Climate change is likely to affect the pattern of disasters in the Pacific and, by extension, the organizations and systems involved in disaster response. This research focused on how immediate humanitarian health-related needs following disasters are met using the concept of adaptive capacity to investigate the resilience of organizations and the robustness of the broader system of disaster response. Four case study countries (Cook Islands, Fiji, Samoa, and Vanuatu) were chosen for deeper investigation of the range of issues present in the Pacific. Key findings were that adaptive capacity was enhanced by strong informal communication and relationships as well as formal relationships, appropriate participation of traditional leaders and churches, and recognition and support for the critical role national disaster management offices play in disaster coordination. Adaptive capacity was found to be constrained by lack of clear policies for requesting international assistance, lack of coordinated disaster assessments, and limited human resources for health in disaster response. Limitations in psychosocial support and Australian medical services to meet specific needs were observed. Finally, the research revealed that both Pacific and Australian disaster-response agencies would benefit from a strengthened 'future' focus to better plan for uncertainty and changing risks.


The brown dog tick (Rhipicephalus sanguineus) is the most prevalent tick in the world and a well-recognized vector of many pathogens affecting dogs and occasionally humans. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Tick saliva contains various non-proteinaceous substances and secreted proteins that are differentially produced during feeding and comprise of inhibitors of blood congealing and platelet aggregation, vasodilatory and immunomodulatory substances, and compounds preventing itch and pain. One of these proteins is Evasin-1, which has a high binding affinity to certain types of chemokines. The binding of Evasin-1 to chemokines prevents the detection and immune response of the host to R. sanguineus, which may result in the successful transmission of pathogens. In this study, we screened potential Evasin-1 inhibitor based on the pharmacophore model derived from the binding site residues. Hit ligands were further screened via molecular docking and virtual ADMET prediction, which resulted in ZINC8856727 as the top ligand (binding affinity: -9.1 kcal/mol). Molecular dynamics simulation studies, coupled with MM-GBSA calculations and principal component analysis revealed that ZINC8856727 plays a vital role in the stability of Evasin-1. We recommend continuing the study by developing a formulation that serves as a potential medicine aid immune response during R. sanguineus infestation.


Train safety systems are complex and expensive, and changing them requires huge investments. Changes are evolutionary and small. Current developments, like faster - high speed - trains and a higher train density on the railway network, have initiated research on safety systems that can cope with the new requirements. This paper presents a novel approach for a safety subsystem that checks the composition of a train, based on opportunistic sensing with a wireless sensor network. Opportunistic sensing systems consist of changing constellations sensors that, for a limited amount of time, work together to achieve a common goal. Such constellations are selforganizing and come into being spontaneously. The proposed opportunistic sensing system selects a subset of sensor nodes from a larger set based on a common context.We show that it is possible to use a wireless sensor network to make a distinction between carriages from different trains. The common context is acceleration, which is used to select the subset of carriages that belong to the same train out of all the carriages from several trains in close proximity. Simulations based on a realistic set of sensor data show that the method is valid, but that the algorithm is too complex for implementation on simple wireless sensor nodes. Downscaling the algorithm reduces the number of processor execution cycles as well as memory usage, and makes it suitable for implementation on a wireless sensor node with acceptable loss of precision. Actual implementation on wireless sensor nodes confirms the results obtained with the simulations.


IMPORTANCE
Although the majority of children with an unplanned admission to the hospital are admitted through the emergency department (ED), direct admissions constitute a significant proportion of hospital admissions nationally. Despite this, past studies of children have not characterized direct admission practices or outcomes. Pneumonia is the leading cause of pediatric hospitalization in the United States, providing an ideal lens to examine variation and outcomes associated with direct admissions.

OBJECTIVES
To describe rates and patterns of direct admission in a large sample of US hospitals and to compare resource utilization and outcomes between children with pneumonia admitted directly to a hospital and those admitted from an ED.

DESIGN, SETTING, AND PARTICIPANTS
Retrospective cohort study of children 1 to 17 years of age with pneumonia who were admitted to hospitals contributing data to Perspective Data Warehouse. We developed hierarchical generalized linear models to examine associations between admission type and outcomes.

MAIN OUTCOMES AND MEASURES
Outcome measures included (1) length of stay, (2) high turnover hospitalization, (3) total hospital cost, (4) transfer to the intensive care unit, and (5) readmission within 30 days of hospital discharge.

RESULTS
A total of 19,736 children from 278 hospitals met eligibility criteria, including 7100 (36.0%) who were admitted directly and 12,636 (64.0%) through the ED. Rates of direct admission varied considerably across hospitals, with a median direct admission rate of 33.3% (interquartile range, 11.1%-50.0%). Children admitted directly were more likely to be white, to have private health insurance, and to be admitted to small, general community hospitals. In adjusted models, children admitted directly had a 9% higher length of stay (risk ratio, 1.09 [95% CI, 1.07-1.11]), 39% lower odds of high turnover hospitalization (odds ratio [OR], 0.61 [95% CI, 0.56-0.66]), and 12% lower cost (risk ratio, 0.88 [95% CI, 0.87-0.90]) than those admitted through the ED, with no significant differences in transfers to the intensive care unit (OR, 1.29 [95% CI, 0.83-2.00]) or 30-day readmissions (OR, 0.80 [95% CI, 0.57-1.13]).

CONCLUSIONS AND RELEVANCE
Increasing rates of direct admission among children with access to outpatient care might be an effective strategy to reduce hospital costs and the volume of patients in the ED. Additional research is needed to establish direct admission policies and procedures that are safe and cost-effective.


An accidental perforation of necrotic sclera, choroid, and retina with a depressor during a reoperation for retinal detachment, and my frustrations during its repair by the usual methods, led to the use of preserved human scleral homografts for patching similar scleral defects and later extending their indications to less desperate situations. To date, this material has been used in 37 operations on 35 selected eyes. It is the purpose of this paper to report on and to encourage the further selected use of preserved eye-bank sclera for homografts in scleral surgery. Background Various materials have been used for scleral repair and reinforcement. These substances have met with varying degrees of success, and most are well known: cartilage, conjunctiva, mucous membrane, fascia lata, synthetic materials, and sclera. The homotransplantation of human sclera is a fairly recent innovation, and although it has not had general acceptance nor widespread use, the donor material


This paper draws on materialist feminist theories to rethink relationships between girls' bodies and agency. New feminist onto-epistemologies redefine agency as 'becomings' that dynamically emerge through assemblages comprising moving bodies, material, mechanical, organic, virtual, affective and less-than-conscious elements. Vignettes from a multi-modal, ethnographic study conducted over three years are used to demonstrate how place influenced young teen girls' body-movement repertoires. The place was a former coal-mining locale with a proud tradition of masculine, working-class labour. The vignettes focus on corporeality and demonstrate wide variations and fluctuations in girls' experiences of agency, which we theorise through the Deleuzeo-Guatarrian concept of 'becoming'. We discuss how material feminism(s) helps us to understand girls' becomings as emergent within assemblages that carry legacies of the past. Some girls experienced becomings that could not easily be spoken about yet which allowed them to imagine expansive futures while others felt unable to move on in life.


A quantitative microbial risk assessment of flooding and gastrointestinal illness was carried out using a combination of floodwater quality data from the existing literature on pathogen concentrations in the various floodwater components, the use of microcosms to determine pathogen die‐off rates in floodwaters and opportunistic sampling of actual UK floodwaters. Two flood‐related scenarios were examined in a hypothetical population to provide an assessment of the likely cases of gastrointestinal illness resulting from contact with floodwater. The results of the study suggest that significant numbers of people are at risk of illness (especially from viral gastroenteritis) during the clean‐up process rather than during the inundation and withdrawal phases. Additional sampling during flood events of water and sediment would strengthen the empirical policy evidence base required for estimating the severity and range of health impacts using the risk assessment methodology developed in this paper.


Phanerochaete velutina is a major agent of wood decomposition in temperate forests. It grows out of woody resources in search of other resources and is then vulnerable to grazing by invertebrates. The aim of this study was to determine how continuous grazing and grazing for only 2 days by different densities of collembola, Folsomia candida, affect mycelial development (radial extension, hyphal coverage and fractal dimension) of P. velutina growing across non-sterile soil. High density (80 collembola) continuous grazing resulted in different mycelial foraging patterns compared to controls and lower density (20 and 40 collembola) continuous grazing: radial extension rate was reduced from 8.4 mm day 1 (control) to 6.9 mm day 1 (80 collembola), hyphal coverage was reduced to 81% of controls and mass fractal dimension increased from 1.68 (control) to 1.72 (80 collembola). There was evidence of over-compensatory growth: when high density grazing ceased the new growth was considerably greater (38%) than in controls. Grazing also resulted in growth stimulation: at low density continuous grazing (20 collembola) hyphal coverage was 15.6% greater than in controls. The ecological implications of compensatory and stimulatory growth in fungal-invertebrate interactions are considered.


Severe influenza A virus infection causes high mortality and morbidity worldwide due to delayed antiviral treatment and inducing overwhelming immune responses, which contribute to immunopathological lung injury. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), was effective in improving clinical outcomes in patients with severe H1N1 infection; however, the mechanisms by which it attenuates acute lung injury have not been elucidated. Here, delayed oseltamivir treatment was used to mimic clinical settings on lethal influenza A (H1N1) pdm09 virus (pH1N1) infection mice model. We revealed that delayed oseltamivir plus sirolimus treatment protects mice against lethal pH1N1 infection by attenuating severe lung damage. Mechanistically, the combined treatment reduced viral titer and pH1N1-induced mTOR activation. Subsequently, it suppressed the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated secretion of interleukin (IL)-1β and IL-18. It was noted that decreased NLRP3 inflammasome activation was associated with inhibited nuclear factor (NF)-κB activation, reduced reactive oxygen species production and increased autophagy. Additionally, the combined treatment reduced the expression of other proinflammatory cytokines and chemokines, and decreased inflammatory cell infiltration in lung tissue and bronchioalveolar lavage fluid. Consistently, it inhibited the mTOR-NF-κB-NLRP3 inflammasome-IL-1β axis in a lung epithelial cell line. These results demonstrated that combined treatment with sirolimus and oseltamivir attenuates pH1N1-induced severe lung injury, which is correlated with suppressed mTOR-NLRP3-IL-1β axis and reduced viral titer. Therefore, treatment with sirolimus as an adjuvant along with oseltamivir may be a promising immunomodulatory strategy for managing severe influenza.


Tensile creep fracture behavior of polycrystalline near-stoichiometric NiAl has been studied between 700 and 1200 K under initial applied stresses varying between 10 and 200 MPa. The stress exponents for fracture varied between 5.0 and 10.7 while the activation energy for fracture was 250 ± 22 kJ mol. The fracture life was inversely proportional to the secondary creep rate in accordance with the Monkman-Grant relation although there was extensive scatter in the data. This observation suggests that the fracture life for near-stoichiometric NiAl was influenced by creep under these stress and temperature conditions. Several different fracture morphologies were observed. Transgranular ductile cleavage fracture occurs at 700 K and at the higher stresses at 800 K. The fracture mode transitions to transgranular creep fracture at 900 and 1000 K and at lower stresses at 800 K, while plastic rupture and grain boundary cavitation occur at 1100 and 1200 K. An experimental fracture mechanism map is constructed for near-stoichiometric NiAl.


The combined method of moments (MoM)-physical optics (PO) approach proposed by Bilow fails in some cases. Based on the geometrical theory of diffraction (GTD), the uniform theory of diffraction (UTD) and the fundamental theory of electromagnetism, Bilow's diffracted current basis function is modified both within and outside the transition regions. The improved MoM-PO technique is validated by comparison with exact solutions for a right-angled perfectly conducting wedge at normal incidence. The analysis of an impedance wedge also yields accurate results that are in good agreement with available UTD results.


The effect of gamma-aminobutyric acid (GABA) on intracellular pH (pHi) was examined in the crayfish stretch-receptor neurone using H(+)-selective microelectrodes and a two-microelectrode voltage clamp. In the presence of 30 mmol l-1 HCO3- (pH 7.4), application of GABA (0.5 mmol l-1) produced a mean fall in pHi of 0.26 units. The initial rate of fall of pHi was attributable to a net influx of acid equivalents of 6.3 mmol l-1 min-1. In the nominal absence of HCO3-, GABA had little effect on pHi. The HCO3(-)-dependent acidosis caused by GABA was inhibited by picrotoxin (0.1 mmol l-1) but not by depletion of extracellular and intracellular Cl-. Acetazolamide (0.1 mmol l-1) decreased the rate of fall of pHi caused by a step increase in CO2 partial pressure as well as by GABA, which indicates that the neurone contains carbonic anhydrase. In the presence of both Cl- and HCO3-, the reversal potential of the GABA-activated current was more positive than under nominally HCO3(-)-free conditions. In line with this, GABA induced a marked HCO3(-)-dependent depolarization, and this depolarizing action was enhanced in the absence of Cl- so as to lead to triggering of action potentials. All these observations support the conclusion that the GABA-induced fall in pHi is due to a net efflux of HCO3- through the inhibitory anion channels.


Fluoroquinolones (FQs) are important drugs to treat drug-resistant tuberculosis. In this review we integrated pharmacokinetic properties (PK) and microbiological susceptibility against M. tuberculosis and eventually evaluated the pharmcodynamic (PD) properties, as well as the influence of co-administered agents on these characteristics, for the currently used FQs (ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin) in TB treatment. Future FQs that are being developed may overcome the problems with FQs that are used in daily practice. Therefore PK and pharmacodynamic (PD) properties of novel FQs (clinafloxacin, garenoxacin, lomefloxacin, sitafloxacin, sparfloxacin, trovafloxacin, gemifloxacin, grepafloxacin and DC-159a) were evaluated in TB treatment as well. Integrating both excellent PK and PD properties, moxifloxacin, possibly at a higher dosage, may fulfil a far more important role in the treatment of multi-drug and early-generation FQ resistant TB than proposed in the current WHO guideline. Sparfloxacin, trovafloxacin and sitafloxacin are upcoming novel FQs that may be useful for drug-resistant TB based on their favourable PK properties or microbiological susceptibility against M. tuberculosis. Finally, the 8-methoxy moiety, as present in the chemical structure of MFX, will possibly provide DC- 159a with promising PK/PD characteristics and consequently this FQ may develop into a key FQ in future drug resistant TB treatment.


The objective of this study was to investigate and evaluate the usage and effectiveness of innovative traffic control devices that can be used in short-term work zones. Any device to be used in short-term work zones should command the respect of drivers, be durable, have an easily understood meaning, be low cost, be quick and easy to install and remove, and be reusable. This study was conducted in three sections: a literature review of previously published research, a nationwide usage survey, and a field test for a selected device, portable plastic rumble strip (PPRS). PPRSs, which have been tested on a closed course, were found to be a device potentially suitable for use at short term work zones. This field study was to investigate the effects of the PPRSs and drivers' response to them at three short-term maintenance work zones in Kansas. The results showed that the effect of PPRSs in speed reductions was more significant on cars than on trucks. The PPRSs reduced car speeds by 4.6 to 11.4 miles per hour. They also created 5.0 to 11.7 miles per hour mean speed reduction for trucks, but the reductions were only at two test sites. It was observed that 30 to 80 percent of truck drivers activated their brakes (indicated by brake light illumination) when they approached the PPRSs. In addition, about five percent of car and truck drivers swerved around the PPRSs. This indicates that additional signage or other supplemental traffic devices would be needed when the PPRSs are implemented.


Subjugated peoples have been used for the majority's entertainment and profit for millennia. This pattern continues in the athletics programs of our U.S. colleges and universities today. In this article, we criticize NCAA amateurism rules which prevent college athletes from sharing in the vast revenues of college sports even though their labor is an essential component of that lucrative product. Moreover, these rules operate to disproportionately burden African Americans and to benefit European Americans. NCAA amateurism requirements are imposed only upon athletes, not upon coaches, athletic directors, university presidents, NCAA officials, or conferences administrators. Focusing on the top-ranked football and men's basketball teams - those programs responsible for the bulk of athletics revenue - we analyzed the racial composition of players as well as key university officials. In doing so, we found that college football and men's basketball players at these major universities are disproportionately of African-American descent, while the beneficiaries of the lucrative enterprise of college sports - coaches and other administrators - are overwhelmingly of European-American descent. By applying only to athletes, NCAA amateurism rules thereby operate to disproportionately burden African Americans and to benefit European Americans, reserving the revenue generated by these young men only for the managers of college sports, not for the laborers. In this manner, the NCAA's amateurism rules have an adversely and grossly disparate impact upon African Americans. The NCAA and its member universities attempt to legitimize their regime by offering "amateurism" as a justification. Amateurism fails as a legitimizing factor, however, because major college sports are decidedly not amateur except in the pernicious sense that the persons most responsible for creating this product - the athletes themselves - are denied all but a sliver of the great wealth they create. In every other way, college sports has become a sophisticated, visible, and highly lucrative commercial enterprise. Until the members of the NCAA acknowledge the commercial nature of the college sports industry and lift the ban on payment for athletic services, then their shameful legacy will be the knowing maintenance of a system that disparately and adversely impacts African Americans. A largely African-American work force generates extraordinary wealth by creating the product of college sports, but those players are forbidden from sharing in that wealth. Instead, NCAA amateurism rules guarantee that the money will be reserved to benefit the overwhelmingly European-American managers of the college sports industry. In essence, we conclude that this regime - in which free market principles determine compensation for coaches and all other economic beneficiaries of college sports, but not for athletes - replicates apartheid-like systems that have existed throughout history and under which members of the racial majority have exploited minorities for entertainment and profit.


BACKGROUND
The RAS/RAF/MEK/MAP kinase pathway is essential to intracellular signaling transduction regulating cell proliferation, differentiation and death. We investigated the occurrence of exon 15 BRAF and KRAS codon 12 mutations among Greek patients with colorectal cancer.

METHODS
Sixty-one samples from patients with sporadic colorectal adenocarcinomas were studied for exon 15 BRAF mutations. DNA from surgically resected specimens was analyzed by a combination of polymerase chain reaction and direct sequencing. KRAS codon 12 mutational analysis was technically possible in 58 samples (58/61) by a combination of polymerase chain reaction and restriction fragment length polymorphism.

RESULTS
No exon 15 BRAF mutations were detected in any of the colon cancer specimens. The frequency of KRAS codon 12 mutations was 29.3% (17/58). Patients aged < or = 70 years more frequently presented carcinomas harboring KRAS codon 12 mutations than patients aged >70 years (p=0.028). Patients between 61 and 70 years of age were more likely to be carriers of this mutation (p=0.040).

CONCLUSIONS
Despite the limited study sample, our data suggest that BRAF mutations might be present less frequently than KRAS mutations in Greek patients with colorectal carcinomas. Further research involving larger patient series will be necessary to confirm these findings and to assess possible ethnic, environmental and lifestyle influences on BRAF and KRAS mutagenesis.


Abstract The temporal and spatial variations of the zonally-averaged ozone beating rate in the middle atmosphere on a global scale are investigated in detail based on a model study. This study shows that the mean ozone heating rate calculation can be made in a realistic manner by taking advantage of the existing two-dimensional ozone distribution and including the effect of the sphericity of the earth's atmosphere. The obtained ozone heating rates have also been Fourier-analyzed. The common features of the first three harmonic components which correspond respectively to the annual, semiannual and terannual variations are (1) the local maximum amplitudes are located in the altitude regions between 45 and 57 km; (2) local maximum amplitude can be found in the polar region; and (3) maximum horizontal gradients of the beating rate are concentrated in the high latitudes from 60 to 90°. It is also found that the amplitude of the second Fourier component at the pole is about six times greater than that at the eq...


We investigate the behaviour of cryptocurrencies' return data. Using return data for bitcoin, ethereum and ripple which account for over 70% of the cyrptocurrency market, we demonstrate that α-stable distribution models highly speculative cryptocurrencies more robustly compared to other heavy tailed distributions that are used in financial econometrics. We find that the Maximum Likelihood Method proposed by DuMouchel (1971) produces estimates that fit the cryptocurrency return data much better than the quantile based approach of McCulloch (1986) and sample characteristic method by Koutrouvelis (1980). The empirical results show that the leptokurtic feature presented in cryptocurrency return data can be captured by an α-stable distribution. This papers covers predominant literature in cryptocurrencies and stable distributions.


Two controlled studies were undertaken to evaluate the effectiveness of comprehensive and continuous pediatric care. In the first study, 220 infants of primiparous adolescents were randomly allocated to either a comprehensive care (CC) or traditional care (TC) group. CC infants received all medical care, preventive and therapeutic, in a hospital-based program staffed by a pediatrician, public health nurse, and social worker. Mothers of TC infants were left to obtain care from emergency rooms, well-baby and outpatient clinics. One year after delivery, each mother was interviewed and her infant's medical records abstracted. No differences were found between CC and TC infants in completeness of immunization, utilization of medical resources, morbidity, or mortality.
 In a second study, it was hypothesized that patient compliance with physicians' recommendations would be favorably influenced by continuous care. Seventy-seven children on daily oral penicillin prophylaxis for history of rheumatic fever (RF) were studied. For one year, compliance was determined by periodic urine tests for penicillin. Patients were then stratified for age, sex, and compliance and randomly allocated to continuous care (CC) or traditional care (TC) groups. CC patients received all medical care, even for problems unrelated to RF, from the same two physicians for 15 months. TC patients continued to receive specialty clinic care, were seen at the RF clinic by different physicians and referred elsewhere for all problems unrelated to RF.
 Urine specimens were tested periodically for penicillin. After 15 months, no differences were observed between CC and TC groups in proportion of noncompliers or in internal shifts in compliance which had occurred during the study. Thus, neither of these studies was able to demonstrate that comprehensive and continuous care was more effective than conventional ambulatory care for children.


Information-seeking dialogue systems, including knowledge identification and response generation, aim to respond to users with fluent, coherent, and informative responses based on users' needs, which. To tackle this challenge, we utilize data augmentation methods and several training techniques with the pre-trained language models to learn a general pattern of the task and thus achieve promising performance. In DialDoc21 competition, our system achieved 74.95 F1 score and 60.74 Exact Match score in subtask 1, and 37.72 SacreBLEU score in subtask 2. Empirical analysis is provided to explain the effectiveness of our approaches.


Lumbar spinal stenosis (LSS) is a common spinal disorder in the older population, and the clinical syndrome consisting of pain in the buttock or lower extremity, with or without low back pain and corresponding imaging findings of narrowing of spaces around neural and vascular elements in the lumbar spine. The diagnosis depends on history, symptoms, physical examination, radiographies. Varieties of non-operative and operative options are available for LSS patients. In this article, an update on the epidemiology, diagnosis and treatment of LSS was reviewed.


SUMMARY The movements of many cytoplasmic vesicles follow the paths of microtubules, some moving in one direction and others moving in the opposite direction on the same microtubule. Recently we have isolated one cytoplasmic motor, kinesin, and defined another, the axoplasmic retrograde factor, both of which are capable of powering anionic latex beads in both directions along polar microtubule arrays. Evidence summarized here supports but does not prove the hypothesis that kinesin and the retrograde motors are indeed responsible for powering vesicle movements.


Electronically collimated gamma cameras based on Compton scattering in silicon pad sensors may improve imaging in nuclear medicine and bio-medical research. The work described here concentrates on the silicon pad detector for a prototype Compton camera. The silicon pad sensors are read out using low noise VLSI CMOS chips and novel fast triggering chips. Depending on the application a light weight and dense packaging of sensors and its readout electronics on a hybrid is required. The authors describe the silicon pad sensor and their readout on the newly designed hybrid. They also present a modular and low-cost data acquisition system (CCDAQ) based on a digital signal processor which is interfaced to the EPP port of widely available personal computers. Using the CCDAQ and the hybrids energy spectra of gamma-ray photons from technetium (/sub 43//sup 99m/Tc) an americium (/sub 95//sup 241/Am) were acquired with an energy resolution of 2.45 keV FWHM for the 140.5 keV photo-absorption line of /sub 43//sup 99m/Tc. For all pads the discrimination threshold in the trigger chip was between (15 and 25) keV.


Abstract Problems involving the simultaneous estimation of multiple parameters arise in many areas of theoretical and applied statistics. A canonical example is the estimation of a vector of normal means. Frequently, structural information about relationships between the parameters of interest is available. For example, in a gene expression denoising problem, genes with similar functions may have similar expression levels. Despite its importance, structural information has not been well-studied in the simultaneous estimation literature, perhaps in part because it poses challenges to the usual geometric or empirical Bayes shrinkage estimation paradigms. This article proposes that some of these challenges can be resolved by adopting an alternate paradigm, based on regression modeling. This approach can naturally incorporate structural information and also motivates new shrinkage estimation and inference procedures. As an illustration, this regression paradigm is used to develop a class of estimators with asymptotic risk optimality properties that perform well in simulations and in denoising gene expression data from a single cell RNA-sequencing experiment.


Convergence across the San Andreas fault (SAF) system is partitioned between strike-slip motion on the vertical SAF and oblique-slip motion on parallel dip-slip faults, as illustrated by the recent magnitude Ms = 6.0 Palm Springs, Ms = 6.7 Coalinga, and Ms = 7.1 Loma Prieta earthquakes. If the partitioning of slip minimizes the work done against friction, the direction of slip during these recent earthquakes depends primarily on fault dip and indicates that the normal stress coefficient and frictional coefficient (�) vary among the faults. Additionally, accounting for the active dip-slip faults reduces estimates of fault slip rates along the vertical trace of the SAF by about 50 percent in the Loma Prieta and 100 percent in the North Palm Springs segments.


Clinical prediction models aim to provide estimates of absolute risk for a diagnostic or prognostic endpoint. Such models may be derived from data from various studies in the context of a meta‐analysis. We describe and propose approaches for assessing heterogeneity in predictor effects and predictions arising from models based on data from different sources. These methods are illustrated in a case study with patients suffering from traumatic brain injury, where we aim to predict 6‐month mortality based on individual patient data using meta‐analytic techniques (15 studies, n = 11 022 patients). The insights into various aspects of heterogeneity are important to develop better models and understand problems with the transportability of absolute risk predictions.


Chapter 1: Distamycin A is a crescent-shaped natural product that preferentially binds to (A,T) sequences in the minor grove of DNA as 1:1 and 2:1 ligand-DNA complex [1,2]. Analogs of the N-methylpyrrole (Py) rings of these polyamides afford a set of five-membered heterocycles that can be combined—as unsymmetrical ring pairs—in a modular fashion to recognize predetermined DNA sequences with affinity and specificity comparable to DNA-binding proteins (Figures 1 and 2) [3,4]. We describe here recent advances in the field of DNA-binding polyamides, including structural verification of binding models, new heterocycles for recognition, cellular and nuclear uptake properties, and recent biological applications.

Chapter 2: A series of hairpin pyrrole-imidazole polyamide-fluorescein conjugates were synthesized and assayed for cellular localization. Thirteen cell lines, representing eleven human cancers, one human transformed kidney cell line, and one murine leukemia cell line, were treated with 5 µM polyamide-fluorescein conjugates for 10-14 h, then imaged by confocal laser scanning microscopy. A conjugate containing a [beta]-alanine residue at the C-terminus of the polyamide moiety showed no nuclear localization, while an analogous compound lacking the [beta]-alanine residue was strongly localized in the nuclei of all cell lines tested. The localization profiles of several other conjugates suggest that pyrrole-imidazole sequence and content, dye choice and position, linker composition, and molecular weight are determinants of nuclear localization. The attachment of fluorescein to the C-terminus of a hairpin polyamide results in an approximate 10-fold reduction in DNA-binding affinity, with no loss of binding specificity with reference to mismatch binding sites.

Chapter 3: A pivotal step forward in chemical approaches to controlling gene expression is the development of sequence-specific DNA-binding molecules that can enter live cells and traffic to nuclei unaided. DNA-binding polyamides are a class of programmable, sequence-specific small molecules that have been shown to influence a wide variety of protein-DNA interactions. We have synthesized over 100 polyamide-fluorophore conjugates and assayed their nuclear uptake profiles in thirteen mammalian cell lines. The compiled dataset, comprising 1300 entries, establishes a benchmark for the nuclear localization of polyamide-dye conjugates. Compounds in this series were chosen to provide systematic variation in several structural variables, including dye composition and placement, molecular weight, charge, ordering of the aromatic and aliphatic amino-acid building blocks, and overall shape. Nuclear uptake does not appear to be correlated with polyamide molecular weight or with the number of imidazole residues, although the positions of imidazole residues affect nuclear access properties significantly. Generally negative determinants for nuclear access include the presence of a [beta]-Ala-tail residue and the lack of a cationic alkyl amine moiety, whereas the presence of an acetylated 2,4-diaminobutyric acid-turn is a positive factor for nuclear localization. We discuss implications of this data on the design of polyamide-dye conjugates for use in biological systems.


It has been increasingly appreciated in recent times that head injury is not a homogeneous concept and is poorly classified for the purposes of treatment. The separation of patients into 3 categories of severity (mild, moderate and severe) remains a blunt measure used to guide therapy in individual patients. Patients with severe traumatic brain injury (TBI), i.e. a Glasgow Coma Score (GCS) ≤8, may have different pathologies, including an extradural haematoma, subdural haematoma, cerebral ischaemia, cerebral hyperaemia, vasospasm, diffuse axonal injury, and / or focal haemorrhagic contusions. Moreover, autoregulation of the links between cerebral blood flow (CBF) and blood pressure, carbon dioxide tension, and cerebral metabolic requirements may be variably impaired in individuals - all of which have major implications for treatment. Yet traditional management tends to treat all individuals similarly. For example, intracranial pressure (ICP) is usually treated in a standardised stepwise approach. Yet in individual patients, elevated ICP may be associated with cerebral hyperaemia or cerebral ischaemia, subclinical seizures, or impaired autoregulation (where it is the elevated blood pressure that is the underlying problem). To target these appropriately would require accurate diagnosis and a different approach to management.


We present CyBERT, a domain-specific Bidirectional Encoder Representations from Transformers (BERT) model, fine-tuned with a large corpus of textual cybersecurity data. State-of-the-art natural language models that can process dense, fine-grained textual threat, attack, and vulnerability information can provide numerous benefits to the cybersecurity community. The primary contribution of this paper is providing the security community with an initial fine-tuned BERT model that can perform a variety of cybersecurity-specific downstream tasks with high accuracy and efficient use of resources. We create a cybersecurity corpus from open-source unstructured and semi-unstructured Cyber Threat Intelligence (CTI) data and use it to fine-tune a base BERT model with Masked Language Modeling (MLM) to recognize specialized cybersecurity entities. We evaluate the model using various downstream tasks that can benefit modern Security Operations Centers (SOCs). The fine-tuned CyBERT model outperforms the base BERT model in the domain-specific MLM evaluation. We also provide use-cases of CyBERT application in cybersecurity based downstream tasks.


OBJECTIVES
The aim of this study was to compare the effectiveness of glucagon versus placebo in resolving esophageal foreign body impaction (EFBI), as well as the length of the procedure and adverse events.

METHODS
This was a multicenter, randomized, double-blind trial involving consecutive patients diagnosed with alimentary EFBI. Participants were randomized to receive either 1 mg of intravenous glucagon or placebo. All patients underwent upper endoscopy, and adverse events were assessed through a protocolized telephonic interview seven days later.

RESULTS
The study included 72 subjects in the glucagon group and 68 in the placebo group. The foreign body was not identified in 23.6% of subjects in the glucagon group and 20.6% of subjects in the placebo group (difference: 3%, 95% CI: - 10.7-16.8%, p=0.67). The median time required to remove the foreign body was similar in both groups: 4 minutes (range 2-10) in the glucagon group and 3.5 minutes (range 2-7) in the placebo group (difference: 0.5 minutes, 95% CI -1.3-2.3; p=0.59). The most common adverse event reported in both groups was mild pharyngeal pain.

CONCLUSIONS
Glucagon is no more effective than placebo in resolving EFBI or shortening the time required to remove the foreign body. (EUDRA-CT number 2019-004920-40).


Controlled substance diversion is a problem all hospitals face with far ranging legal and medical implications. Drug diversion or tampering can take many forms, such as simple theft, theft by substitution, theft by charting, and under-medicating the patient. The diversion of controlled substances by professional staff from patient care areas can frequently be prevented and detected at the nursing staff level. Often, diversion can be detected in daily hospital practice by performing careful narcotic counts, witnessing the "wasting" of partial doses, and routinely examining product packaging. Such procedures should be hospital policy and strictly enforced. Use of the guidelines presented in this report in conjunction with an effective inservice program can educate health care professionals in the problem of drug diversion. Drug diversion must be reported to maintain patient care standards, employee morale, and ultimely provide the necessary help and guidance to an impaired staff member.


Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs)
formed during meat processing may pose health risk to the public. This project
aimed to investigate the occurrence of HCAs and PAHs in highly consumed
cooked meat products including ready-to-eat (RTE) meat, patties and
meatballs, and their health risk was also assessed according to the dietary
pattern. Different strategies including replacing fat with vegetable oils and
adding spices were applied in order to reduce the formation of HCAs and
PAHs in final meat products. In addition, inhibitory mechanism of antioxidants
in oil and spices on the formation of HCAs and PAHs in meat system were
also discussed. In this work, HCAs and PAHs were extracted by solid-phase
extraction and analysed by HPLC- Diode array UV/ Fluorescence detector.
For RTE meat in UK, chargrilled chicken had the highest level of HCAs
(37.45±4.89ng/g) and PAHs (3.11±0.49ng/g), followed by roasted bacon
(HCAs 15.24±1.31ng/g, PAHs 1.75±0.17ng/g) in selected RTE meat products.
Increase intake of chargrilled chicken and ham could increase breast cancer
and colorectal adenoma risk, but other types of meat had relatively lower
health risk.
Replacing pork back fat with vegetable oils including sunflower oil, olive oil
and grape seed oil could not only improve fatty acids profile in cooked meat
products, but also reduce HCAs, which could be attributed to the existence of
tocopherols and polyphenol compounds in the vegetable oils. However,
antioxidants in the oils could not reduce the total amount of PAHs effectively,
while the complexity of oil decomposition and antioxidants performance at
high temperature could partially explain the case.
All 6 spices powder including garlic, onion, red chilli, paprika, black pepper
and ginger reduced the formation of total HCAs, while ginger powder
achieved the highest inhibition efficiency compared with all other spices.
Antioxidant capacity of spices determined their efficiency in prohibiting
formation of HCAs and PAHs in great extent, while meat type only affected
the formation of HCAs (p 0.05). Regression model suggested that both diallyl disulfide and gallic acid contributed similar
inhibitory efficiency on the formation of HCAs and PAHs. Synergistic effect
between diallyl disulfide and gallic acid was observed on reducing HCAs
(p 0.05).


Acute ocular Moraxella bovis infections were induced in the UV-irradiated eyes of 10 calves. Eight calves developed corneal ulcers in at least 1 eye and were used for the treatment experiment. One randomly selected group of 4 calves with corneal ulcers and M bovis infections in 7 eyes was given a long-acting oxytetracycline formulation in 2 IM dosages of 20 mg/kg of body weight each, 72 hours apart. The other 4 calves with corneal ulcers in 6 eyes and M bovis in all 8 eyes served as nontreated controls. Bilateral ocular cultures were obtained and clinical observations were made daily for 20 days after treatment. After administration of the long-acting drug, new ulcers did not develop in the treated calves, whereas 5 new ulcers developed in the control-group calves during this time. The average durations of increased lacrimation/ulcerated eye were 2 and 12 days after treatment in the treatment and control groups, respectively; the average durations of blepharospasm were 3 and 8 days, respectively. Moraxella bovis was not isolated from any of the eyes of the treatment-group calves for the first 6 days after the antibiotic was administered, but was isolated from 1 eye of 1 treated calf on posttreatment day 7 and daily thereafter, for a total of 14 positive cultures of 160 ocular cultures obtained from the treatment-group calves after treatment. The bacterium was isolated from all eyes and from 144 of 160 cultures from the control-group calves during this time.


The performance of the noncoherent differential chaos-shift-keying (DCSK) communication system over a multipath fading channel with delay spread is evaluated. Analytical expressions of the bit error rates are derived under the assumption of an independent Rayleigh fading two-ray channel model. Analytical and simulated results are presented and compared. The multipath performance of the DCSK system is also compared with that of the coherent CSK system as well as conventional generic waveform communication schemes.


Abstract
Use of connective forms in oral narratives is increasingly investigated as a device for signaling higher level discoursal relations, thus serving the stories' global organization. I set out to explore connective forms as both local and global links using Modern Greek storytelling as its data. My aims are to uncover the stories' template of organizational relations and to demonstrate their context sensitivity. This is achieved by looking into linkage forms in storytelling for adults as well as in storytelling addressed to children. The results of the analysis bring to the fore an audience-shaped strategy of conti-nuity and explicit signposting in the case of stories for children, as opposed to a strategy of salient segmentational shifts that mainly relies on devices other than discourse markers in stories for adults. I show that these strategies are revealing of an interaction between the stories' textual choices and their im-mediate context of occurrence. In addition, they index and are shaped by the stories' wider sociocultural context of occurrence.
(Discourse Analysis; Sociolinguistics)


Objective: The aim of this study was to analyze the treatment outcome of patients with maxillofacial abscess and its relationship with socioeconomic status in a major public hospital offering secondary health care.
 Methods: A total of 105 patients presented at the Dental Centre, Central Hospital Benin, Edo State with maxillofacial abscess all of which were of odontogenic origin were seen over a 4-year period.  Age, gender, educational level, occupation, treatment, medication and outcome taken into data of interest considered in this paper.
 Results: The predominant age groups were 11-20- and 21-30-years age group, accounting for 24.8% each. Females outnumbered the males at 52.4%. Length of hospital stay ranged from 5 to 10 days. A wide range of antibiotics were prescribed and some patients required dental extractions. Maxillofacial abscess is a public and personal health issue with potential life-threatening complications.
Conclusion: This study identified effect of socio-economic status on the outcome of treatment of maxillofacial abscess.


Despite the success that programmable devices have enjoyed in the last two decades, architecture synthesis methodologies for Run-Time Reconfigurable (RTR) systems are still in their infancy. As the majority of consumer devices integrate multiple-functionality, the cost-effectiveness becomes the main focus of computing systems design. This thesis presents a novel architecture synthesis methodology for the cost-effective implementation of a multi-task and multi-mode workload. The proposed methodology creates a RTR system that changes its functionality in response to a dynamic environment and enables on-chip assembly of pre-constructed components by synthesizing a workload-specific static architecture. The proposed methodology presents novelties in design abstraction, partitioning method and in the procedure of deciding reconfiguration granularity. The experimental results show the cost benefits of the proposed architecture synthesis methodology saving 73% of area and 29.8% of power compared to fixed design approach


This paper presents a method for target detection and tracking of IR images in the application of avian surveillance. As there are many reports of avian mortality due to collision with turbine blades, the detection and tracking of birds at turbine sites is an important issue. In this work, three different background subtraction techniques are first applied to detect moving objects. Otsu thresholding method is then extended by incorporating an adaptive variable based on the mean of each frame and certain constant value. Filtering using morphological operations is applied. Results of three different techniques are then compared. Selected technique (RA) followed by thresholding and filtering is then used for tracking and information extraction. Results show that proposed method provides the needed accuracy for IR imagery. This method can be effectively used in different applications of IR imaging.


Abstract. Cloud radars are unique instruments for observing cloud processes, but uncertainties in radar calibration have frequently limited data quality. Thus far, no single robust method exists for assessing the calibration of past cloud radar data sets. Here, we investigate whether observations of microphysical processes in liquid clouds such as the transition of cloud droplets to drizzle drops can be used to calibrate cloud radars. Specifically, we study the relationships between the radar reflectivity factor and three variables not affected by absolute radar calibration: the skewness of the radar Doppler spectrum (γ), the radar mean Doppler velocity (W), and the liquid water path (LWP). For each relation, we evaluate the potential for radar calibration. For γ and W, we use box model simulations to determine typical radar reflectivity values for reference points. We apply the new methods to observations at the Atmospheric Radiation Measurement (ARM) sites North Slope of Alaska (NSA) and Oliktok Point (OLI) in 2016 using two 35 GHz Ka-band ARM Zenith Radars (KAZR). For periods with a sufficient number of liquid cloud observations, we find that liquid cloud processes are robust enough for cloud radar calibration, with the LWP-based method performing best. We estimate that, in 2016, the radar reflectivity at NSA was about 1±1 dB too low but stable. For OLI, we identify serious problems with maintaining an accurate calibration including a sudden decrease of 5 to 7 dB in June 2016.


Thirty anthropometric measurements were analyzed in 147 adults with Martin-Bell syndrome (MBS) (56 men and 91 women) and in a random sample of 108 normal women and 111 men. Results of the univariate comparison of the age, height, or weight-adjusted variables between MBS and normal individuals of either sex indicated that a decrease in stature, in upper limb length, and in upper face height, and an increase in jaw length, chest circumference, and waist width occurred in both affected men and in heterozygous women. While the increase in ear height and breadth and in hypermobility of finger joints and decrease in palm width and bigonial diameter occurred only in affected men, increased bispinal and bitrochanteric diameters, upper arm circumference, and palm and wrist widths were characteristic deviations in heterozygous women. Multivariate analysis in the form of principal components showed some differences in the pattern of interrelationships in individual measures between MBS and normal individuals. In particular, and in contrast with both normal groups, height and weight tended to load on separate components (as did head and midfacial measures) in MBS individuals. A discriminant function based on all body measurements included in this study resulted in almost complete separation of discriminant scores of normal from those of MBS men and in good separation of the scores from normal and heterozygous women. Classification rates based on these functions were from 95% in men to 85% in women. These already high classification rates may be further improved mainly by enlarging the samples and including some other category of traits such as dermatoglyphic measurements.


We report a reliable full-angle tomographic phase microscopy (FA-TPM) method for flowing quasi-spherical cells along microfluidic channels. This method lies in a completely passive optical system, i.e. mechanical scanning or multi-direction probing of the sample is avoided. It exploits the engineered rolling of cells while they are flowing along a microfluidic channel. Here we demonstrate significant progress with respect to the state of the art of in-flow TPM by showing a general extension to cells having almost spherical shapes while they are flowing in suspension. In fact, the adopted strategy allows the accurate retrieval of rotation angles through a theoretical model of the cells' rotation in a dynamic microfluidic flow by matching it with phase-contrast images resulting from holographic reconstructions. So far, the proposed method is the first and the only one that permits to get in-flow TPM by probing the cells with full-angle, achieving accurate 3D refractive index mapping and the simplest optical setup, simultaneously. Proof of concept experiments were performed successfully on human breast adenocarcinoma MCF-7 cells, opening the way for the full characterization of circulating tumor cells (CTCs) in the new paradigm of liquid biopsy.


So far, human factors in industrial environments have been considered from the safety perspective. However, beyond this specific field, it has been the need to address human factors as an important element impacting decisions in Operations Management. Within this frame, the talk addresses the research status on identifying, modelling and integrating human factors in Operations Management. The talk is supported by results from case studies and current work on the development of demand forecasting techniques. Indeed, we present a collaborative judgemental approach for demand forecasting in which the mathematical forecasts are adjusted by a structured technique that combines knowledge from different forecasters. The approach is based on the identification and classification of four types of judgemental events. Factors corresponding to these events are evaluated through a fuzzy inference system to ensure the coherence and the consistency of the collaborative aspect of the technique.


Recent insights have shown that there is a triangular relationship between the diet, immune system and intestinal microbiome, in which the gut microbiota is a substantial contributor to human metabolism and health. A better understanding of the relationship between dietary components, including food processing, and the activity of metabolites produced by the gut microbiota on the host, is an essential step in designing food that benefits human health. The nutrient composition of a diet is obviously of importance to health, but the way food is designed also plays an important role in how much reaches the colon, where it is metabolised by the microbiota. Therefore, this thesis describes the effects of different dietary components, (fibres, tryptophan, glucosinolates and polyphenols) on immune modulation during human digestion and fermentation with a main focus on activation of the Aryl hydrocarbon Receptor. The results give insight into the effects of food preparation and microbial fermentation on the potential health properties of food compounds.


Studies of the behavior of animals when confronted with tasks differing in complexity can improve our understanding of animal cognition and learning mechanisms. Coevolutionary interactions between brood parasites and their hosts provide an ideal opportunity for studying animal cognition because egg recognition and rejection are some of the most important adaptations evolved in hosts to counter brood parasitism. The cognitive mechanisms hosts employ in egg recognition have received substantial interest, with 2 main hypotheses being put forward: 1) true egg recognition based on a knowledge of the hosts' own egg appearance (template that is innate and/or learned) and 2) discordancy by which individuals simply recognize eggs that are in minority as parasitic. These hypotheses are not necessarily mutually exclusive. We conducted egg experiments in the ashy-throated parrotbill (Paradoxornis alphonsianus), a common cuckoo (Cuculus canorus) host that lays immaculate, polymorphic eggs, and we obtained support for both hypotheses. Parrotbills use the presence of own eggs as a cue for recognizing parasitic eggs, supporting true recognition, but without the presence of own eggs as a template they failed to recognize the parasitic egg. Furthermore, some individuals erroneously rejected their own eggs when in minority, supporting recognition by discordancy. Such a combination of cognitive mechanisms that involves true recognition and discordancy in egg recognition in a single population has as far as we can tell never previously been described.


Our main objective with this thesis was to analyze how journalism is portrayed in popular culture, and to see if there was any difference in the way women and men were being portrayed. We chose to analyze the TV-series The Wire because it is widely considered to be one of the greatest series ever shown on television. Due to its popularity it certainly had made quite an impact on its audience and was therefore important to analyze. The series fifth and last season's main narrative was about the journalists at The Baltimore Sun and we picked one scene from each episode to see how the journalists were being portrayed and how female and male journalists interacted with and about each other from a gender perspective. Our analysis showed that journalists were portrayed through two types of journalists. One type of journalist that is desperate to keep his/her job and will go as far as making up stories and changing facts to sensationalize journalism in order to please bosses and owners. The other type of journalist is the ambitious type that wants to get under the skin of the obvious story and search for underlying reasons to explain a certain scenario. We also found that it is the first type that gets rewarded and promoted while the honest and ambitious journalist gets stuck where he/she is or gets sent off to another newspaper. Our analysis also showed that there are fewer women than men with important or leading roles in the newspaper. However, the women portrayed in The Wire are treated very similar to men by their bosses.


The motility of the stomach and jejunum in 8 fed dogs with the intact vagus nerves was registered by the balloon method. Subcutaneous injection of benzohexonium (0.125--0.5 ml of 2.5% soltuion) and atropine (0.12--0.25 ml of 0.1% solution) or metacine (0.125--0.25 ml of 0.1% solution) to 6 dogs proved to induce a transition from digestive motility to the periodic form after a transient depression of the digestive motility. The same effect followed injection of 0.5--1.0 ml of 0.1% atropine only in 2 dogs and 1.0 ml of 0.1% metacine in 1 dog. Since retention of periodic motility following food consumption was inherent for vagotomized dogs, a conclusion was drawn that the experimental dog had "pharmacologic vagotomy". It was suggested that the muscarine receptors on the Auerbach's plexus cells exceeded the nicotine receptor in number.


Over the last few decades, there has been considerable interest in gravity waves in stratified (variable density) flow over topography. This has been motivated in the main by studies of windflow in the atmosphere, where gravity wave propagation and wave overturning can influence considerably the results of both large scale meteorological models and smaller models based on specific sites. Most experimental and theoretical work, however, has involved studies of stably stratified fluids flowing over isolated topography of carefully calculated functional form. This thesis is in two main parts; the first is a literature review, containing an introduction to some of the parameters appropriate to the classification of stratified flows and a review of some of the more prominent studies that have been conducted using various approximations to the governing equations of motion. These include Linear theory, Long's Model, anelastic approximations and incompressible models (both weakly and fully nonlinear). This section also contains brief introductions to turbulence models and experimental studies. The second part of this thesis reports on research conducted into the implementation of a viscous upper layer boundary condition (designed to absorb any vertically propagating waves) in the standard Surrey stratified flow numerical codes. The results of testing the modification for two dimensional high Reynolds number flows over a fence and short and long cosine hills are presented, with conclusions and a number of further suggestions made in the final chapter.


Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signaling pathways and transcriptional programs. Forkhead Box G1 (FOXG1) is one of the master regulators that play fundamental roles in forebrain development; from the timing of neurogenesis, to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes, ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits, with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in the neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as the increased yield of information from high throughput omics, have opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of the clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems, to highlight the prospects of research and possible clinical interventions.


The CMS Experiment at the LHC has released many large datasets of proton-proton collision data
as well as simulation to the public as part of its commitment to data preservation and open access.
The collision data released totals around 2 $\mathrm{fb^{-1}}$ at 7 TeV and nearly 12 $\mathrm{fb^{-1}}$ at 8 TeV.

Data preservation describes the efforts to not only preserve the data itself but the conditions
in which it can be analyzed. This requires archiving and documenting information such as run
environment and conditions and tools such as analysis software and workflows. Open access describes
the efforts to share these tools and information with the public, including educators and researchers.

These efforts present many challenges, partly due to the complexity and size of the CMS datasets
and also to the knowledge required to make meaningful use of them. We describe here how we dealt
with these challenges and the usage of CMS open data not only in public education and engagement
but also in fundamental research. Furthermore we describe plans for future releases of data.


This study uses DEA non-parametric approach (Data Envelopment Analysis) to measure the environmental efficiency of 16 Iranian electric power companies during the period (2010-2014). The proposed approach incorporates not only the output separation (desirable and undesirable) but also the input separation (energy and non-energy). This study discusses some non-radial models) slack based measure, Slack based measure based on directional distance function, Range adjusted measure) and compare them with other previous DEA radial models (CCR, Directional distance function) used for the performance evaluation of electric power companies. After the methodological comparison, this study applies the proposed approaches for measuring the environmental efficiency of Iranian fossil fuel power generation. The results show that Kerman and Khuzestan electric power companies belong to a high level of environmental efficiency and the worst performers are Sistan and Baluchestan and Fars companies in term of fossil fuel power generation. Finally, we can conduct a rank sum test based upon their ranking scores to obtain a statistical inference. We find two economic implications. One of the two implications is that no major change has occurred in the operational performance of Iranian electric power industry from 2010 to 2014. The other implication indicates that there are strategic differences in the operation of Iranian electric power firms after the liberalization.


A facile and low cost method to construct a bismuth vanadate thin film photoanode was implemented with the aim of integrating it in a tandem dual water splitting photoelectrochemical cell. Multilayer semi-transparent thin films of BiVO4 were fabricated by a sol–gel process and deposited by dip-coating onto transparent conducting oxide substrates with intermediate annealing treatment between layers and final calcination at a low temperature of 450 °C in air. The effect of the intermediate annealing temperature has a great impact on the porosity, and therefore density, of thin layers of BiVO4 when fabricated by sol–gel dip-coating methods; thus, for optimal activity, the annealing temperature should be kept at 400 °C for thinner layers and 450 °C for thicker layers. The annealing temperature has a direct effect on the size of the crystallites which determines the microstructural density and porosity. In contrast, the final calcination temperature must be 450 °C in order to achieve good electrochemical performances. Optimized BiVO4 photoanodes exhibit a photocurrent of up to 2.1 mA cm−2 with an average Faradic efficiency of 85 % for oxygen evolution in neutral pH potassium phosphate buffer at 1.23 V vs. RHE under 350 mW cm−2 light irradiation.


The treatments used by most doctors are considered conventional medicine. Complementary and alternative medicine (CAM) consists of a group of health care practices and products that are considered out of the mainstream. An "out-of-the-mainstream" treatment is considered complementary if you use it along with conventional medicine. Research shows that 40 percent of women in the United States use some form of CAM. People try CAM for a variety of reasons, including: conventional medicine has not helped solve their medical problem. They believe that products derived from nature are healthier and safer than prescription drugs, even though they may not be. They like the holistic approach taken by CAM therapists. A holistic approach involves paying attention to all of a client's needs to help her regain and maintain her health. These include not just physical but also emotional, social, and spiritual needs. In this review we summarize some indications of herbal medicine in women's health.


Background: Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1α concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1α overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells. Aims: To investigate the prognostic impact of these different HIF-1α overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1). Methods: HIF-1α, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1α. Clinical data included disease free survival, lymph node status, and tumour size. Results: HIF-1α overexpression (44% of cases) had a perinecrotic (13.5%) or diffuse staining pattern (30.5%). CA IX expression was detectable in 12.5% of breast cancers, whereas GLUT-1 expression was seen in 29%, with both showing perinecrotic membrane staining. Perinecrotic HIF-1α overexpression was highly associated with CA IX and GLUT-1 overexpression, and double staining for HIF-1α and CA IX showed strong expression in the same cells. Diffusely overexpressed HIF-1α was not associated with CA IX or GLUT-1 expression. Patients with diffuse HIF-1α staining had a significantly better prognosis than patients with perinecrotically overexpressed HIF-1α. Conclusions: Different regulation pathways of HIF-1α overexpression exist in breast cancer: (1) hypoxia induced, perinecrotic HIF-1α overexpression with strong expression of hypoxia associated genes (CA IX and GLUT-1), which is associated with a poor prognosis; and (2) diffuse HIF-1α overexpression lacking major hypoxia associated downstream effects, resulting in a more favourable prognosis.


Power quality (PQ) regulation is of great importance due to the economical consequences associated with the presence of the disturbances in power systems. Regulations should provide interventions at the system level (transmission and distribution networks) and the local level at the point of common coupling between utilities and customers. This paper proposes an integrated approach for overall voltage quality regulation; in particular, it focuses on regulation at the system level, which seems to be widely applicable. The regulation structures proposed for system regulation use global indices to characterize the voltage quality. A numerical application supports the theoretical considerations.


Given a matrix the seriation problem consists in permuting its rows in such way that all its columns have the same shape, for example, they are monotone increasing. We propose a statistical approach to this problem where the matrix of interest is observed with noise and study the corresponding minimax rate of estimation of the matrices. Specifically, when the columns are either unimodal or monotone, we show that the least squares estimator is optimal up to logarithmic factors and adapts to matrices with a certain natural structure. Finally, we propose a computationally efficient estimator in the monotonic case and study its performance both theoretically and experimentally. Our work is at the intersection of shape constrained estimation and recent work that involves permutation learning, such as graph denoising and ranking.


The rise of health issues such as HIV, pandemic influenza and Ebola on international agendas has led to the framing of threats to health as security issues. This has created an uneasy relationship between politics and health, by moving national interests into an area traditionally dominated by scientific rationalities and a predisposition towards cosmopolitan norms. Framing global health threats as risks, however, appears to be less politically charged and divisive, combining an aura of scientific objectivity with a moral call to action. In this article we argue that, despite its technical use in public health, in the policy discourse on global health the risk frame is not immune to values and interests but inherently political. It privileges a specific approach to global health policy which focuses on potential future catastrophes rather than presently existing health problems, emphasizes technological solutions rather than addressing the socio-economic determinants of health, while there is no single risk frame, but rather multiple risk frames existing simultaneously, as seen during the 2014–15 west African Ebola outbreak. However, framing health in terms of risk is useful in understanding how health issues reflect and contribute to the wider Zeitgeist concerning societal vulnerability: that dangers exist which are uncontrollable and are the product of technical progress. The risk frame allows us to place health issues into this wider context, where disease is just one of a number of concurrent dangers, rather than a separately identifiable hazard.


Factor models have been successfully employed in summarizing large datasets with few underlying latent factors and in building time series forecasting models for economic variables. When the objective is to forecast a target variable y with a large set of predictors x, the construction of the summary of the xs should be driven by how informative on y it is. Most existing methods first reduce the predictors and then forecast y in independent phases of the modeling process. In this paper we present an alternative and potentially more attractive alternative: summarizing x as it relates to y, so that all the information in the conditional distribution of y|x is preserved. These y-targeted reductions of the predictors are obtained using Suffi cient Dimension Reduction techniques. We show in simulations and real data analysis that forecasting models based on suffi cient reductions have the potential of significantly improved performance. JEL Classification Number: C32, C53, C55, E17


Recruitment and retention of specialists to academia appears to be a growing problem in university teaching hospitals. Members of the American College of Veterinary Surgeons (ACVS) believe that the movement of surgery specialists to practice may have an impact on the training of veterinary students and surgery residents. To address these concerns, 1,071 ACVS diplomates and 60 department heads and hospital directors from all veterinary schools in North America were surveyed to determine whether a problem exists, the extent of the problem, and potential reasons for migration of specialists to practice. Responses were obtained from 620 ACVS diplomates (58 per cent) and 38 department heads and hospital directors (63%) from 28 different universities. The responses confirmed a net movement of surgery specialists from academia to practice. Eighty seven percent of department heads and hospital directors believed there was a shortage of small animal surgery specialists in academia; this information was supported by the fact that 47% responded that they had open positions and 68% had difficulty filling positions in the last five years. The demand was slightly less for large animal surgery specialists, and 42 per cent of respondents indicated that they had open positions. Financial considerations were the most common reason for surgery specialists to move from academia to private practice. Seventy-six percent of responding ACVS diplomates in private practice had a total compensation package valued at greater than $125,000 per year, whereas 77.8% of diplomates in academia had total compensation valued at $125,000 or less. Most universities offer starting salaries (not including benefits) for recently certified surgery specialists ranging from $70,000 to $90,000. Reasons for moving from academia to practice besides financial considerations included undesirable location of university hospitals; lack of interest in research; and a belief that university administration was not supportive of surgery specialists. Many academic surgery specialists were frustrated by the requirement for productivity in research, teaching, and service for promotion in tenure-track positions.


Low intensity maintenance therapy with 6-mercaptopurine (6-MP) limits the occurrence of acute lymphoblastic leukemia (ALL) relapse and is central to the success of multi-agent chemotherapy protocols. Activating mutations in the cytosolic 5' nucleotidase II (NT5C2) gene drive resistance to 6-MP in over 35% of early relapse ALL cases. Here we identify CRCD2 as a first-in-class small molecule NT5C2 nucleotidase inhibitor broadly active against leukemias bearing highly prevalent relapse-associated mutant forms of NT5C2 in vitro and in vivo. Importantly, CRCD2 treatment also enhanced the cytotoxic activity of 6-MP in NT5C2 wild type leukemias leading to the identification of NT5C2 S502 phosphorylation as a novel NT5C2-mediated mechanism of 6-MP resistance in this disease. These results uncover an unanticipated role of non-genetic NT5C2 activation as a driver of 6-MP resistance in ALL and demonstrate the potential of NT5C2 inhibitor therapy for enhancing the efficacy of thiopurine maintenance therapy and overcoming resistance at relapse.


Estuaries are places where rivers meet the sea. Estuaries have different characteristics dependent on their location. An important factor is the shape of the estuary. Natural estuaries have a funnel or trumpet shape, which means the estuary, has a large width near the seaward boundary and is converging stream upward. Other estuaries are man-made and have a straight channel from the sea landward; these estuaries are called prismatic estuaries. The Rotterdam Waterway is an example of such a prismatic estuary.
Estuaries are often used as access channel for harbors. Due to economic development and technology development ships size increases, which makes the harbors less accessible. To reduce this problem harbors are deepened to keep them accessible. The effects of the deepening on estuary processes are another key question which is unknown for prismatic estuaries.
The sediment transport processes result in an Estuary Turbidity Maximum (ETM). The ETM is a suspended sediment front near the mixing of the saline and fresh water. The sediment is trapped at this location due to the estuarine circulation. The magnitude of the ETM is determined by several other processes determined by the boundary conditions of the study area. These processes include tidal asymmetry, internal asymmetry, tidal phase lag, turbulence damping and flocculation. The change of the ETM due to these processes in prismatic estuaries is relatively unknown.
The Rotterdam Waterway is used as case study to evaluate the sediment transport characteristics of prismatic estuaries, using the process based numerical model Delft3D. A schematized study area is created which only consists of a straight channel including the fresh water boundary and a schematized sea of 40 kilometers along the coast and 20 kilometer perpendicular to the coast. The model is setup and validated based on available sources.
A sensitivity analysis is done to evaluate the contribution of the different processes towards the hydrodynamics and the sediment transport characteristics. The wave conditions and discharge are changed in the sensitivity analysis. The fresh water discharge is changed towards the 5%, 25%, 75% and 95% discharge of the Rotterdam Waterway. The waves are changed towards the significant wave height during summer, during winter and during storm conditions at the North Sea.
The change in discharge is an important driver for the salinity, hydrodynamics and the suspended sediment concentration. The internal asymmetry does not play a role with the changing fresh water discharge. The increase in tidal asymmetry with increasing discharge increases the available sediment in the water column. A combination of the increased estuarine circulation and the turbulence damping increases the sediment concentration in the lower layers of the water column. The sediment concentration in the top layer increases with decreasing discharge because the turbulence isn't damped anymore.
The waves have only small influence on the hydrodynamics and small influence on the suspended sediment concentration for the Rotterdam Waterway in the short term. If the waves occur for a longer period, the impact ETM increases resulting in the increase of suspended sediment concentration in the ETM.
A scenario study is executed to evaluate the effect of the harbor basins and to determine the effect of deepening. The harbor basins are important for the suspended sediment concentration, in particular for the available sediment in the bottom layer. The sediment settles less in the Rotterdam Waterway, but it settles in the harbor basin instead where the velocities are lower and the turbulence is low.
The effect of deepening is evaluated for two types of deepening. The first deepening is the deepening of the first step in the Rotterdam Waterway and the second deepening is near the location where the ETM moves to and fro in the estuary. The difference between the original depth and the deepened scenario is small for the deepening of the step. The salinity intrusion increased with 3 kilometers with increasing tidal prism. The step deepening results in decreased influence of the discharge on the location of the null point and leads towards a small increase in the suspended sediment concentration under average discharge and yearly average significant wave height due to increased ebb and flood velocities. The long term effect for the 5% discharge decreases, while the effect of the 95% discharge increases.
The impact is small if the deepening is in the area where the ETM occurs. The salt intrusion length is increasing but for the same tidal prism. The salinity intrusion increased with 3 kilometers, and the near bed velocities increase in the first part of the estuary. The influence of the discharge on the salinity null point has also decreased for the ETM deepening, but the difference is smaller compared with the step deepening. The increasing velocities near the bed lead to increased suspended sediment concentration in the ETM. The long term change shows also decreasing effect for the 5% discharge and increasing effect for the 95% discharge.


OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-β) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats weighing 200–250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 µg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing. RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02). CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.


The purpose of this research is to analyse the art museums in Moscow and their usage of social media platforms in order to engage the audiences and attract public. The study is focused on the changes in museums' life and their functions that happened as the result of shift from an 'old' to a 'new museology'. The proponents of new museology emphasize that museums are affected by the growing importance of their visitors and need to shift toward many-to-many communication. The main aim is to compare traditional museums with the history of more than a century with the new upcoming ones. The notion of Bildung and cultural institutions historically rooted devotion to the cultivation of the society is used as an important point of this comparison. Based on Bourdieu's social theory and the idea of struggle for organizational legitimacy it was assumed that the recently established cultural institutions that were introduced in the visitor-centered society would differ from the incumbents and may influence the changes in communication with the visitors. However, there are certain conventional procedures of the field that need to be followed in order to gain respect form the colleagues and audience. Therefore, the paper needs to see whether the difference between the new and traditional institutions is still significant. The analysis is based on the 4 interviews with museum representatives, who work on the development of social media marketing, as well as on 395 media posts, collected from Facebook and Instagram. The sequential multimethod design helps to cover the problem from different perspectives and acquire deeper knowledge of museum practices related to social media: analyse both the goals and actual content. The PR managers' perception of the social media goals revealed that the difference certainly exists, but both traditional and upcoming museums are influenced by the era of edutainment and need to work for wider more diverse audiences, than they were used in the past – the 'elitist' connotation of art museums is blurring. Besides, emerging museums have more freedom to experiment, be creative and innovative while established have strict reputation and more expectations toward their activities. The research also revealed that channel choice plays important role, because each platform has its specific audiences and same museum needs to elaborate different tactics and content for each media platform. Furthermore, museums, especially traditional ones, still do not use the full potential presented by social media and maintain quite formal communication.


In tropical regions of the Western Hemisphere, consumption of high-protein soybean [ Glycine max (L.) Merr.] could improve the human diet. It would be necessary however, to develop adapted cultivars of appropriate seed size. The objectives of this study were to estimate heritabitity and phenotypic and genotypic correlations of agronomic traits, and to compare agronomic and reproductive traits of soybeans grown at different planting dates in Puerto Rico. Eighty-nine F 4:5   individual plants from the cross of IAC-8 [Maturity Group (MG) IX, not adapted for human consumption, and intermediate seed size] x Kanto-101 (MG IX, large-seeded cultivar developed for human consumption), the parents, and checks were planted in December 1992.  F 4:5  lines were evaluated in replicated tests in June and August 1993. Dates of full bloom (R2), of full seed (R6), and of full maturity (R8), plant height, pod width, and 100-seed weight were recorded. On an entry-mean basis, neritability values of all traits were moderately high (0.56) to high (0.96). Phenotypic and genotypic correlations ranged from zero to high (0.96). Rank correlations were moderately high, positive and significant, ranging from 0.41 to 0.79. In general for all traits, genotypes selected in the top 10% in the plantings of June and August, on the basis of entry means, would also have been selected as individual plants in the December planting. These results suggest that in the tropics genotypes may be selected in different planting seasons within the year, initially on the basis of individual plant performance, and later in replicated experiments.


Chlorophyll a (Chl a) and phaeopigments a (Phaeo a) spatial distribution in the Western Black Sea was studied in relation to environmental factors and mesozooplankton community. For that purpose, CTD parameters, nutrients, chlorophyll pigments, and mesozooplankton total density and biomass were measured at 33 stations, distributed along the Romanian shelf waters, in June 2016. The studied area was divided into 4 subareas (NIS – northern inner shelf, NOS – northern outer shelf, SIS – southern inner shelf, and SOS – southern outer shelf). The hydrological regime, characterized by large Danube's flow and a coastal upwelling phenomenon observed both in the NIS and SIS, strongly influenced the spatial variability of Chl a and Phaeo a. Surface Chl a and Phaeo a showed the highest concentrations within NIS, followed by NOS, both subareas subjected to larger freshwater input from the Danube River. The vertical distribution of Chl a in the inner shelf waters generally showed a subsurface maximum layer within 6–24 m (the shallower and stronger ones within NIS). The outer shelf waters displayed two subsurface maxima; an upper one (within 7–20 m) and a deeper one, slightly higher than the upper one, observed both in NOS and SOS at 30–45 m depth. Phaeo a showed relatively similar vertical profiles to Chl a, with a subsurface maximum generally coinciding with subsurface chlorophyll maximum. The meroplankton showed positive correlations with the chlorophyll pigments, which suggest a strong link between pigments abundances and distribution and development and production of larvae in the coastal waters.


This study aimed to present a model for portfolio risk premium assessment of companies listed in Tehran Stock Exchange. In order to achieve this purpose, monthly data of 150 companies listed in Tehran Stock Exchange during 2007-2017 was used. In this study, the predictive powers of FamaFrench three-factor model [11], Carhart four-factor model [1], Fama - French five-factor model [24], Brousseau five-factor model [18] and Roy and Shijin six-factor model [44] have been evaluated using variables used in the mentioned models and then an optimal model has been developed for portfolio risk assessment using stepwise regression. Findings showed that the Carhart four-factor model has higher predictive ability (48.3%) than other mentioned models in the Tehran Stock Exchange. According to the results of stepwise regression, seven variables have been selected as effective variables on portfolio risk premium. The explanatory power and predictive ability of the model developed in the Tehran Stock Exchange was 55.7% indicating higher predictive ability respect to previous models on portfolio risk premium. Investigation of the coefficients of the developed model showed that market risk premium, size factor, value factor, momentum factor and accounting quality factor have positive and significant effects on portfolio risk premium while investment factor and liquidity risk factor have significant negative impacts on portfolio risk premium.


The major circulating hormone dihydrotestosterone (DHT) is responsible for the development and progression of benign prostate hyperplasia (BPH). Dihydrotestosterone (DHT) is by produced by NADPH dependent reduction of testosterone (T) under the catalytic effect of the enzyme 5α-reductase (5 alpha R). Inhibition of 5α-reductase enzyme is the novel approach for treatment of BPH. Present work describes relationship between the 5α-reductase inhibitory activity for structurally related amides and esters of 17a-Aza-D-Homo-17-one derivatives and their physicochemical descriptors in quantitative terms. The statistically validated two-dimensional quantitative structure activity relationship (2D QSAR) model has been obtained through partial least squares (PLS) analysis method using Vlife molecular design suits (MDS). Statistical data of model 3 (r 2 = 0.8860, q 2 =0.7096; F = 44.023, pred r 2 = 0.6884) correlated with human 5α-reductase inhibitory activity. Validation was done with LOO method. Model has included and highlighted the positive and negative correlation of four descriptors with the biological activity. This validated 2D QSAR model may be used to design 5α-reductase derivatives with better inhibitory properties. Keywords: Dihydrotestosterone, benign prostatic hyperplasia, 5α-reductase inhibitors, 2D-QSAR, regression analysis; 17a-aza-steroids Cite this Article Richa Dhingra, Manav Malhotra, T.R. Bhardwaj, Neelima Dhingra. 2D QSAR Studies on Some Novel 17a-aza-D-Homo Steroids as 5α-Reductase Inhibitors. Research & Reviews: A Journal of Drug Design & Discovery. 2016; 3(2): 1–14p


In the Netherlands, an increasing number of patients are dependent on domiciliary ventilation. General practitioners and elderly care physicians caring for these patients are increasingly confronted with problems related to chronic ventilation. Most patients die due to progression of respiratory failure, however, patients may ask their physician to electively withdraw their assisted ventilation. According to the Dutch Medical Treatment Contracts Act, withdrawal of domiciliary ventilation at the request of a patient constitutes normal medical care and concerns neither the assessment of, nor the compliance with, a request for euthanasia. Currently, there is no Dutch guidance or guideline containing practical advice regarding the medical, ethical, organisational and supportive aspects of withdrawal of domiciliary ventilation. This paper addresses the planning necessary for the patient and between treating professionals, for the organisation and implementation of withdrawal of domiciliary ventilation at the patient's home, a nursing home or hospice.


Leiomyomata uteri (i.e., uterine fibroids) are benign tumors arising from the abnormal growth of uterine smooth muscle cells (SMCs). We show here that the expression of platelet-derived growth factor C (PDGFC) is higher in approximately 80% of uterine fibroids than in adjacent myometrial tissues examined. Increased expression of PDGFC is also observed in fibroidderived SMCs (fSMCs) relative to myometrial-derived SMCs (mSMCs). Recombinant bioactive PDGFCC homodimer stimulates the growth of fSMCs and mSMCs in ex vivo cultures and prolongs the survival of fSMCs in Matrigel plugs implemented subcutaneously in immunocompromised mice. The knockdown of PDGF receptor-alpha (PDGFRA) through lentiviral-mediated RNA interference reduces the growth of fSMCs and mSMCs in ex vivo cultures and in Matrigel implants. Furthermore, two small molecule inhibitors of the PDGFR tyrosine kinase (i.e., imatinib and dasatinib) exerted negative effects on fSMC and mSMC growth in ex vivo cultures, albeit at concentrations that cannot be achieved in vivo. These results suggest that the PDGFCC/ PDGFRA signaling module plays an important role in fSMC and mSMC growth, and that the upregulation of PDGFC expression may contribute to the clonal expansion of fSMCs in the development of uterine fibroids. dasatinib, imatinib, lentivirus, PDGF receptor, shRNAmir


Introduction Intravenous corticosteroids have been established as the mainstay treatment of acute severe colitis since 1974.1 BSG and ECCO guidelines advise either IV hydrocortisone 100 mg qds or IV methylprednisolone 30 mg bd in this setting.2,3 The potent mineralocorticoid effect of hydrocortisone however is well known.4 This could predispose to hypokalaemia in this susceptible patient cohort. For this reason, we have recently changed our practice at Glasgow Royal Infirmary (GRI) to treat these patients with methylprednisolone. Methods We performed a retrospective review of electronically held records of patients who presented to GRI with acute severe colitis treated with IV hydrocortisone or methylprednisolone. We collected data on the duration of treatment, potassium level on presentation, nadir potassium level, fall in potassium level and potassium replacement per patient. Results 20 patients were treated with IV hydrocortisone for a median of 6 days, and 16 patients were treated with IV methylprednisolone for a median of 5.5 days (ns). Median serum potassium concentration on admission was 3.8 mol/l (IQR 3.4–4.1 mmol/l) in the cohort receiving hydrocortisone which was not significantly different from 4.1 mmol/l (IQR 3.7–4.1 mol/l) in the cohort receiving methylprednisolone. Following IV steroids, median nadir potassium concentration in the group receiving methylprednisolone was 3.75 mmol/l (IQR 3.5–4.1 mmol/l), not significantly different to pre-treatment values. In those receiving hydrocortisone however, potassium concentration fell by a median of 0.85 mol/l (IQR 0.2–1.1 mol/l) to a nadir of 3.1 mol/l (IQR 2.8–3.3 mol/l), significantly lower than the group receiving methylprednisolone (p < 0.0001). Only 3/16 (19%) patients receiving methylprednisolone needed potassium supplementation (2 oral and one IV). In contrast only 2/20 patients receiving hydrocortisone did not require potassium supplementation, with 10/20 (50%) requiring a median of 80 mmoles of IV potassium chloride (IQR 55–196 mmoles) and 8/20 (40%) requiring oral supplementation. 2 patients receiving hydrocortisone experienced severe hypokalaemia with ECG changes requiring management in the coronary care unit. Conclusion Hypokalaemia is a common occurrence in patients with acute severe colitis treated with IV hydrocortisone but is rare when methylprednisolone is used. Given that both drugs are considered to be equally effective, methylprednisolone appears to be a safer choice of corticosteroid. References 1 Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974;1:1067–1070. 2 BSG Guidelines for management IBD 2011. 3 ECCO consensus guidelines for UC 2012. 4 Ramsahoye BH, Davies SV, et al. The mineralocorticoid effects of high dose hydrocortisone. BMJ 1995;310:656. Disclosure of Interest None Declared