Congenital insensitivity to pain is a rare disorder characterized by the absence of normal response to painful stimuli 1. Sensation to light touch and sensation to temperature are usually present 2. The most common orthopaedic manifestations of congenital insensitivity to pain are recurrent fracture, self-mutilation, autoamputation, osteomyelitis, septic arthritis, Charcot arthropathy, scoliosis, joint laxity, and joint dislocation 3,4. We describe the case of a five-year-old boy with congenital insensitivity to pain in whom osteomyelitis of the calcaneus and avulsion of the Achilles tendon developed. An Ilizarov device was used to reconstruct the severely contracted Achilles tendon. The family of our patient was informed that data concerning the case would be submitted for publication.

A five-year-old boy with congenital insensitivity to pain was treated with a long leg, non-weight-bearing cast because of a tibial fracture. Because the patient had a history of ulceration with casting, large amounts of cotton cast padding and foam padding were used over the heel. The tibial fracture healed after casting for five weeks. However, use of the cast was complicated by the development of a full-thickness ulcer over the calcaneus with exposure of the Achilles tendon. The patient was managed with debridement of the calcaneus and intravenous administration of antibiotics. A free microvascular lateral arm flap was applied to the heel to provide coverage. The flap healed rapidly without complications, and the infection resolved.

Two weeks after the free-flap procedure, the patient had an avulsion of the Achilles tendon underneath the flap. The …


To achieve high-accuracy tracking of dual-linear-motor-driven (DLMD) gantry, high-level synchronization between redundant actuators is a nonnegligible factor and also a difficult issue to be solved prior. Especially, when both XY axes are simultaneously operating to accomplish complex tasks efficiently, additional coupling effects will be generated by the dynamic load presented on the crossbeam, which makes the synchronization issue more complicated compared to the case with static load. However, due to the absence of an accurate model to fully reveal the complete coupling characteristics, existing approaches to this issue still have inherent limitations. Therefore, this paper focuses on the systematic physical modeling and synchronization control of DLMD gantry with a dynamic load presented on the crossbeam. A complete coupling mathematical model is established firstly, by fully considering two linear motions (X-axis and Y-axis) and also including the additional rotational motion of the crossbeam. Built upon the effective model information, corresponding solutions by compensating the dynamic load effects and actively controlling the rotational dynamic to regulate the internal forces have been proposed, leading to a novel adaptive robust synchronization control method. Comparative experiments are carried out, and the results show the effectiveness and superiority of the proposed method in dealing with synchronization issue subjected to dynamic load effects.


Description of larval instars of Deronectes depressicollis Rosenhauer 1856, D. lareynii (Fair-maire 1858), D. latus (Stephens 1829), D. aubei (Mulsant 1843), and Scarodytes halensis (Fabricius 1787) is presented including a detailed chaetotaxic and porotaxic analysis of the cephalic capsule, head appendages, legs, last abdominal scgment and urogomphi. A phylogenetic analysis of 14 genera of the tribe Hydroporini, based on 22 larval characteristics was conducted with Hennig86. Three of the branches of the strict consensus tree have a statistical support greater than 60% according to the Parsimony Jackknifer. One of the supported clades is Antiporus Sharp + Nebrioporus Regimbart + Neonectes J. Balfour-Browne + Oreodytes Seidlitz + Stictotarsus Zimmermann + Scarodytes Gozis, of which the sister-group is the genus Deronectes Sharp. Consequently larval characters, in contrast to adult characters support the inclusion of Antiporus, Neonectes and Oreodytes in the Deronectes-group of genera. All members of this clade are characterized by: (i) presence of an occipital suture in first instar, (ii) presence of a constriction at level of occipital suture, (iii) absence of maxillary cardo, and (iv) insertion of the primary seta MX I on the maxillary stipes. Scarodytes is postulated to share a monophyletic origin with Nebrioporus, Stictotarsus, and Antiporus based on (i) the presence of natatory setae on femora, tibiae, and tarsi and (ii) the shape of the urogomphomere I which is more than 3.10 times longer than urogomphomere 2.


The article responds to a grid created by Leonard Riskin to describe mediator orientations. As Riskin's Grid indicates, many mediators in practice evaluate the fair or likely court outcome when necessary to move forward on a particular issue or on the entire dispute. While this article addresses the dangers of such evaluations if characterized as mediation, in certain instances "mixed' evaluative and facilitative processes nonetheless can prove useful. The article asserts that evaluations by a neutral should not be called "mediation" and that sufficient time exists to remap mediation, particularly in the context of current efforts to regulate the profession. Moreover, the article argues that maps of the mediation process should outline a paradigm that sharply differs from the adjudicative norm, a paradigm that has party self-determination, rather than intervener evaluation and direction, as its primary value.


With recent advancement in technologies used at home, smart home environment allows various resources such as device, network, or content to be connected to one another. Their configurations are changed by dynamic bindings at any time. In this smart home environment, a minor problem in a resource can trigger serious failures in home network services by causing multiple faults to the related resources simultaneously. To solve this problem, it is essential to analyze the dependency between resources and also to diagnose home network faults autonomously. This paper proposes the effective fault diagnosis system based on resource relation map which is dynamically constructed by information convergence model of heterogeneous home resources. The proposed system provides the tracing method for finding the root cause of a fault using the resource relation map. The resource relation map represents the snapshot of home situations at the given time. The proposed fault diagnosis method allows building cost effective remote maintenance system with high availability and manageability by tracing the fault cause along the dependency between resources using graph-style resource relation map as if humans trace the cause of problem. In addition, it can contribute to realize an autonomic fault management system for smart home. In this paper, the prototype of the proposed system is implemented and evaluated for performance in accuracy and latency of fault diagnosis in a real environment. The experimental results show that the proposed system, especially with the suggested back tracing diagnosis system, yields remarkable performance for home network fault diagnosis.


Education is intimately connected to many of the most important and contentious questions confronting American society, from race to jobs to taxes, and the competitive pressures of the global economy have only enhanced its significance. Elementary and secondary schooling has long been the province of state and local governments; but when George W. Bush signed into law the No Child Left Behind Act in 2002, it signaled an unprecedented expansion of the federal role in public education. This book provides the first balanced, in-depth analysis of how No Child Left Behind (NCLB) became law. Patrick McGuinn, a political scientist with hands-on experience in secondary education, explains how this happened despite the country's long history of decentralized school governance and the longstanding opposition of both liberals and conservatives to an active, reform-oriented federal role in schools. His book provides the essential political context for understanding NCLB, the controversies surrounding its implementation, and forthcoming debates over its reauthorization. Using education as a case study of national policymaking, McGuinn also shows how the struggle to define the federal role in school reform took center stage in debates over the appropriate role of the government in promoting opportunity and social welfare. He places the evolution of the federal role in schools within the context of broader institutional, ideological, and political changes that have swept the nation since the 1965 Elementary and Secondary Education Act, chronicles the concerns raised by the 1983 report "A Nation at Risk", and shows how education became a major campaign issue for both parties in the 1990s. McGuinn argues that the emergence of swing issues such as education can facilitate major policy change even as they influence the direction of wider political debates and partisan conflict. McGuinn traces the Republican shift from seeking to eliminate the U.S. Department of Education to embracing federal leadership in school reform, then details the negotiations over NCLB, the forces that shaped its final provisions, and the ways in which the law constitutes a new federal education policy regime - against which states have now begun to rebel. He argues that the expanded federal role in schools is probably here to stay and that only by understanding the unique dynamics of national education politics will reformers be able to craft a more effective national role in school reform.


--- This paper focused on the discussion to answer the problems of regional economic governance and how scientific evidence of the use of Technology can be a prospect and challenge in Indonesia's efforts to develop poor areas into prosperous areas. We study with a phenomenological approach that begins with in-depth data analysis techniques, thorough evaluations, and high interpretations to obtain valid data to answer existing problems. After we develop the data and discuss the results, it can be concluded that the government and other parties can develop the national and local economy by utilizing what Technology works with the prospects and challenges. Technology has brought a life that is now wholly industrialized. Therefore, resources are needed that can manage to see Technology in terms of prospects and challenges so that regional economic governance in Indonesia can be implemented.


Abstract Studies analysing biological motion perception based on reduced number of dots have demonstrated that biological motion can be perceived even when only the lower part of the body is visible or when the number of dots representing the object is reduced. What is the minimal amount of information that enables biological motion to be distinguished from its scrambled version? The results of the current experiment demonstrate that biological motion can be distinguished from its scrambled version when the object is formed of approximately 5 (4.7 ± 0.1) dots. Additionally, we also investigated whether the threshold value for biological motion perception differs in central and peripheral visual fields. By using stimulus magnification, we demonstrate that the number of dots sufficient for biological motion perception is similar in the central visual field and near periphery. Hence, stimulus magnification can compensate for reduced task performance in the peripheral visual field. The current results suggest that reduced performance of biological motion perception in the peripheral visual field (as demonstrated in other studies) is due to difficulties with the global perception of biological motion.


The authors proposed a selective assign shortest path first (SASPF) algorithm for routing and wavelength assignment in the presence of four wave mixing (FWM) in wavelength division multiplexing network with a design parameter Vm. In order to maintain a reasonably good performance in terms of blocking probability to fulfil the connection requests but also to allow acceptable FWM effects, Vm is an important design parameter (number of established optical channels to fulfil the connection requests but also to allow acceptable FWM effects). If its value is too low, many connection requests will not be able to establish, which may lead to higher blocking probability. On the other hand, if its value is too high, it may lead to obvious FWM effects that will affect the network performance. Thus, Vm must be optimum to balance the requirement of the connection requests and also the induced FWM crosstalks. Performance results show that SASPF algorithm outperforms the comparison scheme such as traditional assign shortest path first resulting in low blocking probability with a specific value of Vm.


Gallium nitride self-aligned MOSFETs were fabricated using low-pressure chemical vapor-deposited silicon dioxide as the gate dielectric and polysilicon as the gate material. Silicon was implanted into an unintentionally doped GaN layer using the polysilicon gate to define the source and drain regions, with implant activation at 1100/spl deg/C for 5 min in nitrogen. The GaN MOSFETs have a low gate leakage current of less than 50 pA for circular devices with W/L=800/128 /spl mu/m. Devices are normally off with a threshold voltage of +2.7 V and a field-effect mobility of 45 cm/sup 2//Vs at room temperature. The minimum on-resistance measured is 1.9 m/spl Omega//spl middot/cm/sup 2/ with a gate voltage of 34 V (W/L=800/2 /spl mu/m). High-voltage lateral devices had a breakdown voltage of 700 V with gate-drain spacing of 9 /spl mu/m (80 V//spl mu/m), showing the feasibility of self-aligned GaN MOSFETs for high-voltage integrated circuits.


The GRB outflow driven by superconducting cosmic strings is likely to be an arc rather than a usually-considered spherical cap. In such a case, the afterglows of the cosmic string GRBs could be basically consistent with the observation of the high-redshift GRBs.


Geophysical inversion using least-squares has been a very successful method for UXO discrimination of magnetics. However, the residuals do not follow a normal distribution, which means that the assumptions underlying the inverse problem are violated. Two consequences of this are (i) model bias and (ii) incorrect estimates of model parameter uncertainties. We have found that the residuals are better modeled by an Ekblom distribution which can be designed to be more tolerant of statistical outliers than the Gaussian. To reformulate the inverse problem we are left with the issue of determining the two parameters that define the Ekblom distribution. We appeal to the concept of self-consistency to resolve these parameters; i.e. the statistical distribution used to determine the model parameters should be the same as the distribution of the residuals. To achieve this aim, we set the problem up as a two parameter inverse problem and use the maximum difference between the cumulative density functions of the Ekblom distribution and the residuals as a misfit measure. For magnetic data collected in Montana, the recovered dipole parameters using the Ekblom distribution could be significantly different than those obtained by least-squares. In one case considered in detail, the 95.4% confidence regions for the different solutions didn't even overlap.


We report the results of a 5-year follow-up of the cognitive development of 19 survivors of acute lymphoblastic leukemia, all of whom received 24 Gy cranial irradiation and a course of intrathecal methotrexate. Assessment was made before radiotherapy and annually thereafter. Cognitive impairment was found to be transient in children who did not manifest somnolence who were under 5 years at the time of treatment. Despite having normal IQs and normal CT scans, 9 of 18 survivors in continuous complete remission were having learning problems at school 5 years after diagnosis. Assessment of their intellectual and memory functions revealed that as compared with matched healthy children, patients had lowered IQs but also had a specific auditory learning deficit independent of IQ. Long-term memory was found to be impaired for verbal auditory but not for verbal visual material. Results are discussed in terms of possible remediation of the learning disability.


The paper describes the attributes that should be possessed by a benchmark example for verifying the beam elements used to carry out 3D linear buckling analysis and 3D second-order elastic analysis of steel frames. Based on the attributes described, the paper proposes a suite of benchmark examples selected from the literature. The necessary features of a beam element required to pass the proposed benchmark problems are given, and beam elements that possess these features are cited. The paper also explains the merits of linear buckling analysis examples, and provides a commentary on two well-known examples.


Context. A robust classification of Cepheids into their different sub-classes and, in particular, between classical and Type II Cepheids, is necessary to properly calibrate the period-luminosity relations and for populations studies in the Galactic disc. Type II Cepheids are, however, very diverse, and classifications based either on intrinsic (period, light curve) or external parameters (e.g., [Fe/H], |z|) do not provide a unique classification. Aims. We want to ascertain the classification of two Cepheids, HQ Car and DD Vel, that are sometimes classified as classical Cepheids and sometimes as Type II Cepheids. Methods. To achieve this goal, we examine both their chemical composition and the presence of specific features in their spectra. Results. We find emission features in the Hα and in the 5875.64 Å He I lines that are typical of W Vir stars. The [Na/Fe] (or [Na/Zn]) abundances are typical of thick-disc stars, while BL Her stars are Na-overabundant ([Na/Fe] > +0.5 dex). Finally, the two Cepheids show a possible (HQ Car) or probable (DD Vel) signature of mild dust-gas separation that is usually observed only in long-period type II Cepheids and RV Tau stars. Conclusions. These findings clearly indicate that HQ Car and DD Vel are both Type II Cepheids from the W Vir sub-class. Several studies have reported an increase in the Cepheids' abundance dispersion towards the outer (thin) disc. A detailed inspection of the Cepheid classification, in particular for those located in the outer disc, will indicate whether this feature is real or simply an artefact of the inclusion of type II Cepheids belonging to the thick disc in the current samples.


Variational Auto-encoders (VAEs) have been very successful as methods for forming compressed latent representations of complex, often high-dimensional, data. In this paper, we derive an alternative variational lower bound from the one common in VAEs, which aims to minimize aggregate information loss. Using our lower bound as the objective function for an auto-encoder enables us to place a prior on the bulk statistics, corresponding to an aggregate posterior of all latent codes, as opposed to a single code posterior as in the original VAE. This alternative form of prior constraint allows individual posteriors more flexibility to preserve necessary information for good reconstruction quality. We further derive an analytic approximation to our lower bound, leading to our proposed model - WiSE-VAE. Through various examples, we demonstrate that WiSE-VAE can reach excellent reconstruction quality in comparison to other state-of-the-art VAE models, while still retaining the ability to learn a smooth, compact representation.


Obstructive jaundice caused by duodenal ulcer is uncommon, and only 39 cases have been reported in the literature of the United States. A 40th case is presented here with a discussion of this disease entity. REPORT OF A CASE The patient, a 56-year-old white man, was employed as a packer. He entered the Bronx Veterans Administration Hospital on July 3, 1952. His chief complaint was of jaundice of one month's duration. The patient had been well until June 4, 1952. At that time, there was a sudden onset of severe, crampy, nonradiating, midepigastric pain of one-half hour's duration. This pain caused him to double up. Similar attacks of pain occurred on June 15 and June 23, 1952. On June 5, the day after the first attack, the patient noticed that icterus, associated with dark urine and clay-colored stools, had developed. For eight days prior to admission he had had slight


Neutrophils exhibit a dramatic enhancement of integrin-mediated cell adhesion in response to lipopolysaccharide (LPS). This response requires CD14 on the neutrophil and plasma proteins in solution. We have purified the factor from plasma that facilitates the adhesive response of neutrophil to LPS by using a combination of affinity and ion-exchange chromatography. Previous work has shown that the activity is associated with apolipoprotein A-I (apoA-I), and here we show that this activity is associated with an apoA-I-bearing complex of protein and phospholipid. Native polyacrylamide gel electrophoresis (PAGE) analysis showed a ladder of bands in the Mr 200,000 region, and electron microscopy revealed round, indented particles of 11.4 ± 0.12 nm in diameter. Characterization of these particles revealed a density of 1.219-1.264 g/ml and ∼10 molecules of lipid phosphate per Mr 200,000 complex. SDS-PAGE showed that each of the bands seen in native PAGE was composed of several polypeptides. These were identified as apoA-I, LPS binding protein (LBP), and factor H-related proteins (FHRPs). Physical association of apoA-I, LBP, and FHRP in these particles was further confirmed using double immunodiffusion, and association of LBP and FHRP in plasma was confirmed by coimmunoprecipitation. FHRPs are the numerically dominant protein components in these particles, and all plasma FHRP-1 appears to be associated with these particles. We suggest that FHRPs may be the defining constituent of this novel "lipoprotein" particle.


The rising problem of biocompatibility is encouraging the development of new dialysis membranes, but the high cost of synthetic ones precludes their wide use. The authors compared the biocompatibility of cuprophan (CU), cellulose acetate (CA), and hemophan (HE), evaluating both in vitro and in vivo polymorphonuclear leukocyte (PMN) oxidative metabolism activation by resting chemiluminescence and complement activation by C3a; in vivo PMN counts during dialysis were also performed. The lowest increase in in vitro PMN resting chemiluminescence using HE was + 71.3% with CA, +49.3% with CU, and + 21.4% with HE (p less than 0.001 versus CA and CU); furthermore, HE did not significantly stimulate PMN resting chemiluminescence during in vivo hemodialysis: + 56.6% with CA, + 38.8% with CU, and + 3.7% with HE (p less than 0.01 versus CU and p less than 0.001 versus CA). C3a concentration increased with all membranes both in vitro and in vivo, but HE (in both experimental conditions) showed the lowest increase at any time (p less than 0.001 versus CA and CU). After 15 min of dialysis, PMN count dropped to 20.3% of basal values with CU, to 49.8% with CA, and to 76.5% with HE (p less than 0.001 versus CU and CA). Among cellulosic membranes, HE is the most biocompatible and appears to be an important step in preventing blood-membrane interactions and related complications.


In this paper, diffraction of sound waves through a lined cavity is analyzed rigorously. The inner–outer surfaces of the cavity and the base of the cavity are coated with three different absorbing linings. By using the Fourier transform technique in conjunction with the Mode-Matching method, the related boundary value problem is formulated as a Wiener–Hopf equation. In the solution, two infinite sets of unknown coefficients are involved that satisfy two infinite systems of linear algebraic equations. Numerical solution of this system is obtained for various values of the parameters of the problem. The graphical results are also presented which show that how efficiently the sound diffraction can be reduced by selection of problem parameters.


A trial was carried out at the lowland experimental field of National Cereals Research Institute, Badeggi, Nigeria during the cropping seasons of 2005 and 2006 to determine the effect of preceding lowland rice with cassava/legume intercrop in the dry season on weed dynamics and rice grain yield. The treatments consisted of FARO 52 rice variety cultivated after cassava ( IIT 427 and Bida local ) intercropped with Mucuna pruriens, Soybean TGX 1019 – 2EN and Cowpea IAR 48 and sole cassava ( IIT 427 and Bida local ) and fallow as the control. The treatments were factorials combined and arranged in a randomized complete block design and replicated three times each year. The results indicated that the least weed dry matter and percentage weed cover score were obtained when rice was cropped after cassava IIT 427 intercropped with M. pruriens, also in plots where cassava Bida local was intercropped with M. pruriens. The highest weed dry matter and occurrence of troublesome weeds such as Leersia hexandra, Echinochloa colona and Echinochloa stagnina were recorded in rice grown after fallow. The highest grain was obtained in rice cultivated after cassava cowpea intercrop.


Introducing of financial transmission right (FTR) is a significant trend in transmission congestion management and is also the center of debates. Based on the existing research, this paper introduces the mode of PJM FTR auction market used in congestion management and proposes an integrated process of congestion management including both contract and spot markets. As an analyzing result, this paper points out that FTR used in congestion management is more appropriate to the deregulated environment, which can hedge congestion charges, show the accurate signals, and so on. However, some bidders may have market power to influence the FTR auction clearing price, and as they make inaccurate forecasting of the system operation mode, FTR they owned may become a liability. In addition, in order to assess the bidders' economic effect during the congestion management with FTR, an index zetai called net compensation index (NCI) is defined with which bidders' economic effect can be quantificationally evaluated. The numerical simulation results of IEEE 30-bus system demonstrate that the efficiency of the suggested approach with NCI.


This article describes the synthesis of donor–acceptor (D–A) type copolymers based on benzo[1,2-b:4,5-b′]dithiophene and 2,1,3-benzothiadiazole via direct-arylation cross-coupling polycondensation. To achieve high performance polymerization, we have systematically investigated the reaction factors including catalysts, solvents, ligands, bases, additives, concentration of reactants and phase transfer agents. In particular, 1,2-dimethylbenzene (ODMB), as a nonpolar high boiling point solvent, is a superior medium to perform this direct-arylation polymerization. In this nonpolar aromatic solvent, Pd2dba3/(o-MeOPh)3P, accompanied with a base potassium carbonate and an additive pivalic acid, serves as an efficient catalyst system to obtain high-quality polymers. Our optimized condition gave the polymer with a weight-average molecular weight (Mw) as high as 60 kg mol−1 in nearly quantitative yield and excellent C–H selectivity.


Ultrasonography with graded compression was performed in 525 patients with clinical signs of acute appendicitis. Of 207 patients with surgically proven appendicitis the inflamed appendix (diameter ≧ 6 mm) had been visualized sonographically in 177 (86 per cent). The score for non‐perforated appendicitis (91 per cent) was higher than for perforated appendicitis (55 per cent). Twenty‐four patients in whom an inflamed appendix was seen on ultrasonography did not undergo surgery because of rapidly subsiding symptoms ('abortive appendicitis'). Four of these 24 developed recurrent appendicitis warranting surgery. Two underwent elective appendicectomy and 18 have remained symptom‐free. Of 155 patients with a subsequently confirmed alternative condition, ultrasonography made the correct diagnosis in 140: bacterial ileocaecitis (69), mesenteric lymphadenitis (eight), gynaecological conditions (34), urological conditions (eight), caecal diverticulitis (six), perforated peptic ulcer (six), Crohn's disease (two) and miscellaneous conditions (seven). Of 139 patients in whom no definite diagnosis was made ultrasonography showed no abnormalities in 138. In four patients a false positive sonographic diagnosis of appendicitis was made and in two patients with appendicitis an alternative condition was incorrectly diagnosed. During the last 3 years of the study the negative appendicectomy rate was 7 per cent and delay beyond 6 h after admission occurred in only 2 per cent of patients with surgically proven appendicitis. When used to complement the clinical diagnosis ultrasonography improves the diagnostic accuracy and patient management in those suspected of having acute appendicitis.


The electrical characteristics of GaAs-metal and GaAs-electrolyte Schottky barrier diodes have been studied as a function of applied voltage and of frequency, using conventional Schottky barrier C-V analysis and I-V measurements. For forward voltages approaching the flat-band voltage, i.e. the diffusion voltage, the measured capacitance deviates from a linear C-2 versus V dependence, i.e. the C-2 value drops steeply and a 'knee' in the Mott-Schottky plot is observed. This effect is found for the equivalent series capacitance Cs as well as for the equivalent parallel capacitance Cp, but in a different voltage range. The 'knee' in the Cp-2 versus V and in the Cs-2 versus V plots is explained. The difference between these two plots is attributed to the forward current.


Transcriptional activation of NF-kappaB is mediated by signal-induced phosphorylation and degradation of its inhibitor, IkappaBalpha. NF-kappaB activation induces a rapid resynthesis of IkappaBalpha which is responsible for postinduction repression of transcription. Following resynthesis, IkappaBalpha translocates to the nucleus, removes template bound NF-kappaB, and exports NF-kappaB to the cytoplasm in a transcriptionally inactive form. Here we demonstrate that IkappaBalpha interacts directly with another nucleocytoplasmic shuttling protein, hnRNPA1, both in vivo and in vitro. This interaction requires one of the N-terminal RNA binding domains of hnRNPA1 and the C-terminal region of IkappaBalpha. Cells lacking hnRNPA1 are defective in NF-kappaB-dependent transcriptional activation, but the defect in these cells is complemented by ectopic expression of hnRNPA1. hnRNPA1 expression in these cells increased the amount of IkappaBalpha degradation, compared to that of the control cells, in response to activation by Epstein-Barr virus latent membrane protein 1. Thus in addition to regulating mRNA processing and transport, hnRNPA1 also contributes to the control of NF-kappaB-dependent transcription.


OBJECTIVE
To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment.

METHODS
Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide).

RESULTS
The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension.

CONCLUSION
In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.


Cultures of Chloropseudomonas ethylica strain 2-K obtained from several laboratories were examined. All cultures examined to date in this laboratory contained nonmotile, green, photosynthetic bacteria (Chlorobiaceae) identical to published descriptions of Chlorobium limicola and at least one colorless, motile bacterium. All attempts to isolate motile photosynthetic bacteria corresponding to published descriptions of C. ethylica from such cultures have been unsuccessful. Several physiological characteristics previously ascribed to C. ethylica 2-K are expressions of mixed cultures rather than the property of a single species.


ABSTRACT This paper considers the twin forces of an ageing population and climate change effects in the context of global warming. Inclusive and Sustainable Design approaches respectively attempt to respond to one but not both of these phenomena, producing 'unsustainable inclusivity' and 'deterministic sustainability' outcomes. Both produce counterfactual, even perverse, social and environmental effects, including the failure of design and other standards and guidance to produce the desired benefits. By drawing on the author's empirical research on sustainable urban environment and transport projects, a science-technology-design conceptual approach is explored in order to bridge these design and society-nature divides by integrating inclusive/human-centred and environmental/sustainable design fields. The paper suggests Science Technology Society (STS) studies rather than fragmented design specialisms as an alternative perspective to address these wicked problems.


The Victoria mode (VM) represents the second dominant mode (empirical orthogonal function, EOF2) of North Pacific variability, independent of the Pacific Decadal Oscillation and is defined as the EOF2 of SST anomalies in the North Pacific poleward of 20°N. The present study indicates that the VM is closely linked to the development of El Niño–Southern Oscillation (ENSO). The VM may effectively act as an ocean bridge (or conduit) through which the extratropical atmospheric variability in the North Pacific influences ENSO. The VM can trigger the onset of ENSO via the following two dominant processes: (1) surface air‐sea coupling associated with the VM in the subtropical/tropical Pacific and (2) evolution of subsurface ocean temperature anomalies along the equator associated with the VM. These two processes may force sufficient surface warming to occur in the central eastern equatorial Pacific from spring to summer, which in turn initiates an ENSO event. The VM influence on ENSO relies on a basin‐scale air‐sea interaction dynamic, as opposed to more local‐scale dynamics typically associated with the seasonal footprinting mechanism or Pacific meridional mode. The majority of VM events are followed by ENSO events. These ENSO events triggered by VM include El Niño Modoki (EM) as well as conventional El Niño. There is no evidence that the VM tends to be more conducive to the initialization of EM than conventional El Niño.


Purpose: To compare the size of the masseter and lateral pterygoid muscle between the affected and the unaffected side of the patients who have the chief complaints of the mandibular asymmetry. Materials and Methods: Twenty two patients (male: 4, female: 18, average age: 21.3 year-old) were radiographed using posterior-anterior (P-A) cephalography and computed tomography (CT). On P-A cephalography, the degree of deviation was determined by the distance from the mentum to the vertical reference line through the crista galli and the anterior nasal spine. On the scanned tracing papers of the maximum cross-sectional area of the masseter and lateral pterygoid muscle using axial CT images, the pixel number was measured. The ratio of the affected : unaffected sides were obtained. For the masseter and lateral pterygoid muscle, the relationship between the muscular volume and degree of skeletal hypoplasia was studied. Results : The half cases showed no skeletal asymmetry. The lateral pterygoid muscle of the affected side was larger significantly than unaffected side (p


Wideband radars are promising systems that may provide numerous advantages, like simultaneous detection of slow and fast moving targets, high range-velocity resolution classification, and electronic counter-countermeasures. Unfortunately, classical processing algorithms are challenged by the range- migration phenomenon that occurs then for fast moving targets. We propose a new approach where the range migration is used rather as an asset to retrieve information about target velocities and, subsequently, to obtain a velocity dealiased mode. More specifically three new complex spectral estimators are devised in case of a single low-PRF (pulse repetition frequency) wideband waveform. The new estimation schemes enable one to decrease the level of sidelobes that arise at ambiguous velocities and, thus, to enhance the discrimination capability of the radar. Synthetic data and experimental data are used to assess the performance of the proposed estimators.


A difficult problem in robotics is enabling a robot to navigate autonomously through a previously unexplored indoor environment. Part of this difficulty stems from the stringent requirements on the mobility and the power of a robotic platform. It is necessary that the platform has sufficient maneuverability to operate in a cluttered area and that it has sufficient power to carry the necessary sensors to operate autonomously. The Segway Robotic Mobility Platform (RMP) combines unusually high mobility with the power to carry a sufficient number of sensors to navigate in an indoor environment. This paper discusses how, using a laser range finder, a stereo camera, and the Segway's on-board encoders, the Segway RMP can be enabled to perform tasks of autonomous navigation while navigating through an area with obstacles.


We derive one loop constraints on the anomalous quartic gauge couplings using a general non-forward dispersion relation for the elastic scattering amplitude of two longitudinally polarized vector bosons. We show that for exactly chiral theories more stringent bounds can be obtained by the assumption that the underlying theory satisfies the causality principle of Special Relativity.


This study proposes a methodology for estimating places where people may perform additional activities with utilizing the concept of space-time prism. Decision about travel behaviour can be affected by time constraints of their life and spatial structure where they live. Considering such constraints is important to estimate which place is likely to be chosen for the additional activities. This study develops a method to estimating the place which people may choose as an additional destination. This method proposes the concept of path constrained potential path area (P-PPA) by incorporating the concept of space-time prism with information of revealed trip trajectories which can be taken by position detection tools such as GPS and so on. An efficient calculation algorithm with considering actual network structure is proposed. An empirical test has been carried out in the real network to check the proposed methodology.


A simple in vitro biosensor for the detection of β-amyloid 42 in phosphate-buffered saline (PBS) and undiluted human serum was fabricated and tested based on our platform sensor technology. The bio-recognition mechanism of this biosensor was based on the effect of the interaction between antibody and antigen of β-amyloid 42 to the redox couple probe of K4Fe(CN)6 and K3Fe(CN)6. Differential pulse voltammetry (DPV) served as the transduction mechanism measuring the current output derived from the redox coupling reaction. The biosensor was a three-electrode electrochemical system, and the working and counter electrodes were 50 nm thin gold film deposited by a sputtering technique. The reference electrode was a thick-film printed Ag/AgCl electrode. Laser ablation technique was used to define the size and structure of the biosensor. Cost-effective roll-to-roll manufacturing process was employed in the fabrication of the biosensor, making it simple and relatively inexpensive. Self-assembled monolayers (SAM) of 3-Mercaptopropionic acid (MPA) was employed to covalently immobilize the thiol group on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N–hydroxysuccinimide (NHS) was undertaken for cross-linking antibody of β-amyloid 42 to the carboxylic groups on one end of the MPA. The antibody concentration of β-amyloid 42 used was 18.75 µg/mL. The concentration range of β-amyloid 42 in this study was from 0.0675 µg/mL to 0.5 µg/mL for both PBS and undiluted human serum. DPV measurements showed excellent response in this antigen concentration range. Interference study of this biosensor was carried out in the presence of Tau protein antigen. Excellent specificity of this β-amyloid 42 biosensor was demonstrated without interference from other species, such as T-tau protein.


OBJECTIVE
The aim of this study was to evaluate the effect of micro ribonucleic acid (miR)-26a on myocardial ischemia-reperfusion (I/R) injury in rats and to explore its potential mechanism. Our findings might help to provide references for clinical prevention and treatment of myocardial I/R.

MATERIALS AND METHODS
A total of 60 male Sprague-Dawley (SD) rats were randomly divided into three groups using a random number table, including: Control group (n=20), I/R group (n=20) and I/R + miR-26a siRNA group (n=20). I/R model was established via recanalization after ligation of left anterior descending coronary artery (LAD). The model of miR-26a knockdown was established in rats of I/R + miR-26a siRNA group via tail intravenous injection of miR-26a siRNA. Ejection fraction (EF%) and fractional shortening (FS%) of rats in each group were detected via echocardiography. The infarction area of each group was detected via 2,3,5-triphenyltetrazolium chloride (TTC) assay. Subsequently, morphological changes in myocardial cells of each group were detected via hematoxylin-eosin (H&E) staining. Myocardial apoptosis level was measured via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. At the same time, the expression levels of pro-apoptotic proteins Bcl-2 associated X protein (Bax) and cleaved (C)-caspase3 in myocardial tissues of the three groups were determined using Western blotting. Finally, the effects of miR-26a knockdown on the expressions of glycogen synthase kinase (GSK)-3β/β-catenin signaling pathway-related proteins were detected via Western blotting and immunohistochemistry.

RESULTS
The expression of miR-26a in myocardial tissues of I/R group increased significantly when compared with that in Control group (p<0.05). Knockdown of miR-26a significantly improved cardiac insufficiency caused by I/R, which also obviously increased both EF% and FS% in rats (p<0.05). In addition, knockdown of miR-26a significantly inhibited myocardial infarction caused by I/R injury, and reduced infarction area from (43.08±2.43) to (21.54±1.82) (p<0.05). The results of H&E staining revealed that in I/R + miR-26a siRNA group, myofilaments were arranged more orderly, the degree of degradation and necrosis was significantly lower, and cellular edema was significantly alleviated when compared with I/R group. Subsequent TUNEL staining demonstrated that rats in I/R + miR-26a siRNA group showed a remarkably lower level of myocardial apoptosis than I/R group (p<0.05). Meanwhile, the protein expression levels of Bax and C-caspase3 were remarkably declined in I/R + miR-26a siRNA group (p<0.05). Furthermore, the results of Western blotting showed that miR-26a siRNA could significantly reverse the inhibition of GSK-3β/β-catenin signaling pathway induced by I/R injury (p<0.05).

CONCLUSIONS
Knockdown of miR-26a could significantly improve I/R-induced myocardial injury and promote cardiac function in rats. The possible underlying mechanism might be related to targeted regulation of miR-26a on GSK-3β/β-catenin signaling pathway. Therefore, miR-26a was expected to be a new therapeutic target for myocardial I/R injury.


My object in this paper will be to point out some of the various modes in which the continued existence and integrity of each of the great kingdoms of organized nature are made to be dependant upon the continuation of the same conditions on the part of the other. To show how the animal races of the present era are indebted to the agency of vegetable life in former geological epochs for the perfect adaptation of our atmosphere, and of the superficial strata of the solid globe, to their physical requirements; and how, by the mutual reactions, and counteractive influences of plants and animals, the atmosphere, the waters, and the more solid materials of the surface of our planet, are now retained permanently in a condition most exactly adapted to the necessities of both. Thus evincing most clearly that animal, vegetable, and mineral are all the results of the agency of one Mind, and that a Mind of benevolence and perfect wisdom.

It will be seen that for several of the facts and conclusions adduced in this paper, I am indebted to the writings of organic chemists of our own day; more particularly of Liebig, Dumas, and Boussingault, whose penetration and research have disclosed to us so many facts before hidden, relating to the more remote and intimate changes which take place in the performance of the functions of organised beings. Besides these, the views of botanists and physiologists of our own country have been likewise considered.

Our planet is, ...


In depth study of NO reveals that NO is a bioactive molecule that exerts a number of roles in many physiological and pathological process.NO is produced in response to drought,salinity,temperature shock and pathogen attack.NO rapidly reacts with ROS,ABA and other hormones and directly or indirectly regulate ethylene biosynthesis.The authors review the response of between plant NO and kinds of stresses,and possible mechanism was discussed.


In this paper, we establish multilinear BMO estimates for commutators of multilinear fractional maximal and integral operators both on product generalized Morrey spaces and product generalized vanishing Morrey spaces, respectively. Similar results are still valid for commutators of multilinear maximal and singular integral operators.


Holt-Oram syndrome is a rare, autosomal dominant syndrome characterized by upper extremity skeletal abnormalities and cardiac defects. The most common skeletal anomalies involve the thumbs and range from minor radiographic abnormalities to phocomelia. The most common cardiovascular abnormality is ostium secundum ASD, followed by ventriculo-septal defect and ostium primum ASD. MVP and hypoplastic peripheral vasculature of the upper extremities have been reported only rarely. We have reported the case of a patient with HOS who has both hypoplastic peripheral upper extremity vasculature and evidence of MVP.


Alternative to the least square coefficient of determination, R-squared OLS, the coefficient of determination based on median absolute deviation, R-squared MAD, is an attractive consideration in the construction of goodness-of-fit test based on regression and correlation, due to its robustness. This book focused on the observations made from the resulting plots and descriptive measures obtained from contaminated standard logistic distribution. Contamination is introduced to investigate perseverance of robustness property of R-squared MAD for samples from the standard logistic distribution. The early section of the book is devoted to the investigation of the symmetricity of the sampling distribution of R-squared MAD and its confidence intervals in the presence of outliers. This is followed by constructing tables of critical values for samples from the standard logistic distribution. Then a power study on the goodness-of-fit test using test statistic ZMAD and ZOLS is conducted via simulation. The results indicated that the test statistic ZMAD is able to discriminate the sample that comes from alternative distributions as the test statistic ZOLS.


This study aims to see and analyze the readiness of teachers and students in the National Assessment. The research was conducted with a survey method through the distribution of google form questionnaires. The data obtained were analyzed using descriptive statistics. The results of the study group of students showed that 46.6% of students understood national assessment and 53.2% of students did not understand well about national assessment. This is due to the fact that the education unit has not yet disseminated the implementation of the national assessment which has three instruments including the Minimum Competency Assessment (AKM), learning surveys and learning environment surveys. The results of the teacher group research stated that 75% of teachers understood national assessment and 25% of teachers did not understand national assessment. A national assessment is carried out to evaluate the input, process, and quality of teaching and learning in the classroom so as to improve the quality of Indonesian education.


This paper proposes an H ∞ controller design method for Takagi-Sugeno (T-S) fuzzy systems using a fuzzy basis-function-dependent Lyapunov function. Sufficient conditions for the guaranteed H ∞ performance of the T-S fuzzy control system are given in terms of linear matrix inequalities (LMIs). These LMI conditions are further used for a convex optimization problem in which the H ∞ -norm of the closed-loop system is to be minimized. To facilitate the basis-function-dependent Lyapunov function approach and thus improve the closed-loop system performance, additional decision variables are introduced in the optimization problem, which provide an additional degree-of-freedom and thus can enlarge the solution space of the problem. Numerical examples show the effectiveness of the proposed method.


The effect of temperature, milk acidity and time of curd holding on the degree of passage of enzymic coagulating preparations, was studied. It was found that the degree of the passage of the examined preparations was increasing together with the rise of temperature and milk acidity. Any significant effect of the curd's holding on the quantity of the preparation in the cheese grain was not found.


Farmers are increasingly turning to aerial applications of pesticides, fertilizers and other materials. Sometimes uneven distribution of the chemicals is caused by worn nozzles, improper alignment of spray nozzles or system leaks. If this happens, job must be redone with added expense to both the pilot and customer. Traditional pattern analysis techniques take days or weeks. Utilizing NASA's wind tunnel and computer validation technology, Dr. Roth, Oklahoma State University (OSU), developed a system for providing answers within minutes. Called the Rapid Distribution Pattern Evaluation System, the OSU system consists of a 100-foot measurement frame tied in to computerized analysis and readout equipment. System is mobile, delivered by trailer to airfields in agricultural areas where OSU conducts educational "fly-ins." A fly-in typically draws 50 to 100 aerial applicators, researchers, chemical suppliers and regulatory officials. An applicator can have his spray pattern checked. A computerized readout, available in five to 12 minutes, provides information for correcting shortcomings in the distribution pattern.


This study was designed to detect biofilm and bacteria on right heart flow-directed catheters using scanning electron microscopy and culture following scraping and dispersion of biofilm by sonication. We examined 20 consecutive catheters removed from 18 critically ill patients, an average of 2.6 days after insertion. On scanning electron microscopy, all catheters were found to be covered by a biofilm, with bacteria visible on 50 percent of them. Cultures of specimens from 40 percent of the catheters grew skin organisms (Staphylococcus warneri, Diphtheroid), anaerobes (Propionibacterium), and other potential pathogens (Proteus vulgaris, Enterobacter cloacae). Combination of the two techniques produced a bacterial detection rate of 75 percent. This study demonstrates that the presence of biofilm with bacterial adherence is common on right heart flow-directed catheters. The phenomenon could play a significant role in endogenous infection in critically ill patients.


In everyday life people are simultaneously exposed to several annoying sources (sounds, vibrations and odours), which emerge from background of considerable variability of land uses, infrastructures, residential patterns, topography, meteorology condition, and standards quality of life. The European Union has provided in recent years (and is going to update) several tools to harmonize noise mapping methodologies and relative Noise Action Plans through directives and guidelines. Unfortunately the same efforts have not been put in the harmonization of approaches in other annoying sources like odours. As a consequence, each European Member State at national or even at local level defined its own direct or indirect approach to limit odour impacts, usually considerably different one from the others. The most common approach to deal with noise impact at a policy, economic and strategy level is the use of priority indices focused to highlight areas more sensitive and where mitigation actions will be more advisable or urgent. Locations that for their specific land use are more sensitive to noise impacts (e.g. residential areas) are generally also sensitive to odour impacts. According these, the aim of the present research is to provide a brief review of the most used European strategies in noise action plans end try to extend their approaches for the definition of a nuisance action plan, able to control both odour and noise. Paper present a possible implementation of integrated nuisances action plan in the municipality of Palma Campania (Campania Region, Italy). The analysis underlines that is possible define, under the same set of nuisance indicators, the degree of sensitivity of areas according to population, land uses, levels of exposures and/or distance from the annoying sources. Nuisance acceptability levels are then definable according to the sensitivity degree of the locations. Factors related to vibrations and visual perception of the landscape can further contribute to control total sensorial annoyance in the land planning.


Acute haemorrhage from ruptured oesophageal varices is a serious consequence of portal hypertension in cirrhotic patients. It represents a medical emergency with a high morbidity and mortality rate. Studies over the years have shown a direct link with chronic alcoholism in the development of such complications. Although the gastrointestinal system accounts for a few numbers of sudden deaths, bleeding through ruptured varices represent a life-threatening condition. The role of forensic pathologist is vital in dealing with sudden deaths. Here, we report a case of a 46-year-old man who died suddenly following the rupture of oesophageal varices.


Introduction:  Tobacco is the single most important avoidable cause of premature morbidity and mortality in the world. Tobacco dependence is a chronic condition that often requires repeated interventions. Since oral medicine experts are the first to note any changes that can occur in the oral cavity, they can play a major role in its prevention and intervention. There are well-tried and cost-effective methods for interventions. An oral medicine expert can play an effective role in tailoring a special and specific cessation programme for every individual to improve quit rate and prevent relapse.
Objective: This review is prepared with the objective to help Oral Medicine Experts to guide differential prescribing practices and tailoring pharmacotherapy for tobacco cessation.
Conclusion: Interventions by Oral Medicine Experts have been found to be effective in helping people to quit tobacco.

Keywords: Tobacco dependence, tobacco cessation, oral medicine expert, nicotine replacement therapy.


The final article of this four-part series explores the appendicular skeleton. The term 'appendicular skeleton' derives from the Latin word appendic--to hang on. The appendicular skeleton consists of the four limbs and the pectoral (shoulder) and pelvic girdles, which connect them to the axial skeleton (see part 3 of this series; Docherty, 2007). It has a total of 126 bones.


Since the multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study was published, the pursuit of tight glycemic control (TGC) among intensive care unit (ICU) patients has been seen as counterproductive and moderate glycemic control has become standard practice in ICUs. However, thus far, there is good evidence that hypoglycemia and hyperglycemia are associated with worse outcomes in ICU patients. Recently, the importance of improving time in band and reducing hypoglycemic episodes and glycemic variability has been more recognized. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can have greater clinical benefit in terms of the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and accurately. In this review, modern methods for glucose control in the ICU are presented, as well as future perspectives including the development of CGM and semiautomated glucose control, such as closed-loop systems.


The severity of SARS-CoV-2 infection is marked by elevated cytokines and chemokines levels like interleukin 6 (IL-6), interferon-gamma (IFN-γ), tumour necrosis factor (TNF), IL-2 and monocyte chemotactic protein 1 This hyperactive pro-inflammatory response identified as the Cytokine Storm (CS) complicates the disease leading to extensive damage of the host tissue, Acute Respiratory Distress Syndrome (ARDS), which further result in multiple organ failures CS is very critical for the disease progression and is responsible for high death rate in an infected patient Accordingly, various therapeutic modalities are currently investigated for their effectiveness in subsiding the hyper-inflammatory syndrome either using immunomodulatory agents or anti-inflammatory therapies Phytochemical (herbal) compounds are demon-strated to possess anti-inflammatory, antimicrobial or antioxidants proper-ties Various signalling pathways and molecules exacerbating the inflammation state complicate the pathophysiology of COVID-19 Cucurbitacins are tetracyclic bioactive phytochemical compounds found in cucurbitaceous plants More than 100 species of cucurbitacins possess various pharmaco-logical properties, including anti-inflammatory Cucurbitacin E and R have shown to be down-regulated the expression of TNF alpha and IL-1beta Cucur-bitacin II B also alleviates the expression of TNF-α as well as IFN-γ and IL-6 Cucurbitacin1 has the potential to reduce the oxidative stress-induced with the reactive oxygen species, and thus prevents cardiovascular damage Thus cucurbitacins may be pharmacologically manipulated to establish its clinical efficacy in minimizing the disease state and improvising the prognosis of the patients


Small telescopes can play an important role in the search for exoplanets because they offer an opportunity for high cadence observations that are not possible with large aperture telescopes. However, there is a shortage of high resolution spectrometers for precision Doppler planet searches. We report on an innovative design for CHIRON, an inexpensive spectrometer that we are building for the 1.5-m telescope at CTIO in Chile.The resolution will be R >80.000, the spectral format spanning 410 to 880 nm. The total throughput of the telescope and spectrometer will be better than 12%, comparable with the efficiency of state-of-the-art spectrometers. The design is driven by the requirements for precision Doppler searches for exoplanets using an iodine cell.The optical layout is a classical echelle with 140 mm beam size. The bench-mounted spectrometer will be fibre-fed followed by an image slicer. An apochromatic refractor is used as the camera. Image quality and throughput of the design are excellent over the full spectral range. Extensive use of commercially available components and avoidance of complicated custom optics are key for quick and resource-efficient implementation.


Background: Hyperglycaemia on presentation with acute ischaemic stroke (AIS) is associated with poor outcome, but intervention is unproven. We investigated the safety and tolerability of one method of glycaemic control. Methods: Patients within 24 h of AIS and plasma glucose 8–20 mmol/l were randomised to receive either rigorous glycaemic control (RC) or standard management (SM) for 48 h. RC comprised i.v. insulin at a variable rate adjusted for target glucose concentration of 5–8 mmol/l, and intravenous crystalloid. The SM group received intravenous crystalloid alone in an open-label design. Results: Thirteen patients were randomised to RC and 12 to SM (age 75 ± 6.2 years; 40% male; 20% lacunar stroke; time to treatment 8 ± 6.1 h; plasma glucose 10.6 ± 0.9 mmol/l; known diabetes 52%; NIHSS 8, range 2–28). The glucose concentration-time curve was reduced in the RC group (AUC 324 ± 15 versus 385 ± 28 h·mmol/l, p = 0.04). By 48 h, plasma glucose in both groups was 6.8 ± 1.1 and 7.5 ± 1.3 mmol/l respectively, but mean hourly insulin requirements in the RC group had dropped from 3.25 ± 0.32 units to 1.25 ± 0.5 units (p < 0.01). One transient episode of hypoglycaemic symptoms occurred in the RC group. Conclusion: Glycaemic control with sliding scale insulin for 48 h is feasible and well-tolerated after AIS. Treatment after 48 h may be unnecessary.


In June 2011, Dr. Willmar Schwabe Pharmaceuticals sponsored a two-day expert meeting in Amsterdam, The Netherlands. The meeting brought together 19 dementia experts from a range of disciplines and countries to review preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of recent developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease (AD). Ginkgo biloba special extract EGb 761® is formally approved and reimbursed for the symptomatic treatment of age-related cognitive decline or dementia by numerous authorities worldwide. The meeting therefore focused on relevant research questions and potential study designs with appropriate target populations to prove the efficacy of Ginkgo biloba special extract EGb 761® as a disease-modifying product in AD and to reveal further relevant modes of action.

This supplement summarizes the key presentations and discussions from the meeting. The first two papers set the scene by looking at the current status of research in the field of brain aging and AD in general. Professor Christian Behl argues that research has tended to focus on particular pathways and mechanisms at the expense of other theories and so might be slowing progress in the field. He proposes new avenues for research exploration that may lead to a better understanding of the pathophysiology of AD and therefore to improved approaches to its prevention and treatment. Professor Harald Hampel discusses the challenges that face those developing therapies for AD, with many drugs that show promise at one stage of research falling at the next hurdle and many drugs currently under investigation acting perhaps too late in the disease process to have meaningful effects. He proposes new models of disease, biomarkers, outcomes and endpoints that may allow targeting of specific mechanism-derived therapies at different points in the disease process in order to increase opportunities for preventative intervention in the early stages.

In the next three papers, the focus turns to preclinical research with Ginkgo biloba special extract EGb 761®. Dr. Anne Eckert describes the role of oxidative stress and mitochondrial failure in the early stages of AD development. She reviews data showing that a combination of several compounds within Ginkgo biloba special extract EGb 761® produces protective effects such as a reduction in oxidative stress and long-term regulation of mitochondria. Professor Walter Muller and colleagues describe data showing that the active fractions of Ginkgo biloba special extract EGb 761® improve neuroplasticity, which is increasingly impaired as people age and in patients with AD. The enhancement of endogenous neurogenesis employing Ginkgo biloba special extract EGb 761® might therefore be a promising option for the treatment of AD. Professor J. Kehr et al. describe a study investigating the effects of Ginkgo biloba standardized extract EGb 761® on extracellular levels of neurochemicals in rats. The study provides evidence that subacute treatment with EGb 761® and its flavonol constituents increases release of dopamine and acetylcholine release in the rat medical prefrontal cortex and suggest that Ginkgo- specific acylated flavonol glycosides actively contributed to these effect. The direct involvement of these two flavonol derivatives in the increase of dopaminergic and cholinergic neurotransmission in the prefrontal cortex may be one of the underlying mechanisms behind the reported effects of EGb 761® on improvement of cognitive functions.

Two further papers look at data available from clinical research with Ginkgo biloba special extract EGb 761® , which has been ongoing for many years. Professor Ralf Ihl reviews the clinical data obtained with Ginkgo biloba special extract EGb 761® in patients with dementia, which show that this product improves cognitive function, neuropsychiatric symptoms, activities of daily living and quality of life in patients with mild to moderate dementia compared with placebo. It also proves to be at least as effective as memantine, galantamine and donepezil regarding improvements in neuropsychiatric symptoms, and has no important safety concerns. Professor Siegfried Kasper reviews the body of research into early intervention for AD and dementia, which has involved cohort data from large epidemiological studies and specifically designed intervention trials. Although conclusions from the large trials are limited by poor medication adherence, Ginkgo biloba special extract EGb 761®, with its long history of use and excellent safety record, does seem to have potential benefits in terms of reduced incidence of dementia of the AD type, reduced progression in terms of the clinical dementia ratings, and improvements in attention and memory.

In the final paper, Professor Nicola Lautenschlager and colleagues summarize the conclusions of the meeting. Ginkgo biloba special extract EGb 761® is a multi-target compound with activity on distinct pathophysiological pathways in AD and age-related cognitive decline. Although symptomatic efficacy in dementia and mild cognitive impairment has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The wealth of promising preclinical and clinical data makes future research with the compound targeting cognitive impairment in old age a worthwhile activity.


The synaptic action of afferent fibers on motoneurons in the spinal cord is among the longest studied problems in the central nervous system but is still far from being fully understood. This article reports on the remarkable feat of recording from a single motoneuron activated by a single fiber, followed by labeling of both to identify unequivocally the relevant synapses.


Exercise can be used as a mood regulator but, in the eating disorder literature, exercise has sometimes been found to be compulsive, detrimental to physical health, and regarded as one maladaptive strategy used to regulate emotions. This study examined longitudinal associations between emotion regulation styles and this compulsive exercise in 572 adolescents who completed measures of compulsive exercise and emotion regulation. Twelve months later they completed measures of compulsive exercise. Compulsive exercise was predicted by Internal Dysfunctional emotion regulation in girls and boys, even after controlling for initial levels of compulsive exercise. Adolescents displaying compulsivity to exercise may require intervention programmes to alter their emotion regulation strategies.


Introduction: Enlargement of lymph nodes is one of the most common presentations in inflammatory and neoplastic disorders. Persistent enlargement of lymph nodes requires detailed investigations to reveal an underlying pathology. Clinical features and radiology images may not be sufficient for diagnosing lymph node lesions. Hence, histopathology has become a mandatory tool to arrive at a definitive diagnosis. Aim: To evaluate histopathological patterns of various lymph node lesions. Materials and Methods: The present prospective study was undertaken in the Department of Pathology, Maharashtra Institute of Medical Sciences and Research, Latur, Maharashtra, India, from October 2016 to September 2018. Information regarding clinical history, and examination was noted from case sheet of patients. Total 104 lymph nodes were grossly examined and processed in routine paraffin technique and then stained with haematoxylin and eosin. Meticulous histopathological examination was done in each case to arrive at correct histopathological diagnosis. Special stains and immunohistochemistry were performed wherever mandatory or indicated. Qualitative data was presented as frequency and percentages. Results: Total 104 patients were studied, majority were males {n=56 (53.8%)} and mean age was 46 years. Reactive lymphadenitis was the most common cause of lymphadenopathy forming 60 (57%) cases. The metastatic lesions were in 23 (21.1%) cases. Other lesions encountered were tubercular lymphadenitis in 15 (14.3%) cases, diffuse large B-cell lymphoma in 3 (2.9%) cases, 58 (55.7%) patients had cervical lymphadenopathy and 35 (33.6%) patients had axillary lymphadenopathy. Conclusion: Reactive lymphadenitis was the most common cause of lymphadenopathy in present study. Causes of lymphadenopathy can be suspected on clinical grounds, but histopathological examination is gold standard for early diagnostic and prognostic purpose. Special stains and immunohistochemistry should be done wherever mandatory or when indicated.


Analgesia for many open thoracic and abdominal procedures has traditionally been accomplished through neuraxial techniques or paravertebral blocks. Erector spinae plane (ESP) blocks purport effective analgesia over a similar anatomical distribution with a more favorable side effect profile and complication rate than epidurals. However, the extent of clinical applicability for ESP blocks has yet to be elucidated. In this case series, we demonstrate the efficacy of ESP blocks for 3 distinct etiologies of acute pain: planned perioperative analgesia, rescue postoperative analgesia, and traumatic pain.


To lower maintenance costs and improve a metro company's competitiveness, this research came up with an innovative technique using a considering sensitivity and analytic hierarchy process (CSAHP). Along with interviews with managers and workers at the Taipei Rapid Transit Corporation, this study was able to undertake quantitative analysis. To determine which subsystems and metro lines should be prioritized for outsourcing based on the CSAHP framework, we used the criterium decision plus (CDP) program. This research adds to the existing body of knowledge by advancing the existing analytic hierarchy process (AHP) technique and recommending the CSAHP strategy for assessment. According to the findings, the power supply system was the most in need of outsourcing, followed by air conditioning, firefighting, and elevator systems. When considering which of the four metro lines to outsource first, the blue line came out on top, followed by the red, green, and brown lines. By prioritizing the outsourcing of the power supply system as a result of this research, the Taipei Rapid Transit Corporation may cut the system's maintenance expenditures from USD 1.57 million to USD 1.33 million, saving 15% on maintenance costs. Applying these findings can improve the economic benefits of outsourced maintenance for the Taipei Rapid Transit Corporation.


The authors hereby propose diffraction imaging as a tool to de-risk small-scale features, as those related to a fractured carbonate reservoir. Diffraction imaging has indeed increasingly generated interest as a method for the detection and delineation of small-scale (less than the wave length) subsurface elements such as faults, pinchouts, karsts, fracture corridors, injectites, etc. These elements cause sharp changes/contrasts in the subsurface physical properties and geometry, and they are generic sources that scattered/diffracted seismic energy (Landa 2012). The diffracted energy carries however much lower intensity than the reflected one and this fact hinders the confident identification and delineation of the small-scale objects with standard methodologies. Therefore, the main aspect in diffraction imaging is the accurate separation of the diffracted and reflected components of the total wave field. Such separation can be performed efficiently in the structural dip-angle domain (Landa et al. 2008). In this study we present examples of diffraction imaging and interpretation for carbonate reservoirs. The results achieved show the high resolution and reliability of the proposed methodology.


Load forecasting plays an important role in power system planning and operation. In the present complex power system network under deregulated regime, power generating companies must be able to forecast their system demand and the corresponding price in order to make appropriate market decisions. Therefore, load forecasting, specially the short-term load forecasting (STLF) plays an important role for energy efficient and reliable operation of a power system. It provides input data for many operational functions of power systems such as unit commitment, economic dispatch, and optimal power flow and security assessment. This paper proposes a new and simple technique to calculate short term load forecasting using historical data and applied it to the Damodar Valley Corporation (DVC) grid operating under Eastern Grid (ERLDC-Eastern Regional Load Despatch Centre), India. This gives load forecasts half an hour in advance. The forecast error i.e. difference between calculated forecast load and real time load is a measure of the accuracy of the system, is found to be lower than other existing techniques like Holt's Method, Chow's Adaptive Control Method, Brown's One-Parameter Adaptive Method.


Trials were established in a highly eroded Ultisol soil of sandy loam texture, of poor fertility, acid, and low in phosphorus and organic matter, located in the locality of La Lena in Pinar del Rio province, Republic of Cuba. A study was carried ont in 1996 in two watersheds, in which were implemented conservation practices consisting of live barriers of Gliricidia Sepium L. (in the first watershed) and Vetiveria Ziznoide L. (in the second watershed) complemented with ground cover of maize associated with legumes followed by beans in succession. Results showed slight changes in slope between barriers with respect to the initial value (10% vs 9%). Values of total dry biomass in the associations were 17 and 15 t/ha, and ground coverage at 30 days was more than 70%. Profuse root colonization presented by the associations indicated an improvement in porosity of the soil, reflecting a positive tendency in the internal structure that has evolved to a porous state. Yields of maize were 2900 and 2000 kg/ha, and of bean were 1800 and 1630 kg/ha, which are relatively high values, considering the degraded condition of the soil.


Background Evidence shows lack of competency among health care professionals (HCPs) to demonstrate correct inhaler technique to patients.

Aim: We conducted a multicentre RCT at 2 tertiary hospitals to investigate whether simulation-based training using Aerosol Inhalation Monitor (AIM) and written information is more effective compared to training using written information alone.

Method 160 HCPS (69 doctors, 80 nurses, 8 physiotherapists, 3 pharmacists) were randomised into 2 groups of simulation and written information (Intensive Intervention Arm (IIA; n=80)) and written information only (Minimal Intervention Arm (MIA; n=80)) arms. Inhaler technique was assessed using the AIM machine and checklist score (maximum score 20; 10 for MDI and 10 DPI) which were conducted immediate-post teaching and 1-week after.

Results: Cumulative combined (MDI+DPI) median scores for the IIA group showed significant improvement at post-teaching compared to MIA at 1-week (p<0.001). However the significant improvement shown in the cumulative DPI group median score at 1-week from post-teaching (p <0.001) was not shown in cumulative MDI group (p=0.38).

Conclusion: Our study showed significant overall improvement in combined inhaler technique scores at 1-week using simulation with the AIM machine compared to written information alone. Surprisingly, the addition of simulation only improved DPI technique scores, but this was not reciprocated in MDI technique scores. These results need confirmation in longer and larger duration studies.


MR‐CAT (combined acquisition technique), a modular hybrid imaging concept, was introduced recently. In this article it is demonstrated that the CAT principles can be applied to form a versatile combination of spin and gradient echoes for abdominal imaging. This CAT approach, which essentially integrates RARE and EPI modules in a sequential fashion, was used to implement a set of segmented and single‐shot RARE/EPI‐CAT imaging techniques. CAT was used in in vivo studies to perform high‐resolution abdominal imaging in five healthy subjects. The results demonstrate the feasibility of abdominal imaging using the proposed CAT approach and the potential of this technique to reduce imaging time while preserving image quality. Magn Reson Med 47:425–432, 2002. © 2002 Wiley‐Liss, Inc.


In process-driven software development environment, process management plays an important role during the process execution. In order to achieve effective management of software processes, managerial decision makings on development process need to be based on the analysis of the software processes regarding the development environment. In this paper we propose a new approach to process management through the formal process modeling and analysis techniques, called MAM nets based on Pr/T net formalism. For the effective modeling and analysis, MAM nets provide high-level modeling constructs for both process activities and human resources. MAM nets not only support the standard Petri-net analysis techniques but also provide additional analysis techniques as well as the process enactment mechanism for the effective management of software processes.


Aiming at providing 100% throughput with bounded packet delay, we consider traffic scheduling in high-speed routers with optical switch fabrics. Because of the switch reconfiguration overhead, a speedup in the switch fabric is essential. For a given packet delay bound, our objective is to minimize the overall speedup S = Sreconfigure times Sschedule so as to lower the implementation cost. Leveraging on the existing ADAPTIVE and DOUBLE algorithms, we show the speedup can be reduced by improving scheduling efficiency. Specifically, following the traffic matrix decomposition in ADAPTIVE and DOUBLE, we shift some packets from the residue matrix R to the quotient matrix Q, while keeping the number of configurations required to cover each matrix the same. We reduce the number of time slots required to send the diminished residue matrix. In case of DOUBLE, this translates into a 12.5% cut in Sschedule (from 2 to 1.75). We call the resulting algorithm Scheduling Residue First (SRF).


Image clustering is a crucial but challenging task in machine learning and computer vision. Existing methods often ignore the combination between feature learning and clustering. To tackle this problem, we propose Deep Adaptive Clustering (DAC) that recasts the clustering problem into a binary pairwise-classification framework to judge whether pairs of images belong to the same clusters. In DAC, the similarities are calculated as the cosine distance between label features of images which are generated by a deep convolutional network (ConvNet). By introducing a constraint into DAC, the learned label features tend to be one-hot vectors that can be utilized for clustering images. The main challenge is that the ground-truth similarities are unknown in image clustering. We handle this issue by presenting an alternating iterative Adaptive Learning algorithm where each iteration alternately selects labeled samples and trains the ConvNet. Conclusively, images are automatically clustered based on the label features. Experimental results show that DAC achieves state-of-the-art performance on five popular datasets, e.g., yielding 97.75% clustering accuracy on MNIST, 52.18% on CIFAR-10 and 46.99% on STL-10.


The authors show possible variations of number changes of the Pacific salmon population. There are cyclic or regular fluctuations or chaotic dynamics. Far East salmon are classical example of nonuniform populations. A discrete mathematical model is suggested for the analysis of such population number dynamics. The basic model was investigated by analytic and numerical methods. This work discusses results of numerical investigations of number fluctuations of four real Kamchatka populations.


This article explores the difficulty that criminal justice social work (CJSW) might have in implementing a desistance approach to work with offenders. Supporting desistance requires responsive, autonomous social workers and this article questions whether criminal justice agencies, characterised by risk aversion and managerialism, would be able to tolerate the anxiety this would inevitably, and properly, generate. Suggestions are made regarding the place of desistance work within a positive human rights framework, which might provide a force against the corrosive progression of popular punitivism – a major factor in the persistence of risk averse, managerial practice.


For classical transformation (q1, q2) → (Aq1 + Bq2, Cq1 + Dq2), where AD – CB ≠ 1, we find its quantum mechanical image by using LDU decomposition of the matrix . The explicit operators L̂, D̂, and Û are derived and their physical meaning is revealed, this also provides a new way for disentangling some exponential operators.


The counselling and psychotherapy profession is changing. For the first time in its history, it has begun to receive substantial Government funding in the UK and it also has to contend with the principles of evidence-based practice and the policies of the New Public Management systems in many countries. This paper argues that such recent developments present challenges to the profession's historical apolitical standpoint. More importantly, it argues that the present social and political climate offers many opportunities such as the possibility of learning from psychosocial practices in other countries. The paper will look, in particular, at what can be learned from Latin America and India where mental health care and psychological therapy have adopted grassroots involvement, health-focused approaches and innovatory therapeutic methods.


PURPOSE
To study the alterations of the trabecular meshwork of Belgian and Congolese patients with open angle glaucoma (OAG).

METHODS
A trabeculectomy was performed in 27 OAG patients from Belgium and 24 from Congo; the trabecular specimens were fixed, embedded, stained, and studied by light microscopy. These specimens were compared with the trabecular meshworks from 5 Belgian non-glaucomatous eyes.

RESULTS
The mean number (+/- standard deviation) of trabecular cells per field was 69 (+/- 10) in Belgian normal eyes, 34 (+/- 17) in Belgian OAG patients, and 10 (+/- 6) in Congolese OAG patients. The trabecular meshwork was collapsed and Schlemm's canal was closed in the cases with a diminished number of cells. Pigmentation was present in 79% of the Congolese and in 35% of the Belgian specimens.

CONCLUSION
The trabecular meshwork from OAG patients has a lower cellularity than normal, and the effect is much more pronounced in the trabecular meshwork from Congolese patients. This may be a possible explanation for the racial differences in OAG and the more severe forms of glaucoma in black people.


Energy piles are subjected to shortand long-term cyclic thermal loads due to their unique role as heat exchangers. Their response to monotonic temperature change has been investigated by various researchers from both experimental and numerical points of view. Yet, their behaviour during cyclic temperature changes remained to be an obscure area to this date. To investigate this knowledge gap, a two-dimensional finite elements model has been developed employing the load-transfer approach coupled with Masing's Rule. The model has been validated by the results of an in-situ test which involved application of multiple temperature cycles to a full-scale energy pile.


An accelerating global energy demand, paired with the harmful environmental effects of fossil fuels, has triggered the search for alternative, renewable energy sources. Biofuels are arguably a potential renewable energy source in the transportation industry as they can be used within current infrastructures and require less technological advances than other renewable alternatives, such as electric vehicles and nuclear power. The literature suggests biofuels can negatively impact food security and production; however, this is dependent on the type of feedstock used in biofuel production. Advanced biofuels, derived from inedible biomass, are heavily favoured but require further research and development to reach their full commercial potential. Replacing fossil fuels by biofuels can substantially reduce particulate matter (PM), carbon monoxide (CO) emissions, but simultaneously increase emissions of nitrogen oxides (NOx), acetaldehyde (CH3CHO) and peroxyacetyl nitrate (PAN), resulting in debates concerning the way biofuels should be implemented. The potential biofuel blends (FT-SPK, HEFA-SPK, ATJ-SPK and HFS-SIP) and their use as an alternative to kerosene-type fuels in the aviation industry have also been assessed. Although these fuels are currently more costly than conventional aviation fuels, possible reduction in production costs has been reported as a potential solution. A preliminary study shows that i-butanol emissions (1.8 Tg/year) as a biofuel can increase ozone levels by up to 6% in the upper troposphere, highlighting a potential climate impact. However, a larger number of studies will be needed to assess the practicalities and associated cost of using the biofuel in existing vehicles, particularly in terms of identifying any modifications to existing engine infrastructure, the impact of biofuel emissions, and their chemistry on the climate and human health, to fully determine their suitability as a potential renewable energy source.


This research was aimed at finding answers to the question how preservice teachers use creative thinking skills in a digital teaching material development process. The mixed method using both quantitative and qualitative methods was preferred in the research. The Torrance Tests of Creative Thinking (TTCT) Figural Form A was applied to the preservice teachers at the beginning and the end of the research. The SPSS software was used for analyzing the quantitative data. According to the pretest and posttest results of TTCT Figural Form A, the preservice teachers had significantly higher scores in the fluency, originality and elaboration factors in the posttest but no significant difference was observed in favor of the posttest scores in the abstractness of titles and resistance to premature closure factors. Interviews with the preservice teachers, observations and video records constitute qualitative data sources. It was aimed with the qualitative data triangulation to examine the effect of digital teaching material development process on preservice teachers' creative thinking skills. Descriptive analysis and content analysis methods were used for analyzing the qualitative data. The results showed that the preservice teachers had positive opinions of the course in general, and they reported that they had fun and spent productive time as they did something practical.


A variety of sugar compounds have been used as additives to protect various biocontrol yeasts from adverse environmental stresses. However, studies on maltose and lactose as sugar protectants are limited, and their protective effect is not clear. In the present study, exposure of the biocontrol yeast Candida oleophila cells to 45°C for 10 min, while immersed in either 5 or 10% (w/v) maltose or lactose, provided a significant protective effect. The addition of maltose and lactose significantly enhanced enzyme activity and gene expression of catalase, thioredoxin reductase, and glutathione reductase, relative to cells that have been immersed in sterile distilled water (controls) exposed to 45°C. In addition, C. oleophila cells suspended in maltose and lactose solutions also exhibited higher viability and ATP levels, relative to control cells. Notably, the biocontrol efficacy of C. oleophila against postharvest diseases of apple fruit was maintained after the yeast was exposed to the high temperature treatment while immersed in maltose and lactose solutions. These results demonstrate the potential of maltose and lactose as sugar protectants for biocontrol agent against heat stress.


Objective: To investigate the in vitro antimicrobial activity of panipenem/betamipron to common clinical isolates, determine its pharmacokinetics in patients with pulmonary infection and evaluate its effectiveness and safety in treatment of pulmonary infection. Methods: (1) The minimal inhibition concentrations of panipenem/betamipron were determined in 247 clinical isolates by agar dilution method. The minimal bactericidal concentrations of panipenem/betamipron for some clinical isolates were also determined. (2) Twenty cases of pulmonary infection were treated with intravenous dripping of panipenem/betamipron at 500/500 mg every 12 h for 3-7 d. Panipenem/betamipron concentration in the plasma was consecutively measured, and bacterial culture was conducted and the efficacy was evaluated. Results: (1) The in vitro antimicrobial activity of panipenem/betamipron was almost the same as that of panipenem, indicating that panipenem played the major role in antimicrobial reaction. Panipenem/betamipron had a strong antimicrobial activity against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, β-Streptococcus hemolytic, Streptococcus pneumonia, micrococcus, Escherichia coli and Klebsiea pneumonia. The drug also showed a potent effect against Haemophilus influenzae,Enterobacter cloacae, Proteus and Pseudomonas aeruginosa (2) The peak value of panipenem/betamipron in plasma was (30.25±5.43) mg/L and the level decreased to (0.66±0.34) mg/L 6 h later. The half-life of distribution and elimination of panipenem in the plasma was (0.34±0.18) h and (1.42±0.31) h, respectively. (3) The eradication rate of bacteria was 77.8% and the effective healing rate was 75%. No adverse drug reaction was found. Conclusion: Panipenem/betamipron has a strong antimicrobial activity against clinical isolates and is effective and safe for treatment of pulmonary infection.


ABSTRACT Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer. In two independent breast cancer cohorts, the expression of MLKL and DFNA5 was decreased at the mRNA levels in tumor as compared with normal tissues. Moreover, MLKL expression exhibited a strong positive correlation with genes reflecting the presence of B, NK and T lymphocytes in the tumor bed, in multiple distinct breast cancer subtypes. In contrast, the positive correlation between RIPK3 and lymphoid cells was restricted to HER2+ and triple negative/basal-like breast cancer. Moreover, the expression of DFNA5, which mediates post-apoptotic secondary necrosis, mostly correlated with the monocytic lineage and macrophages in ER+/luminal A breast cancers. MLKL (and to some extent RIPK1 and RIPK3) was strongly associated with the local expression of genes involved in interferon-α and interferon-γ responses. Altogether, these results support the idea that pro-necrotic signaling facilitates intratumoral immune responses in human breast cancer.


The development of combination therapies is important to cancer treatment due to the potential to target multiple oncogenic pathways together, which may lead to enhanced anti-tumor activity and decreased chance for resistance. The RAS/RAF/MEK/ERK (MAP kinase) and PI3K/AKT/mTOR pathways are well-known pathways driving the oncogenic process in many cancer types; therefore, the simultaneous inhibition of these pathways may produce increased anti-tumor activity. It is important to find ideal cancer indications and molecular subtypes that may be most sensitive to drug combination inhibiting these pathways; this requires understanding of the molecular and genetic underpinnings. In this study, an in-vitro cell viability assay on 240 cancer cell lines was used to reveal the synergy mechanisms of the combination of investigational agents MLN0128 (mTORC1/2 inhibitor) with TAK733 (MEK1/2 inhibitor). Cells were administered with MLN0128 and TAK733 in DMSO in ten 2-fold serial dilutions and cell viability was measured using Promega9s CellTiter-GLO® assay after a 72 hour incubation period. The 100 data points (10×10) were fit to a 9-parameter model to obtain a response surface for each cell line and the effect of the combined administration was measured using a non-linear blending score. Our previous study found that genes in the MAP kinase pathway such as KRAS, NRAS, or BRAF were mutated in cell lines demonstrating synergy. In this study, a 76-gene expression signature was additionally identified using a regression-based analysis. The 76 mRNAs include some genes within the two oncogenic pathways, as well as those that regulate feedback of the MAP kinase pathway and cross-talk between the pathways. A pathway and protein-protein interaction network-based analysis of the 76-gene signature and mutated genes suggest that the activation of the MAP kinase pathway in cells originally resistant to MLN0128 may be essential for a synergistic outcome from the MLN0128 and TAK733 combination. Cell lines with activating mutations or over-expressed genes in MAP kinase pathway are generally sensitive to TAK733 administration; these cell lines also demonstrated synergy to the combination of MLN0128 and TAK733. On the other hand, cell lines with highly expressed PI3K tend to antagonistically respond to the combination. In conclusion, our study suggests the key molecular conditions of cell lines in order to achieve increased anti-tumor activity by the combination of MLN0128 and TAK733. These findings can be utilized to establish a better-differentiated strategy in terms of patient stratification for the combination therapy using MLN0128 and TAK733. Citation Format: Hyunjin Shin, Andrew Krueger, Bin Li, Derek Blair, William L. Trepicchio, Jeffrey Ecsedy. Identification of key molecular characteristics for achieving increased anti-tumor activity by combined mTORC1/2 and MEK1/2 investigational agents. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-59.


Objective: Recent studies have begun to look at the impact of the economic crisis on mental health. This paper tries to summarize the most important findings with regard to effects of the economic crisis on mental health in Spain on the basis of a comprehensive literature review. Results: Most of the studies agree on the negative consequences on mental health of the Spanish economic crisis. A decrease in self-perceived mental health, an increase of depression and anxiety and an increase in consumption of antidepressant and anxiolytic drugs is observed during the economic crisis. The consequences of the economic crisis differ by sub-groups. Empirical Spanish studies have shown different effects of the recession on mental health depending of individuals' socioeconomic position and educational level. Among immigrants and especially men, unemployed people and low-salary employees, the prevalence of poor mental health was higher after the economic crisis. Higher levels of education act as a protective factor against the deterioration of mental health following the economic crisis. Conclusion: The economic crisis has had negative effects on mental health in Spain, and further studies in this area could help provide useful information with a view to improving the mental health status of the Spanish population.