Madam, Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases in the ageing population globally, affecting 219 per 100,000 individuals in Pakistan.(1) This complex disease is characterised by motor symptoms (tremors, rigidity, akinesia, and postural abnormalities), and a spectrum of non-motor symptoms (autonomic manifestations, neuropsychiatric disorders, sensory symptoms, and sleep problems). Since the outbreak of coronavirus disease (COVID-19) pandemic, prolonged lockdowns have significantly hampered the neurorehabilitation services across Pakistan. This, coupled with the lack of tele-medicine in the tertiary-care public hospitals, perpetuates interruptions in medical care and exacerbates the symptoms of PD.
A survey of 142 patients afflicted with PD revealed that 40% of the respondents reported a decline in their physical and psychological health, In contrast the cessation in rehabilitative care or reduction in physical activity during Covid-19 was the most prominent reason for worsening PD symptoms.(2) Another study from Italy highlighted that the Covid-19 quarantine resulted in deterioration of cognitive (39.6%), pre-established (37.5%), and acquired (26%) behavioural symptoms, and motor symptoms (35.4%), causing an additive caregiver burden in 26% of cases.(3).
Physical inaccessibility to medical care, termination of visits by the healthcare provider and the fear associated with Covid-19 are  deleterious to PD's motor and cognitive aspects. (2) Since physical activity and exercise during lockdowns displayed favourable effects on PD outcomes regardless of the exercise being performed remotely, under or without supervision, the introduction of tele-medicine and zoom-based rehabilitation is a plausible option.(4) The feasibility of tele-medicine use in routine PD care during the pandemic was also divulged by a study conducted in Italy that employed web-based video evaluation to assess the impairment of non-motor PD symptoms.(5).
It is pertinent to note that most patients visiting tertiary-care public hospitals from remote areas in Pakistan, cannot seek medical care due to lockdown-imposed restrictions. Thus, tele-medicine will be particularly advantageous in continuing PD care in such patients while reducing travel expenses and time. Additionally, physicians should consider the distance of the patient's residence from the hospital or clinic when accepting new PD cases and suggest a nearer facility that is easier to visit routinely, or alternative follow-up methods besides in-person appointments.
Considering the dearth of tele-medicine in Pakistan, or it being limited to a few private healthcare systems, lockdowns precipitate the existing burden of PD. With the advent of tele-medicine, and the adoption of video-based rehabilitative care, outcomes of PD can be considerably improved.


Activation of group III metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7, and mGluR8) has been established to be neuroprotectivein vitro and in vivo. To disclose the identity of the receptor subtype(s) that exert(s) the protective effect, we have used group III agonists in combination with mGluR4 subtype-deficient mice (−/−). In cortical cultures prepared from wild-type (+/+) mice and exposed to a toxic pulse of NMDA, the selective group III agonist (+)-4-phosphonophenylglycine [(+)-PPG] reversed excitotoxicity with an EC50 value of 4.9 μm, whereas its enantiomer (−)-PPG was inactive. This correlated closely with the potency of (+)-PPG in activating recombinant mGluR4a. In cortical neurons from −/− mice, (+)-PPG showed no protection against the NMDA insult up to 300 μm, whereas group I/II mGluR ligands still retained their protective activity. Classical group III agonists (l-2-amino-4-phosphonobutyrate andl-serine-O-phosphate) were also substantially neuroprotective against NMDA toxicity in +/+ and heterozygous (+/−) cultures but were inactive in −/− cultures. Interestingly, −/− cultures were more vulnerable to low concentrations of NMDA and showed higher extracellular glutamate levels compared with +/+ cultures. We have also examined neurodegeneration induced by intrastriatal infusion of NMDA in wild-type or mGluR4-deficient mice. Low doses of (R,S)-PPG (10 nmol/0.5 μl) substantially reduced NMDA toxicity in +/+ mice but were ineffective in −/− mice. Higher doses of (R,S)-PPG were neuroprotective in both strains of animals. Finally, microdialysis studies showed that intrastriatal infusion of NMDA increased extracellular glutamate levels to a greater extent in −/− than in +/+ mice, supporting the hypothesis that the mGluR4 subtype is necessary for the maintenance of the homeostasis of extracellular glutamate levels.


Augmentation of invisible information with respect to many hypothetical
models of background and signal processes, can highly improve the performance of the
machine learning classifiers for HEP event discrimination. In this regard di-Higgs searches
in the channels with multiple invisible final states, is one of the most important applications.
Focusing on the di-Higgs channels with 2 bottom quarks + 0/1/2-leptons/taus + MET
from $bbWW$ and $bb\tau\tau$ productions, we introduce various augmentation schemes and ways
to build better multi-class classifiers using deep neural networks. We conclude our study
with demonstration how much the new deep learning classifiers supervised by physical
augmentation, can improve the discovery potential of di-Higgs production at the LHC, and
discuss on the implications for future collider study.


Decapod crustacean specimens recently collected from new and previously reported localities of USA, Mexico, and Colombia, as well as a review of species of uncertain affinity, add important information to complete the descriptions and paleobiological knowledge of some Cretaceous primitive crabs. The stratigraphic range for the genus Cenomanocarcinus is formally extended from the upper Albian to Campanian, based on occurrences from Colombia, Oklahoma and Mexico. Specimens of Cenomanocarcinus vanstraeleni from the Turonian of Mexico and Colombia include features not described previously for this species, such as variation in the shape and ornament of chelae. Necrocarcinus renfroae is here included in the genus Cenomanocarcinus, based on features of dorsal and ventral carapaces, as well as shape of pereiopods, and its occurrence is documented from the upper Albian of Colombia. Orithopsis tricarinata is reported for the first time in America from upper Albian deposits of Oregon and Colombia; the shape of the sternum confirms close affinities with the Cenomanocarcinidae and the family Orithopsidae is here included in the section Raninoida and restricted to the genus Orithopsis.


Accidents and incidents, such as the capsizing of the anchor handling vessel Bourbon Dolphin in 2007 and the unintended list of the drilling rig Scarabeo 8 in 2012, underline the need for addressing sensemaking in safety-critical situations in the maritime domain to reduce risks. Sensemaking and risks must be understood as a part of the organizational context of the incidents. This paper presents the results of a comprehensive qualitative literature review conducted to establish more knowledge on sensemaking in the context of safety-critical situations and on the relation between the concepts of sensemaking and resilience. In the obtained literature sensemaking is used as a frame of reference for understanding accidents; it is used in relation to critical situations or complex operations in general; it is described by some as a process creating situational awareness; and it is explained by others mainly in terms of how it relates to resilience. Sensemaking creates the context for being resilient; at the same time sources of resilience help to make sense of the situation. Few authors provide explicit characteristics of sensemaking in safety-critical situations, where discrepancies can be supported by redundant systems or by training to ensure the needed questioning attitude. There is a lack of literature regarding sensemaking in safety-critical situations and in relation to resilience that also addresses important aspects of training and system design.


INTRODUCTION
Burn care requires multiple disciplines to collaborate to achieve best patient care. Because of this, rounds involve a very large burn team to assess patients' wounds and formulate plans. To decrease the amount of team members on rounds, our burn center implemented a new budding technology: telemedicine. We created "Zoom Rounds," a Health Insurance Portability and Accountability Act (HIPAA)-compliant, secure videoconferencing system to relay patient wound evaluations to a remote conference room where team members can participate digitally. We sought to evaluate this new rounding process by querying the burn team, patients, and families regarding their experience.

METHODS
Surveys were developed for each group and were distributed over a 2-month period. Respondents were asked to rate the videoconferencing rounding experience and comment on the educational experience (staff/providers) and one's personal experience (patient/family). We analyzed both the quantitative data with the qualitative responses. Qualitative data analysis for content was used to independently code and analyze responses to the open-ended survey questions by two authors and verified by adjudication review.

RESULTS
Thirty-three patients/families and 69 burn staff members completed the confidential survey (response rate of 90% and 83%, respectively). Coded responses identified several themes: inconsistent technology, improved visualization and communication regarding the wounds, better learning experience, and improved patient experience by decreased crowds in the room.

CONCLUSIONS
There was strong support for the use of videoconferencing for patient wound rounds among providers, burn center staff, and patients/families. Telemedicine is a promising technology to improve inpatient burn rounds.


Maladaptive daydreaming (MD) is a newly described mental disorder characterized by extensive mental fantasy activity featuring addiction-like longing for fantasizing, accompanying repetitive movement, and feeling hindered in everyday life. This study describes the first validation of a non-English version of the Maladaptive Daydreaming Scale (MDS) and provides additional evidence for MD as a clinical phenomenon. The Maladaptive Daydreaming Scale–Hebrew version (MDS-H) is an adaptation of the 14-item English MDS (Somer, Lehrfeld, Bigelsen, & Jopp, 2016), a self-report questionnaire developed on the basis of qualitative information provided by self-identified maladaptive daydreamers (MDers). The MDS-H was administered to 280 individuals aged 13 to 73 years, including 45 self-identified MDers. Findings confirmed the expected 3-factorial structure, scalar invariance in comparison to the English MDS validation sample, and good psychometric properties. MDS-H scores were associated with dissociation, obsessive-compulsive behavior, and attentiondeficit/hyperactivity. Given high sensitivity and specificity separating MDers and non-MDers, the MDS-H represents a useful tool to assess MD among Hebrew speakers, suggesting the relevance of MD in a non-English speaking culture, and highlighting the potential value of the MDS for world-wide investigation of this condition.


We study Cantor staircases arising from different problems in Physics. Each staircase is endowed with the Farey structure in the vertical axis, the underlying cantordust set Ω having a fractal dimension strictly between 0 and 1. We find that length and distribution of stairsteps follow hyperbolic laws related to the Poincare measure in the hyperbolic half-plane. The geometry of the underlying Ω is studied with the same tools.


Inter-organizational networks are a resource-saving and risk-sharing strategy, especially in the field of innovation and for Small and Medium Enterprises (SMEs). The study investigates the role of innovation in interfirm linkages by combining a theoretical approach with an empirical case study. We link the concept of 'Regional Innovation System' (RIS) with the concept of 'embeddedness'. Starting from a network analysis of SMEs in the autonomous province of Bolzano – South Tyrol (Italy), the analysis shows that, in the field of innovation, relations are not based purely on a market logic and that the linkages between firms, institutions and research institutes are not enough to be innovative; rather, a RIS is part of a particular social system, where the relational and social aspects of embeddedness and trust are of foremost significance.


Introduction Endoscopy tolerance is improved in patients with higher sedation scores;1however, endoscopists underestimate procedure related pain2and consider it unlikely to be remembered by patients.3We compared the medication dose and endoscopist's assessment of pre-procedure anxiety, sedation score, patients' pain and anticipated procedure recall with a post-procedure patient comfort questionnaire. Method Endoscopist's assessment of patient comfort and recall were recorded at the time of procedure, patient survey was completed by a specialist nutrition team the day after the PEG. Results 67 procedures were included; 56 endoscopist assessments and 51 nutrition team visits, of these 20 patients were excluded due to communication issues. Midazolam was used in all procedures, average 2.0–3.0 mg, Fentanyl was used in 5 procedures, 63/67 were judged as drowsy or lightly asleep, 4 were felt to be awake. 39/49 procedures took <15 mins, longer procedures were judged more difficult by endoscopist's. Patients didn't report increased discomfort with longer procedures. Average patient pain score was 5/10. Endoscopist's felt that drowsier patients were more comfortable; however, 65% patients reported moderate or severe discomfort independent of drowsiness level. Patients judged to have no or mild pain by endoscopists reported moderate or severe pain in 14/23 cases (61%).Abstract PTH-005 Figure 1 Endoscopists felt that 37/50 patients wouldn't recall the procedure; patients seeming to be more uncomfortable were judged more likely to recall the procedure. Patients giving higher discomfort scores were more likely to recall the procedure; however, endoscopists judged 25% patients (4/16) who recalled the procedure as unlikely to do so. Conclusion Endoscopists were poor at assessing patient discomfort, patient discomfort increased with increased awareness and lower Midazolam dose. Increasing the use of sedation and adding Opiod analgesia during PEG may help improve patient comfort and reduce recall post procedure. Disclosure of interest None Declared. References Abraham N, Barkun A, Larocque M, Fallone C, Mayrand S, Baffis V, Cohen A, Daly D, Daoud H, Joseph L. Predicting which patients can undergo upper endoscopy comfortably without conscious sedation. Gastrointest Endosc. 2002;56(2):180–9 Thanvi BR, Munshi SK, Vijayakumar N, Taub N, Lo TC. Acceptability of oesophagogastroduodenoscopy without intravenous sedation: patients' versus endoscopist's perception with special reference to older patients. Postgrad Med J. 2003;79(937):650–1 Von Delius S, Hollweck R, Schmid RM, Frimberger E. Midazolam-pain, but one cannot remember it: a survey among southern German endoscopists. Eur J Gastroenterol Hepatol. 2007;19(6):475–70


In a study involving 382 Ss in introductory psychology, rating and pair-comparison procedures for assessing the importance of terminal and instrumental values were compared with the standard ranking procedure developed by Rokeach. Effects of order of presentation of the value sets (terminal/instrumental versus instrumental/terminal) were also investigated. Results indicated that assessment procedure per se had little effect on the average value systems that were obtained. Nor were there replicable order effects across procedures. Some sex differences in the importance assigned to particular values were, however, replicated. Advantages and disadvantages of ranking, rating, and pair-comparison procedures for assessing the importance of values were discussed.


The ileal digestion of 3 milk substitutes in which skim milk powder was either the only protein source (control diet) or was partially replaced (50%) by a heated soybean flour (SF diet) or an alcohol-treated soyabean protein concentrate (SC diet) was studied in 6 preruminant calves which were fitted with an ileo-caecal re-entrant cannula. The apparent digestibility of total nitrogen and amino acids was lower with the SF and SC diets than with the control diet (0.89, 0.89 and 0.94, respectively, for amino acid nitrogen). Assuming that true digestibility was complete with the control diet, the values were lower with the SF and SC diets, especially for cystine, threonine, valine, isoleucine, leucine and histidine. With the SF and SC diets, digesta contained more aspartic acid and glutamic acid but less threonine, sulfur amino acids, lysine, serine and alanine than with the control diet. The additional undigested fractions obtained with the SF and SC diets compared to the control diet were rich in aspartic and glutamic acids, and poor in arginine, suggesting that partially degraded dietary fractions different from the whole soyabean escaped digestion in the small intestine; these fractions probably originated mainly from glycinin. No significant differences were observed between the 2 soyabean diets.


This paper reports on the initial findings of a major new piece of research that highlights the importance of non-agricultural sources of income to the UK rural economy. Prompted by the recent significant falls in agricultural income, farmers have been looking to convert redundant farm buildings to commercial use in order to redress the deficit. Meanwhile the forces of counter urbanisation have identified accessible areas as pleasant places to work but not necessarily in the activities normally associated with the rural economy (Breheny 1999). However, prompted by the need to achieve sustainable development, the UK government is seeking through policy to guide economic development back into urban areas where the infrastructure is already in place.


BARD1 is the main binding partner of BRCA1 and is required for its stability and tumor-suppressor functions. In breast cancer and other epithelial cell carcinomas, alternatively spliced isoforms of BARD1 are highly upregulated and correlated with poor outcome. Recent data indicate that germline mutations of BARD1 may predispose to breast and/or ovarian cancer. To evaluate the role of BARD1 germline mutations in predisposition to ovarian cancer we scanned a cohort of 255 patients for the presence of previously reported mutations located in exons 5, 8 and 10 using high-resolution melting analysis. Within this group we identified single-patients carrying mutation in exon 8 (c.1690C>T, p.Gln564Ter), two different variants in exon 10 (c.1972C>T, p.Arg658Tyr; c.1977A>G, p.=) and a carrier of novel missense mutation located in exon 5 (c.1361C>T, p.Pro454Leu). Three out of four identified mutations alter exonic splicing enhancing motives and result in expression of incorrect splicing skipping of exons 5, 8, and 2-9, respectively. Our data indicate that BARD1 variants may predispose to ovarian cancer in limited number of patients although based on actual data it is difficult to estimate its actual penetrance.


It is known for ten years that self-dual Yang-Mills theory is the effective field theory of the open N=2 string in 2+2 dimensional spacetime. We uncover an infinite set of abelian rigid string symmetries, corresponding to the symmetries and integrable hierarchy of the self-dual Yang-Mills equations. The twistor description of the latter naturally connects with the BRST approach to string quantization, providing an interpretation of the picture phenomenon in terms of the moduli space of string backgrounds.


Advances in computer animation are more apparent with the explosion in satellite television. This feature explores the concept of synthetic actors, a combination of diverse methods of computerised animation. The boom in satellite broadcasting and the proliferation of extra channels demand advances in computer simulated motion. The concept of the synthetic actor represents a fusing of previously separate aspects of animation and is a qualitative leap forward. Synthetic actors have scientific as well as artistic applications. They enable the simulation of physiological disorders and the effects of accidents, explosions, etc., on the human body. The difficulties in creating synthetic actors-3D characters with the behaviour of real people-are outlined


The popularity of online auctions is growing with the participation of businesses and individual customers in various forms of auctions to buy and sell goods and services. This form of electronic commerce is expected to grow and become a significant form of exchange of goods and services competing in a global scale with traditional fixed-price commerce. A good understanding of the workload of auction sites should provide insights about their activities and help in the process of designing business-oriented metrics and designing novel resource management policies based on these metrics. This paper provides a workload characterization of auction sites including i) a multi-scale analysis of auction traffic and bid activity within auctions, ii) a closing time analysis in terms of number of bids and price variation within auctions, iii) the characteristics of the auction winner in terms of entry time, entry price, and bidding activity, and iv) unique bidder analysis.


Resonance Raman spectra in the frequency region 200–3200 cm–1 are reported for very dilute aqueous solutions of the following compounds: cyanocobalamin (vitamin B12), aquocobalamin (B12a), hydroxocobalamin (B12b), dicyanocobinamide, the alkaline hydrolysis products of B12(penta- and hexa-carboxylate derivatives), aquocobalamin (B12r), and {cobalamin}–cobalt(I)(B12s). The spectra were excited by lines from an argon laser, selected so as to coincide with bands in the visible absorption spectra of the compounds, and to satisfy the conditions for rigorous resonance enhancement of selected vibrational band intensities. The CoIII compounds all gave closely similar spectra, with no major changes being induced by coordination displacement even of the large 5,6-dimethylbenzimidazole base group from the metal. However, large changes in the structure of the spectra resulted from reduction of B12 to B12r and B12s; these changes appear to be related to conformational changes in the corrin ring chromophor.


AIM AND OBJECTIVES
To evaluate and determine the characteristics of a critical care clinical placement programme affecting the critical care nursing competency of baccalaureate nursing students.

BACKGROUND
The increase in global demand for competent critical care services and human resources translates to an educational focus in preparing students for their eventual role as critical care health professionals. Albeit clinical placement in critical care units can promote competency, evidence supporting such claim remains inadequate.

DESIGN
Cross-sectional, descriptive correlational design.

METHOD
Employing structural equation modelling, 236 randomly selected baccalaureate nursing students from a clinically intensive university in the Philippines were recruited from January-March 2016. A three-part online survey, composed of the robotfoto, Critical Care Nursing Rotation Evaluation Questionnaire, and Intensive and Critical Care Nursing Competence Scale, was completed. The STROBE checklist was followed in reporting this study.

RESULTS
Five characteristics of clinical placement were extracted as follows: sufficient clinical exposure, adequate area orientation, supportive clinical instructor, diversified medical cases and supplemental learning resources. Four characteristics affected critical care nursing competency and built a good model (χ2 /df = 1.52; comparative fit index = 0.94; parsimonious normal fit index = 0.77; root mean square error of approximation = 0.047). Adequate area orientation had the most diverse influence on all competency domains, while supportive clinical instructor had the strongest positive influence on critical care nursing skill (β = 0.30, p = 0.005).

CONCLUSION
The model highlights the characteristics of a critical care clinical placement programme which influences critical care nursing competency among nursing students. It emphasised the importance of a supportive clinical instructor and adequate area orientation in promoting critical care nursing skills and values and attitude.

RELEVANCE TO CLINICAL PRACTICE
The proposed model highlights the role of clinical instructors and appropriate orientation which provides impetus in improving the clinical placement design to maximise competency development.


Studies were carried out in order to determine the factors influencing myocardial 201Tl uptake. A total of 158 patients was examined with regard to both 201Tl uptake and the assessment of left ventricular and coronary function (e. g. quantitative ventriculography, coronary arteriography, coronary blood flow measurements). Moreover, 42 animal experiments (closed chest cat) were performed. The results demonstrate that: 1) 201Tl uptake in the normal and hypertrophied human heart is linearly correlated with the muscle mass of the left ventricle (LVMM); 2) 201Tl uptake is enhanced in the inner (subendocardial) layer and is decreased in the outer (subepicardial) layer of the left ventricular wall. The 201Tl uptake of the right ventricle is 40% lower in comparison to the left ventricle; 3) the basic correlation between 201Tl uptake and LVMM is influenced by alterations of both myocardial flow and myocardial oxygen consumption; and 4) inotropic interventions (isoproterenol, calcium, norepinephrine) as well as coronary dilatation (dipyridamole) may considerably augment 201Tl uptake in accordance with changes in myocardial oxygen consumption and/or myocardial flow. It is concluded that myocardial 201Tl uptake is determined by multiple factors. The major determinants have been shown to include (i) muscle mass, (ii) myocardial flow and (iii) myocardial oxygen consumption. The clinical data obtained from patient groups with normal ventricular function, with coronary artery disease, with left ventricular wall motion abnormalities and with different degree of left ventricular hypertrophy are correlated with quantitated myocardial 201Tl uptake.


Introduction: Cervical cancer is a leading cause of mortality worldwide. According to the 2009 World Health Organization (WHO) report in Ethiopia 7619 annual number of new cases and 6081 deaths every year. Despite this fact, very few women receive screening services in Ethiopia.
Material and methods: Data on new cases of cervical cancer registered annually at the cancer registry of the Tikur Anbessa Specialize Hospital (TASH) over a period of sixteen years were obtained and analysed for trends using SPSS Version 20.
Results: There were 5293 new cases of cervical cancer registered at the cancer registry during the16-year period. The peak age of incidence was between 40-49 years. Most of the cases were found in Addis Ababa, where the hospital is situated. An increase in trend of cervical cancer case was observed.
Discussion: The number of cases per regions depended on their distance from Addis Ababa unrelated to population size. This may be due to poor awareness, most women was present with late stage of cervical cancer.
Conclusion: There is the need to step up activities on; vaccination, screening programs and trainings on selfawareness for community.


This study evaluated intra- and inter-examiner reproducibility for a conventional manual probe versus a computer-interfaced force-controlled periodontal probe. 2 examiners recorded probing depths (PD) and relative attachment levels (AL) at 1128 sites in 15 periodontal maintenance patients. Each site was evaluated 2x, 7 to 10 days apart by both examiners. Probing force for the electronic probe was 15 g. PD intra-examiner reproducibility (within +/- 1.0 mm) for shallow sites (PD < or = 3 mm) was 98.6% versus 91.5% for the conventional versus the electronic probe for examiner 1 and 98.5% versus 88.7% for examiner 2. Corresponding values for deeper sites (PD > 3 mm) were 96.4% versus 85.9% for examiner 1 and 95.1% versus 77.0% for examiner 2. Generally, AL intra-examiner reproducibility was 1 to 3% lower than for PD. PD inter-examiner reproducibility (within +/- 1.0 mm) was 99.2% versus 90.7% for the conventional versus the electronic probe, respectively, for shallow sites and 95.4% versus 76.9% for deeper sites. AL inter-examiner reproducibility (within +/- 1.0 mm) was 1 to 5% lower than for PD. Both intra- and inter-examiner reproducibility was higher for anterior than for posterior sites. Mean PD and AL were similar for both examiners. However, the electronic probe consistently recorded 0.1 to 0.2 mm higher values than the conventional probe. Standard deviations indicated a greater variability for electronic than for manual probing. The results suggest that intra- and inter-examiner reproducibility may not necessarily be higher with an electronic, force-controlled periodontal probe than with a conventional manual probe.


The internet plays an important role in day-to-day life. The people can transfer important data through the internet such as Email, banking transaction and online purchase. In order to get secured transaction, network security is essential. Network security is mostly achieved through the use of cryptography. Cryptography refers to the art and science of transforming the message to make them secure and immune to attacks. Different algorithms and protocols are used to protect the data. The efficiency of the algorithm is measured by execution time and throughput. Using of larger key size may affect the efficiency of the algorithm. Blowfish is a symmetric block cipher with a 64 bit block size and variable key length from 32 bits to 448 bits. The Blowfish algorithm keeps two sub key arrays: four Sboxes and single P-box. Focus of this research is to optimize the four S-boxes into two S-boxes in original Blowfish algorithm to increase the speed and examine the effectiveness and limitations of some Block cipher algorithms. The program simulation result provides the better performance as well as security


In everyday practice, surgeons have to deal with bone atrophy. These rehabilitations are even more complex in the posterior mandible, and it is still unclear in the literature which fixed rehabilitation option is best. The purpose of this article was to help oral surgeons to choose the proper and updated treatment for their atrophic patients. Posterior mandible bone atrophies were divided into four main groups depending on the bone height measured above the inferior alveolar nerve: (1) ≤ 4 mm; (2) > 4 mm ≤ 5 mm; (3) > 5 mm ≤ 6 mm; (4) > 6 mm < 7 mm. Different approaches were proposed for each group, considering patient expectations. If ≤ 4 mm of bone height was available, guided bone regeneration was used as the adequate approach. For bone heights > 4 mm and ≤ 6 mm, the "sandwich" technique and/or short implants were used, depending on esthetics. In cases with > 6 mm and < 7 mm above the mandibular canal, short implants might be the proper option. The authors' clinical experience and the literature were considered in order to suggest a possible correct treatment decision based on the residual bone height in the posterior mandible.


ITER or any other future fusion device will operate in H-mode to take advantage of the improved confinement. Stationary operation in H-mode, however, requires the occurrence of ELMs, and the resulting power load on the divertor target plates is not acceptable from the engineering point of view. Beyond this, the present divertor concepts rely on a cold and dense (possibly detached) divertor plasma. Large type-I ELMs, however, carry too large a power and possibly burn through such cold divertor plasmas. The completely detached H-mode (CDH-mode), recently established in ASDEX Upgrade shows detachment at both divertor target plates and small ELMs (so-called type-III ELMs), that do not burn through the divertor plasma. The extrapolation of this scenario to ITER, however, is an important question.


We study games with almost perfect information and an infinite time horizon. In such games, at each stage, the players simultaneously choose actions from finite action sets, knowing the actions chosen at all previous stages. The payoff of each player is a function of all actions chosen during the game. We define and examine the new condition of individual upper semicontinuity on the payoff functions, which is weaker than upper semicontinuity. We prove that a game with individual upper semicontinuous payoff functions admits a subgame perfect ϵ-equilibrium for every ϵ > 0, in eventually pure strategy profiles.


: Pathological general adaptive reactions of the body (GARs) were found out to occur on 33.8 +/- 5.0 of patients with chronic pathologies of the urinary and digestive organs, arriving at the Truskavets health resort from the areas contaminated with radionuclides, compared with 7.0 +/- 2.1% of diseased controls. Complex spa treatment during a period of two weeks involving ingestion of the mineral water "naftusia" has a beneficial effect on pathologic and premorbid GARs though not effectively so. Adaptogenic effect of balneotherapy is potentiated by use of balsam "Kryms'kyĭ" but not a home preparation ginseng.


With the rise of ion‐based devices using soft ionic conductors, ionotronics show the importance of matching electronic and biological interfaces. Since textiles are conformal, an essential property for matching interfaces, light‐weight and comfortable, they present as an ideal candidate for a new generation of ionotronics, i‐textiles. As fibers are the building blocks of textiles, ionically conductive fibers, named ionofibers, are needed. However, ionofibers are not yet demonstrated to fulfill the fabric manufacturing requirements such as mechanical robustness and upscaled production. Considering that ionogels are known to be conformal films with high ionic conductivity, ionofibers are produced from commercial core yarns with specifically designed ionogel precursor solution via a continuous dip‐coating process. These ionofibers are to be regarded as composites, which keep the morphology and improve the mechanical properties from the core yarns while adding the (ionic) conductive function. They keep their conductivity also after their integration into conformal fabrics; thus, an upscaled production is a likely outlook. The findings offer promising perspectives for i‐textiles with enhanced textile properties and in‐air electrochemical applications.


The malignant tumors of multiple tissues or adenosarcomas of the child9s kidney form a group the appearance of which, in spite of an extreme polymorphism, is still characteristic enough so that their diagnosis is easily made by any experienced histologist. Classical Data on the Structure of the Adenosarcomas Renal Blastema: The diagnosis of renal adenosarcoma depends upon the existence of a special tissue complex, the varied aspects of which can easily be related one to another in the same fashion as are stages of histogenic development. In its primitive state this complex has a mesenchymatous foundation which is highly vascularized, with stellate cells forming a loose network through the interstices of which run collagen fibers. In this basic tissue are collections of cells, compressed one against the other, which are so poor in cytoplasm that their rounded or oblong nuclei are almost contiguous. These dense collections are not vascularized; they have the appearance of nodules or of irregularly ramifying cords beaded with swellings. Their peripheries are always vague and indefinite throughout their extent, formed by cells which are more and more widely separated, branching and in continuity with the surrounding mesenchymatous network. In places these borders appear distinct and the nodules or cords seem to push back the loose mesenchyme about them; but an examination with high magnification shows after all a symplastic continuity between the cell groups and the loose mesenchyme which surrounds them in such a fashion that the compact masses and the basic mesenchyme form a whole and seem to correspond to two states of a single tissue.


Anisotropic microparticles have plenty of applications for their asymmetric structure and precisely modified surface. In our research, the uniform anisotropic microparticles with benzyl chloride group were synthesized successfully via emulsion interfacial polymerization. By varying the degree of cross-linking and the concentration of slightly hydrophilic monomer 4-vinyl benzyl chloride (VBC), several types of microparticles with different concavities and different shapes of microparticles (hemisphere, bowl-like, egg-like, etc.) were obtained. Nanoporous microparticles with a walnut-like heterostructure were achieved with modified hydrophilic seeds with the same strategy. The potential applications of shape-controllable fluorescent microparticles and surface modification of microparticles by thiol-click reaction were explored. The modified microparticles achieved in this study are very useful in labeling, tracing, protein separation, and other biomedical fields.


Globally, obesity is a major contributor to the burden of several chronic metabolic diseases, including type 2 diabetes mellitus and cardiovascular diseases. With changing life style, obesity has now become a global phenomenon affecting all socioeconomic groups, irrespective of age, sex or ethnicity. Morbid obesity and co morbidities of metabolic syndrome, such as hypertension, dyslipidemia and glucose intolerance are now increasingly recognized in young adults predisposing them to early cardiovascular diseases. Obesity is now viewed as a low grade inflammatory disease, characterized by increased levels of inflammatory markers like C-reactive protein, TNF- α, interleukins and other adipokines that promote insulin resistance in liver and skeletal muscle ultimately leading to the clinical expression of various metabolic disorders. Because of the reversibility of obesity related diseases with suitable interventional strategies, it is important to identify and treat the pro inflammatory state of obesity to prevent premature deaths due to metabolic diseases. The relationship between obesity, inflammation and metabolic disorders was investigated extensively in several populations. This review aims at giving a general view on the role of inflammation in obesity related metabolic disorders and summarizing the recent progress. Elucidation of the mechanisms that link obesity with inflammation and metabolic disorders will not only contribute to the understanding of the patho physiology of obesity, but also open to novel strategies for prevention and treatment of pro-inflammatory state of obesity and obesity related metabolic disorders.


The study of potential wild mammal reservoirs is necessary for the surveillance of leishmaniosis, as Leishmania protozoans have been isolated from a wide range of wild and domestic animal species, including Leporidae. Recently, it has been demonstrated that both hares and wild rabbits can act as sylvatic reservoirs of Leishmania. In Spain, most of the research involving wild rabbits has been developed in the central area of Madrid and in the southeastern Mediterranean coast. We studied the presence of Leishmania infantum in 116 wild rabbits (Oryctolagus cuniculus) captured in Santovenia de Pisuerga, Valladolid, Spain. Hair samples were analyzed by real time PCR. L. infantum kinetoplast DNA (kDNA) was detected and quantified in 4 out of 116 analyzed animals. The estimated number of parasites obtained were quite variable, ranging from 2.60 to 276.60. Hair samples can be collected by non-invasive methods, being a proper sample for Leishmania detection in wild Leporidae, which have an important role as reservoirs of Leishmania. Our findings enhance the need for more extensive studies in different geographical areas.


The purpose of this study was to have secondary school students scale eight instructional techniques that they believe would be the most beneficial in terms of science achievement. Within the scope of this purpose, techniques were determined according to expert opinions. Data was collected from 221 sixth grade students from several public schools. In this research successive intervals scaling method depends on categorical judgments law was carried out. Scale values of instructional tecniques (the stimuli) was calculated and commented. Also, relationship between scale values of males and females determined by using Spearman-rho rank order correlation coefficient. The students preferred the experiment in the first order as the technique that made the biggest contribution to their achievement in the science lessons while large group discussion and educational play made the smallest. The experiment technique was followed by question-answer, demonstration, educational video, trip-observation and group study technique. The correlation analysis indicated that females and males had different rank of preferences.  According to results; students mostly link  success to hands-on instructional tecniques. The value of instructional techniques depends on how they are implemented, which is often determined by the relationship between teacher and learners. It is expected that this research will lead to a more explanatory evaluation of  technique preference of students, particularly given the likely emergence of research on topics like teacher competency, learning topic and the frequence of utilization of the techniques.


BACKGROUND
Coronary artery bypass grafting (CABG) has become a safer procedure in recent years.

AIMS
We aimed to compare complications and early outcome of CABG in patients without history of general risk factors with those in patients with at least one general risk factor for coronary artery disease (CAD).

SETTINGS AND DESIGN
Cross-sectional study.

MATERIALS AND METHODS
Postoperative in-hospital complications, 30-day mortality rate and length of stay in hospital of 708 patients without preoperative general risk factors undergoing CABG in three university hospitals were assessed and compared with 10,844 patients undergoing CABG with at least one general risk factor as controls. In addition, the association of the studied variables with patients' early outcome was evaluated.

STATISTICAL ANALYSIS
SPSS software with Pearson's chi2 test; independent sample t test, Mann-Whitney test and univariate analysis were used.

RESULTS
All studied in-hospital complications were similar between the two groups. Thirty days mortality rate (0.7% in study group and 1.4% in control group) was similar between groups, whereas prolonged length of stay (>12 days) was more frequent in control group (61.33% vs. 71.36%, P<0.0001). Atrial fibrillation (P<0.0001) was a strong predictor for prolonged length of stay in hospital.

CONCLUSION
Most aspects of early complications after CABG, as well as 30-day mortality rate, were similar between patients with and without general risk factors for coronary artery disease undergoing CABG.


Finding
sustainable resources has always been a strong research due to the current massive
consumption of non-renewable fossil fuels on a global scale. Recently, the
transformation of renewable biomass into value-added chemicals has become a
crucial alternative to solve this problem. Levulinic acid (LA) and glucose are
the most significant biomass-derived compounds and γ-valerolactone (GVL) is considered to be the important
intermediate of chemicals and fuels. However, the safety and cost of external
hydrogen are the main obstacles for the production of GVL from biomass and its
derived chemicals by catalytic transfer hydrogenation process. Herein, we
introduce the conversion of LA and glucose-derived LA into GVL without an
external hydrogen donor, respectively. One process is the production of GVL
from LA in a maximum yield of 99% at relatively mild conditions (150 oC)
for 3 h with hydrogen, which is from the decarboxylation reaction of formic
acid (FA) in water with Raney Ni. The other process is conversion of glucose
into LA and GVL in two steps. More than 50% yield of LA and 67% yield of GVL could
be obtained from glucose with 3% HCl solution and Raney Ni.


Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Anti angiogenic agents that target the VEGF pathway (bevacizumab, sorafenib and sunitinib (SU)) have demonstrated improved clinical benefit as single agents or in combination with chemotherapy in a variety of solid tumor types. Although this class of agents has provided an improved treatment option to certain tumor types, it is evident that some patients do not respond to therapy or will relapse despite an initial response to treatment due to an acquired resistance. To better understand this mode of acquired resistance to this class of agents, a model of Renal Cell Carcinoma (RCC) which has shown regression, eventually developed evasive resistance during long term administration of the single agent sunitinib (a small-molecule inhibitor of the VEGF-1, 2, 3, PDGF-α,β, KIT, CSF-1R and FLT-3 receptor tyrosine kinases). Despite the observation that resistant tumors under continuous treatment with sunitinib (60 mg/kg PO, QD) demonstrated a gross phenotypic reduction of micro-vascular density (MVD), they continued to show a progressive increase in size. Because the observed low MVD phenotype was suggestive of an ability of resistant tumor cells to survive in an increasingly hypoxic environment with a reduced functional vasculature, emphasis was placed on identifying tumor cell derived resistance factors. Gene expression and/or proteomic profiling studies accompanied by confirmatory immunoblotting indicated a subset of differentially expressed genes and/or proteins in resistant vs. sensitive treated tumors. Although profiling studies did not clearly elucidate definitive resistance mechanisms, the dysregulation of EGFR, FGFR1, & TGFB1 pathways and downstream signaling through PI3K and MEK were potentially implicated. Comparative genomic hybridization studies did not identify any resistance mechanisms at the cytogenetic level. Sunitinib combination studies designed to target pathways potentially involved in resistance (SU + a PI3K/mTOR inhibitor; SU + a MEK inhibitor) demonstrated the ability to restore sensitivity in the sunitinib resistance model. The ability to identify and characterize resistance mechanisms and circumvent resistance through combination approaches may have utility in developing future combination regimens for anti angiogenic therapies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 387.


A range of learning opportunities needs to be afforded to coaches to support the complexity of effective coaching. Coaches learn to coach in formal and informal settings. Much research has advocated collaborative coach learning, but there is a need to conduct research in order to evidence reliable ways to support collaborative coach learning. Self-study has been effective to support practitioners' learning in teacher education and physical education teacher education. To date, there has been a very limited application of self-study in coaching contexts. This Insights paper advocates the use of collaborative self-study as a reliable and valid approach to support meaningful coach learning. This paper documents the researchers' own experiences of learning to coach within a collaborative self-study. The coaches focused on developing an athlete-centred coaching approach. This paper illustrates how self-study supported collaboration, reflection, and pedagogical innovation over the course of a Gaelic football season. The authors outline implications for future research into coaching and coach education.


This study aims at showing the types of turn-taking and its relation to cooperative principle and Grician maxims, which organize speech information and duration of speech of the participants. It is hypothesized that the adjacency pair is the dominant type that controls the conversation, and the classroom conversation is a formal conversation rather than being informal, regardless the age and gender of students and teacher. Some selected conversations of different environments will be analysed according to the types of turn-taking which is posed by Cook (1989). It is obvious that classroom conversation contains a lot of questions which require answers. Thus, the students frequently answer the questions that are posed by the teacher. This gives an indication that the adjacency pair is used a lot in the classroom, which organizes the role of each participant. Also, the overlapping is few in the classroom, because the conversation in such environment is systematic more than other places. The formality of school obliges teachers and students to use formal language as an academic institution, beside the formal language of the books. The study involves an introduction, a theoretical background, data analysis and results, and finally conclusions. Keywords: turn-taking, Teacher, conversation.


Media surroundings through the ubiquity of the Internet are changing as quickly and as broadly as it changed in the 1940s through the ubiquity of television. The popularity of the Internet news media that allows for both the preservation of the newspaper format and the prompt reporting of broadcasting is changing the characteristics of typical journalism. This tendency gives challenges to typical mass media that have been facing several limitations about public journalism. The goal of public journalism is that mass media guide the public (people) to discuss and participate in public issues and give the public a chance to participate in making policy. This public journalism can be materialized more actually through utilizing the Internet. Therefore, public journalism can be formed, and Internet journalism can be a distinguished unique news media through having the characteristics of public journalism. In the recent decade in Korea with development of the Internet, several Internet newspapers were established. Now, Korean media scholars assume that the Internet can be a good way of public journalism. Thus, this study will examine whether Korean Internet newspapers accomplish the function of public journalism or not, and how the Internet newspapers can be used to develop democracy through public journalism. Therefore, the purpose of this study is to research public journalism as a new journalism format and the characteristics of the Internet newspaper as a medium. To do this, I will examine the meaning and essence of public journalism, and then discuss the practical possibility of public journalism through the Internet newspaper.


ABSTRACT This study examines the current status of immunization among 0–3 year old children in Bakersfield and identifies barriers that prevent families from immunizing their children. A survey research design using a stratified sampling method was employed to collect data from 207 randomly selected English and Spanish speaking households having at least one child between the ages of 0–3 in Bakersfield. The findings reveal that 49% of the parents had no shot cards regarding children's immunization status. However, a significant majority of them immunized their children despite having no records. The most commonly reported consumer related barrier for late immunization was having a sick child followed by lack of parental memory and fear of side effects. The major provider-related barriers included lack of an opening for an appointment with the health care provider, limited clinic hours, and long lines in clinics. Lack of transportation was the single most systemic barrier. These findings suggest that reminder calls, increased transportation, weekend clinics and better rapport with parents can improve the immunization rates in ethnically diverse rural communities.


The article presents the dynamics of the media effects of the coronavirus infodemic (COVID-19). A set of methods is used: case study, systematization, intent analysis, and secondary analysis of sociological and statistical data. Timeline of the study: March 1 – June 30, 2020. Based on the results of the study, it is concluded that the first "wave" of the coronavirus pandemic most clearly demonstrated the replacement of dominant media effects. If from mid-March to the end of April 2020, the construction of moral panic was observed, then from the beginning of May to mid-June 2020, compassion fatigue became prevalent in society. The factors that inspired such media effects are indicated. Cause-and-effect relationships between moral panic and compassion fatigue are fixed. On the basis of the results obtained, it is stated that at the turn of the 2010–2020s, a stress society was formed as a special social system, social ties, positions, and dispositions in which are largely explained through the factors of turbulence that exist in modern times and replace each other, leading to a paradigmatic loss of social, political, economic, and cultural stability, causing the permanent finding of individuals in a state of increased psycho-physiological stress. The legitimacy of putting forward the concept of a society of stress is substantiated, based on the existing socio-political, socio-economic, and socio-cultural (including media communication) determinants. A perspectivization of the study is being built, which implies further conceptualization of this concept. The necessity of incorporating the category of stress society into the academic discourse of the social sciences is proved. Such methodological foundations will allow for systematic research of cultivated social reactions (primarily media effects), taking into account cause-and-effect relationships and interdependent patterns.


Caregivers play an important role in the in-home care of community dwelling older adults living with Alzheimer's disease or related dementias (ADRD); however, many of these caregivers lack training in caring for this vulnerable population. In 2015, we developed and implemented an interactive, community-based, knowledge and skills-based training program for In-Home Supportive Services (IHSS) caregivers. This report shares the results of a process evaluation of this training program as it evolved over the course of three training sessions in Riverside County, California. Our iterative evaluation process reveals the unique needs of training and assessing a population of demographically diverse adult learners and provides guidance for those planning to implement similar training in underserved communities. Factors such as reliance on self-reported abilities, language readability level, and test anxiety may have confounded attempts to capture learner feedback and actual knowledge gains from our caregiver training program.


Fundamental joint principles on expert opinions according to the social law code no. IX (SGB IX) and their application to a virtual individual case history were published recently in this journal. They are based on the ICF (International Classification of Functioning, Disability and Health, WHO 2001). A visionary review of the chances and prospects for the further development of the rehabilitative system is outlined and the necessary steps for their implementation are demonstrated.


Of all the regional areas in the field of otolaryngology, the tonsils are second only to the larynx and esophagus in the rarity with which infections extend into the intracranial space. Nevertheless, such complications do occur and present considerable variation in the routes by which infection reaches the intracranial space and the nature and extent of the intracranial lesion. It is the object of this contribution to review the literature concerned with the problem, to study the pathogenesis and nature of the consequent lesions and to report 2 cases which have come to our attention. INCIDENCE In a survey of a series of 25,000 autopsies performed in the Los Angeles General Hospital one of us (Dr. Courville) found only 1 instance of intracranial complication of tonsillar origin, the report of which appears in this paper. In a series of 10,000 cases of tonsillectomy, Leatherwood 1 cited the case of a child


BACKGROUND
Thalidomide was approved in Japan for multiple myeloma treatment in October 2008. A program called the Thalidomide Education and Risk Management System (TERMS®) was established to help ensure that every effort is made to use the drug safely.

PURPOSE
We report the use of thalidomide to treat multiple myeloma, and describe problems arising in the Thaled® outpatient department.

PATIENTS AND METHODS
Multiple myeloma patients treated with thalidomide at Hitachi General Hospital.

INTERVENTION
Monitoring of the efficacy and safety of thalidomide, and a questionnaire survey conducted at the Thaled® outpatient department.

RESULTS
The thalidomide response rate was 41. 7%. In 5 cases, all patients received steroids along with thalidomide. After auto-PBSCT, 1 of 2 cases demonstrated a good response (PR 1). After treatment with bortezomib, 1 of 2 cases demonstrated a good response (MR 1). After auto-PBSCT and treatment with bortezomib, 1 of 4 cases demonstrated a good response (PR 1). In a case demonstrating hematotoxicity Grade 3 (in addition to neutropenia), administration was discontinued. Regarding problems in the Thaled® outpatient department, the medical staff indicated that TERMS® is a very complicated program, while the patients requested prolongation of the prescription days and reduction of the economic burden of medication costs.

CONCLUSION
Thalidomide showed some success in treating multiple myeloma either after auto-PBSCT or following treatment with bortezomib. In the case demonstrating hematotoxicity Grade 3 (in addition to neutropenia), grave complications could have very easily developed, thus underscoring the importance of careful monitoring. Based on a questionnaire survey conducted in the Thaled® outpatient department, the medical staff made comments and patients raised issues that should be examined in the future.


The data presented furnishes no evidence that atopic hypersenstiveness is inherited conjointly with the serological group, in other words, atopic children may or may not have the blood-group of the atopic parent.


Together with the Welsh language, mediaeval Welsh law has long been regarded as critical to Welsh national identity. The ongoing significance of the 'law of Hywel', together with the traditionally philological orientation of Celtic Studies as a discipline, have shaped the questions scholars have put to the laws over the past several decades. This article traces the manner in which the field has evolved, from an interest in Common Celtic institutions and comparisons with early Ireland, to the more contemporary emphasis on the Welsh lawbooks as part of the European-wide resurgence of law in the 12th and 13th centuries. It suggests that the way forward lies both in providing modern editions of texts not yet accessible, and in incorporating new theoretical perspectives now being put to use in other legal history fields into the study of the laws.


The Plug-in Hybrid Electric Vehicle (PHEV) is becoming the most significant component of the future advanced transportation system and an important part of the smart grid. The energy management issue of charging a large number of PHEVs parked in a municipal parking lot with a limited amount of power available from the grid can be formulated as an optimization problem. Since the problem is basically a scalable resource allocation problem, a proportional allocation mechanism in auction theory is used to address the issue as a market-based tool. Also, a decentralized algorithm based on auction theory is developed that furnishes an updating rule to the vehicles as bidders to make the optimal decision about their next bid. This decision considers their previous bids and the price they have received from the market manager as a feedback. In this paper, considering PHEVs as price-taker bidders, we apply the auction theory method to solve the PHEV parking lot optimization problem for 10 vehicles, as a small example, and then for a large number of vehicles. The results are presented for both cases and compared to the Particle Swarm Optimization (PSO) as a well-known population-based optimization method.


The paper concerns the method of determining the probability of unproductive manipulations during operations, maintenance or repairs on an inland intermodal terminal. The method is mathematically based on the semi-Markov process. The developed method enables revision of unproductive manipulation frequency and duration. It provides an opportunity to analyse and change inland terminal operations so as to increase productivity.


The inevitable development of clinical drug resistance presents a common challenge for targeted cancer therapy. In non-small cell lung cancer (NSCLC) patients with ALK and ROS1 rearrangements, the emergence of mutations in the targeted oncogenes was identified as one of the mechanisms that confer drug resistance. In particular, a group of mutations known as solvent front mutations, such as ALKG1202R and ROS1G2032R, render common resistance to ALK and ROS1 inhibitors. Similar solvent front mutations, such as TRKAG595R and TRKCG623R, have also been identified in cancer patients with rearrangement of NTRK family genes who developed resistance to TRK-targeted therapies. TPX-0005, a compact three-dimensional macrocyclic molecule, was designed to completely locate at the adenine binding site of ATP in order to efficiently target the active kinase conformation and systematically circumvent the steric interference from various clinical resistant mutations, especially the solvent front mutations. TPX-0005 is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. TPX-0005 demonstrated potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3. In patient derived xenograft tumor models, TPX-0005 treatment resulted in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibited marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation. Taken together, these pre-clinical studies have demonstrated the potent activities of TPX-0005 against not only wild type oncogenic ALK, ROS1, TRK fusions but also their corresponding solvent front mutations, which will bring in a new therapy for cancer patients resistant to currently available ALK, ROS1, and TRK inhibitors in clinic. Citation Format: Wei Deng, John Huang, Dayong Zhai, Evan Rogers, Jean Cui. Overcoming acquired drug resistance by TPX-0005, an ALK, ROS1 and pan-TRK inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3168. doi:10.1158/1538-7445.AM2017-3168


Working towards remote steering of distal guide-wire in arteriovenous fistula angioplasty procedures, we develop a magnetically actuated robotic guide-wire manipulation system involving electromagnetic coils and a flexible guide-wire with a magneto-responsive attachment. By varying the coil voltages, we show the controlled deflections of the distal guide-wire. Specifically we are investigating the guidewire actuation mechanism under controlled electromagnetic field, the transfer function of the system, and the steering experiments in a custom phantom. The studied phenomenon has importance for guide-wire placement in minimally invasive cardio-vascular surgeries. A video demonstration is available at: http://bioeng.nus.edu.sg/mm/magnetically-actuated-guide-wire-steering.


Introduction: American cockroaches, Periplaneta americana, are the most important pests in hospitals and dwelling environments. They are mechanical vectors of some bacterial pathogens. Goal: The present investigation was carried out in Ghods hospital and 5 dwelling localities of Paveh city to evaluate bacterial infestations of American cockroaches in this region of Iran. Methods: The samples were randomly collected from hospital environments and toilets and kitchens of the dwelling localities from December-March 2012 and July-September 2013. The samples were captured using sterile test tubes and sterile hand gloves. Results: Totally, 98 cockroaches were collected from hospital (45.9%) and dwelling (54.1%) environments. Eight groups of bacteria including: Pseudomonas spp., Proteus spp., Klebsiella spp., Staphylococcus spp., Bacillus spp., Serratia spp., Entrobacter spp. and Escherichia coli were extracted. Conclusions: The findings of the present study revealed that the American cockroaches are very important in transmission of some bacterial pathogens, so health education and using the effective control methods to elimination and reduction of cockroaches are necessary.


Abstract Flour properties of 37 Australian wheat samples were examined for their relationship to white salted noodle quality. Flour Rapid Visco Analyser pasting properties and flour swelling power were correlated to the smoothness and softness of cooked noodles. Although different Rapid Visco Analyser profiles could be used to enhance relationships with noodle parameters, the flour swelling power test appeared to be more useful assay for smoothness and softness. The addition of sodium chloride improved these relationships for both the Rapid Visco Analyser and swelling power tests. Viscosity properties were not changed proportionally with salt addition and there appeared to be an interaction with individual wheat varieties. Noodle elasticity and eating quality were closely correlated with Mixograph time to maximum bandwidth, flour protein content and thousand kernel weight. Addition of sodium chloride to Mixograph doughs appeared to be valuable for the study of white salted noodles. The results also indicated that dough rheological properties need to be considered for these noodles, in addition to the physical and chemical properties of starch. About two thirds of total noodle quality were accounted for by physicochemical properties including Rapid Visco Analyser final viscosity, Mixograph time to maximum bandwidth (both parameters measured with salt addition), thousand kernel weight and Minolta b* value examined in this study.


Scratch testing is a contact mechanics based nondestructive testing method that, if correctly evaluated, can give a lot of information about the material and tribological behavior of a material. In contrast to the situation with another contact-based method, indentation testing, wear characteristics can also be investigated, for example. In order to get results of practical importance from a scratch test, it is necessary to have evaluation formulae available. Indeed, such formulae exist for scratch testing but can be substantially influenced by frictional effects. For this reason, closed-form analytical relations have been suggested for the purpose of accounting for such effects during scratching and in particular the plowing frictional effect. As a major benefit, these relations can also be of assistance during material characterization through scratch testing. However, the proposed existing relations are based solely on theoretical/numerical analyses and, remembering that the scratch test of course is an experimental approach, verification by experiments is a necessity. Such a task is performed in the present study and it is shown that, based on standard contact global properties, the relations are accurate for most polymeric materials but could also be used for some metallic ones.


There is a growing diversity of client devices that have access to the Internet. However, much of the content on the Internet cannot be handled by the devices that have limited communication, processing, storage and display capabilities. In order to improve the utility of a wide range of client devices, we propose a network-based solution for transcoding Internet content. The system uses an InfoPyramid for representing and transcoding video, images, audio and text. The InfoPyramid manipulates the content along the dimensions of fidelity and modality, and aggregates the methods for content analysis, translation, filtering and selection. The InfoPyramid utilizes a policy engine, which incorporates user and publisher preferences, various transcoding policies, device descriptions, and real-time network constraints in order to adapt the Internet content to the client devices.


We present results from a study of 12 X-ray bright clusters at 1.4 GHz with the 100 m Green Bank Telescope. After subtraction of point sources using existing interferometer data, we reach a median (best) 1σ rms sensitivity level of 0.01 (0.006) μJy arcsec−2, and find a significant excess of diffuse, low surface brightness emission in 11 of 12 Abell clusters observed. We also present initial results at 1.4 GHz of A2319 from the Very Large Array. In particular, we find: (1) four new detections of diffuse structures tentatively classified as two halos (A2065, A2069) and two relics (A2067, A2073); (2) the first detection of the radio halo in A2061 at 1.4 GHz, which qualifies this as a possible ultra-steep spectrum halo source with a synchrotron spectral index of α ∼ 1.8 between 327 MHz and 1.4 GHz; (3) a ∼2 Mpc radio halo in the sloshing, minor-merger cluster A2142; (4) a >2× increase of the giant radio halo extent and luminosity in the merging cluster A2319; (5) a ∼7× increase to the integrated radio flux and >4× increase to the observed extent of the peripheral radio relic in A1367 to ∼600 kpc, which we also observe to be polarized on a similar scale; (6) significant excess emission of ambiguous nature in three clusters with embedded tailed radio galaxies (A119, A400, A3744). Our radio halo detections agree with the well-known X-ray/radio luminosity correlation, but they are larger and fainter than current radio power correlation studies would predict. The corresponding volume-averaged synchrotron emissivities are 1–2 orders of magnitude below the characteristic value found in previous studies. Some of the halo-like detections may be some type of previously unseen, low surface brightness radio halo or blend of unresolved shock structures and sub-Mpc-scale turbulent regions associated with their respective cluster merging activity. Four of the five tentative halos contain one or more X-ray cold fronts, suggesting a possible connection between gas sloshing and particle acceleration on large scales in some of these clusters. Additionally, we see evidence for a possible inter-cluster filament between A2061 and A2067. For our faintest detections, we note the possibility of residual contamination from faint radio galaxies not accounted for in our confusion subtraction procedure. We also quantify the sensitivity of the NVSS to extended emission as a function of size.


The main objective of the paper is to analyze Police role and their steps in providing legal protection against children as victims of sexual abuse. This study is using the normative research which is a study of legal principles concerning the substance of legislation. This study is using the secondary data as the main data and the primary data as support. The result found that the police role in dealing with a criminal act of sexual violence in children in general already showed his role with a maximum of law enforcement and guidance of society. In addition, the police also in dealing with the case of criminal act in particular in the case of criminal acts of sexual violence not always running in accordance with the expected, this is because by the time constraints and means in dealing with each case that there. While the steps taken is collecting evidence of a strong, giving protection to the victim and running cooperation with the local community. With these steps are expected to maximize the police work in dealing with the case of sexual abuse in children Keywords: Police, Indonesia, Child Abuse, Law protection


In this work the study of the optical properties and the high resolution electron microscope (HREM) lattice images was performed on the Ge/sub 2/Sb/sub 2/Te/sub 5/ phase change optical discs. In the as-deposited recording layer, the dominant amorphous states coexisted with some nanocrystals.


Paediatric Project ECHO® is an innovative, interactive educational model for healthcare providers (HCP) based on the community of practice (CoP) concept, that expands access to and capacity for providing evidence-informed care. This study examined the development of a CoP in Paediatric Project ECHO and barriers and facilitators to its development. A qualitative description design was undertaken with semi-structured, audio-taped interviews. Twenty-one HCPs participants were interviewed. Participants' responses indicated evidence for CoP concepts including social interaction, knowledge sharing, knowledge creation, and identity building. The main barriers to CoP development were differences in participants' perceptions of the program aims and challenges in making time to participate in the program. The main facilitator was the interactive program format. This is one of few studies to demonstrate how knowledge creation occurs in an intentionally created CoP. Further development and clarification of the CoP concept for the ECHO model is needed to enhance program delivery.


In the article "Progressive dialysis encephalopathy" (Ann Neurol ~ 4 : 199-204, 1978) , Drs Lederman and Henry considered the role of aluminum in the origin of dialysis encephalopathy 3s speculative. W-e were astonished that aluminum blood levels were not reported for their 9 patients. Like other authors 11, 31, we believe that aluminum toxicity probabl\, plays a role in the production of dialysis encephalopathv, at least in some cases. T h e following arguments favor o u r belief. First, neuropathological studies have not shown major lesions even under electron microscopy 12 I , which suggests a metabolic mechanism. Second, demographically, dialysis encephalopathy has a higher incidence in regions where the aluminum dialysate content is increased 1'11. Third, early interruption of aluminum intake has been reported to reverse the encephalopathy 151. Recently we have observed 6 patients i n whom the clinical and electroencephalographic findings were identical to those reporreti elsewhere in dialysis encephalopathy and to the 9 cases reporteci by Drs Lederman and Henry. In our 6 patients, psychic troubles and repeated somnolence were present in all, dysarthria in 5 , myoclonic jerks in 4 , and epileptic seizures in 1 . In all 6 patients the EEG was disturbed and showed bilateral symmetrical, periodic, monomorphic, slow activity; in 3 patients, biphasic and triphasic spike conhgurations were noted. The average serum aluminum level was 407 pg per liter in the acute phase, 161 pg per liter in the remission phase with an average delay of six weeks, and 123 pg per liter three months later with maintained remission. (The normal serum aluminum level i s 4 0 pg per liter as determined by flameless-oven atomic sl-'ectrophotometry. ) Following interruption of the oral and ilidysate aluminum intake, remissions were permanently mainrained. In 2 cases, transient oral readministration o f aluminum to treat hyperphosphatemia was followed 13, recurrent encephalopathy, reversed only when aluminum intake was stopped again.


To prevent extubation, nasogastric tubes (NGT) were attached to a fine bore polyurethane tube, which loops loosely around the nasal septum. In a prospective study 180 cases were evaluated concerning the efficacy and possible complications related to this techniques. On average, a nasal septal loop (NSL) remained 20.1 +/- 1.3 days and a NGT 14 +/- 0.9 days. Complications were rare. In 45 of the cases NGT had to be replaced after self extubation and in 2.2% extubation presented more than twice. We think NSL is an easy and useful technique to secure NGT in non-cooperative and/or agitated patients for a relatively short term enteral nutrition or gastric decompression.


This paper explores the convergence of age at death inIndiain terms of average life loss using estimated single year age specific probabilities of dying as input from the Heligman Pollard equation for the Sample Registration System. ForIndiaas a whole and for all major states in the country, the average life loss is declining over time with increased life expectancy at birth, assuring convergence in age at death. The decomposition analysis found that for state with low life expectancy, improvement in infant and child mortality contributes significantly to reducing average life loss and accelerates convergence of age at death. For state with higher life expectancy, the reduction in adult and old age mortality adds to the pace of convergence of age at death. Akansha SINGH, Professor, Department of Mathematical Demography and Statistics, International Institute for Population Sciences, Mumbai, India. E-mail: firstname.lastname@example.com . Laishram LADUSINGH, International Institute for Population Sciences, Govandi Station Road, Deonar, Mumbai-400088, India. E-mail: firstname.lastname@example.com .


Background Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. Methodology/Principal Findings We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-β treatment. CD-1 mice were administered acetaminophen (APAP), interferon-β (IFN-β) or a combination of IFN-β+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-β. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IκBK/NF-κB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. Conclusions/Significance A significant change in the transcriptional response was observed following co-administration of IFN-β+APAP relative to IFN-β treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-β treatment.


Contextualization has become the reigning shibboleth of historical analysis, especially for intellectual and cultural history. Although acknowledging the achievements of the Cambridge School of historians, led by Quentin Skinner, who have done so much to promote awareness of the need to situate texts in their original illocutionary contexts, this essays explores two critical responses. The first focuses on challenges to contemporary historians to establish the relevant explanatory contexts without bringing to bear current perspectives and knowledge of developments after the original period. The second turns to the events themselves and draws on recent French theory, in particular the phenomenological work of Claude Romano, to question whether all historical phenomena can be understood by situating them in their generative contexts.


Treponema pallidum is a highly invasive spirochete that disseminates to organ sites distal to the site of primary infection and is able to cross both the blood-brain and placental barriers during the course of infection. The corkscrew motility used by T. pallidum undoubtedly contributes to its invasive nature. However, this signature motility is shared with other spirochetes and thus the factors responsible for the widespread dissemination capability that is unique to T. pallidum remain unknown. We have identified the treponemal-specific, surface-localised protein pallilysin as a dual functioning adhesin/metalloprotease that exhibits specific attachment to, and degradation of, multiple extracellular matrix components. Pallilysin is produced as an inactive proprotease that can be activated via either autocatalytic cleavage or host-originating thrombin cleavage. Purified recombinant pallilysin, as well as a non-invasive model treponeme heterologously expressing pallilysin on its surface, exhibit specific degradation of fibrin clots. Pallilysin immunisation alters the course of T. pallidumdissemination following challenge within the rabbit model of syphilis infection, with immunised rabbits exhibiting a reduced bacterial burden within organs distal to the site of challenge compared to unimmunized control rabbits. Further, rabbit infectivity tests (RIT) showed that rabbits receiving lymph nodes from challenged, unimmunized rabbits seroconverted and developed orchitis by 30 days post-transfer, while 66% of RIT rabbits receiving lymph nodes from challenged, pallilysin-immunised rabbits remained seronegative and had no signs of orchitis at the termination of the experiment (day 185 post-transfer). Collectively these studies identify pallilysin as a T. pallidum-specific metalloprotease that (1) exploits the host coagulation cascade to facilitate protease activation, (2) plays a central role in treponemal dissemination and (3) shows promise as a novel syphilis vaccine candidate.


Swarm intelligence is a relatively new approach to problem solving that takes inspiration from the social behaviors of insects and other animals. Ants, in particular, have inspired a number of methods and techniques among which the most studied and successful is the general-purpose optimization technique, also known as ant colony optimization, In computer science and operations research, the ant colony optimization algorithm (ACO) is a probabilistic technique for solving computational problems which can be reduced to finding good paths through graphs.  Ant Colony Optimization (ACO) algorithm is used to arrive at the best solution for TSP. In this article, the researcher has introduced ways to use a great deluge algorithm with the ACO algorithm to increase the ability of the ACO in finding the best tour (optimal tour). Results are given for different TSP problems by using ACO with great deluge and other local search algorithms.


We develop a new type of convolution between two signals on the 2-sphere. This is the first type of convolution on the 2-sphere which is commutative. Two other advantages, in comparison with existing definitions in the literature, are that 1) the new convolution admits anisotropic filters and signals and 2) the domain of the output remains on the sphere. Therefore, the new convolution well emulates the conventional Euclidean convolution. In addition to providing the new definition of convolution and discussing its properties, we provide the spectral analysis of the convolution output. This convolutional framework can be useful in filtering applications for signals defined on the 2-sphere.


The article emphasizes the importance of taking into account and evaluating the environmental aspects of goods, services, and solutions (technological, organizational and marketing nature), when planning innovations in the enterprise. The aim of the article is to characterize the possibilities of use and functionality of modern software developed to assess the environmental aspects of innovation during the development of plans for innovation projects and investment proposals. Within the research framework, the main indicators that can be used to assess the environmental friendliness of innovations are described, in particular: water footprint, land footprint, material input per service unit, carbon footprint. The article provides a detailed review of software (foreign and domestic developments) that can be used to automate the process of assessing the environmental aspects of innovative projects and business in general: outlines the functionality (detailing indicators for evaluation) and features of use, indicates the possibility of software use for planning. The foreign developments explored provide an assessment of the environmental impact throughout the life cycle and, as a rule, can be applied to various industries. Almost all the software presented provides a carbon footprint assessment and is suitable for eco-design purposes. In addition to directly assessing the environmental impact, many tools provide an opportunity to assess the costs associated with the environmental impact along the life cycle or with the material / energy flows. Domestic developments are mainly of a marketing nature (aimed at attracting new customers rather than assessing environmental aspects). For the most part, the functionality of these developments is related to energy efficiency issues. No domestic software provides a comprehensive environmental impact assessment throughout the life cycle. However, there is the wide range of available (in terms of conditions of use and functionality) foreign software tools for assessing the environmental aspects of innovation, which can be used to plan and develop investment proposals by domestic business structures.


The density functional theory, simplified by the local density approximation and mean-field approxi-mation, is applied to study the surface properties of pure non-polar fluids. A reasonable long rang correction is adopted to avoid the truncation of the potential. The perturbation theory is applied to establish the equation for the phase equilibrium, in which the hard-core chain fluid is as the reference fluid and the Yukawa potential is used as the perturbation term. Three parameters, e/κ, d and ms, are regressed frorn the vapor-liquid equilibria, and the surface properties, including density profile, surface tension and local surface tension profile are predicted with these parameters.


Adult pigtailed macaques (Macaca nemestrina) were evaluated for their usefulness as a primate model for chancroid. To initiate infection, 10(7)-10(8) cfu of Haemophilus ducreyi were inoculated into the foreskins of 5 adult males and into the vaginal labia of 4 adult females. Lesions developed in the male macaques that were similar in appearance, histopathologic changes, and progression to those of human disease, including the development of ulcers 6-12 days after infection. In addition, H. ducreyi could be recovered from the lesions up to 20 days after inoculation, humoral antibodies were induced beginning 1 week after inoculation, and inguinal lymphadenopathy was noted in 4 of the 5 males. None of the 4 female macaques inoculated with the same preparation of live H. ducreyi developed comparable lesions. Thus, experimental chancroid in adult male macaques closely resembles human disease and should be useful for future studies of the pathogenesis of chancroid.


Sick sinus syndrome (SSS) is a term used for a variety of disorders defined by abnormal cardiac impulse formation and by abnormal propagation from the heart's sinoatrial node. In this study, we present a case from a Chinese family in which two closely related individuals had the symptoms and electrocardiographic evidence of SSS. We hypothesized that multiple individuals affected by the disease in the family was an indication of its genetic predisposition, and thus performed high-throughput sequencing for the participants from the family to detect potential disease-associated variants. One of the potential variants that was identified was a KCNG2 gene variant (NC_000018.9: g.77624068_77624079del). Further bioinformatic analysis showed that the observed variant may be a pathogenic mutation. The results of protein-protein docking and whole-cell patch clamp measurements implied that the deletion variant in KCNG2 could affect its binding the Kv2.1 protein, and finally affect the function of Kv channel, which is an important determinant in regulation of heartbeat. Therefore, we inferred that the variable KCNG2 gene may affect the function of Kv channel by changing the binding conformation of KCNG2 and Kv2.1 proteins and then adversely affect propagation from the sinoatrial node and cardiac impulse formation by changing the action potential repolarization of heart cells. In summary, our findings suggested that the dominant KCNG2 deletion variant in the examined Chinese family with SSS may be a potential disease-associated variant.


Substances that are airborne and toxic by inhalation are usually evaluated by sampling and analysis of the relative or absolute concentration of the substance in air. First it is necessary to state the reason for evaluation: determining the sources of emissions in work processes; determining the quantity of emissions to the environment; determining compliance with regulations and guidelines; determining the exposure distribution for affected persons; determining the effect of process modification on exposure; and determining risk of disease. Once the desired outcome has been clearly stated it is possible to consider a strategy for sampling that involves sample number, distribution and timing. The sampling strategy also affects the selection of sampling and analysis methods, including requirements of selectivity, sensitivity and accuracy. Methods may be prescriptive, and following such methods strictly may be a requirement under regulation or for accreditation. Conversely, today's technology allows many options and variations that may not have been available in the past. Changing requirements, such as changes to concentration limit values, require a degree of flexibility. This chapter describes the theory and technology for sampling aerosols in general and beryllium aerosols in particular, with sufficient background and discussion to allow the user to select with confidence from the available options the tools and techniques most applicable to the desired outcome. It must be kept in mind that an air sample is only ever an estimate of exposure with an uncertainty that is associated with the methodology both of the strategy and the procedure.


We analyze a vertically differentiated market for an imperfectly durable good served by a monopolist in an infinite-horizon, discrete-time game. Our goal is to identify the Markov perfect stationary equilibria where the seller can maintain his monopoly power. We establish that the set of parameters supporting a monopoly outcome is larger when the seller offers different quality versions of the same product. Hence, our results suggest that, when the innate durability of a product is high, the seller should offer different quality versions of the product.


In earlier studies of Astra Tech and Brånemark System implants, high survival rates and small marginal bone changes have been demonstrated. The aim of this study was to compare the two systems, primarily with regard to marginal bone changes, but also with regard to other clinical variables of interest. The present paper describes the results after three years. Sixty-six patients were included in the study and randomly assigned to treatment with Astra Tech implants (n = 184) or Brånemark System implants (n=187). The marginal bone level was radiographically examined at fixture insertion, at abutment connection, at baseline (delivery of the prosthetic construction) and at 1- and 3-year follow-up examinations. Between fixture insertion and the baseline examination, the pattern of marginal bone resorption differed between the two systems. However, there was no significant marginal bone change between baseline and the 1-year examination or between the 1- and 3-year examinations. Nor were there any differences between the systems. The mean bone loss in the upper jaw between BL (baseline) and 3 years was 0.2 +/- 0.3 mm for Astra Tech implants and 0.2 +/- 0.1 mm for Brånemark System implants. The corresponding figures for the lower jaw were 0.3 +/- 0.2 mm and 0.2 +/- 0.1 mm. The survival rate of Astra Tech implants was significantly higher (98.9%) than for Brånemark System implants (95.2%). However, five of the nine implant losses in the Brånemark group occurred in one patient. For that reason, this result must be interpreted with caution. The number of patients with implant losses did not differ significantly between the systems. Few complications were recorded up to 3 years.


Information--and communication technology is one of the most important cornerstones in more and more data and knowledge intensive health care sector. However these factors don't create financial gains and productivity benefits spontaneously. They need organisational and social innovations and new business models. The growth of productivity is connected to the process and organisational innovations and not to the number of computers and the growth of using ICT. One of the problems prohibiting health care profession to move to real e-work environment is the lack of the reliable measures and on these measures based performance measurement and strategic management. Health care can be improved by utilizing ICT and tools like performance measuring are key weapons in the arsenal of new e-work environment and measuring based new strategic management. Neither public sector nor not-for-profit hospitals look for financial rewards as their ultimate proof of success. Instead, they seek to achieve ambitious missions aimed at improving the health standards and wellbeing of the citizens. ICT- based new way of managing in the public sector is just beginning to gain a critical level of digitalization and will most likely come to its own in the coming years. Therefore, it is essential to research on how the health care sector can be moved towards new regional models and clinical workflow using intelligent standard based strategic management and performance measurement. If the breakthrough of the eight-hour working day and shortening of working time are evaluated afterwards, it can be stated that they have made the society more anthropocentric and humane. During one century the annual working time has shortened from 3000 hours to 1700 hours in the European Union countries. These foundations of a more humane society--eight-hour working day and shortening of regular working time--are however disappearing in the post-industrialized information society. There are various grounds for the eight-hour working day. These grounds relate to quality of life, occupational safety and health and productivity of work. It is worth asking if the nature of work has changed in a way that the truths of an industrialized society do not hold true or has the development of working time in health care sector become uncontrolled in some new way?


Abstract Epilepsy is a common neurological disorder. About one-third of epilepsy patients have a multidrug resistance (MDR) phenotype and develop refractory epilepsy (RE). Changes in the properties of the antiepileptic drugs (AEDs) targets resulting in reduced drug sensitivity, can't explain the MDR phenotype. This particular refractoriness is now attributed to overexpression of multidrug transporters in brain, leading to impaired access of AEDs to CNS targets, and it was documented in both human as well as in experimental models of RE. Single nucleotide polymorphism (SNP) identified in the MDR1-ABCB1gene (C3435T/CC-genotype) is associated with increased intestinal expression of P-glycoprotein (P-gp) that affects levels of AEDs in plasma. The functional studies of P-gp using P-gp inhibitors could show the still unclear clinical impact of ABCB1 polymorphisms on AEDs resistance. Some drug-drug interactions previously believed to be cytochrome P450 (CYP) mediated are now also considered to be due to the modulation of multidrug-transporters. Because in certain cases pharmacoresistance can be overcome by add-on therapy, co-administered P-gp inhibitors could contribute to the effectiveness of AEDs treatment in RE. And in this regard, perhaps we can postulate to P-gp as a new clinical therapeutic target in multidrug-refractory epilepsy.


This article aims to analyze the limits of representation theory in Freudian metapsychology. It is a theoretical research on psychoanalysis, through a methodology of historical and epistemological analysis of Freud's texts. The Freudian metapsychology is based on a theory of drives that is tributary to the principles of a theory of the mental representation. However, the changes required by the introduction of the concepts of narcissism and identification, along with recognition of the repetition compulsion as something beyond the pleasure principle led to a redesign of the drive theory, a new topical description and a reformulation of the theory of anxiety. The hypothesis is that the representational theory finds limits in two different directions: the identification and the impossibility of representation as, respectively, a beyond and a beneath of Freudian metapsychology.


Care for youth with pediatric inflammatory bowel disease (IBD) is the focus of ImproveCareNow (ICN), an international learning health system devoted to quality care and improved outcomes through collaboration, data sharing, and research. Known to be significantly disruptive to normative social development and quality of life, pediatric IBD significantly increases the risk of internalizing distress and secondary developmental sequelae. While multidisciplinary support including psychosocial care (from social workers and pediatric psychologists) is growing, this evidence-based and beneficial set of services is not universally available to youth with IBD. In a survey sent to the more than 100 established ICN centers, psychosocial providers attempted to identify the coverage and practice scope of psychosocial providers within the network. Results indicated that support varies widely by service type and availability of providers. Recommendations for further research and considerations for centers seeking to expand supports are considered.