from assessing its applicability by determining positional accuracy. Methods Printouts of satellite imagery combined with Global Positioning System receivers were used to locate and to verify the locations of sample structures (simple random selection; weighted-stratified sampling). Positional accuracy was assessed by study site and administrative subareas by calculating normalized distances (meters) between coordinates taken from the sampling frame and on the ground using receivers. A higher accuracy in conjunction with smaller distances was assumed. Kruskal-Wallis and Dunn multiple pairwise comparisons were performed to evaluate positional accuracy by setting and by individual surveyor in Pietermaritzburg. Results The median normalized distances and interquartile ranges were 0.05 and 0.03–0.08 in Pikine, 0.09 and 0.05–0.19 in Pietermaritzburg, and 0.05 and 0.00–0.10 in Wad-Medani, respectively. Root mean square errors were 0.08 in Pikine, 0.42 in Pietermaritzburg, and 0.17 in Wad-Medani. Kruskal-Wallis and Dunn comparisons indicated significant differences by low- and high-density setting and interviewers who performed the presented approach with high accuracy compared to interviewers with poor accuracy. Conclusions The geospatial approach presented minimizes systematic errors and increases robustness and representativeness of a sample. However, the findings imply that this approach may not be applicable at all sites and settings; its success also depends on skills of surveyors working with aerial data. Methodological modifications are required, especially for resource-challenged sites that may be affected by constraints in data availability and area size. [ABSTRACT FROM AUTHOR]

The publicly funded screen development agency, Northern Ireland Screen, has been the key institutional actor in the exponential growth of the screen industries in Northern Ireland. The most prominent production to be based in Northern Ireland has been Home Box Office's Game of Thrones, which had much of its eight seasons filmed in the region. Significant amounts of public finance have been offered to the screen industries, with direct funding provided to augment United Kingdom-wide tax breaks. However, there has been a lack of critical analysis of the recipients of this finance, on the precarious nature of many of the jobs that have been created, or on the stated benefits to the economy. This article subjects the role of Northern Ireland Screen to policy analysis to attempt to fill this scholarly gap. Setting the subject into the context of public support for film and television across the United Kingdom, it is argued that the economic argument for providing direct financial support to the screen industries needs to be viewed in the context of the overall impact on society. [ABSTRACT FROM AUTHOR]

Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines. [ABSTRACT FROM AUTHOR]

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition. [ABSTRACT FROM AUTHOR]

If a radiological incident such as a nuclear power plant accident, a radiological dispersal device, or detonation of an improvised nuclear device occurs, significant areas may be contaminated. Initial cleanup priorities would likely focus on populated areas, leaving the forested areas to pass several seasons where the overhead canopy materials would fall to the forest floor. In the event of a wildfire in a radionuclide-contaminated forest, some radionuclides would be emitted in the air while the rest would remain in the ash. This paper reports on a laboratory simulation study that examines the partitioning of cesium-133 (a nonradioactive isotope of cesium) between airborne particulate matter and residual nonentrained ash when pine needles and peat are doped with cesium. Only 1-2.5% of the doped cesium in pine needles was emitted as particulate matter, and most of the cesium was concentrated in the particulate fraction greater than 10 µm in aerodynamic diameter. For peat fires, virtually all of the cesium remained in the ash. The results from this study will be used for modeling efforts to assess potential exposure risks to firefighters and the surrounding public. Implications: There is a potential for emissions of radionuclides such as cesium-137 from a wildfire over a radionuclide-contaminated forest. This paper reports on a laboratory simulation study of a wildfire with two types of biomass doped with nonradioactive cesium. This simulation suggests that only 1-2.5% of the cesium in the biomass will be emitted from the wildfire, while the rest will reside in the residual ash. In this study, pine needles were the only contributor to the air emissions of cesium; duff was not a source of cesium emissions. In this study, cesium emitted from the simulated wildfire was concentrated in the particle sizes larger than 10 µm. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial- resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to determine the frequency and outcomes of breast malpractice suits among all enrollees in One Call Medical Inc.'s panel of interpreting radiologists nationally and to evaluate state‐by‐state variations. The 8401 radiologists enrolled had 4764 suits, of which 826 were related to breast disease. In New York and New Jersey, the ratio of breast suits to One Call Radiologists was 0.28 and 0.27, twice as much as in any other state. Breast suits in radiology have a wide variation in frequency across the country with New York and New Jersey far exceeding all others in relative frequency and number of radiologists with multiple breast suits. [ABSTRACT FROM AUTHOR]

Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks. [ABSTRACT FROM AUTHOR]

A concern for Catholic educators is how to keep Catholic schools viable and healthy in a milieu of diminishing numbers of religious as well as a very complex and changing world. This article addresses the Augustinians' response to the challenge to keep the Order's mission of education alive and thriving in the 21st century. This article hopes to accomplish two goals: first, to articulate the meaning of the three core values of Unitas (Unity), Veritas (Truth), and Caritas (Charity). Secondly, to report the results of a study of the Augustinian Values Institute (AVI), a program that engages participants in reflection on the core values and how they might be applied to their classroom pedagogies. The article concludes with some discussion about future directions for the Institute. [ABSTRACT FROM AUTHOR]

Due to its low cost, biocompatibility and slow bioresorption, poly-ε-caprolactone (PCL) continues to be a suitable material for select biomedical engineering applications. We used a combined atomic force microscopy (AFM)/optical microscopy technique to determine key mechanical properties of individual electrospun PCL nanofibers with diameters between 440–1040 nm. Compared to protein nanofibers, PCL nanofibers showed much lower adhesion, as they slipped on the substrate when mechanically manipulated. We, therefore, first developed a novel technique to anchor individual PCL nanofibers to micrometer-sized ridges on a substrate, and then mechanically tested anchored nanofibers. When held at constant strain, tensile stress relaxed with fast and slow relaxation times of 1.0 ± 0.3 s and 8.8 ± 3.1 s, respectively. The total tensile modulus was 62 ± 26 MPa, the elastic (non-relaxing) component of the tensile modulus was 53 ± 36 MPa. Individual PCL fibers could be stretched elastically (without permanent deformation) to strains of 19–23%. PCL nanofibers are rather extensible; they could be stretched to a strain of at least 98%, and a tensile strength of at least 12 MPa, before they slipped off the AFM tip. PCL nanofibers that had aged for over a month at ambient conditions became stiffer and less elastic. Our technique provides accurate nanofiber mechanical data, which are needed to guide construction of scaffolds for cells and other biomedical devices. [ABSTRACT FROM AUTHOR]

Most studies of road dust composition have sampled a very wide range of particle sizes, but from the perspective of respiratory exposure to resuspended dusts, it is the PM 10 fraction which is of most importance. The PM 10 fraction of road dust samples was collected at two sites in Birmingham, UK (major highway and road tunnel) and one site in New Delhi, India. Dust loadings were found to be much higher for New Delhi compared to Birmingham, while concentrations of several species were much higher in the case of Birmingham. Detailed chemical source profiles were prepared for both cities and previously generated empirical factors for source attribution to brake wear, tyre wear, and crustal dust were successfully applied to the UK sites. However, 100% of the mass for the Indian site could not be accounted for using these factors. This study highlights the need for generation of local empirical estimation factors for non-exhaust vehicle emissions. A limited number of bulk road dust and brake pad samples were also characterized. Oxidative potential (OP) was also determined for a limited number of PM 10 and bulk road dust samples, and Cu was found to be a factor significantly associated with OP in PM 10 and bulk road dust. [ABSTRACT FROM AUTHOR]

Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular ‘interference’ of fibrin's native polymerization mechanism. We have previously reported that engagement of fibrin's polymerization ‘ hole b ’, also known as ‘b-pockets’, through PEGylated complementary ‘ knob B ’ mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B -fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, K d , increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its K d but increases extensibility of fibers at concentrations above its K d . The data suggest this bimodal behavior is due to the individual contributions knob B , which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine the prevalence, causes, and outcomes of GI malpractice suits in a survey of 8,401 radiologists. The malpractice histories of 8,401 radiologists from 47 states were evaluated from credentialing data of all radiologists participating in the network of One Call Medical Inc. Thirty-two percent of radiologists were defendants in at least one malpractice suit. Of the 4,073 total claims, 346 (8.49 %) were related to the gastrointestinal system. The most frequent primary allegations were failure to diagnose, 65.9 %, and procedural complications, 17.1 %. The commonest missed diagnoses were malignancy, 31.6 %; pneumoperitoneum, 19.3 %; and appendicitis, 14.5 %. Payment to the plaintiff occurred in 75.8 % of claims pertinent to cancer, 73.2 % for missed pneumoperitoneum, and 62.5 % related to appendicitis. Of cases in which a ruling was made in favor of the plaintiff, median payments for pneumoperitoneum was $215,000, for primary cancer $200,000, and for appendicitis $60,000. Among procedurally related errors resulting in judgment against a defending radiologist, 78.6 % of claims regarding retained foreign body, 75 % of barium enema cases, and 62.5 % of liver biopsy resulted in a payment to the plaintiff. Among all resolved cases, the median award was $30,000 for unrecognized foreign body retention, $100,000 for barium enema complications, and $400,000 for liver biopsy complication. Of all GI malpractice claims, failure to diagnose was the most prevalent. Among them, approximately three fourths of claims related to either the diagnosis of primary cancer or for detection of a pneumoperitoneum. [ABSTRACT FROM AUTHOR]

A synthesis of protected homochiral tetrahydropteridines from (2 S )-malic acid has been developed. This presents methodology for the synthesis of reduced pteridine coenzymes and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhi, the cause of typhoid, is host restricted to humans. S. Typhi has a monophyletic population structure, indicating that typhoid in humans is a relatively new disease. Antimicrobial usage is reshaping the current S. Typhi global population and may be driving the emergence of a specific haplotype, H58, that is well adapted to transmission in modern settings and is able to resist antimicrobial killing more efficiently than other S. Typhi. Evidence gathered through genomics and functional studies using the mouse and in vitro cell systems, together with clinical investigations, has provided insight into the mechanisms that underpin the pathogenesis of human typhoid and host restriction. Here we review the latest scientific advances in typhoid research and discuss how these novel approaches are changing our understanding of the disease. [ABSTRACT FROM AUTHOR]

The objective of this study was to present the characteristics of non-spinal musculoskeletal malpractice suits with attention to rates, anatomic location, and payments in a survey of 8,265 radiologists. The malpractice histories of 8,265 radiologists from 36 states were evaluated from credentialing data required of all radiologists participating in the network of One Call Medical, Inc., a broker for imaging tests in workmen's compensation cases. Twenty six hundred of the 8,265 radiologists (31.5 %) had at least one suit. Of the 4,741 total claims, 627 (13.2 %) were related to the bones and soft tissues. Four hundred seventeen (66.1 %) of them involved the musculoskeletal system other than the spine. A cause was known for 400. Of these, 91.8 % (367/400) resulted from an alleged failure to diagnose. The foot was the most common site with a rate 6.00 cases/1,000 radiologist's person years (95 % confidence interval (CI), 4.68-7.68), and the hip was second with a rate of 5.30 cases/1,000 person years (95 % CI, 4.15-6.76). The highest median payment related to ankle injuries with a median settlement of $72,500 (interquartile range (IQR), $40,000-$161,250). The state in which the highest median settlement occurred was Maryland ($125,000; IQR, $95,000-$230,000)) whereas Utah had the highest rate of suits (5.24 cases per 1,000 person years; CI, 3.03-9.04). Claims regarding foot and hip injury were the most common, but ankle settlements incurred the highest awards. [ABSTRACT FROM AUTHOR]

The objective of this study was to present the characteristics of non-spinal musculoskeletal malpractice suits with attention to rates, anatomic location, and payments in a survey of 8,265 radiologists. The malpractice histories of 8,265 radiologists from 36 states were evaluated from credentialing data required of all radiologists participating in the network of One Call Medical, Inc., a broker for imaging tests in workmen's compensation cases. Twenty six hundred of the 8,265 radiologists (31.5 %) had at least one suit. Of the 4,741 total claims, 627 (13.2 %) were related to the bones and soft tissues. Four hundred seventeen (66.1 %) of them involved the musculoskeletal system other than the spine. A cause was known for 400. Of these, 91.8 % (367/400) resulted from an alleged failure to diagnose. The foot was the most common site with a rate 6.00 cases/1,000 radiologist's person years (95 % confidence interval (CI), 4.68-7.68), and the hip was second with a rate of 5.30 cases/1,000 person years (95 % CI, 4.15-6.76). The highest median payment related to ankle injuries with a median settlement of $72,500 (interquartile range (IQR), $40,000-$161,250). The state in which the highest median settlement occurred was Maryland ($125,000; IQR, $95,000-$230,000)) whereas Utah had the highest rate of suits (5.24 cases per 1,000 person years; CI, 3.03-9.04). Claims regarding foot and hip injury were the most common, but ankle settlements incurred the highest awards. [ABSTRACT FROM AUTHOR]

To present overall rates, anatomic location, percent of adverse settlements to the radiologists, and average payments to the plaintiff in spinal-related malpractice suits in a survey of 8,265 radiologists. The malpractice histories of 8,265 radiologists from 36 states were evaluated from credentialing data required of all radiologists participating in the network of One Call Medical Incorporated, a broker for CT/MR in workmen's compensation cases. Two hundred twenty-six of the 8,265 radiologists (31.5 %) had at least one suit. Of the 4,741 total claims, 627 (13.2 %) were related to the bones and adjacent soft tissue. Two hundred and ten (32.9 %) involved the spine. Of these, 70.2 % (134/191) were settled in favor of the plaintiff. One hundred and sixteen (68.2 %) involved the cervical spine with an average settlement of $483,156. Lumbar cases accounted for 28 (16.5 %) of spinal suits, with an average settlement of $119,272. Thoracic cases (26) accounted for only 15.3 % of spinal cases and had an average settlement of $481,608. An allegation of spinal malpractice resulting in a settlement or judgment against the radiologist occurred at a rate of 29.5 cases per 1,000 radiologists' person years. Of the three spinal regions, the cervical spine was the most frequent anatomic site of a malpractice suit and among all those cases settled incurred the highest payment in judgment to the plaintiff. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hormone affinity, efficacy, and mass action produce biological potency thresholds. [•] Normal endocrine system functioning requires and depends upon potency thresholds. [•] Exogenous chemicals that act through hormonal mechanisms must also have thresholds. [•] Principles of endocrinology and endocrine pharmacology dictate potency thresholds. [•] The addition to background theory is inconsistent with principles of endocrinology. [Copyright &y& Elsevier]

Abstract: Purpose: To survey the nearly 100 year history of metaphoric sign naming in radiology describing the pace of their overall accumulation in the radiology canon, their specific rates of growth by modality and subspecialty and the characteristics of the referents to which the signs are attached. Materials and methods: A comprehensive list of metaphoric signs was compiled from a search of articles in several major English language radiology journals, from a roster compiled in a monograph on the subject published in 1984 and from a search of several databases to find signs published in the first half of the 20th century. Results: The growth of radiological metaphorical signs naming was slow for several decades after the first one was published in 1918. It then increased rapidly until the 1980s encompassing all modalities and subspecialties. Recently the practice has shown a marked and steady decline. Conclusion: Metaphoric sign naming was a frequently reported contribution to the radiological literature in the second half of the 20th century corresponding with Radiology's growth as a descriptive discipline. Its decline since then may be a consequence of Radiology's evolution into a more analytic, data-driven field of inquiry. [Copyright &y& Elsevier]

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery, spreading efficiently via low-dose fecal-oral transmission. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality. Classical approaches have shown that S. sonnei is genetically conserved and clonal. We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage. [ABSTRACT FROM AUTHOR]

The authors discuss the role of media platforms in facilitating economic policy reforms and cultural development in Northern Ireland as of April 2012. Topics include the Good Friday agreement of 1998, economic conditions in Great Britain following the 2008 international economic crisis, and competition in the newspaper industry. Films mentioned include "The Mighty Celt" and "The Boxer," which depict paramilitaries. Television programs such as the program "Eureka Street," which criticizes the position of Ireland in global economics, are also mentioned.

Abstract: Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5μm wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30–200nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress–strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2GPa while the relaxed elastic modulus was 3.7GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2s and 11s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. [Copyright &y& Elsevier]

The use of boron in small-molecule pharmaceuticals is increasing. Boron's ubiquitous occurrence in nature and the recent success of a boronic acid drug (Velcade®) in the clinic have alleviated many concerns over its use in pharmaceuticals. In addition, the unique physicochemical properties of boronic acids make them an attractive addition to the medicinal chemists toolbox. This tutorial reviewwill discuss these properties and potential benefits for anyone interested in finding novel enzyme inhibitors. An exceptional class of boronic acids, the oxaboroles, will be highlighted and their properties and uses will be discussed in detail. Finally, the current paradigm for the reaction of boronic acids with enzyme nucleophiles will be summarized. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare through questionnaires the test-ordering behavior of college health professionals and emergency physicians with respect to the choosing of computed tomography scans under two clinical scenarios-suspicion of appendicitis and nondescript abdominal pain. Surveys were sent to physician members of both the American College Health Association and the American College of Emergency Physicians. The recipients were asked if their initial workup would include a computed tomography (CT) scan for either clinical scenario. They were queried on their estimation of the importance of physical examination findings, practice standards, economic considerations, and interpersonal factors on the decision to obtain a CT. They were also asked if their decision to order a CT was related to physical exam findings, parental influence, established protocol, costs to student, insurance considerations, medical literature recommendations, and relationship with radiologist. For the first presentation, a clinical suspicion of appendicitis, there was little difference between the choices of the two groups. Seventy seven percent of the college health professionals would obtain one and 76% of the ER physicians would do the same. However, for the workup of nondescript pain, three times as many ER physicians as college health professionals would obtain a CT scan (34% vs 11%). Of the seven factors, the most important determinant for both groups of physicians was the results of physical exam and least important by far was the relationship to the radiologist. [ABSTRACT FROM AUTHOR]

Technological advances in high-throughput genome sequencing have led to an enhanced appreciation of the genetic diversity found within populations of pathogenic bacteria. Methods based on single nucleotide polymorphisms (SNPs) and insertions or deletions (indels) build upon the framework established by multi-locus sequence typing (MLST) and permit a detailed, targeted analysis of variation within related organisms. Robust phylogenetics, when combined with epidemiologically informative data, can be applied to study ongoing temporal and geographical fluctuations in bacterial pathogens. As genome sequencing, SNP detection and geospatial information become more accessible these methods will continue to transform the way molecular epidemiology is used to study populations of bacterial pathogens. [ABSTRACT FROM AUTHOR]

Because cerebrospinal fluid (CSF) abnormalities in presymptomatic subjects with PSEN1 (presenilin 1) mutations may be observed 4 to 12 years prior to the estimated age at onset, it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity. It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein E?4. To our knowledge, the only putative therapy thus far tested in such a common design has been statin therapy. The results of these tests show increases in soluble amyloid precursor protein (sAPP)α correlating with statin-induced decreases in serum cholesterol levels in the non-PSEN1 subjects. This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimer's disease recently reported in the Rotterdam study, a large, long-term prospective statin trial. Statin therapy significantly decreased both sAPPα and sAPPβ in presymptomatic PSEN1 subjects. Initially, elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy, possibly indicative of a prophylactic effect. These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects [ABSTRACT FROM AUTHOR]

Radiographic series of the foot are often obtained in conjunction with ankle X-rays when the clinical presentation is limited to trauma to the ankle. The Ottawa Ankle and Foot Rules were established in 1992 and serve as reliable guidelines to determine when an ankle or foot series is warranted in patients who have sustained minor ankle and/or foot injury. We retrospectively reviewed radiographic studies of all patients over a period of 18 months who simultaneously had ankle and foot plain radiographs performed for acute complaints limited to the ankle alone. Of the 243 patients who met our inclusion criteria, 55 patients had fractures, 46 in or near the ankle joint, and nine which were located at the base of the fifth metatarsal bone. No fractures or dislocations were noted elsewhere in the foot. All of the fifth metatarsal fractures were evident on adequately performed ankle series. Our findings suggest that films of the foot are not necessary when trauma is limited to the ankle and when an appropriately performed ankle series has been completed. [ABSTRACT FROM AUTHOR]

Post-translational histone modifications are crucial for the regulation of numerous DNA-templated processes, and are thought to mediate both alteration of chromatin dynamics and recruitment of effector proteins to specific regions of the genome. In particular, histone Ser/Thr phosphorylation regulates multiple nuclear functions in the budding yeast Saccharomyces cerevisiae, including transcription, DNA damage repair, mitosis, apoptosis and sporulation. Although modifications to chromatin during replication remain poorly understood, a number of recent studies have described acetylation of the histone H3 N-terminal α-helix (αN helix) at Lys 56 as a modification that is important for maintenance of genomic integrity during DNA replication and repair. Here, we report phosphorylation of H3 Thr 45 (H3-T45), a histone modification also located within the H3 αN helix in S. cerevisiae. Thr 45 phosphorylation peaks during DNA replication, and is mediated by the S phase kinase Cdc7–Dbf4 as part of a multiprotein complex identified in this study. Furthermore, loss of phosphorylated H3-T45 causes phenotypes consistent with replicative defects, and prolonged replication stress results in H3-T45 phosphorylation accumulation over time. Notably, the phenotypes described here are independent of Lys 56 acetylation status, and combinatorial mutations to both Thr 45 and Lys 56 of H3 cause synthetic growth defects. Together, these data identify and characterize H3-T45 phosphorylation as a replication-associated histone modification in budding yeast. [ABSTRACT FROM AUTHOR]

Background: Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. Methods: We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. Results: Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. Conclusions: Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period. [ABSTRACT FROM AUTHOR]

Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area. [ABSTRACT FROM AUTHOR]

The Typhoid Fever Surveillance in Africa Program (TSAP) was established in 2009 to fill the data void concerning invasive Salmonella disease in sub-Saharan Africa, and to specifically estimate the burden of bloodstream infections caused by the key pathogen, Salmonella enterica serovar Typhi. TSAP has achieved this ambitious target, finding high incidences of typhoid fever in both rural and urban populations in several countries in sub-Saharan Africa. The results of TSAP will undoubtedly dictate the direction of future typhoid fever research in Africa, and at last provides a key piece of the disease burden jigsaw puzzle. With the dawn of new Vi conjugate vaccines against Salmonella Typhi, the next priority for the typhoid community must be providing the required data on these vaccines so they can be licensed and provided to those in high-risk groups and locations across sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Emergency radiology as an academic discipline and practice activity is clearly recognized as a distinct category within the community of radiologists in the USA. But, its place among the other branches of diagnostic imaging is as an outlier. Emergency radiology is not recognized as a separate course of study in the curriculum of training. It is not a component of the qualifying exam of the American Board of Radiology. It has few fellowships. It has not engendered a specific designation of care personnel for trauma centres. Moreover, its situation with respect to emergency physicians is bound, by neither regulation nor tradition, to be intellectually or physically close. Yet, it is recognized as encompassing an established society of teachers, practitioners and investigators. Its journal is a repository of new knowledge. Thus, it occupies a definitive if still anomalous position in American medicine in general and radiology in particular. [ABSTRACT FROM AUTHOR]

Purpose: Although a 12-month clinical internship is the traditional precursor to a radiation oncology residency, the continuance of this mandated training sequence has been questioned. This study was performed to evaluate the perceptions of current radiation oncology residents with respect to the value of their internship experience. Methods and Materials: A survey was sent to all US radiation oncology residents. Each was queried about whether they considered the internship to be a necessary prerequisite for a career as a radiation oncologist and as a physician. Preferences were listed on a Likert scale (1 = not at all necessary to 5 = absolutely necessary). Results: Seventy-one percent considered the internship year mostly (Likert Scale 4) or absolutely necessary (Likert Scale 5) for their development as a radiation oncologist, whereas 19.1% answered hardly or not at all (Likert Scale 2 and 1, respectively). With respect to their collective considerations about the impact of the internship year on their development as a physician, 89% had a positive response, 5.8% had a negative response, and 4.7% had no opinion. Although both deemed the preliminary year favorably, affirmative answers were more frequent among erstwhile internal medicine interns than former transitional program interns. Conclusions: A majority of radiation oncology residents positively acknowledged their internship for their development as a specialist and an even greater majority valued it for their development as a physician. This affirmative opinion was registered more frequently by those completing an internal medicine internship compared with a transitional internship. [Copyright &y& Elsevier]

Abstract: A series of phenoxy benzoxaboroles were synthesized and screened for their inhibitory activity against PDE4 and cytokine release. 5-(4-Cyanophenoxy)-2,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2728) showed potent activity both in vitro and in vivo. This compound is now in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. [Copyright &y& Elsevier]

Salmonella pathogenicity island 7 (SPI-7) in Salmonella enterica serovar Typhi appears to be related to other genomic islands. Evidence suggests that SPI-7 is susceptible to spontaneous circularization, loss, and transposition. Here, we demonstrate that a region within SPI-7 has the ability to mobilize the small incQ plasmid R300B. [ABSTRACT FROM AUTHOR]

Abstract: Adenosines bearing 5′-modification in conjunction with an N6-substituent have previously been shown to act as partial agonists at the A1 adenosine receptor. Our current work investigates the effect of modifying the 5′-position in conjunction with efficacious bicyclic and tricyclic N6-substituents. Several highly potent agonists for the A1 adenosine receptor were identified; however, all of these compounds behaved as full agonists. In keeping with previous reports, 5′-halogen and 5′-sulfide derivatives of N 6-(endo-norborn-2-yl)adenosine were, in general, low nanomolar agonists of the A1 adenosine receptor. The known partial agonist, N 6-cyclopentyl-5′-deoxy-5′-ethylthioadenosine (2), also behaved as a full agonist in our assay. [Copyright &y& Elsevier]

The process by which bacteria regulate flagellar expression is known as phase variation and in Salmonella enterica this process permits the expression of one of two flagellin genes, fliC or fljB, at any one time. Salmonella Typhi ( S. Typhi) is normally not capable of phase variation of flagellar antigen expression as isolates only harbour the fliC gene (H:d) and lacks an equivalent fljB locus. However, some S. Typhi isolates, exclusively from Indonesia, harbour an fljB equivalent encoded on linear plasmid, pBSSB1 that drives the expression of a novel flagellin named H:z66. H:z66+ S. Typhi isolates were stimulated to change flagellar phase and genetically analysed for the mechanism of variation. The phase change was demonstrated to be unidirectional, reverting to expression from the resident chromosomal fliC gene. DNA sequencing demonstrated that pBSSB1 linear DNA was still detectable but that these derivatives had undergone deletion and were lacking fljAz66 (encoding a flagellar repressor) and fljBz66. The deletion end-point was found to involve one of the plasmid termini and a palindromic repeat sequence within fljBz66, distinct to that found at the terminus of pBSSB1. These data demonstrate that, like some Streptomyces linear elements, at least one of the terminal inverted repeats of pBSSB1 is non-essential, but that a palindromic repeat sequence may be necessary for replication. [ABSTRACT FROM AUTHOR]

Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad-spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690 has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosisand the American Pharmacists Association J Pharm Sci 96: 2622–2631, 2007 [ABSTRACT FROM AUTHOR]

The generation of complete genome sequences provides a blueprint that facilitates the genetic characterization of pathogens and their hosts. The genome of Salmonella enterica serovar Typhi (S. Typhi) harbors ∼5 million base pairs encoding some 4000 genes, of which >200 are functionally inactive. Comparison of S. Typhi isolates from around the world indicates that they are highly related (clonal) and that they emerged from a single point of origin ∼30,000–50,000 years ago. Evidence suggests that, as well as undergoing gene degradation, S. Typhi has also recently acquired genes, such as those encoding the Vi antigen, by horizontal transfer events. [ABSTRACT FROM AUTHOR]

Unlike the majority of Salmonella enterica serovars, Salmonella Typhi (S. Typhi), the etiological agent of human typhoid, is monophasic. S. Typhi normally harbours only the phase 1 flagellin gene (fliC), which encodes the H:d antigen. However, some S. Typhi strains found in Indonesia express an additional flagellin antigen termed H:z66. Molecular analysis of H:z66+ S. Typhi revealed that the H:z66 flagellin structural gene (fljBz66) is encoded on a linear plasmid that we have named pBSSB1. The DNA sequence of pBSSB1 was determined to be just over 27 kbp, and was predicted to encode 33 coding sequences. To our knowledge, pBSSB1 is the first non-bacteriophage-related linear plasmid to be described in the Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Abstract: This study examined the full range of effects associated with “semantic access impairment” – namely, refractory variables (semantic relatedness, speed of presentation and item repetition), inconsistency, the absence of frequency effects and facilitation by cues – in a series of stroke patients with multimodal semantically impairment. By investigating all of these factors in a group of patients who were not specifically selected to show “access” effects, we were able to establish (1) whether this pattern is a common consequence of infarcts that produce semantic impairment and (2) if these symptoms co-occur. All of the patients showed effects of cueing and an absence of frequency effects in comprehension. Patients whose brain damage included the left inferior prefrontal cortex (LIPC) also showed marked effects of refractory variables; in contrast, two patients with temporal–parietal but not frontal lesions were less sensitive to these variables. Parallel results were obtained for cyclical naming and word–picture matching tasks suggesting that the LIPC plays a role in semantic selection as well as lexical retrieval. Rapid presentation and item repetition is likely to have increased the selection demands in both of these tasks in a similar fashion. Unlike patients with classical “semantic access impairment”, our semantically impaired stroke patients showed significant test–retest consistency, indicating that their difficulties did not result from an unpredictable failure of semantic access—instead, their deficits were interpreted as arising from failures of semantic control. [Copyright &y& Elsevier]

The article presents the study on safety engineering focusing on the investigation of injury mechanisms associated with tempered and laminated side glazing in automobile rollover collisions. It has been known that an automobile side glazing is generally composed of 4 millimeter thick sheets of either tempered safety glass (TSG) or laminated safety glass (LSG). According to industrial safety analysts, LSG is more safety and convenient to use than TSG. However, most passenger vehicles are still using TSG.

Abstract: A series of borinic acid picolinate esters were synthesized and screened for their minimum inhibitory concentration (MIC) against Gram-positive and -negative bacteria. Our lead compounds were then screened for anti-inflammatory activity. From these studies, we identified 3-hydroxypyridine-2-carbonyloxy-bis(3-chloro-4-methylphenyl)borane (2g, AN0128) as having the best combination of anti-bacterial and anti-inflammatory activities. This compound is now in clinical development for dermatological conditions. [Copyright &y& Elsevier]

This article examines how the alternative press in Northern Ireland interpreted the peace process and Good Friday Agreement. While mainstream news greeted the peace accord as an historic opportunity for Northern Ireland to break with its violent past, the alternative publications of the loyalist and republican press were usually less enamoured. Most rejected the Agreement and contextualised contemporary events within long historical memories of struggle, adversity and political betrayal. Since the signing of the Agreement Northern Ireland has suffered a protracted period of political crisis and instability. In this context the dissident views of the alternative press have looked more prescient than mainstream media support for the peace deal. The author argues that paying greater attention to alternative sources of news and information provides a more intriguing insight into the political process and a better understanding of the dynamics of political conflict. [ABSTRACT FROM AUTHOR]

The divergence of Salmonella enterica and Escherichia coli is estimated to have occurred approximately 140 million years ago. Despite this evolutionary distance, the genomes of these two species still share extensive synteny and homology. However, there are significant differences between the two species in terms of genes putatively acquired via various horizontal transfer events. Here we report on the composition and distribution across the Salmonella genus of a chromosomal region designated SPI-10 in Salmonella enterica serovar Typhi and located adjacent to tRNAleux. We find that across the Salmonella genus the tRNAleux region is a hypervariable hot spot for horizontal gene transfer; different isolates from the same S. enterica serovar can exhibit significant variation in this region. Many P4 phage, plasmid, and transposable element-associated genes are found adjacent to tRNAleux in both Salmonella and E. coli, suggesting that these mobile genetic elements have played a major role in driving the variability of this region. [ABSTRACT FROM AUTHOR]