Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA

Antibody drug conjugates (ADCs) are anti-cancer agents that more selectively deliver potent cytotoxins to tumors via targeted antigens. ADCs are modular biotherapeutics composed of antibody (Ab), linker (L), and payload (P). The LP may be conjugated to different antibody locations, including endogenous cysteine or lysine residues; recent advances in conjugation technology also have enabled site-specific conjugation to engineered cysteine, glutamine, or other sites. Pfizer has utilized a platform approach to identify novel LPs and ADCs, hence large numbers of linkers and payloads have been synthesized and conjugated to many different antibodies at conventional and site-specific locations. This has generated thousands of permutations of antibody, conjugation site, linker, and payload. Moreover, there are large volumes of metadata and analytical data associated with each ADC component as well as with the final conjugated product. Hence, there is an avalanche of data that must be tracked and accessed in order to ensure efficient decision making and communication as ADCs advance through our biological testing funnel. To handle this information challenge, we designed and implemented a new ADC tracking system. First, we created a systematic nomenclature to enable automated assignment of ADC names. ADC names are concatenated in the format "Ab-(site)\_L\_P". In addition, specific antibody properties are defined within the Ab portion of the name, such as antigen, clone ID, mutation, isotype, etc. Second, we built a Java web-start enabled desktop application known as Antibody Conjugate Tracker (ACT). ACT integrates ADC bioanalytical and structural information into a user-friendly interface. The application recapitulates our synthesis and testing workflow: antibody inventory, LP inventory, project team synthesis requests, ADC registration, and sample physical inventory. ACT enables system-generated ADC name assignment by defined rules as well as registration of every ADC with corporate identifiers to allow biological data reporting. The systematic naming allows for facile uniqueness checking, thus eliminating possible redundancies and minimizing confusion about ADCs that use similar components. Third, we integrated ACT with the corporate registration system and the biological results database, allowing seamless access of in vitro and in vivo screening data for each ADC. By tracking both platform and program ADCs via ACT, we now have a rich database of constructs and biological results that can be used to interrogate structure-activity relationships (SAR) of new linker-payloads. Overall, benefits of the ACT system include more efficient conjugation workflows, inventory tracking, enhanced communication among scientists from synthesis to testing, and streamlined SAR analysis of novel linker-payloads. These efficiencies have ensured accurate tracking and delivery of innovative ADCs into our clinical development pipeline.

Citation Format: Frank Loganzo, Ellie Muszynska, Nathan Tumey, Megan Tran, Tianhong Zhang. The first ACT: an efficient data tracking and sharing tool for ADC and linker-payload development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5279.


This study extends the classic constructive dialogue/debate between self-concept and self-efficacy researchers (Marsh, Roche, Pajares, & Miller, 1997) regarding the distinctions between these 2 constructs. The study is a substantive-methodological synergy, bringing together new substantive, theoretical, and statistical models and developing new tests of the classic jingle-jangle fallacy. We demonstrate that in a representative sample of 3,350 students from math classes in 43 German schools, generalized math self-efficacy and math outcome expectancies were indistinguishable from math self-concept, but were distinct from test-related and functional measures of self-efficacy. This is consistent with the jingle-jangle fallacies that are proposed. On the basis of pretest variables, we demonstrate negative frame-of-reference effects in social (big-fish-little-pond effect) and dimensional (internal/external frame-of-reference effect) comparisons for three self-concept-like constructs in each of the first 4 years of secondary school. In contrast, none of the frame-of-reference effects were significantly negative for either of the two self-efficacy-like constructs in any of the 4 years of testing. After controlling for pretest variables, each of the 3 self-concept-like constructs (math self-concept, outcome expectancy, and generalized math self-efficacy) in each of the 4 years of secondary school was more strongly related to posttest outcomes (school grades, test scores, future aspirations) than were the corresponding 2 self-efficacy-like factors. Extending discussion by Marsh et al. (1997), we clarify distinctions between self-efficacy and self-concept; the role of evaluation, worthiness, and outcome expectancy in self-efficacy measures; and complications in generalized and global measures of self-efficacy.


This paper proposes a novel approach aiming to counteract short term voltage fluctuations and transient instability by employing centralized emergency demand response. The objectives in this optimization model include a proposed short-term voltage stability index, inversed transient stability margin and system operation cost. Combined demand response actions of load shedding and load recovery are applied during the corrective period. To reduce computational complexity, load shedding bus candidates are selected based on trajectory sensitivity ranking with respect to the load shedding quantities. Then the optimization model is solved via multiobjective evolutionary algorithms (MOEAs). Compared with existing practices, this work not only coordinates between preventive control (PC) and corrective control (CC) actions, but also considers a proposed user disruption indicator to reflect power supply deviation from nominal demand during load shedding and load recovery periods. A comprehensive three-dimensional Pareto-optimal tradeoff solution is computed for decision-making. The proposed method is verified by simulation results on the IEEE 39-bus system.


Older adults are at a higher risk of developing serious illness and mortality from COVID-19. Among a multitude
of factors, cellular senescence associated with ageing, obesity, cardiovascular diseases, and diabetes seems to be statistically
correlated with severe SARS-CoV-2 infections and mortality. Surface proteins such as vimentin and CD26 that are
differentially expressed on senescent cells seem important for SARS-CoV-2 attachment and internalization. Potential
therapeutic agents against this novel virus also exhibit senolytic and anti-inflammatory actions, implicating that their
beneficial effects could, in part, be attributed to their senescent cell removal and the associated inflammatory phenotype
neutralizing properties. Elucidating the underlying molecular mechanism involved in cellular senescence and severity of
SARS-CoV-2 virus might help direct towards development of effective therapeutics for elderly patients of COVID-19.


Many occupational practitioners have to face emergencies in occupational setting, from life-threatening emergencies to current urgent care. Actually, workplace emergencies have singularities that usual emergency teams are not aware of – like use of hazardous substances, dangerous working conditions. Furthermore, responders and emergency professionals have to face to major hazards requiring prevention. In the context of a new scientific committee created in ICOH in 2015 about Emergency Preparedness and Response in Occupational Health (EPROH), we aimed to take different examples to illustrate the importance for workers and population health and well-being, including emergency responders. Perspectives and challenges for next decades will be discussed.


Objective: COVID-19 has been introduced by the World Health Organization as a health emergency worldwide. Although more than 5% of the patients with COVID-19 require hospitalization, there are still no clear guidelines on patients' discharge time and factors influencing post-discharge outcomes. This study aimed to determine risk factors for readmission in the patients with COVID-19 admitted to hospital. In this prospective study, 416 discharged patients with a minimum follow-up of one month and the need for readmission were recorded. Evaluated characteristics included age, gender, CT scan, RT-PCR test and treatment modalities. After describing the data, any relationship between the patients' characteristics and readmission was assessed and predictive factors of readmission risk were estimated using regression model. The data were analyzed through STATA and P value less than of 0.05 was considered significant.Results: Regarding readmission, 51 patients were readmitted during the study period. The median follow-up time was 20 days (IQR: 7-120) and the mean follow-up time was 61±11.2 days. The mean duration of first hospitalization was 5.5 days and the rate of readmission of the patients between 30 and 60 days after discharge was 7.6% and 8.1%, respectively. The median age of these patients was 67 years (IQR: 53-78). About 65% of readmitted patients had underlying disease. The difference in readmission time was based on blood creatinine level and lung involvement. The odds ratio of readmission in the patients with abnormal creatinine levels (higher and equal to 1.2 mg/dl) and diabetes was equal to 2.15 and 3.43, respectively. Also, the odds ratio of readmission in the patients with basal lung involvement was 4.16. The highest readmission rate was 30 days after discharge. Age over 60 years, underlying disease especially diabetes, high creatinine level and lung involvement were the most important predictors of readmission in the patients with COVID-19.


Objective: The existing literature of 18 F-FDG PET/CT in Ewing sarcoma investigates mixed populations of patients with both soft tissue and bone primary tumors. The aim of our study was to evaluate whether the maximum standardized uptake value (SUVmax) obtained with 18F-FDG PET/CT before and after induction chemotherapy can be used as an indicator of survival in patients with Ewing sarcoma originating exclusively in the skeleton. Materials and Methods: A retrospective database search from 2004-2011 identified 28 patients who underwent 18 F-FDG PET/CT before (SUV1, n= 28) and after (SUV2, n=23) induction chemotherapy. Mean follow up was 3.3 years and median follow up for survivors was 6.3 years (range: 2.6-9.8 years). Multivariate and univariate Cox proportional hazard model was used to assess for correlation of SUV1, SUV2, and the change in SUVmax with overall survival (OS) and progression-free survival (PFS). Results: Mean SUVmax was 10.74 before (SUV1) and after 4.11 (SUV2) induction chemotherapy. High SUV1 (HR = 1.05, 95% CI: 1.0-1.1, P = 0.01) and SUV2 (HR =1.2, 95% CI: 1.0-1.4, P = 0.01) were associated with worse OS. A cut off point of 11.6 was identified for SUV1. SUV1 higher than 11.6 had significantly worse OS (HR = 5.71, 95% CI: 1.85 - 17.61, P = 0.003) and PFS (HR = 3.16, 95% CI: 1.13 - 8.79, P = 0.03, P < 0.05 is significant). Conclusion: 18F-FDG PET/CT can be used as a prognostic indicator for survival in primary Ewing sarcoma of bone.


The authors presented an innovative technology for the fabrication of a biocompatible parylene-based high lead count retinal prosthesis in which a prefabricated stand-alone application-specific integrated circuit (ASIC) is placed directly into the fabrication process of the other system components. The package is fabricated in such a way that the ASIC-to-electrode interconnects are patterned using standard photolithography. The density of interconnects is fully scalable to the limits of lithography. This packaging scheme also enables the simultaneous integration and interconnection of discrete components such as chip capacitors with the rest of the system. Electrical test results verify the efficacy of this cost-effective and high-yield packaging scheme, and pave the way for a monolithic implantable parylene-based intraocular system.


The entanglement concentration protocols (ECPs) are presented for distilling the maximally entangled state from a known partially entangled n-photon Bell-class and W state, respectively, only resorting to the linear optical elements and quantum nondemolition detector. Different from the traditional parity check with a single photon as an ancilla, we use linear optical elements for changing the photon paths to realize the concentration. The total success probability of the concentration for n-photon entangled states is calculated. The present protocols only require a partially entangled state and do not need any single auxiliary particle. By iterating the ECP repeatedly, the maximal success probability can be increased. Meanwhile, the present protocols are more suitable for the photon system due to the simple operations.


In this paper, a motion-based approach for detecting high-level semantic events in video sequences is presented. Its main characteristic is its generic nature, i.e. it can be directly applied to any possible domain of concern without the need for domain-specific algorithmic modifications or adaptations. For realizing event detection, the examined video sequence is initially segmented into shots and for every resulting shot appropriate motion features are extracted. Then, Hidden Markov Models (HMMs) are employed for performing the association of each shot with one of the high-level semantic events that are of interest in any given domain. Regarding the motion feature extraction procedure, a new representation for providing local-level motion information to HMMs is presented, while motion characteristics from previous frames are also exploited. Experimental results as well as comparative evaluation from the application of the proposed approach in the domain of news broadcast video are presented.


This article analyses the toy house as an object away from its usual context, using a socio-anthropological approach. In an earlier publication (2003), Brougère analysed the social dimension of the toy where it was viewed as part of a socially built system of networks involving many actors (manufacturers, parents, children and others) and many processes (manufacturing, distributing, advertising, buying, giving presents, using, playing, destroying). However, this interdependent system must be considered first through the objects that form the nodes of this network as only by examining its material culture can we can better understand the way it functions.


Recent research has identified the need for the development of a comprehensive in-vehicle information system for independent self-drive travellers (iVisit) in regional and remote Australia. The purpose of iVisit is to facilitate location based two way communication between travellers and relevant information providers (destination management organisations, emergency services, local government, or tourism businesses) in remote destinations. This paper looks at the feasibility of such a location based information system in remote areas and reports on the results of a workshop conducted with stakeholders of a particular remote destination in South Australia - the Oodnadatta Track. A detailed user needs analysis was conducted with workshop participants to develop a set of user needs specifications for iVisit. The paper argues that existing technical barriers to improved location based communication in remote Australia are likely to be short-term only. With rapidly changing communication technologies, the development of new and innovative information systems should be primarily concerned with organising and managing the required information architecture rather than focusing too much on specifying technological aspects.


The similarity of quasar line spectra has been taken as an indication that the emission line clouds have preferred parameters, suggesting that the environment is subject to a fine-tuning process. We show here that the observed spectrum is a natural consequence of powerful selection effects. We computed a large grid of photoionization models covering the widest possible range of cloud gas density and distance from the central continuum source. For each line only a narrow range of density and distance from the continuum source results in maximum reprocessing efficiency, corresponding to "locally optimally emitting clouds" (LOCs). These parameters depend on the ionization and excitation potentials of the line and its thermalization density. The mean QSO line spectrum can be reproduced by simply adding together the full family of clouds, with an appropriate covering fraction distribution. The observed quasar spectrum is a natural consequence of the ability of various clouds to reprocess the underlying continuum, and can arise in a chaotic environment with no preferred pressure, gas density, or ionization parameter.


The analysis of the data published in the special literature indicates that forensic-medical aspects of the injuries inflicted by blank shots fired from a variety of small-arms weapons remain poorly known or virtually unexplored. Despite considerable variability of such injuries, their forensic-medical examination should include three basic components, viz. the proof of the absence of the injurious action of the shot, differential diagnostics of the consequences of injuries attributable to each traumatic factor of the shot, and experimental simulation of the damages to the human body and the clothes taking into account concrete models of the weapons and the blank cartridge.


The magnetically tuned insulator‐metal transition in magnetic semiconductors is one of the most striking demonstrations of the interaction between localized magnetic moments and carriers.1 On the metallic side of the transition, it is believed that magnetotransport arises from electron‐electron interactions in the presence of a giant Zeeman splitting of the conduction band. However, magnetotransport in the insulating phase is not well understood. The discovery of persistent photoconductivity in Cd1−xMnxTe:In2 has made it possible to control carrier concentration by illumination. This enables us to make transport measurements over a wide range of carrier concentrations in one single sample, ultimately leading to the phototuning of the Mott–Anderson transition in this magnetic semiconductor. In the present work, we report an investigation of magnetotransport and permittivity as a function of carrier concentration in Cd0.92Mn0.08Te:In(2×1018 cm−3). In the insulating phase, the resistivity shows an exp[(T0/T)...


Mevalonate pyrophosphate decarboxylase (MPD) in mouse liver was purified by affinity chromatography. The purified enzyme was a homodimer of 46-kDa subunits and had an isoelectric point of 5.0. Kinetic analysis revealed an apparent Km value of 10 microm for mevalonate pyrophosphate. The enzyme required ATP as a phosphate acceptor and Mg as a divalent cation, which could be substituted with Mn or Co. Its optimum pH was 4.0-7.0. A comparison with MPD from various other sources revealed the mouse MPD to have essentially the same properties as rat MPD, expect for the optimum pH range. An excess of rabbit anti-rat MPD antibody deleted approximately 80% of the MPD activity in the crude extract of mouse liver. These results suggested that the homodimer of 46-kDa subunits represents the major active form of MPD in mice.


A novel opto-chemical sensor instrumentation based on fiber optical micro-sensors for the simultaneous detection of pO2 and pCO2 in tissues is presented. The adopted sensing principle for both parameters is the measurement of luminescence lifetime via phase modulation fluorometry. Respect to currently used blood-gas analysers that require blood sampling and are associated with blood loss, this instrumentation allows on-line continuous measurements. Compared to electrochemical micro sensors, it is advantageous because of intrinsic higher sensitivity, no analyte consumption and less electromagnetic interferences. The results of the laboratory characterization and of tests in in vivo experiments of the proposed instrumentation are reported.


Protothecosis is a rare infection by algae without chloroplasts. We report a case of an immunocompetent patient who had visited countries of south-east Asia. The lesion was present on the elbow, and consisted of a granuloma studded with cells and sporangiae of Prototheca. A computerized image analysis revealed large variations in the size and shape of the organisms. The lesion was successfully treated with itraconazole.


Graphene films are used to detect the presence and transition of spin crossover nanoparticle aggregates. Experiments performed far from the graphene neutrality point, combining impedance spectroscopy and Hall measurements, provide better insight into the mechanism for the change of impedance of the graphene layer in proximity with different states of the molecular structure. We observe that the change of spin state shifts the graphene Fermi level and its intrinsic resistance, with resulting positive insight into using this type of hybrid device for fast molecular electronics purposes.


Viruses possessing a non-segmented genome require a specific recognition of their nucleic acid to ensure its protection in a capsid. A similar feature exists for viruses having a segmented genome, usually consisting of viral genomic segments joined together into one viral entity. While this appears as a rule for animal viruses, the majority of segmented plant viruses package their genomic segments individually. To ensure a productive infection, all viral particles and thereby all segments have to be present in the same cell. Progression of the virus within the plant requires as well a concerted genome preservation to avoid loss of function. In this review, we will discuss the "life aspects" of chosen phytoviruses and argue for the existence of RNA-RNA interactions that drive the preservation of viral genome integrity while the virus progresses in the plant.


Ms Arlington has taken the trouble to research the literature and pose pertinent questions regarding our report on the treatment of mild to moderate hypertension with low-dose captopril. She has, however, confused several very separate questions. The question posed by the Veterans Administration Cooperative Study Group on Antihypertensive Agents was whether low-dose captopril was capable of reducing blood pressure in a cohort of patients with mild to moderate hypertension and whether it might have fewer associated adverse effects than the previously used high doses. Our study clearly answers these questions affirmatively. The second issue pertains to the level of systolic or diastolic blood pressures above which patients ought to be subjected to drug therapy. By selectively referring to some therapeutic trials and not to others, Ms Arlington concludes that treatment of patients with diastolic blood pressures between 92 and 109 mm Hg was entirely unjustified. However, she has left out


With the increasing demands for new data and real-time services, wireless networks should support calls with different traffic characteristics and different Quality of Service (QoS)guarantees. In addition, various wireless technologies and networks exist currently that can satisfy different needs and requirements of mobile users. Since these different wireless networks act as complementary to each other in terms of their capabilities and suitability for different applications, integration of these networks will enable the mobile users to be always connected to the best available access network depending on their requirements. This integration of heterogeneous networks will, however, lead to heterogeneities in access technologies and network protocols. To meet the requirements of mobile users under this heterogeneous environment, a common infrastructure to interconnect multiple access networks will be needed. In this chapter, the design issues of a number of mobility management schemes have been presented. Each of these schemes utilizes IP-based technologies to enable efficient roaming in heterogeneous network. Efficient handoff mechanisms are essential for ensuring seamless connectivity and uninterrupted service delivery. A number of handoff schemes in a heterogeneous networking environment are also presented in this chapter.


The visibility is a crucial quality parameter in grating-based X-ray phase-contrast imaging as it directly influences the noise of the obtained phase signal. In order to evaluate its behaviour with respect to energy, we used the photon counting semiconductor detector Timepix to obtain a series of measurements at different energy thresholds. These energy-dependent measurements of the visibility response of a Talbot-Lau Interferometer for X-ray phase-contrast imaging are presented in this paper. Furthermore, we report on the results of our effort to model this behaviour in our simulation, where a very good agreement between measurement and simulation could be achieved for two available setups. With this tested workflow we are now able to predict the expected visibility response of a specific setup. This capability is an important prerequisite for the optimisation of an X-ray Talbot-Lau Interferometer. It is predicted that the visibility of our current laboratory setup could be doubled by choosing an appropriate X-ray spectrum or filter material.


In this paper we report the observation of a proposed Bose–Einstein condensation (BEC) of magnons in a temperature range of around 15–20 K in nanostructured films of Gd with grain sizes that are much larger than the size range where superparamagentism is expected. The observation was carried out using magnetic as well as high precision resistivity and magnetoresistance (MR) measurements performed to low temperatures. We observe that the experimental observations depend crucially on one parameter, namely softening of the spin wave stiffness parameter D at BEC and the resistivity as well as MR can be related quantitatively to magnetic measurements through the temperature variation of the constant D in the vicinity of the transition. This paper establishes that the BEC reported before in nanocrystalline Gd can be extended to a somewhat larger size range.


In the last few years, there has been a great interest in extending the information-theoretic scenario for the non-asymptotic or one-shot case, i.e., where the channel is used only once. We provide the one-shot rate region for the distributed source-coding (Slepian-Wolf) and the multiple-access channel. Our results are based on defining a novel one-shot typical set based on smooth entropies that yields the one-shot achievable rate regions while leveraging the results from the asymptotic analysis. Our results are asymptotically optimal, i.e., for the distributed source coding they yield the same rate region as the Slepian-Wolf in the limit of unlimited independent and identically distributed (i.i.d.) copies. Similarly for the multiple-access channel the asymptotic analysis of our approach yields the rate region which is equal to the rate region of the memoryless multiple-access channel in the limit of large number of channel uses.


This paper presents a sonar specific methodology to detect and classify underwater unexploded ordnance (UXO) in the low resolution sonar data captured by the DIDSON US300. This technique, known as the Multiple-Aspect Fixed-Range Template Matching (MAFR-TM) algorithm, is designed to detect and classify a target of high characteristic impedance in an environment that contains similar shaped objects of low characteristic impedance. The MAFR-TM is based on the proven concept of template matching, which is a two-dimensional correlation between a reference image (template) and an image collected during field operations (source image). In the MAFR-TM algorithm, the template matching method is efficiently implemented in the wave number domain using two-dimensional Fast Fourier Transforms (2D-FFT) and wave number leakage is reduced with an optimized separable two-dimensional Kaiser window. Experimental results are provided to demonstrate the performance of the proposed approach.


Binding of sulbenicillin (SBPC) isomers to human serum albumin (HSA) was stereoselective. There were at least two classes of binding sites on HSA for SBPC isomers. At the stereoselective high affinity site, binding was in favor of R-SBPC, the binding constant of R-SBPC being approximately 2.3-fold greater than that of S-SBPC. By using site marker ligands, it was revealed that the stereoselective site was Site I (warfarin binding site). Affinity for the low affinity (nonstereoselective) site was similar for the diastereomers, approximately 7--30-fold lower than for the stereoselective site. R-SBPC and S-SBPC appeared to displace each other competitively at both binding sites. On the other hand, R-SBPC was degraded much faster than S-SBPC in the presence of HSA, with a degradation rate constant approximately 7-fold greater for R-SBPC than for S-SBPC. The degradation of R-SBPC was inhibited in the presence of warfarin and dependent on the concentration of R-SBPC bound to Site I. The results demonstrate that Site I is responsible for the stereoselective degradation.


BACKGROUND
Cell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate ethanol (EtOH) on sonic hedgehog (SHh) signaling in regulating possible stem cell antigen-1 positive (Sca1+ ) progenitor stem cell involvement during pathologic arterial remodeling.

METHODS
Partial ligation or sham operation of the left carotid artery was performed in transgenic Sca1-enhanced green fluorescent protein (eGFP) mice gavaged with or without "daily moderate" EtOH.

RESULTS
The EtOH group had reduced adventitial thickening and less neointimal formation, compared to ligated controls. There was expansion of eGFP-expressing (i.e., Sca1+ ) cells in remodeled vessels postligation (day 14), especially in the neo intima. EtOH treatment reduced the number of Sca1+ cells in ligated vessel cross-sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 and Gli2, and RT-PCR of whole-vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1-eGFP mice with the SHh signaling inhibitor cyclopamine diminished SHh target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh-induced differentiation to vascular smooth muscle cells.

CONCLUSIONS
EtOH reduces SHh-responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.


The detection of copy number variation is important to understand complex diseases such as autism, schizophrenia, cancer, etc. In this paper we propose a method to detect copy number variation from next generation sequencing data. Compared with conventional methods to detect copy number variation like array comparative genomic hybridization (aCGH), the next generation sequencing data provide higher resolution of genomic variations. There are a lot of methods to detect copy number variation from next sequencing data, and most of them are based on statistical hypothesis testing. In this paper, we consider this problem from an optimization point of view. The proposed method is based on optimizing a total variation penalized least square criterion, which involves ℓ-1 norm. Inspired by the analytical study of a statics system, we propose an iterative algorithm to find the optimal solution of this optimization problem. The comparative study with other existing methods on simulated data demonstrates that our method can detect relatively small copy number variants (low copy number and small single copy length) with low false positive rate.


OBJECTIVE
African Americans are at a greater risk of cardiovascular hyperactivity to stress than Caucasians; however the risk factors for this activity are not clearly delineated for African Americans. The purpose of this study was to determine the ability of fasting serum cholesterol concentration and fasting serum glucose (FSG) to predict cardiovascular reactivity to stress in African Americans.

DESIGN, SETTING, PARTICIPANTS
Serum cholesterol concentration and FSG levels were measured in 48 (40 women, 8 men) African American college students aged 18-30 years. Heart rate, cardiac output, stroke volume, mean arterial pressure and systolic and diastolic blood pressure were measured as the participants viewed a racially noxious scene on a digital video disc. Measurements were taken prior to the scene (pre stressor period), during the scene (stressor period), and while the participant recovered from the scene (recovery period).

RESULTS
A multiple regression analysis revealed that total serum cholesterol and LDL significantly predicted diastolic blood pressure during the pre-stressor period. FSG significantly predicted mean arterial pressure during the recovery period, and predicted stroke volume during the pre-stressor period, stressor period, and the recovery period.

CONCLUSIONS
FSG was a better predictor of cardiovascular reactivity to stress than serum cholesterol concentration, predicting mean arterial pressure and stroke volume. This finding may be due to the association of glucose with diabetes, which is more prevalent in African Americans.


The clinical usefulness of cyclosporin A (CsA) in organ transplantation is limited by its intrinsic nephrotoxicity, the mechanisms of which have not yet been completely elucidated. Various processes could be responsible for the CsA-induced nephrotoxicity including an interaction with glutathione metabolism, a lipoperoxidative process, or an interaction with platelet-activating factor (PAF). Therefore, the aim of this study was to assess the potential role of PAF in CsA-induced nephrotoxicity using a new PAF antagonist, BN50726. CsA alone provoked a significant increase in serum urea, urinary gamma-glutamyl transferase activity and oxidized glutathione level of kidney cortex in the rat. In contrast, when rats were treated with CsA plus BN50726, urinary gamma-glutamyltransferase activity was similar to that of controls and oxidized glutathione was significantly lower than that measured in rats treated with CsA alone. However, serum urea remained increased as it was in the CsA group. Our results suggest that BN50726 is able to prevent the damage of renal membranes probably by an antiperoxidative activity. These data indicate the potential therapeutic capacity of a PAF antagonist, BN50726, in reducing CsA nephrotoxicity and suggest interactions between PAF and CsA in the mechanism of renal injury.


The structure of wages in any economy has profound implications for labour utilization, income distribution and the incentive to invest in human capital. This paper aims at measuring and analysing the leveland trend of nominal and real wages in different sectors of the economy of Pakistan for the 1970-84 period. The broad patterns of wage change are then looked at in terms of their implications for employment promotion, human capital formation and other related policy issues. The analysis is based on the best available information but the usual caveats appropriate to empiricalwork in Pakistan apply.


The effects of electrical stimulation of the medial preoptic area (MPO) upon unit firing in the periventricular arcuate nucleus, and that of the dorsal hippocampus (DHPC) on medial septo-preoptic and arcuate (ARC) neurons, were investigated in Wistar and Sprague-Dawley female rats throughout the 4-day estrous cycle. Unit activity was recorded using stereotaxically-oriented tungsten microelectrodes under light urethane anesthesia. Repetitive stimulation of monophasic square waves varying only in current intensity was used. The following results were obtained: (a) An increase in activity of all ARC neurons recorded was induced by MPO stimulation on each day of the estrous cycle. (b) The minimum current (threshold) effective in increasing activity in the ARC neurons varied throughout the estrous cycle; the lowest threshold was observed in proestrus and the highest on the first day of diestrus. Also, the threshold current of MPO stimulation required in increase ARC activity was found to be elevated after ovariectomy and markedly reduced to the levels of the proestrous animal by estrogen treatment. (c) Stimulation of the DHPC (field CA3) increased activity in the medial septum but decreased activity in the MPO. Two pools of neurons, one increased and one decreased by DHPC stimulation, were observed in the ARC. (d) Variation in the threshold hippocampal stimulation during the estrous cycle was observed in the response of MPO and ARC neurons (the stimulation was effective only in proestrus and estrus); but not in that of medial septal neurons. (e) In addition, the spontaneous activity of septal; MPO; and ARC neurons was increased at proestrus or after estrogen injection. The present results suggest that plasma levels of estrogen play an essential role in the cyclic process of the regulation of ovulation by way of the selective facilitation of neuronal excitability in specific functional neural pathways. Furthermore, the results support the existence of a hippocampal inhibitory projection originating in field CA3 and terminating in the final common pathway, MPO to ARC.


Term extraction is one of the layers in the ontology development process, which has the task to extract all the terms contained in the input document automatically. The objective of this process is to generate a list of terms that are relevant to the domain of the input document. In this study, we present a hybrid method for improving the precision term extraction using a combination of Continuous Particle Swarm Optimization (PSO) and Discrete Binary PSO (BPSO) to optimize fuzzy systems. In this method, PSO and BPSO are used to optimize the membership functions and rule sets of fuzzy systems, respectively. The method was applied to the domain of tourism documents and compared with other term extraction methods: TFIDF, Weirdness, GlossaryExtraction and TermExtractor. From the experiment conducted, the combination of PSO-BPSO showed their capability to generate an optimal set of parameters for the fuzzy membership functions and rule sets automatic adjustment. Findings also showed that fuzzy system performance after optimization achieved significant improvements compared with that before optimization and gave better results compared to those four algorithms.


The article solves the problem of which sets can be the set of values of the spectral multiplicity function of an ergodic (strictly ergodic) interval exchange transformation and also of a simply ergodic dynamical system. By means of the method of geometric representations subsets of transformations are constructed that are generic in the metric and topological sense in the respective subclasses, and whose spectral multiplicity function has a prescribed set of values (in naturally). These classes of transformations exhibit a new spectral effect: the component of multiplicity 1 in the spectrum is not the same as the spectrum of any factor of these transformations. Specific examples of strictly ergodic interval exchange transformations are constructed whose spectral multiplicity functions have all possible sets of values.


The equivalent generalised permittivity of a system composed of dielectric spheres in a conductive continuum is calculated. The diffusion effects are taken into account by characterising the continuous phase by its ion charges, mobilities and equilibrium concentrations. The results obtained, which reduce to the Maxwell-Wagner results in the limit of low diffusion at constant conductivity or large dispersion radii, do not agree with those deduced by Bonincontro et al (1980). They show the Maxwell-Wagner approximation always leads to an overestimation of both the dielectric increment and the relaxation time. These differences could be important in some cases of interest.


The objective of the study was to evaluate the results of refractive lensectomy with implantation of an IOL in patients with hypermetropia gravis. The authors included in the group patients operated at the Ophthalmological Clinic in Hradec Králové between May 1995 and April 1997 with a refraction of +7.2 +/- 1.76 D and axial length of 19.91 +/- 1.23 mm. The mean value of IOL was 32 +/- 1.8 (+30.0 to +35.0 D). The group comprised 124 men and 23 women (range 21-67 years, mean age 45.8 +/- 10.5 years). From the total number of 94 eyes 22 were operated, while the patients were hospitalized, 72 were operated at the out-patient department. Visus of 6/12 and better with supplementary correction was achieved in 73 eyes, i.e. 77% during the last check up. Before operation thist was the case in 70 eyes, i.e. 75.3%. The mean refraction after operations was -0.25 +/- 1.05 D. Lensectomy in hypermetropia gravis with implantation of an intraocular lens is according to the achieved functional results a fully justified method for resolving the problem of severe far-sightedness.


Between literary and cultural comparative studies The article constitutes an attempt to present in a synthetic way the main assumptions behind the fundamental trends in the comparative studies of the 19th and 20th centuries, as well as their evolution. Following the predominance of the influential model which had developed since the middle of the 19th century and focused chiefly on the genetic research of literary affiliations, and which had assumed the existence of a national literature as an organic entity, since the sixties of the 20th century, there arises a new perspective in comparative studies, where the fundamental role is played by thematic and structural categories (motif, concept, topic, genre, current etc.). The nineties of the 20th century bring yet another attempt to reformulate the methods of comparative studies and to abandon focusing on literary studies, in favor of cultural research in comparative studies, where the fundamental role is played, among others, by issues such as the concept of power, gender, race and also review and multi-, inter- and transculturalism


A study of the essential oil content in basil (Ocimum sanctum) and red lemongrass (Cymbopogon nardus L. Rendle) originally grown in Flores island has been conducted. The purpose of this study was to identify the chemotype of the essential oils obtained over stahl distillation using GC-MS. The Ocimum mainly consisted of 55% eugenol following by minor trans-alfa-bergometena, patchulana, and linalool. Meanwhile, the chemotype of the red lemongrass (Cymbopogon nardus L. rendle) were citronellol (22%), citronella, cyclohexamethanol, and viridiflorol.


91 Background: To present outcome and morbidity of high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for localized high risk prostate cancer.

METHODS
Between May 2005 and April 2009, 122 patients underwent Ir-192 HDR brachytherapy with EBRT and passed after HDR bachytherapy more than one year. The median follow-up was 46 months (range 2-76 months). All patients were high risk and localized prostate cancer. Median PSA was 40.2ng/ml (range 4.1-366ng/ml). Median Gleason Score was 8 (range 6-10). All patients were treated over six months neo-adjuvant hormonal therapy and over twenty-four months adjuvant hormonal therapy.

RESULTS
Only one patient had died of lung small cell carcinoma. 14 patients had revealed biochemical failure(BCF) by Phoenix definition. 5-year biochemical free rate was 78%. Clinical T3 group is significant worse than clinical T1-T2 group(5-y BCF 73% vs 81%, p<0.05). Of the 122 patients, only one patient displayed Grade 3 late GI toxicity. There were no other acute nor late severe toxicity.

CONCLUSIONS
HDR brachytherapy for localized high risk prostate cancer resulted in good outcomes and had comparatively minor toxicity. Clinical T3 patients was poor outcome than clinical T1-2.


Objectives/Aims Functional neurological disorders are the second most common reason for outpatient review by a neurologist. The frequency of lower urinary tract symptoms in functional neurological disorders has not been described. Our aim was to carry out a deep phenotyping of patients diagnosed with functional motor and/or dissociative symptoms and to record the prevalence of lower urinary tract dysfunction. Methods A retrospective notes review was undertaken involving consecutive patients attending a specialist functional neurological disorders clinic in Edinburgh between October 2019-February 2020 for non-urological presentation. Results In a one hundred and fifty-eight patient cohort, 78% of patients were female (n=123) and the mean age was 42. When categorising predominant functional symptoms, 52% of patients had a purely motor disorder (n=82), 17% of patients had a dissociative disorder alone (n=27) and 31% a mixed motor and dissociative disorder (n=49). Fifty percent of patients reported urinary symptoms (n=79). In total, 28% reported storage symptoms (n=45), 9% voiding symptoms (n=15), and 9% had mixed storage and voiding symptoms (n=15). 15% of patients attended a specialist clinic regarding their urinary symptoms (n= 23). Patients with a motor disorder had the highest prevalence of lower urinary tract dysfunction (56%) and the dissociative group the lowest (26%). Storage symptoms were the most prevalent symptom (35% in motor, 15% in dissociative, 24% in mixed) and patients with storage or mixed LUTS were most likely to have a motor disorder (n=29, 64%; n=12, 80%), whereas those with voiding symptoms were more likely to have mixed functional neurological symptoms (n=10, 67%). 20% of patients reported urinary retention and/or voiding dysfunction (n = 32). 100% of these patients had motor or mixed symptoms. 11% of patients reported urinary retention (n=17) comprising 14 females and 3 men, with an average age of 36.4. 59% of patients with urinary retention were on opioid medication. Conclusions 50% of patients with functional neurological disorders report lower urinary tract dysfunction however just 15% of patients attended a specialist clinic regarding their urinary symptoms. This research has provided an insight into the potential associations between urological symptoms and functional neurology and may impact or change future management.


CASTRO, C.M., and A.C. KING. Telephone-assisted counseling for physical activity. Exerc. Sport Sci. Rev., Vol. 30, No. 2, pp. 64–68, 2002. Different methods of intervention have been tested to promote physical activity at the individual level. The telephone is an excellent form of media for delivering exercise counseling and advice. This review highlights important clinical trials that have documented the success of telephone-assisted exercise counseling for promoting physical activity in a variety of populations.


On March 28, 1941, at the height of Hitler's victories during the Second World War, Virginia Woolf filled her pockets with stones and drowned herself in the River Ouse near her home in Sussex. Since that time, Woolf's suicide has been the subject of controversy for the media, for literary scholars, and for her biographers. At the time of her death some voices in the press attacked her for showing cowardice in the face of the enemy and for setting a bad example to the general population. Just when it may seem that nothing else could be said about Virginia Woolf and the ambiguous details of her suicide, this unique volume provides an entirely fresh perspective by making available to a wide readership for the first time the letters sent to Leonard Woolf and Vanessa Bell (Virginia Woolf's sister) in the aftermath of the event. The volume brings together over two hundred letters from T. S. Eliot, H. G. Wells, May Sarton, Vita Sackville-West, Edith Sitwell, E. M. Forster, Radclyffe Hall, and many others, including political figures and religious leaders. In addition, informative annotations reveal the identities of many unexpected condolence-letter writers from among the general public. In her introduction, editor Sybil Oldfield confronts the contemporary controversy over Woolf's suicide note, arguing that no one who knew Woolf or her work believed that she had deserted Britain. The ensuing collection of letters supports Oldfield's assertion. In elegant prose that rises to the stature of the occasion, these writers share remembrances of Virginia Woolf in life, comment on the quality of her work and her anti-fascist values, and occasionally reveal previously unknown facets of her capacity for friendship. A richly deserved tribute to the life of an extraordinary woman as well as a testimony to the human capacity for sympathy, Afterwords is essential reading for anyone interested in the life, death, and enduring impact of Virginia Woolf.


Global migration has contributed to greater language diversity in many parts of the world. Many migrants experience language barriers in their adopted countries. Language barriers hinder access to healthcare, including mental health. There exists little research on the extent of communication difficulties during language discordant mental health services. A cross-sectional observational study design was used to examine prevalence of communication challenges, use of communication best practices, and training needs among mental health providers and interpreters working with immigrants with Limited English Proficiency (LEP) in the United States. Using snowball sampling methods, 38 providers and 34 interpreters were recruited to complete online surveys. Challenges reported by interpreters pertained to technicalities of communication, while those reported by providers pertained to content of communication. Communication best practices such as pre-session briefings and post-session debriefings were used infrequently by providers in the sample. Providers with higher education levels were more likely to endorse some best practices. Fifty-four percent of the providers and 84% of the interpreters were interested in additional training in working with patients with LEP. Findings suggest the need for customized trainings for providers and interpreters to improve the quality of mental healthcare for patients with LEP.


I was profoundly honoured when Arena asked me to review its contributions on the Middle East. No other independent publisher has been so committed to the task of both (re-)describing our geopolitical situation and offering prescriptions for redress that are neither shrill nor doctrinaire. Admirably, Arena has resisted the professionalized peer-reviewed journal's drift towards specialization and coterie discussion; it has taken no notice of the niche journal's fetish for theoretical shadow-boxing, the narcissism of small differences that has increasingly depoliticized academic discussion. Instead, in Arena's pages, sober analysis of current affairs shares space with philosophical meditation, expansive cultural criticism and utopian speculation. For Arena the only remit that matters is that of urgent and robust critique. Still, I have to confess to approaching the task of reviewing Arena's commentary on the Israeli-Palestinian conflict with a degree of dread. Arena's record of unflinching analysis of Israel's colonial dispossession of the Palestinians, a project that continues unabated despite sporadic and often disingenuous protests from the international community, and its incisive discussion of the failings of the Arab state system, promised to be little more than an accurate but over familiar record of human misery, failed aspirations and the various ruses by which the US-Israeli alliance has sought to subjugate and remake the Middle East according to its own interests. However, what I discovered in Arena's coverage of the Israeli-Palestinian conflict since the Oslo peace process of the early 1990s - my focus in this short essay - is a testament to the enlarged sympathies and reconstructive imagination of dissident intellectuals who have found a ready home in Arena's pages. In this short review I will focus on just a few contributors who have articulated transformative possibilities.


: A globally acknowledged growing phenomenon – ageing of the population – translates into an unprecedented reality. In 2015, the number of people aged 50 and over (seniors) reached 1.6 billion worldwide, with projections pointing to 3.2 billion by 2050. In the United States of America (US) alone, there were 111 million such senior citizens, representing one-third of its total population in 2015 (Oxford Economics 2016). Europe is confronted with a similar 'greying' trend as emphasized in official documents. The 2018 Ageing Report projects significant changes in the age structure of the European Union's (EU) population in the coming decades, resulting in complex major impacts at all levels of the society. According to the document, the old-age dependency ratio (people over 65, relative to those aged 15 – 64), for example, might rise to 51.2 per cent by 2070 (EC 2018c). Romania is not an exception to this demographic trend. However, just as in other countries, the challenges generated by the country's ageing population are accompanied by many opportunities to foster entrepreneurship, particularly senior entrepreneurship, as underlined further in this chapter.


The catfishes Brachyplatystoma filamentosum (Kumakuma), Brachyplatystoma vaillantii (Laulao catfish), and Brachyplatystoma rousseauxii (gilded catfish) are important fishery resources in Brazil, where they are sold both fresh and in the form of fillets or steaks. These species have morphological similarities, thus, they can be easily misidentified or substituted, especially after processed. Therefore, accurate, sensitive, and reliable methods are needed for the identification of these species to avoid commercial fraud. In the present study, we develop two multiplex PCR assays for the identification of the three catfish species. Each multiplex protocol combined three species-specific forward primers and a universal reverse primer to produce banding patterns able to discriminate the target species unequivocally. The length of the cytochrome C oxidase subunit I (COI) fragments was approximately 254 bp for B. rousseauxii, 405 bp for B. vaillantii, and 466 bp for B. filamentosum, while the control region (CR) assay produced fragments of approximately 290 bp for B. filamentosum, 451 bp for B. vaillantii, and 580 bp for B. rousseauxii. The protocols were sensitive enough to detect the target species at a DNA concentration of 1 ng/µL, with the exception of the CR of B. vaillantii, in which the fragment was only detectable at 10 ng/µL. Therefore, the multiplex assays developed in the present study were sensitive, accurate, efficient, rapid, and cost-effective for the unequivocal identification of the target species of Brachyplatystoma. They can be utilized by fish processing industries to certify their products, or by government agencies to authenticate products and prevent fraudulent commercial substitutions.


links in the pathogenesis of pregnancy toxaemias, particularly in hyperemesis gravidarum. In this disease a state of inanition and altered hormonal conditions associated with pregnancy lead to B, deficiency. In consequence, an increased B, utilization is set up with damage to the tissues. Evidence of this is found in the clinical picture of B, deficiency in large numbers of patients and the prompt therapeutic response to administration of synthetic vitamin B,. Most of us seem to under-estimate the need for B, in the function and life of the cells; if there is the slightest shortage the cells suffer and disease follows (Williams, Peters). H. L. Sheehan in his recent pathological work on fatal cases of toxic hyperemesis proved this conclusively. Mr. Nixon's recent research is certainly of great importance in relation to the whole question of diet in pregnancy, especially under wartime conditions. The abundance of toxaemias in the last months treated in our hospital and in the ante-natal clinics of the Surrey County Council suggests malnutrition in this area. Our results with B, treatment in different types of toxaemias in pregnancy are very encouraging, but it is too early at present to draw definite conclusions. Fuller clinical study of a large number of patients is necessary and is being carried out by the whole department under Mr. J. V. O'Sullivan.-I am, etc., WALTER SPITZER, M.D.Prague, M.R.C.S., L.R.C.P. County Hospital, Kingston-upon-Thames.


The admittance behavior of high-efficiency high-power low-high-low GaAs Schottky IMPATT diodes is significantly different than those of Si Read type IMPATT structures. Using small signal analysis the admittance of such low-high-low structures is investigated, and the influences of the multiplication factor, recombination current, and dielectric relaxation are included. The calculations obtained on the basis of the analysis support, in general, experimental behavior observed in such diodes. Specifically, it is observed that the order in which the cutoff and resonant frequencies occur, for such structured devices, are substantially different from those of silicon devices


This paper discusses the types and properties of microorganisms found in avian ceca, with special reference to the chicken. Microbial activity in the cecum is primarily fermentative, but there has been little evidence of cellulose fermentation, and the predominant bacterial types are relatively inactive against other high-molecular-weight compounds of dietary origin. In all avian species examined, the consistent presence of large populations of uric acid-degrading bacteria supports the view that microbial populations in the ceca permit reabsorption of water and possibly nonprotein nitrogen from the backflow of urine. These capabilities may be of particular importance to wild birds under conditions of water and food deprivation.


The randomized clinical trial (RCT) has become generally accepted as the most valid study mechanism for assessment of therapeutic regimens. Because random allocation of treatment guards against any systematic association of treatment assignment with prognosis, differences in outcome that are observed among treatment groups in an RCT will tend to result from treatment effects and not from inherent differences among the groups. Studies in which treatment allocation is by design associated with patient characteristics—eg, where treatment is selected individually for each patient, or according to the clinic to which the patient comes, or according to the time period in which the patient is treated—are vulnerable to selection bias. This bias is incurred whenever patients with differing prognoses have differing probabilities of receiving the treatments to be compared. In an article in this issue (p 2455), Horwitz and Feinstein explore the potential usefulness of another approach to the evaluation of therapeutic


Abstract Carpinus (Betulaceae) has approximately 52 species distributed in the Northern Hemisphere, with many species of Carpinus found in China. However, the species boundaries and phylogenetic relationships remain poorly understood. This study reported ITS sequences for 225 individuals of 33 Carpinus species, mainly from China. We also included eight Ostrya species in our analyses, the closely related sister group of Carpinus. We aimed to delimit these species based on ITS sequences and clarify their phylogenetic relationships by constructing tree-like topology and networks at population level. We found that only 17 of 33 species could be delimited from the closely related ones based on species-specific mutations in ITS sequence variation, including all species of sect. Distegocarpus, and sect. Carpinus subsect. Carpinus. Carpinus subsect. Carpinus contained two endangered species, although one seemed to be a recently originated allopolyploid species with genetic additivity from two likely parents in the ITS sequence variation. Sixteen species of sect. Carpinus subsect. Polyneurae were classified into three species complexes, in each of which two or more could be not distinguished from each other. The closely related species of these complexes may still diverge at the early stage without genetic distinction in the nuclear ITS sequences because of too short of divergence time and frequent gene flow. Otherwise, some species may be established based on the intraspecific variations without genetic bases for an independently evolving unit.


Objectives The aims of this study were to investigate the added value of diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET) evaluation and to compare magnetic resonance imaging (MRI) to 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) results. Methods Morphological MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and 68Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per-patient and per-lesion detection rates (pDR and lDR, respectively) were calculated. Apparent diffusion coefficient values were compared among pNET and surrounding and normal pancreas (control group, 18 patients). Apparent diffusion coefficient and standardized uptake value (SUV) values were compared among different grading and staging groups. Results No statistically significant differences in PET/CT and MRI session detection rates were found (morphological MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; 68Ga-DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI + PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value was significantly lower compared with surrounding and normal parenchyma (P < 0.01). The apparent diffusion coefficient and SUV values of pNETs among different grading and staging groups were not statistically different. Conclusions Conventional MRI, DW-MRI + T2-w sequences, and 68Ga-DOTANOC PET/CT can be alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in patients with clinical suspicion but negative conventional imaging findings. However, the consensus reading of the 3 techniques seems the best approach.


This paper describes a methodology for the analysis of Prestressed Reinforced Concrete Tall Pier bridge, which are typically used in deep valley bridge viaducts. Piers are usually considered tall when the shaft has a height excess of 30 m. parametric study has been done for various pier heights and varying deck length considering various loading conditions. Various analysis has been performed for the Prestressed RC bridge with help of CSI BRIDGE Software. The main objective of the study is to determine for which load case in bridge is governing for design and having high displacement and moment value.


The effect of acute and chronic venous hypertension on the lymph draining from the hind limb has been studied in 10 dogs. Acute venous hypertension was produced by venous occlusion, and chronic venous hypertension by fashioning an arteriovenous fistula in the groin. Acute venous hypertension trebled the lymph flow and doubled its fibrinogen concentration thus increasing the net transport of fibrinogen across the interstitial space by 600 per cent. Chronic venous hypertension had a similar effect and caused the appearance of α‐2‐antiplasmin in the lymph. The fibrinolytic activity of the lymph did not change significantly in either group of experiments. These results suggest that the deposition of interstitial fibrin seen in the skin of the postphlebitic limb is related to an increased concentration of interstitial fluid fibrin, and to the appearance of the fibrinolytic inhibitor, α‐2‐antiplasmin, without a concomitant increase of fibrinolytic activator.


Pelvic inflammatory disease (PID) is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and/or ovaries. It is typically an ascending infection, spreading from the lower genital tract. The majority of cases PID are related to a sexually transmitted infection. The diagnosis of PID is primarily clinical and should be suspected in female patients with lower abdominal or pelvic pain and genital tract tenderness. During the patient's evaluation, other etiologies of pain including ectopic pregnancy should be considered and ruled out. PID is treated with antibiotics to cover the primary pathogens including Neisseria gonorrhoeae and Chlamydia trachomatis. Short-term complications include tubo-ovarian or pelvic abscess. Long-term complications include ectopic pregnancy, infertility, and chronic pelvic pain. Early diagnosis and treatment can potentially prevent complications.


In an era of increasing technological transformation, industries, competitors, and companies are combining platforms to create unique methods for engagement. Survival and growth in a rapidly changing marketplace require companies to embrace internal innovation that adds value for both channel members and customers. The fourth industrial revolution has already begun to take shape, on the road to an end-to-end value chain, by using Industrial Internet of Things (IIoT) and decentralized intelligence in manufacturing, production and logistics. The world is heading toward a digitized future. Already, an entire generation has grown up immersed in the digital world. This paper focus on the following fields: General Strategy and Procedural Aspects of Digital Transformation, Digital Transformation and Lean, Lean Digital Management, Applying Lean Digital Transformation and Transformation of Enterprise Resource Planning Systems to Smart Engaged Systems. Finally, this research study the challenges of Digital Transformation in Energy Industry of Utilities.


COVID-19 has presented significant challenges for higher education. These challenges were compounded for those teaching or studying towards healthcare degrees, where students were still undertaking clinical placements and delivering care in clinical practice. As the number of deaths from COVID-19 continued to rise, health disparities amongst Black, Asian and minority ethnic (BAME) populations became increasingly apparent. In April 2020, a weekly virtual wobble room was created to support student  wellbeing, alleviate distress and to strengthen student-staff partnerships in a large School of Health Sciences in the East Midlands . The BAME virtual wobble room provided a 1.5 hour weekly virtual drop-in session. Each wobble room was facilitated by four staff sponsors on a rotational basis and were attended by an average of 20 students each week, from undergraduate and postgraduate healthcare courses, including nursing, midwifery, physiotherapy, and those studying for a PhD in health science. This paper reports on the approaches and outcomes of the wobble room, which continues to run, including lessons learnt through co-production methods between students and staff, in developing a safe space to address inequalities and structural disparities.


In this work we consider a quite general class of two-species hyperbolic reaction-advection-diffusion system with the main aim of elucidating the role played by inertial effects in the dynamics of oscillatory periodic patterns. To this aim, first, we use linear stability analysis techniques to deduce the conditions under which wave (or oscillatory Turing) instability takes place. Then, we apply multiple-scale weakly nonlinear analysis to determine the equation which rules the spatiotemporal evolution of pattern amplitude close to criticality. This investigation leads to a cubic complex Ginzburg-Landau (CCGL) equation which, owing to the functional dependence of the coefficients here involved on the inertial times, reveals some intriguing consequences. To show in detail the richness of such a scenario, we present, as an illustrative example, the pattern dynamics occurring in the hyperbolic generalization of the extended Klausmeier model. This is a simple two-species model used to describe the migration of vegetation stripes along the hillslope of semiarid environments. By means of a thorough comparison between analytical predictions and numerical simulations, we show that inertia, apart from enlarging the region of the parameter plane where wave instability occurs, may also modulate the key features of the coherent structures, solution of the CCGL equation. In particular, it is proven that inertial effects play a role, not only during transient regime from the spatially-homogeneous steady state toward the patterned state, but also in altering the amplitude, the wavelength, the angular frequency, and even the stability of the phase-winding solutions.


Background Enterotoxigenic Escherichia coli (ETEC) is a common enteric pathogen that causes diarrhoea in humans and animals. Lactobacillus zeae LB1 has been shown to reduce ETEC infection to Caenorhabditis elegans and Salmonella burden in pigs. The present study was to evaluate the effects of L. zeae LB1 on the gut health of lactating piglets that were challenged with ETEC.Results Six-four 7-day-old piglets were assigned into 8 groups: 1) control group (basal diet, phosphate buffer saline); 2) CT group (basal diet + 40 mg/kg colistin); 3) LL group (basal diet + 1 × 107 CFU/pig/day LB1); 4) HL group (basal diet + 1 × 108 CFU/pig/day LB1); 5) ETEC group: (basal diet + ETEC challenged); 6) CT + ETEC group (basal diet + CT + ETEC); 7) LL + ETEC group (basal diet + 1 × 107 CFU/pig/day LB1 + ETEC); 8) HL + ETEC group (basal diet + 1 × 108 CFU/pig/day LB1 + ETEC). The trial lasted ten days including 3 days of adaptation. Several significant interactions were found on blood parameters, intestinal morphology, gene, and protein expression. ETEC infection disrupted the cell structure and biochemical indicators of blood, undermined the integrity of the intestinal tract, and induced oxidative stress, diarrhoea, intestinal damage, and death of piglets. The supplementation of L. zeae LB1 alleviated ETEC's adverse effects by reducing pig diarrhoea, oxidative stress, and death, modulating cell structure and biochemical indicators of blood, improving the capacity of immunity and anti-oxidation of pigs, and restoring their intestinal integrity. At the molecular level, the beneficial effects of L. zeae LB1 appeared to be mediated by regulating functional related proteins (including HSP70, Caspase-3, NLRP3, AQP3, and AQP4) and genes (including RPL4, IL-8, HP, HSP70, Mx1, Mx2, S100A12, Nrf2, GPX2 and ARG1). Conclusions These results suggest that dietary supplementation of L. zeae LB1 improved the intestinal functions and health of piglets.


Background While the public is under serious pressure from the coronavirus disease 2019 (COVID-19), the final impact and possible contributing factors to postpartum depression symptoms (PPDS) remain unknown. Therefore, a meta-analysis to investigate the association between PPDS and the COVID-19 pandemic was carried out by comparing the data between pre-pandemic and post-pandemic timeframes and exploring the influencing factors. Methods This systematic review was prospectively registered and recorded in a study protocol (Prospero CRD42022336820, http://www.crd.york.ac.uk/PROSPERO). A comprehensive search of PubMed, Embase, Web of Science, CINALH, Cochrane and Scopus was cmpleted on June 6, 2022. Studies that compared the prevalence of PPD before and during the COVID-19 pandemic period were included. Results Of 1766 citations identified, 22 studies were included with 15,098 participates before the COVID-19 pandemic and 11,836 participants during the COVID-19 pandemic. Overall, the analysis showed that the epidemic crisis was associated with an increased prevalence of PPDS (OR: 0.81 [0.68, 0.95], P = 0.009, I2 = 59%). Subgroup analysis was conducted according to the study characteristics and regions. Within the study characteristics classification, results showed an obvious increase in the prevalence of PPDS during the COVID-19 pandemic if PPDS cutoff was defined as Edinburgh postpartum depression score (EPDS) ≥13 points (OR: 0.72 [0.52, 0.98], P = 0.03, I2 = 67%) and an increased prevalence in follow-ups that happened after 2 weeks (≥ 2 weeks postpartum) (OR: 0.81 [0.68, 0.97], P = 0.02, I2 = 43%). Selected studies that were high-quality (OR: 0.79 [0.64, 0.97], P = 0.02, I2 = 56%) demonstrated an increased prevalence of PPDS during the COVID-19 pandemic period. Sorting by regional factors, studies conducted in Asia (OR: 0.81 [0.70, 0.93], P = 0.003, I2 = 0%) showed an increase of PPDS prevalence rates during the COVID-19 period, while studies conducted in Europe (OR: 0.82 [0.59, 1.13], P = 0.23, I2 = 71%) and North America (OR: 0.66 [0.42, 1.02], P = 0.06, I2 = 65%) showed no significant difference. All studies conducted in the developed (OR: 0.79 [0.64, 0.98], P = 0.03, I2 = 65%) and developing countries (OR: 0.81 [0.69, 0.94], P = 0.007, I2 = 0%) showed an increase of PPDS during the COVID-19 period. Conclusions The COVID-19 pandemic is associated with an increased prevalence of PPDS, especially after long-term follow-up and among the group with a high possibility of depression. The negative influence from the pandemic, causing more PPDS was significant in studies from Asia.


Background: MicroRNAs are small non-coding RNAs essential for immune function and lung development. Previously, we had found increased pulmonary expression of miR-17, -144 & miR-21, correlating with decreased mRNA & protein levels of the putative targets CREB1 and its co-activators CRTC 1&3 in mice with ova-induced asthma. Expressions were modulated by in vitro overexpression/silencing of the miRNAs. We now hypothesized that miR-17, -144 &-21 regulate CREB1/CRTC-mediated gene transcription in experimental asthma and sought to identify new targets of relevance for asthma. Methods: Murine lung epithelial cells (MLE-12) or human bronchial epithelial cells (16-HBE) were transfected with precursor miRNAs/antimiRs. Expression of miRNAs/targets was evaluated by RT-qPCR and Western blotting. For selection of CREB1 targets down-regulated genes in lungs of mice with ova-induced asthma were screened for CRE elements in their promoter region. Lung sections were histologically assessed by periodic acid schiff (PAS) stain and SEC14L3 immunostaining. Results: Among the 35 candidate CREB1 targets we chose SEC14L3 & LTBP4 as both were already brought into context with asthma. Their mRNA expressions were influenced by in vitro overexpression/ silencing of the candidate miRNAs in a CREB1-dependent manner. For SEC14L3 we confirmed this in vivo deregulation on protein level by western blot and immunostainings of lung sections, where it coincided with goblet cell metaplasia. Conclusion: Using miRNA profiles as preselection tools, we identified SEC14L3 as new target that might be useful for monitoring the integrity of the respiratory epithelium in experimental asthma.


The multinational corporation is a network of activities located in different countries. The value of this network derives from the opportunity to benefit from uncertainty through the coordination of subsidiaries which are geographically dispersed. We model this coordination as the operating flexibility to shift production between two manufacturing plants located in different countries. A stochastic dynamic programming model treats explicitly this flexibility as equivalent to owning an option, the value of which is dependent upon the real exchange rate. The model is extended to analyze hysteresis effects and within-country growth options. We show that the management of across-border coordination has led to changes in the heuristic rules used for performance evaluation and transfer pricing.


The objective of this study is to explore the contributory factors responsible for road accidents and identifies the black spots on the three motorways; M1 (Peshawar-Islamabad), M2 (Islamabad-Lahore), and M3 (Pindi BhattianFaisalabad) in Pakistan. Five years' road accident data was obtained from the National Highways and Motorway Police (NHMP), Pakistan. The database of this study included six hundred road accidents on a total of 574 kilometers long routes of M1, M2 and M3. The reliability analysis approach was used to locate black spot locations on each motorway. For the visualization and mapping of black spots on each motorway, a Geographic Information System (GIS) was used. The results explored that vehicle condition was the significant contributory factor responsible for the maximum number of road accidents on M1 and M3, while for M2, it was drowsy driving. It is also found that a maximum number of road accidents on M2 and M3 occurred in late-night, while for M1, it was day timing. Furthermore, road accidents were relatively higher in May-July and December on M1 and M2, which shows that extreme weather influences the occurrence of road accidents. On the contrary, no substantial variation of road accidents was examined for M3 month-wise. Finally, black spots on each motorway were located and their georeferenced coordinates were presented for future use. As a result, precautionary measures and provisions are suggested for concerned authorities to mitigate road safety problems.


A 3-D solid-state drive system with through-silicon via (TSV) technology and boost converter is presented in this paper. The proposed boost converter enables the supply voltage reduction to 1.8 V and smaller NAND Flash memory chips. From the simulation results, the conventional bonding-wire technology can achieve only eight NAND chip integrations not only due to their structural problem but also due to the performance degradation. On the other hand, 128 NAND Flash memory chips can be integrated into a package with full-copper TSVs and the proposed system has about 1.70 μs of rise time for 20 V, 74.2 nJ of the energy dissipation, and 225 μm2 of additional Si area consumption for a NAND chip. Even if poly-Si TSVs are used, because of the process restriction, 64 NAND chips can be stacked with about 34% longer rise time and 22% degradation of energy dissipation compared to a full-copper TSV by grinding the Si-substrate to 10 μm .


Surgical scene segmentation is fundamentally crucial for prompting cognitive assistance in robotic surgery. However, pixel-wise annotating surgical video in a frame-by-frame manner is expensive and time consuming. To greatly reduce the labeling burden, in this work, we study semi-supervised scene segmentation from robotic surgical video, which is practically essential yet rarely explored before. We consider a clinically suitable annotation situation under the equidistant sampling. We then propose PGV-CL, a novel pseudo-label guided cross-video contrast learning method to boost scene segmentation. It effectively leverages unlabeled data for a trusty and global model regularization that produces more discriminative feature representation. Concretely, for trusty representation learning, we propose to incorporate pseudo labels to instruct the pair selection, obtaining more reliable representation pairs for pixel contrast. Moreover, we expand the representation learning space from previous image-level to cross-video, which can capture the global semantics to benefit the learning process. We extensively evaluate our method on a public robotic surgery dataset EndoVis18 and a public cataract dataset CaDIS. Experimental results demonstrate the effectiveness of our method, consistently outperforming the state-of-the-art semi-supervised methods under different labeling ratios, and even surpassing fully supervised training on EndoVis18 with 10.1% labeling. Our code is available at https://github.com/yangyu-cuhk/PGV-CL.


The development of a pH sensitive, biodegradable polymer from the combination of Shellac (a natural polymer secreted by lac insect) and polyamidoamine (PAA) (a synthetic polymer) yielded a new biocompatible polymer Shellac-PAA in a photopolymerization process. Scanning electron micrograph of Shellac-PAA shows an interesting heterogeneous surface morphology supported with observation of two different melting temperatures obtained from differential scanning calorimetric measurement. The equilibrium swelling properties of the polymeric material was studied as a function of pH and time in buffer solutions similar to that of gastric and intestinal fluids. The controlled release kinetics of a model colon specific drug 5-aminosalicylic acid showed Fickian diffusion behavior. The new polymer is biocompatible, biodegradable and, hence, projected as a new kind of polymer with improved properties, which can be a potential candidate for controlled release of therapeutic agents in colon specific diseases. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012


The study of the pressure distribution within the dam-break flow over mobile bed is very important because it allows to discuss the hydrostatic pressure distribution, which is the main assumption for the validity of the shallow water equations (SWE). Indeed, this assumption is not always valid, especially when the streamlines are not straight and not perpendicular to the gravity acceleration direction. The flow varies abruptly in the first instants of the falling dam-break wave evolution, but it tires towards a stationary motion during time. To better characterize this phenomenon it is important to examine the evolution of each component of velocity vector field and the distribution of the pressure, which is compared to the hydrostatic distribution. Moreover, the present study considers the distribution of pressure linked with the distribution of the shear stress, through the Navier-Stokes equations. The final object of this work is to characterize the dam break experiment over mobile bed by means of forces acting during the event. The dam-break experiment under examination has been performed in a dedicated flume designed at the laboratory of Civil Engineering Department, Universite catholique de Louvain. The analysis of this very transient flow it is now possible and more accurate thanks to the application of non-intrusive new techniques, such as PIV.


PIC is a language for drawing simple figures on a typesetter. The basic objects in PIC are boxes, circles, ellipses, lines, arrows, arcs, spline curves, and text. These may be placed anywhere, at positions specified absolutely or in terms of previous objects. The example below illustrates the style and basic capabilities of the language. document PIC TBL/EQN (optional) TROFF typesetter This picture was created with the input .PS ellipse "document" arrow box "PIC" arrow box "TBL/EQN" "(optional)" dashed arrow box "TROFF" arrow ellipse "typesetter" .PE PIC is a TROFF preprocessor; it passes most of its input through untouched, but translates commands between .PS and .PE into TROFF commands that draw the pictures. This manual describes the version of PIC made available in December, 1984.


A cross-coupled relaxation oscillator has two outputs of the same frequency, which are in quadrature. In this paper a comparative study of the phase noise in a cross-coupled relaxation oscillator is given. We present a high level (system) study of the oscillator and analyse the oscillator stability. The derivation proves analytically that cross-coupling reduces the influence of a perturbation (noise) on the oscillator output. Both high-level and circuit simulations at 5GHz are presented to confirm the theoretical results. Close to 10dB improvement in phase noise performance due to coupling was found, and the phase noise performance compared with that of a coupled LC oscillator was achieved.


In this work, the annealing effect on the microstructure of metallic glasses (MGs) was investigated, by using molecular dynamics simulation in a ZrCu model. An approach for calculating free volume was adopted, by which the free volume dependence on the annealing temperature was evaluated. It was found that there was a perfect linear relationship between free volume and the annealing temperature, and that the slope was influenced by the annealing time. This work provides a feasible strategy for estimating free volume in an annealed MG, and an in-depth understanding of the change in free volume induced by annealing.


Accurate description of the ionization process in DNA is crucial to the understanding of the DNA damage under exposure to ionizing radiation and the exploration of the potential application of DNA strands in nanoelectronics. In this work, by employing our recently developed Green's function coupled-cluster library on supercomputing facilities, we have studied the spectral functions of several guanine-cytosine (G-C) base pair structures ([G-C]n, n = 1-3) for the first time in a relatively broad near-valence regime ([-25.0, -5.0] eV) in the coupled-cluster with singles and doubles level. Our focus is to give a preliminary many-body coupled-cluster understanding and guideline of the vertical ionization energy (VIE), spectral profile, and ionization feature changes of these systems as the system size expands in this near-valence regime. The results show that, as the system size expands, even though the lowest VIEs keep decreasing, the changes of spectral function profile and the relative peak positions get unexpectedly smaller. Further analysis of the ionized states associated with the most intensive peak in the spectral functions reveals non-negligible |2h, 1p⟩'s in the ionized wave functions of the considered G-C base pair systems. The leading |2h, 1p⟩'s associated with the main ionizations from the cytosine part of the G-C base pairs feature a transition from the intra-base-pair cytosine π → π* excitation to the inter-base-pair electron excitation as the size of G-C base pairs expands, which also indicates the minimum quantum region in the many-body calculations of DNA systems.


Title: Institutional voids and their impact on entry decisions and strategy implementation. Author: Agata Owczarek This research investigates the ways institutional voids affect the process of internationalization of a firm entering an emerging market in the energy sector. More precisely, the study presented aims to draw conslusions about the importance of institutional context for entry decisions and strategy implementation when expanding to an emerging market. To answer this research question, a case study on the internaitonalization process of EDP in Peru was conducted. The results obtained suggest that companies become more and more aware of the importance of institutional voids for the future of the projects in emerging markets. Before the entry decision takes place, company analyzes deeply the institutional context. Entry mode changes accordingly to the perceived risk coming from the insuffcient institutionalization. Overall strategy connected with different areas, for instance capital and labor markets and various stakeholders like government and society is adjusted accordingly to the characteristics of the market. The final conclusion is that the overall strategy has to be tailored to the specific institutional context. Sometimes the difference between the home and host country is rather a matter of nuance and the art of addressing it, makes companies successful.


PURPOSE
When mobility deficits persist after stroke or spinal cord injury (SCI), outpatient neurorehabilitation services are required. This study aimed to explore the current practice of German outpatient neurorehabilitation services and identify factors associated to this practice.

METHODS
This was a qualitative observational study in which semi-structured interviews were conducted with professionals from outpatient neurorehabilitation services and mobility-impaired patients. A qualitative content analysis with a data-driven coding process was used.

RESULTS
Three general practitioners, five physical, five occupational, and one speech therapist, one neuropsychologist, two outpatient nurses, one rehabilitation technician, one social worker, two patient advocates (long-term survivors, each stroke and SCI), and 20 patients (10 after stroke, 10 after SCI, all first-ever affected since approximately one year) participated. The reported experiences ranged from high satisfaction to perceived deficits in participation-oriented, evidence-based, and coordinated care. Identified associated factors were: (a) availability of specialised therapists and professional education, (b) outpatient service catalogue, (c) cost coverage, (d) setting rehabilitation goals, and (e) physician as care coordinator.

CONCLUSION
Areas of improvement identified focused on: setting rehabilitation goals towards participation, training therapists on evidence-based treatments and shared decision-making, updating the outpatient service catalogue, and implementing coordination actions. Implementation of these recommendations should be evaluated.


As the hyped concept of post-truth began occupying various discourses of politicians, commentators and journalists in the recent years especially in the West, this article attempts to bring a critical reflection to the concept by carrying out an integrative literature review. Our aim is to critically examine and analyse the literature and main perspectives and relationships of the issue. Therefore, different perspectives of scholars and journalists who are well-versed in their domain/tradition are combined and integrated together. On the grounds that the emerging themes create a broader dichotomy and a field of tension between two broader views- post-truth as a new era and post-truth as time-immemorial or post-truth as unfolding through the years, the article will be divided into two main sections. This will be followed by further critical elaboration and discussion on the responses being taken regarding the "truth" of the "post-truth" phenomenon principally from the perspective of democracy, power and free speech.


Heredofamilial cases of restless leg syndrome are presented. In a family a father (50-year-old) and his daughter (19-year-old) were investigated. Moreover, his mother and sister gave the history of restless leg syndrome. The father complained of a disturbing feeling at his legs which urged him unwillingly to move his legs and arms, causing insomnia for 20 years. In order to prevent this impulsive feeling that forced him to move his legs, he wrapped his legs into nylons, towels, hit his legs with his hands, got up and walked around or snack. The patient who coped with these symptoms till late hours of the night could only fall asleep at dawn. He had no complaint during daytime. The sleep EEG investigations demonstrated that the patient had severe sleep disturbance and the sleep switched from second period to first period or from the first period to awakening. His daughter (19 years old) occasionally had a feeling that as if her feet did not belong to her during sleep for 2 years. This urged her to keep her feet in planter flexion. Sometimes she wrapped and squeezed her ankles with a rope, and only through the pain due to this squeezing she could avoid of this feeling. If she still could not get rid of this feeling she lied down on her abdomen and moved her legs up and down. After getting tired, she could go to sleep. Both father and daughter complained insomnia and this was confirmed by sleep EEG investigations. The severity of symptoms varied among the members of the family. In addition to familial cases presented above a single case with restless leg syndrome is presented. A 26-year-old male complained unusual feeling at his right leg, which caused movement or the right leg and hitting of the heel since he was 14. The symptoms not only occured night, but also during the day. The patient needed to move his legs in order to get read of unpleasant feeling. The etiology, pathophysiology and the treatment of the restless leg syndrome are unknown. None of the treatment modalities used in the father gave satisfactory results.


Operation parameters of magnetic quantum cellular automata are evaluated for the purposes of reliable logic operation. The dynamics of the nanomagnets is simulated via the Landau-Lifshitz-Gilbert equations with a stochastic magnetic field corresponding to thermal fluctuations. It is found that in the macrospin approximation, the switching speed does not change under scaling of both size and distances between nanomagnets. Thermal fluctuations put a limitation on the size of nanomagnets: when we consider a majority gate that features a biaxial anisotropy as a stabilizing mechanism and a uniform clocking field, the gate error rate becomes excessive for nanomagnets smaller than about 200 nm at room temperature.


Studies evaluating the safety and efficacy of Listex TM P100 to reduce Listeria monocytogenes contamination on raw fish were assessed. The material should not present human toxicological problems because the bacteriophage P100, used as active principle, is not regarded as harmful to consumers nor to organisms other than Listeria spp., and because the fabrication parameters do not include anything obvious that might compromise safety. Data of studies considered indicate that Listex TM P100 is listericidal on inoculated catfish and salmon samples, but do not allow definitive conclusions on efficacy in reducing L. monocytogenes counts on raw fish nor on its impact on L. monocytogenes contamination levels in finished product. It was not possible to estimate the potential listeriosis risk reduction by treating raw fish with ListexTM P100. The data were not adequate to allow firm conclusions on persistence or activity of P100 in stored fish. The proposed use of Listex TM P100 is unlikely to result in emergence of reduced susceptibility to biocides and/or resistance to key therapeutic antimicrobials: however, this conclusion may need verification. No information was provided on survival of P100 in processing wastewater or the environment, or on the potential accumulation of naturally P100 resistant L. monocytogenes variants. Pilot and industrial scale studies should consider parameters affecting decontaminating efficacy, and should verify that application on raw fish has an impact on reduction of L. monocytogenes contamination on the final product. The persistence or activity of P100 as well as potential changes in L. monocytogenes counts should be evaluated during fish storage. Tests to investigate potential development of resistance or reduced susceptibility to biocides and key therapeutic 1 On request from the European Commission, Question No EFSA-Q-2011-00959, adopted on 08 March 2012. 2 Panel members: Olivier Andreoletti, Herbert Budka, Sava Buncic, John D Collins, John Griffin, Tine Hald, Arie Havelaar, James Hope, Günter Klein, Kostas Koutsoumanis, James McLauchlin, Christine Müller-Graf, Christophe Nguyen-The, Birgit Nørrung, Luisa Peixe, Miguel Prieto Maradona, Antonia Ricci, John Sofos, John Threlfall, Ivar Vågsholm and Emmanuel Vanopdenbosch. Correspondence: email@example.com 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on the evaluation of the safety and efficacy of Listex P100 for the removal of L. monocytogenes of raw fish: Sava Buncic, James McLauchlin, John Sofos, Juan Evaristo Suarez and John Threlfall for the preparatory work on this scientific opinion and the member of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Martinus Løvik for providing information on the allergenicity potential, and EFSA staff: Winy Messens (BIOHAZ), Anne Theobald (Food Ingredients and Packaging) and Leng Heng (NDA) for the support provided to this scientific opinion. * Editorial amendment on page 1: "Suggested citation...EFSA Journal 2012;10(3):2615. [43 pp.] doi:10.2903/j.efsa.2012.2615..." and in the footer of pages 2-43 "EFSA Journal 2012;10(3):2615" Safety and efficacy of Listex TM P100 for removal of Listeria monocytogenes on raw fish EFSA Journal 2012;10(3):2615 2 antimicrobials, following use of Listex TM P100, are recommended. The continuous effectiveness of Listex TM P100 against L. monocytogenes and the potential for selection and dominance of strains naturally-resistant to P100 should be monitored. © European Food Safety Authority, 2012


— Nierite (Si3N4) is a new mineral that has been found in perchloric acid-resistant residues of three ordinary chondrites (Adrar 003 [LL3.2], Inman [L3.4] and Tieschitz [H3.6]) and one enstatite chondrite (Indarch [EH4]). This mineral occurs as very small (∼2 × 0.4 μm) lath-shaped grains, which have been characterised by transmission electron microscopy. The d-spacings of nierite are, within errors, comparable to those of synthetic α-Si3N4, which has trigonal symmetry (P31c, a = 0.7758 nm, c = 0.5623 nm, V = 0.2931 nm3 Z = 4). Energy-dispersive x-ray analyses confirm that nierite is a Si- and N-rich mineral. A few nierite crystals in the Indarch, Inman and Tieschitz residues are intergrown with whiskers of another nitride. Only two crystals of this additional nitride were found that were of sufficient size to give electron diffraction patterns uncontaminated by nierite reflections. The d-spacings of this second nitride are comparable to those of β-Si3N4, the hexagonal polymorph of synthetic Si3N4.

The majority of nierite crystals in Indarch are interpreted to have formed by exsolution of Si and N from kamacite, perryite and schreibersite during parent-body metamorphism. Some grains have evidence for two discrete episodes of nierite crystallization. The origin of nierite in Adrar 003, Inman and Tieschitz is not known, but formation during exsolution is again possible. The petrographic relationships between nierite and β-Si3N4 in Indarch, Inman and Tieschitz suggests that the β-Si3N4 whiskers predated nierite and acted as a seed on which nierite crystals later nucleated. The nierite/β-Si3N4 ratio in ordinary chondrites is controlled by their metamorphic grade and possibly also their oxidation state.