Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

The discovery of somatic mutations in epidermal growth factor receptor (EGFR) and the development of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have revolutionized treatment for non-small cell lung cancer (NSCLC). Resistance to TKIs emerges in almost all patients, but currently no effective treatment is available.Therefore, novel strategies to either prevent or overcome resistance are sorely needed. Here we show that β-catenin is essential for development of EGFR mutated lung cancers. We found that β-catenin was upregulated, translocated to the nucleus, and subsequently activated in both EGFR mutated lung cancer cell lines and EGFR mutation driven lung tumors. We demonstrated that mutant EGFR preferentially bound to β-catenin and caused tyrosine-phosphorylation of β-catenin. Tyrosine-phosphorylation of β-catenin led to stabilization, nuclear translocation, and transcriptional activity particularly in cells harboring EGFR-L858R (LR)-T790M (TM). Pharmacological β-catenin inhibition using ICG-001, which specifically blocks the CBP-β-catenin interaction, suppressed growth of both H1975 cells harboring EGFR-LR-TM and lung tumors in EGFR-LR-TM transgenic mice. To further examine whether β-catenin plays an important role in lung tumorigenesis, we generated an EGFR-LR-TM lung cancer mouse model in which the β-catenin gene (Ctnnb1) can be conditionally deleted. Genetic deletion of Ctnnb1 dramatically reduced lung tumor formation and showed significantly longer survival. Taken together, our data suggest that β-catenin plays an important role in mutant EGFR-driven lung tumorigenesis and that targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development and/or overcome resistance to EGFR TKIs.

Citation Format: Sohei Nakayama, Natasha J. Sng, Julian Carretero, Robert Welner, Yuichiro Hayashi, Mihoko Yamamoto, Tan J. Alistair, Norihiro Yamaguchi, Hiroyuki Yasuda, Li Danan, Kenzo Soejima, Soo A. Ross, Costa B. Daniel, Kwok-Kin Wong, Susumu S. Kobayashi. β-catenin plays an important role in lung tumor development induced by EGFR mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 968. doi:10.1158/1538-7445.AM2014-968


I use a well‐recorded earthquake sequence to investigate the uncertainties of earthquake stress drops calculated using an empirical Green's function (EGF) approach. The earthquakes in the largest (M ~ 2.1) repeating sequence targeted by the San Andreas Observatory at Depth (SAFOD), Parkfield, California, are recorded by multiple borehole stations and have simple sources, well‐constrained stress drops, and abundant smaller earthquakes to use as EGFs. I perform three tests to estimate quantitatively the likely uncertainties to arise in less optimal settings. I use EGF earthquakes with a range of cross‐correlation values and separation distances from the main earthquakes. The stress drop measurements decrease by a factor of 3 as the quality of the EGF assumption decreases; a good EGF must be located within approximately one source dimension of the large earthquake, with high cross correlation. I subsample the large number of measurements for the main earthquakes to investigate the expected stress drop uncertainties in studies where fewer stations or EGFs are available. If only one measurement is available, the uncertainties are likely to be at least 50%. The uncertainties decrease to <20% with five or more measurements; using multiple EGFs is a good alternative to multiple stations. To investigate the effects of limited frequency bandwidth, I recalculate the corner frequencies after progressively decimating the sample rate. Decreasing the high‐frequency limit of the bandwidth decreases the estimate of the corner frequency (and stress drop). The corner frequency may be underestimated if it is within a factor of 3 of the maximum frequency of the signal.


Multisystem inflammatory syndrome in children (MIS-C) is known to represent a hyperinflammatory state with multi-organ involvement. Many cardiac manifestations of MIS-C have been described in the literature, including myopericarditis, congestive heart failure, and arrhythmias. We present a 17-year-old male who initially presented in shock with multi-organ failure and met the diagnostic criteria for MIS-C to develop atrial fibrillation later. Atrial fibrillation resolved after initiating treatment for MIS-C. In this paper, we will discuss arrhythmias linked to MIS-C and will describe the course that our patient followed.


PURPOSE
To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma following total abdominal hysterectomy and bisalpingo-oophorectomy (TAH BSO).

MATERIALS AND METHODS
Twenty patients originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or II) following TAH BSO developed isolated vaginal recurrences and were referred to our radiation oncology department for definitive treatment. The median time between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Median prescribed dose was 3500 cGy to the vagina mucosa surface for the HDRB only group. These patients were followed for a median duration of 47.5 months following treatment for isolated vaginal recurrence.

RESULTS
Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications. Three patients developed grade 2 late complications from treatment; all 3 were from the combined modality group (HDRB + EBRT).

CONCLUSION
The use of HDRB resulted in high complete response rates and durable long-term disease-specific survival in a substantial percentage of patients. To our knowledge, this study represents the first published results on treatment of vaginal recurrences with HDRB. Although the number of patients in this study is small, treatment results compare favorably to those obtained from patients treated with low-dose-rate brachytherapy +/- EBRT from other studies.


Goethite (gt), 2-line (21fh), 6-line ferrihydrite (61fh), and schwertmannite (shm) were reacted with H2S under steady-state conditions at pH 2.5-5 using a novel setup that consisted of an electrochemical sulfide generator transporting H2S into a suspension of oxides in a fluidized bed-reactor. The reactants were stoichiometrically converted into Fe2+ and So. Sulfate significantly inhibited the rates. Surface area normalized rates increased with pH. They depended on the mineral type following the order gt > 21fh > 61fh, contrasting previous observations at circumneutral pH with an inverse order. The rate of shm dissolution was highest probably due to direct reduction of dissolved ferric iron by H2S. A linear relationship between the observed rate and the surface species of H2S was derived from a surface complexation approach that allowed for the estimation of intrinsic rate constants kintr for the various oxides (38 min(-1), 1.4 min(-1), 0.29 min(-1) for gt, 21fh, and 61fh, respectively). kint decreased with increasing deltaGf for the reactions and seems to depend on the reduction potential of the solution. From this observation we derived the hypothesis that kint is determined by the flat-band potential of the mineral/solute interface at low pH while being affected by surface interactions at higher pH.


Indonesia has a potency to produce its own propoifs, however the propolis market in Indonesia is dominated by imported product, such as from Brazil. Currently, still there is no reasearch which evaluate bioactive compound and nutrient content of Indonesian Propolis (lP) compare with Brazilian Propolis (BP). The objec tives of this study were ta analyze bioactive compounds and nutrient contents of IP compared to BP. Bioactive compounds and nutrients content were analyzed by gas chromatography-mass spectrophotometry. The re sults showed both IP and BP contain fenol, a-amyrin, cylolanost, and pyrimidines. Biooctive compounds which specifically found in IP were eudesmane compound, ethyl acridine, lupeol, friedooleanan; while B amyrin and cinnamic acid compound only found in BP. The nutrient contents of IP were higher than BP except for vitamin A. In conclusion, IP might have potential health benefit, similar to BP.


Civil engineers use during tests various mechanisms and tools to estimate deformation of structures and materials such as the strain gage, which measures superficial deformation in cylindrical or block pieces, thus registering dimensional changes. Sometimes such experiments cause the destruction of the sensor element, increasing their cost and industrial liter, proportionally to the number of tests. This paper proposes the use of Computer Vision Techniques to estimate deformation. The experimental setups uses a painted pattern on the sample and perform a deformation estimation by regions on the block. The results are promising, the proposed procedure is able to detect unit deformations of around 0.0025 mm a distance of 39 cm from the object.


A number of the test programs currently in progress at the Halden Project are aimed at evaluating Zircaloy cladding performance in terms of corrosion behavior, particularly at high burnup. A pressurized water reactor (PWR) facility has been used to determine the effects of high (4 to 4.5 ppm) lithium on the corrosion behavior of Zircaloy-4 cladding material exposed to nucleate boiling (1% void) and to one-phase cooling conditions. The test employed four fuel rod segments, base-irradiated to an average burnup of 28.5 MWd/kg UO{sub 2} in a commercial power plant, and with average initial oxide layers of either 10, 20, or 40 {mu}m, respectively, respectively. Four sets of oxide layer thickness measurements were performed on the four rods during the course of the investigation. Pre-test eddy current measurements were performed on the as-received segments and two interim sets of measurements were made after 80 and 245 full power days of irradiation. Final oxide measurements were made after 425 full power days, when maximum rod burnup was 45 MWd/kg UO{sub 2}. Average oxide layer increases of 30 and 55 {mu}m were observed for the rods exposed to one-phase cooling and nucleate boiling conditions, respectively. Although maximum oxide thickness exceeded 95 {mu}m,more » no evidence of spalling was apparent. The measured oxide layer thicknesses compared favorably with predicted values based on model calculations derived from power plant data, with little evidence of enhanced corrosion rates in the presence of increased lithium concentrations.« less


Expansion was invented at the end of the 1970s for calculating principal typings for λ-terms in type systems with intersection types. Expansion variables (E-variables) were invented at the end of the 1990s to simplify and help mechanise expansion. Recently, E-variables have been further simplified and generalised to also allow calculating type operators other than just intersection. There has been much work on denotational semantics for type systems with intersection types, but none whatsoever before now on type systems with E-variables. Building a semantics for E-variables turns out to be challenging. To simplify the problem, we consider only E-variables, and not the corresponding operation of expansion. We develop a realisability semantics where each use of an E-variable in a type corresponds to an independent degree at which evaluation occurs in the λ-term that is assigned the type. In the λ-term being evaluated, the only interaction possible between portions at different degrees is that higher degree portions can be passed around but never applied to lower degree portions. We apply this semantics to two intersection type systems. We show these systems are sound, that completeness does not hold for the first system, and completeness holds for the second system when only one E-variable is allowed (although it can be used many times and nested). As far as we know, this is the first study of a denotational semantics of intersection type systems with E-variables (using realisability or any other approach).


The MHD Falkner–Skan equation arises in the study of laminar boundary layers exhibiting similarity on the semi‐infinite domain. The proposed approach is equipped by the orthogonal Sinc functions that have perfect properties. This method solves the problem on the semi‐infinite domain without truncating it to a finite domain and transforming domain of the problem to a finite domain. In addition, the governing partial differential equations are transformed into a system of ordinary differential equations using similarity variables, and then they are solved numerically by the Sinc‐collocation method. It is shown that the Sinc‐collocation method converges to the solution at an exponential rate. Copyright © 2010 John Wiley & Sons, Ltd.


The complexity of integrated circuits continues to grow, and chips with over 108 transistors will be in widespread use by the late 1990s. These chips will combine general purpose processors with subsystems for communications and other specialized tasks. They will be far too complex for the design to be tested, and manufacturing volumes will be far too high for the design to be wrong! Mathematical techniques have already been applied to the design of parts of VLSI chips. Most of this work is experimental, and requires an unusual combination of engineering, mathematical and programming skills. Sometimes new theoretical work is needed, and specialized tools may have to be constructed. Despite these difficulties, mathematical techniques are playing an important role in the design of microprocessors at Inmos, and techniques suitable for incorporation in standard computer-aided design systems are emerging.


In this paper we propose to provide a concept of Comprehensive Sexual Education and identify arguments based on International Human Rights Law that shoulddefine its scope and the extension of the obligations of the States in the region. In particular, we will identify five standards linked to sex education and its normative regulation; namely: a) legality, b) comprehensiveness, c) transversality, d) teacher training and e) role of families. In our opinion, these standards constitute indicators that should be considered by any public policy of Comprehensive Sexual Education. Based on this, we propose to critically analyze the regulations on sex education that exist in fifteen countries of the region. This, in order to identify aspects that could be relevant when designing a public policy of Comprehensive Sexual Education that is in accordance with international human rights standards in the matter.


The Nordic welfare states are considered to be universalistic, and to provide generous benefits and services. It is however possible to question whether using aggregate national expenditure data is an appropriate analytical strategy to study social care services dispersion. National equality presupposes centralized schemes executed through national agencies. In the Nordic countries, the municipalities calibrate and provide care services. This article first explores the extent of municipal variation in elder care service provision between Norwegian municipalities. It then asks whether considerations regarding national equality or local autonomy can explain these differences. National equality is operationalized as the state system of monetary transfers to the municipalities, a variable that is exogenous to the municipalities. Local autonomy is operationalized as local party politics. The data are municipal registry data from Statistics Norway. From a regression analysis of data from 2014, the main finding is that the state transfer system is the main variable explaining the current municipal variation in elder care services in Norway. The conclusion is that policies at the national level matter more than local politics when explaining the current differences in service provision between municipalities.


Major medical needs are still unmet for many non- institutionalized ethnic minorities in the inner city even though important policy changes have certainly improved the medical care of the elderly. An ethnographic and survey study (conducted be- tween 1985 and 1989) of 48 elderly Latinos in East Harlem in New York City examined the impact of several aspects of social networks on two health-related measures: meeting medical needs and mode of utilization of the medical system. Our main finding was that strong social networks predict addressing medical needs and uti- lizing the health care system on a more regular basis. We discuss the implications of these findings for health care and public policy.


A series of aggregation-deficient (aggregateless) mutants were isolated in genetically marked haploid strains of the cellular slime mould Dictyostelium discoideum. Diploids were produced from pairs of such haploid mutants by a fusion system based on this organism's parasexual cycle. The diploids were isolated from the haploids by using complementation of non-allelic growth-temperature-sensitive mutations and selection at the restrictive temperature. Complementation between the aggregateless mutations uas then assessed in 419 diploids so formed. The non-complementing aggregateless mutations fell into five complementation groups (ago A, B, C, D, and E) and a dominant aggregation class that allowed little or no aggregation when present in a diploid with any of the other mutations tested or the parental wild type. Complicating factors, including partial dominance, multiple mutations, and possible interallelic conplementation, are discussed. Data on the linkage of the aggregateless mutations was obtained by using recessive drug resistance mutations on three linkage groups to segregate haploids from the diploids. Calculations from our results suggest a genetic complexity of about 50 genes that are specific and essential for aggregation.


The effect of strenuous, competitive exercise on the human heart and life expectancy has long been a subject of debate. For centuries, the general belief was that vigorous, competitive exercise was harmful and decreased life expectancy. However, a number of studies of the early 20th century, together with more recent data in elite athletes, strongly support the notion that participation in competitive sports is associated with normal or increased life expectancy, with a special beneficial effect of aerobic type of activities. In terms of genetics, current humans are citizens of the Paleolithic era living in the 21st century, so that those who better match with an active lifestyle will likely have a longer life expectancy and a reduced risk of chronic diseases. Endurance athletes might be such an example.

The effect of strenuous, competitive exercise on human life expectancy has long been a subject of debate. Since the classical antiquity, the prevailing belief has been that vigorous, competitive exercise is harmful. Hippocrates wrote about athletes that '…the truth is, however, that no one is in a more risky state of health than they….'1 Similar was the opinion of the Greek physician–philosopher Galen. Galen's beliefs were that 'Athletes live a life quite contrary to the precepts of hygiene…when they give up their profession, they fall into a dangerous condition; as a fact, some die shortly afterwards, others live for some little time but do not arrive at old age..'2 The belief that vigorous exercise was harmful remained for centuries. In 1968, Moorstein3 stated that all members of the 1948 Harvard rowing crew had died early from 'various cardiac diseases.' A number of studies of the early 20th century and thereafter, however, showed that participation in endurance competitive sports increased life expectancy (table 1).

View this table:

Table 1
Summary of the main …


The implementation of the instruction issuer for a superscalar asynchronous microprocessor (SCALP) is described as a case study in asynchronous design. The issuer accepts five instructions at a time from the memory interface and issues them out of order to five parallel functional units. SCALP's architecture is designed to reduce the complexity of the instruction issuer by removing the need to detect dependencies between instructions as they are issued. The design has a regular cellular structure suitable for VLSI implementation. The issue's performance is sufficient that no bottleneck forms in the SCALP pipeline.


Decelerating generation of intermediate magnitude earthquakes (preshocks) in a narrow region (seismogenic region) and accelerating generation of relatively larger such earthquakes in a broader region (critical region) has been proposed as an appropriate model for intermediate-term earthquake prediction. We examined the seismic activity which preceded the M w =7.7 (October 28, 2012) thrust event that occurred off the west coast of Haida Gwaii, Canada (formerly the Queen Charlotte islands), by applying the decelerating-accelerating seismic strain model. We found that this mainshock was preceded by a pronounced accelerating seismic sequence with the time to the mainshock, as well as by an equally easily identifiable decelerating seismic sequence. Both precursory seismic sequences occurred in different space, time and magnitude windows. The behavior of previous mainshocks that occurred close to the 2012 earthquake was also examined by the time and magnitude predictable regional model. An attempt was also made to identify such seismic strain patterns, which may also be related to the generation of strong mainshocks along the western coast of Canada.


Cold-sensitive mutants of the eucaryote Neurospora crassa have been isolated by a modification of the filtration-enrichment technique of Catcheside. The mutants include osmotic remedial, auxotrophic, transport, and incorporation deficient isolates.


Due to the superiority and noteworthy progress of Quantum Computing (QC) in a lot of applications such as cryptography, chemistry, Big data, machine learning, optimization, Internet of Things (IoT), Blockchain, communication, and many more. Fully towards to combine classical machine learning (ML) with Quantum Information Processing (QIP) to build a new field in the quantum world is called Quantum Machine Learning (QML) to solve and improve problems that displayed in classical machine learning (e.g. time and energy consumption, kernel estimation). The aim of this paper presents and summarizes a comprehensive survey of the state-of-the-art advances in Quantum Machine Learning (QML). Especially, recent QML classification works. Also, we cover about 30 publications that are published lately in Quantum Machine Learning (QML). we propose a classification scheme in the quantum world and discuss encoding methods for mapping classical data to quantum data. Then, we provide quantum subroutines and some methods of Quantum Computing (QC) in improving performance and speed up of classical Machine Learning (ML). And also some of QML applications in various fields, challenges, and future vision will be presented.


Abstract. This paper investigates the physical and chemical characteristics of aerosols at ground level at a site heavily impacted by biomass burning. The site is located near Porto Velho, Rondonia, in the southwestern part of the Brazilian Amazon rainforest, and was selected for the deployment of a large suite of instruments, among them an Aerosol Chemical Speciation Monitor. Our measurements were made during the South American Biomass Burning Analysis (SAMBBA) field experiment, which consisted of a combination of aircraft and ground-based measurements over Brazil, aimed to investigate the impacts of biomass burning emissions on climate, air quality, and numerical weather prediction over South America. The campaign took place during the dry season and the transition to the wet season in September/October 2012. During most of the campaign, the site was impacted by regional biomass burning pollution (average CO mixing ratio of 0.6 ppm), occasionally superimposed by intense (up to 2 ppm of CO), freshly emitted biomass burning plumes. Aerosol number concentrations ranged from ~1000 cm−3 to peaks of up to 35 000 cm−3 (during biomass burning (BB) events, corresponding to an average submicron mass mean concentrations of 13.7 μg m−3 and peak concentrations close to 100 μg m−3. Organic aerosol strongly dominated the submicron non-refractory composition, with an average concentration of 11.4 μg m−3. The inorganic species, NH4, SO4, NO3, and Cl, were observed, on average, at concentrations of 0.44, 0.34, 0.19, and 0.01 μg m−3, respectively. Equivalent black carbon (BCe) ranged from 0.2 to 5.5 μg m−3, with an average concentration of 1.3 μg m−3. During BB peaks, organics accounted for over 90% of total mass (submicron non-refractory plus BCe), among the highest values described in the literature. We examined the ageing of biomass burning organic aerosol (BBOA) using the changes in the H : C and O : C ratios, and found that throughout most of the aerosol processing (O : C ≅ 0.25 to O : C ≅ 0.6), no remarkable change is observed in the H : C ratio (~1.35). Such a result contrasts strongly with previous observations of chemical ageing of both urban and Amazonian biogenic aerosols. At higher levels of processing (O : C > 0.6), the H : C ratio changes with a H : C / O : C slope of −0.5, possibly due to the development of a combination of BB (H : C / O : C slope = 0) and biogenic (H : C /O :C slope =−1) organic aerosol (OA). An analysis of the ΔOA /ΔCO mass ratios yields very little enhancement in the OA loading with atmospheric processing, consistent with previous observations. These results indicate that negligible secondary organic aerosol (SOA) formation occurs throughout the observed BB plume processing, or that SOA formation is almost entirely balanced by OA volatilization. Positive matrix factorization (PMF) of the organic aerosol spectra resulted in three factors: fresh BBOA, aged BBOA, and low-volatility oxygenated organic aerosol (LV-OOA). Analysis of the diurnal patterns and correlation with external markers indicates that during the first part of the campaign, OA concentrations are impacted by local fire plumes with some chemical processing occurring in the near-surface layer. During the second part of the campaign, long-range transport of BB plumes above the surface layer, as well as potential SOAs formed aloft, dominates OA concentrations at our ground-based sampling site. This manuscript describes the first ground-based deployment of the aerosol mass spectrometry at a site heavily impacted by biomass burning in the Amazon region, allowing a deeper understanding of aerosol life cycle in this important ecosystem.


Abstract International students, who study a foreign language abroad, experience more adversities than their domestic peers. The social challenges they face include problems with immigration status, isolation, difficulty speaking a new language, and learning unfamiliar customs. There is limited research focused on the coping strategies of these individuals. A growing body of research suggests storytelling may provide an important role in promoting resilience, defined as an individual's ability to bounce back or recover from stress. The study investigated possible relationships between experiencing storytelling as a child and adult resilience. The sample consisted of 21 international college students studying Chinese or English. Students were examined with a survey, a narrative interview, and the brief resilience scale. Data were analyzed quantitatively and qualitatively. The quantitative results produced significant correlations between resilience scores and the survey scores for adults who reported using storytelling in their own teaching of a second language to peers and children. Qualitative results identified five protective factors for resilience: (1) social competence, (2) problem-solving skills, (3) autonomy, (4) sense of purpose, and (5) use of storytelling. Implications of the findings for research and intervention are discussed.


abstract:This essay is a work of comparative theology regarding the sociopolitical and moral dimensions of the idea of spiritual friendship. It specifically analyzes the points of connection between the spiritali amicitia of twelfth Cistercian monk Aelred of Rievaulx with the Kalyāṇa-mittatā of select Suttas from the Buddhist Pali canon. Both texts argue for the importance of friendship, particularly what they each call spiritual friendship, the highest form of friendship, for the holy and moral life. Such friendship subverts oppressive power structures, particularly legalistic static hierarchies, by catalyzing a new and just "relational hierarchy" in which spiritual friends serve one another as moral exemplars. The essay especially focuses on the way in which those with a higher station in life—socially, economically, politically, spiritually—invite into friendship those who are marginalized, which disrupts social orders intended to protect the wealthy and powerful that benefit by maintaining class distinctions. When these distinctions are undermined through spiritual friendship, the friends can find freedom, salvation, and enlightenment.


We estimate the global rate of biogenic silica production in the ocean to be between 200 and 280 × 1012 mol Si yr−1. The upper limit is derived from information on the primary productivity of the oceans, the relative contribution of diatoms to primary production and diatom Si/C ratios. The lower limit is derived independently using a multi-compartment model of nutrient transport and biogenic particle flux, and field data on the balance between silica production and dissolution in the upper ocean. Our upper limit is 30–50% lower than several previous estimates, due to new data indicating lower values for both the relative contribution of diatoms to primary productivity and their Si/C ratios. Globally, at least 50% of the silica produced by diatoms in the euphotic zone dissolves in the upper 100 m, resulting in an estimated export of 100–140 × 1012 mol Si yr−l to the deep ocean. Our estimates correspond to a global mean rate of biogenic silica production between 0.6 and 0.8 mol Si m−2 yr−1. Incubation experiments indicate that silica production rates exceed that mean by a factor of 3–12 in coastal areas and are 2–4 times less than the global average in the oligotrophic mid-ocean gyres. The mean silica production rate in waters overlying diatomaceous sediments (approximately 10–12% of the surface area of the oceans) is 0.7–1.2 mol Si m−2 yr−1. That rate is only slightly higher than the global average, indicating that the silica produced in those regions is only 10–25% of the global total. The estimated production of biogenic silica in surface waters of the mid-ocean gyres is approximately equal to that for all major areas of opal sediment accumulation combined. Regional comparison of silica production and accumulation rates suggests a strongly bimodal character in the efficiency of opal preservation in the sea. In waters overlying diatom-rich sediments 15–25% of the silica produced in the surface layer accumulates in the seabed, while virtually none of the silica produced in other areas is preserved. The global burial/production ratio of ˜ 3% is a composite of those two very different systems. The mechanisms leading to more efficient opal preservation in regions of silica accumulation are presently unknown, but they have no simple relationship to primary productivity. Regional differences in opal preservation appear to be controlled by factors such as low surface temperature, selective grazing and aggregate formation, which diminish the rate of silica dissolution in surface waters and/or accelerate its transport to the seafloor.


ABSTRACT Background: Work related musculoskeletal disorders (WMSD) among elderly care home workers is related to the type of movement and work environment. Frequency and burden of manual handling while assisting elderly residents and domestic tasks contributed to the MSD symptoms over several body parts such as neck, shoulder, forearm, hand, lower back leg and foot. The objectives of this study are to determine the prevalence of MSD among elderly care home worker, associated factors and predictors contribute to MSD symptoms among the workers. Materials and Methods: A cross sectional study was conducted in eight elderly care home in West Coast Malaysia from February until July 2016. Eight elderly care home was selected. A total of 252 workers were randomly selected based on simple random sampling method. Validated and reliable self-administered questionnaire was used. The dependent variable was worker with MSD symptoms and independent variable were socio demographic factors organizational and factors ergonomic factors. Analysis was done using SPSS Version 22. Chi-square test and logistic regression was used for analysis. Result: Based on respondents report, prevalence rate of WMSD in the previous 12 months was 50%. Prevalence rate was highest at lower back (33.8%). Twenty three percent (23%) of them needed to get treatment and 15.3% needed to take sick leave due to MSD. Highest prevalence rate of WMSD was among female (56.9%) and assistant nurse (55.6%). The predictors for WMSD were female (AOR=2.0, 95% CI=1.1-3.6) and burden of manual task (AOR=2.2, 95% CI=1.3-4.0). Conclusion: The prevalence of WMSD was high among the female workers and assistant nurses. Burden of manual handling tasks was an important factor associated with MSD. Hence ergonomic intervention is important to reduce prevalence of WMSD among the workers. Keywords: Work related musculoskeletal disorders, elderly care home workers, physical demand tasks.


When pursuing change, legacies of policy goals and instruments from an established paradigm often present constraints on fully embracing a newer paradigm, resulting in the layering of new policy goals and instruments on top of the existing base. In this article, we investigate the effect of layered paradigms on policy capacity at three different levels of policy making in the Canadian transportation sector. Using analysis of government publications and budget data, virtual policy network analysis, quantitative analysis of data from a survey of Canadian policy analysts, and direct interviews with policy managers in two provinces, we demonstrate how this layering of legacy goals (and consequent policy incapacity) is occurring at the macro, meso, and micro levels of policy making. We conclude that the layering of a new policy paradigm for climate change on top of the established paradigm for transportation development constrains policy capacity in this subsystem.


During my PhD activities, I studied the introduction of carbon-based nanofillers in materials at different scales, while focusing primarily on fibres and fibrillar materials. Several production techniques were exploited.
Little is known about the interaction of graphene with electrospun polymeric fibres. Manufacturing composite fibres is complex since fillers have lateral sizes nearing that of the embedding fibre. Indeed, graphene has a direct effect in both the assembly of the electrospun composite fibres and their mechanical performance. Moreover, the tensile behaviour of hollow micrometric electrospun fibres was compared with macroscopic hollow structures such as drinking straws. The acquired insights helped to explain the toughening mechanisms at the micro-scale and develop a model capable of predicting the stress-strain response of such structures.
Among natural materials, wood has the most relevant structural applications even at large scales. Its main structural component is cellulose that has a high resistance and a low light absorption. Several structural modifications of wood derived materials were recently investigated in order to enhance the mechanical and optical properties of cellulose. These enhancements can take place after the internal structure is chemically modified with the removal of lignin and after a structural densification. Potentially, any type of wood-like materials, such as giant reed (that is a fast-growing and invasive species), can be turned into a strong structural composite. Such modifications lead to an open and interconnected internal structure that is the ideal scaffold for nanoparticle intercalation. Graphene oxide and silicon carbide nanoparticles were intercalated into densified reed. They produced an even stiffer, stronger and tougher composite compared to the best up-to-date process available. Moreover, its capabilities to resist fire and water-absorption were tested.
Finally, the previous process was further developed on wood to achieve a combination of improved transparency and electrical conductivity. Graphene and carbon nanotubes were introduced into the structure of wood to foster conductivity and explore the viability of its application as a self-strain sensor.


Over the last decade, laser facilities with peak intensity I > 5 ∗ 10 W cm2 have pushed the limits of ion acceleration [1], x-ray generation [2], and laboratory astrophysics [3] to exciting new extremes. The essential element for all of these phenomena is the population of relativistic electrons produced by the laser-plasma interaction (LPI), often in the preformed plasma created by amplified spontaneous emission incident on the target starting a few ns before the short-pulse laser. The typical observed electron energy spectrum [4–7] can be broken into three different energy ranges. The low energy region (up to a few MeV) is poorly connected to the LPI as it is strongly modified by large rear-surface fields and ion production [7]. The second group of electrons, whose energy distribution is ponderomotive, has been described by several scaling laws [8–11] and is still not fully understood. For instance, reference [8] finds that


Corals and coral reefs have recently experienced widespread decline attributed to anthropogenic pressure on reef systems. Studies have demonstrated that nutrient and pCO2 stress effect coral growth and calcification, but study of specific effects on coral tissue is lacking. The objective of this research was to examine wound healing in corals and how it is affected by exposure to elevated nutrients and pCO2. Coral tissue repair and regeneration during wound healing in Montastraea cavernosa and Porites astreoides were assessed histologically and ultrastructurally by examining colony fragments exposed to elevated nitrate, phosphate, and pCO2. In M. cavernosa, tissue repair was facilitated by granular amoebocytes, and the zooxanthellae population size increased under enriched nutrient conditions. In P. astreoides, zooxanthellae chloroplasts were markedly abnormal in phosphate-enriched corals, and the concentration of chromophore cells at the healing tissue front was markedly lower under elevated nutrient conditions. The area of wound healed was higher after 14 days under every experimental condition in M. cavernosa compared to P. astreoides. In both species, phosphate enrichment had the most deleterious effect on repair and regeneration.


Routing in Mobile Ad-hoc Networks has received a lot of attention due to the challenges posed by the self-organizing nature of the network, the dynamic topology, and the unreliable wireless medium. One of the most critical issues for MANETs is how to increase network lifetime, since nodes are typically battery powered. In this paper we consider the proactive MANET protocol OLSR to improve the network lifetime, we propose a novel multiple metric routing scheme for MANET, based on energy efficient and path reliability metrics, integrating it to standard OLSR, named Energy Efficient and Path Reliability OLSR (EEPR-OLSR), in which we investigate cross layer parameters that effect the network lifetime and a prediction-based link availability estimation is introduced. Simulation results, by NS3 simulator, show that the proposed EEPR-OLSR provides significant performance gains in both the network lifetime and packet delivery ration (PDR), compared to the standard OLSR.


The synthesis and characterization of a new 4 x 4 library of block copolymers based on polystyrene and poly(ethylene oxide) connected by an asymmetrical octahedral bis(terpyridine) ruthenium complex at the block junction are described, while initial studies on the thin film morphology of the components of the library are presented by the use of Atomic Force Microscopy, demonstrating the impact of a library approach to derive structure-property relationships.


Introduction In this study, we aimed to retrospectively evaluate the clinical and laboratory findings and complications of 28 common variable immunodeficiency (CVID) patients. Material and methods The clinical features and laboratory data of 28 CVID patients were evaluated. Results Nineteen patients were male. In 53.5% of the cases, complications included inflammatory bowel disease, cytopenia, bronchiectasis, granulomatous lymphocytic interstitial lung disease (ILD) and asthma. In their immunological evaluations, IgG, IgM, and IgA mean values were 474.8 ±214.1 mg/dl; 56.7 ±41.9 mg/dl; 35.3 ±58.2 mg/dl, respectively, and the vaccine response was positive in 64.2% of the cases. In all age groups, absolute lymphocyte counts, naive (CD19+IgD+27-), nonswitch (CD19+IgD-27+) memory B cells were numerically higher when compared to the data of healthy children; however, although switch memory (CD19+IgD+27+) B cells were proportionally low in the 4-8 and 12-18 age groups, they were low both numerically and proportionally in the 8-12 age group. No statistically significant difference was found between the cases with complications and without complications. But the cases with pulmonary complications were compared within the group, the CD8 ratio was high but the IgA level was low in patients with bronchiectasis and CD3 was numerically and proportionally low in the cases with ILD compared to others. According to the Paris classification, 11/27 (40.7%) of the cases, 3/27 (11.1%) of them and 13/27 (48.2%) of them were evaluated as MB0, MB1, and MB2, respectively. Conclusions In genetic studies, TACI (trans-membrane activator and calcium-modulating cyclophilin ligand interactor – TNFRSF13B) mutation was found positive in 25% of the cases.


Five girls aged 4 to 13 years presented with clinical features of classical Rett syndrome - loss of acquired developmental skills including speech and hand function, progressive microcephaly and characteristic stereotyped "hand washing" movements. Two patients had generalized tonic, clonic seizures and one had atonic seizures with electroencephalogram (EEG) evidence of Lannox Gastaut syndrome. Cranial CT was normal in all except two patients, which showed marked perisylvian atrophy, and metabolic screening revealed non specific mild hyperammoniaemia in three. The aim of the study is to illustrate the unique clinical features of Rett syndrome and reiterate the importance of the diagnosis of this rare condition, clinically.


Summary

Benzylglucosinolate (BG) was extracted by 70% methanol from maca and purified on acidic alumina column and semi-preparative Cosmosil cholester column. The purified sample was verified as BG by electrospray ionisation mass spectrometry (ESI-MS) and nuclear magnetic resonance spectra. The purity was 98.3% as determined by HPLC-MS. BG content of maca was quantified using external standard method by HPLC. Effect of physical and thermal processing on BG content of maca was investigated. When maca was steamed for 5 min before shredding, no significant difference of BG content was observed during postshredding time, while raw maca lost 57.2% of BG in 24 h. Steamed maca showed no significant loss of BG after drying at the temperature from 20 to 80 °C in 24 h. Thermal degradation was described by the first-order kinetics–Arrhenius equation for BG in the temperature range of 90–100 °C.


Two species of ixodids , Ixodes arboricola Schulze et Schlottke and I. frontalis ( Panzer ), new for the fauna of Armenia are given. Larvae and nymphs of these ticks were found on birds in the forest zone and gardens.


The potential of Fourier transform infrared (FT-IR) spectroscopy, multispectral imaging (MSI), and electronic nose (E-nose) was explored in order to determine the microbiological quality of gilthead sea bream (Sparus aurata) fillets. Fish fillets were maintained at four temperatures (0, 4, 8, and 12 °C) under aerobic conditions and modified atmosphere packaging (MAP) (33% CO2, 19% O2, 48% N2) for up to 330 and 773 h, respectively, for the determination of the population of total viable counts (TVC). In parallel, spectral data were acquired by means of FT-IR and MSI techniques, whereas the volatile profile of the samples was monitored using an E-nose. Thereafter, the collected data were correlated to microbiological counts to estimate the TVC during fish fillet storage. The obtained results demonstrated that the partial least squares regression (PLS-R) models developed on FT-IR data provided satisfactory performance in the estimation of TVC for both aerobic and MAP conditions, with coefficients of determination (R2) for calibration of 0.98 and 0.94, and root mean squared error of calibration (RMSEC) values of 0.43 and 0.87 log CFU/g, respectively. However, the performance of the PLS-R models developed on MSI data was less accurate with R2 values of 0.79 and 0.77, and RMSEC values of 0.78 and 0.72 for aerobic and MAP storage, respectively. Finally, the least satisfactory performance was observed for the E-nose with the lowest R2 (0.34 and 0.17) and the highest RMSEC (1.77 and 1.43 log CFU/g) values for aerobic and MAP conditions, respectively. The results of this work confirm the effectiveness of FT-IR spectroscopy for the rapid evaluation of the microbiological quality of gilthead sea bream fillets.


The cost of capital is important in the financial management of agricultural cooperatives. A measure of the cost of capital is required when evaluating various aspects of strategic business plans, e.g., selecting a financial leverage position, calculating the profitability of alternative investment opportunities, measuring economic value-added, and comparing various merger and acquisition plans. The task of determining the appropriate cost of capital to use requires a careful analysis of the effect of alternative financing choices which are open to a cooperative. This report considers the close relationship between the cost of capital and capital structure. Ways are examined to determine the cost of capital by a cooperative. The report sequentially identifies: principles of capital structure and cost of capital, guidelines for capital structure choice, and applications of these guidelines through cooperative case examples. These applications are a starting point for cooperatives to develop capital positions and consider alternative assumptions about financing sources and their potential impacts on the overall cost of capital. To determine the overall cost of capital for a selected capital structure, a cooperative must first determine its cost of equity capital. The cost of equity capital cannot be derived directly from the market, as in the case of a publicly traded firm. Thus, there is no ideal method for determining the cost of capital for a cooperative. So an innovative approach is needed. The opportunity cost of funds approach relates the cost of capital to the rates of return from alternative uses of capital (i.e., the assets side of the balance sheet). The focus is on the expected (or required) rates of return from alternative investments which reflects the degree of risk involved. The discounted cash flow approach relates the cost of capital to the alternative sources of capital (i.e., the liabilities and equity capital side of the balance sheet). The component costs of equity and debt capital are combined into an overall cost of capital for the cooperative. Both approaches require making some assumptions to determine the cost of equity capital for a cooperative.


Polyhydroxyalkanoates (PHAs) have emerged as a promising biodegradable and biocompatible material for scaffold manufacturing in the tissue engineering field and food packaging. Surface modification is usually required to improve cell biocompatibility and/or reduce bacteria proliferation. Picosecond laser ablation was applied for surface micro structuring of short- and medium-chain length-PHAs and its blend. The response of each material as a function of laser energy and wavelength was analyzed. Picosecond pulsed laser modified the surface topography without affecting the material properties. UV wavelength irradiation showed halved ablation thresholds compared to visible (VIS) wavelength, revealing a greater photochemical nature of the ablation process at ultraviolet (UV) wavelength. Nevertheless, the ablation rate and, therefore, ablation efficiency did not show a clear dependence on beam wavelength. The different mechanical behavior of the considered PHAs did not lead to different ablation thresholds on each polymer at a constant wavelength, suggesting the interplay of the material mechanical parameters to equalize ablation thresholds. Blended-PHA showed a significant reduction in the ablation threshold under VIS irradiation respect to the neat PHAs. Picosecond ablation was proved to be a convenient technique for micro structuring of PHAs to generate surface microfeatures appropriate to influence cell behavior and improve the biocompatibility of scaffolds in tissue engineering.


We have investigated influence of thickness of the Cr buffer layer on the glass substrate in the growth process of carbon nanotubes (CNTs) by chemical vapor deposition method. The Cr film of 3, 35 or 100 nm as a buffer layer was formed on a glass substrate by RF-sputtering method. A catalyst such as Fe, Co, or Ni in the CNT growth was also deposited on the buffer layers. The Cr buffer layer with a catalyst and the CNTs grown on the surfaces were observed by scanning electron microscopy. The lengths and the densities of the CNTs grown on the surfaces decreased with the increase in thickness of the Cr buffer layers.


Mobile Ad hoc Network (MANET) is a multi-hop wireless network, without having pre-existing infrastructure and centralized administration. Each node participating in the network acts both as host as well as a router. Prominent characteristics of Ad Hoc Networks viz. Dynamic topology, Limited Physical Security, Energy Constrained operations throw challenge in the development of robust and efficient routing protocols. The Ad Hoc Routing protocols can be categorized broadly into Proactive, Reactive and Hybrid Routing Protocols. This literature is an attempt to understand the behavior of three Ad hoc routing protocols which falls in three different categories of routing. The protocols under consideration for study are Ad hoc On Demand Distance Vector Routing Protocol (AODV) which follows Reactive Routing scheme, Destination Sequence Distance Vector Routing Protocol (DSDV) is categorized as Proactive and Zone Routing Protocol (ZRP) is Hybrid in nature. The performance differentials shall provide an insight about the sensitivity of the protocols when operating in more challenging environment such as rapid change in network topology or the density of the network.


Objective rhuMAb 2C4 (pertuzumab, RO4368451), a human epidermal growth factor receptor-2 (HER2) targeted antibody that binds to an epitope distinct from trastuzumab, blocks ligand-associated heterodimerization of HER2 with other HER receptor family members. This study evaluated the toxicity, pharmacokinetics and anti-tumor activities of pertuzumab in Japanese patients with solid tumors. Methods Patients with solid tumors refractory to standard therapy were administered pertuzumab 5, 10, 15, 20 and 25 mg/kg intravenously once every 3 weeks. Grade 3 toxicities were considered as dose limiting. The maximum tolerated dose (MTD) was a dose at which two out of six patients had Grade 3 toxicities. Results Eighteen patients, aged 38–66 (median 57) years, with solid tumors were enrolled and a total of 32 cycles of pertuzumab were administered. Toxicities were generally acceptable. Grade 3 elevation of gamma-glutamyl transpeptidase was observed in one patient at 25 mg/kg and was considered to be dose limiting. MTD was not reached up to a dose level of 25 mg/kg. The serum concentration of pertuzumab declined slowly (terminal half-life is approximately 3 weeks). The AUC proportionally increased over the dose range tested. There was limited evidence of activity (stable disease 2; progressive disease 13; and not evaluable 3); however, tumor shrinkage and tumor marker decrease were observed in an ovarian cancer and a non-small-cell lung cancer patient, respectively. Conclusions Pertuzumab is well tolerated up to 25 mg/kg. Although objective tumor response was not observed, it is worth evaluating as a flat dose and in combination with other cytotoxics and molecular-targeted agents.


This paper analyses the light trapping effect and finds out that the light path enhancement factor of cells with an ideal Lambertian back reflector (BR) could be as high as n(n+1)2, instead of general quoted 4n2. The program PVOPTICS developed by NREL has been used to modeling the light trapping effect. It is found that 1) the texture angle is more critical than the texture height in determining the light trapping effect, but the latter of which was the only mentioned parameter in general light trapping designs; 2) Inserting a ZnO buffer layer can largely increase the Si absorption, while ZnO thickness does not affect the light trapping obviously, which were confirmed by experimental results; 3) Different impacts of texture starting from a-Si/ZnO or ZnO/metal interface on light trapping effects are studied. For ZnO/Al BR, the texture starting from the a-Si/ZnO interface will lead to a larger absorption in the Si layer; while for ZnO/Ag BR, the texture starting from the a-Si/ZnO interface or ZnO/Ag interface leads to similar results.


This article presents an indoor positioning and communication platform, using fluorescent lights. We set up a practical implementation of a VLC (Visible Light Communication) system in a University building. To finalize this work, it is important that we analyze the properties of the reception signal, especially the length of the data string that can be received at different walking speed. In this paper, we present a model and a series of formulae for analyzing the relationship between positioning signal availability and other important parameters, such as sensor angle, walking speed, data transmission rate, etc. We report a series of real-life experiments using VLC system and compare the results with those generated by the formula. The outcome is an improved design for determination of the reception area with more than 97% accurate signals, and an optimal transmission data length, and transmission rate.


OBJECTIVE
To study the association between reasons for smoking and results related to successful smoking cessation.

METHODS
A community-based case-control study was conducted with 642 male adults recognized as successful spontaneous smoking quitters being the subject cases while another 700 male adults who had failed to quit smoking were served as the controls. Russell Reason for Smoking Questionnaire (RRSQ) was used to investigate the reasons for smoking. Dominance logistic regression was performed to determine the relative importance of reasons for starting smoking and the endpoint of successful quit smoking.

RESULTS
After adjusting the potential confounders of age, age of smoking initiation, marital status, profession, and education, the adjusted means of sedative and stimulation of RRSQ in the successful quitters were significant lower than that in the failed quitters. Results from the dominance logistic regression showed that the first two important factors for smoking cessation were sedative and stimulation of RRSQ, followed by psychological image, automatic, hand-mouth activity, indulgence, and addiction.

CONCLUSION
This study demonstrated that factors as dependence-addiction showed more important impacts than the social-psychological ones on the endpoint of successful smoking cessation.


Introduction : Immunotherapy is an exciting new option to stimulate a "host-vs.-cancer" effect. Such treatment regimens are dominated by Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) immune checkpoint inhibitors. However, not all patients respond to PD-1/PD-L1 inhibition as confirmed by results from an "all-comers" clinical strategy. These inherent clinical gaps are addressed in studies by incorporating PD-L1 expression as inclusion criteria and combining PD-1/PD-L1 inhibitors with other drug agents. Unfortunately these outcomes have not been clinically beneficial and cause unnecessary toxicity to patients and unmet needs.

Here we develop personalized methodologies to predict a response to PD-L1/PD-1 inhibitors based on two factors. First, PD-L1 is not the only immune checkpoint; other signaling between cancer and immune cells needs to be incorporated to predict non-responders to a PD-L1/PD-1 inhibitor. Second, precision medicine and personalization is driven by patient tumor genomics. A recent retrospective study correlated NRAS with PD-L1/PD-1 treatment responses. Beyond a single gene mutation or aberration, the holistic consideration of all gene mutations, copy number variations, and methylation status would impact immune signal activators and inhibitors from the cancer cell.

We used a predictive simulation model of multiple myeloma and dendritic cells with corresponding in-vitro models. We developed an immunotherapy response phenotype, which is a function of bio-markers representing immune evasion, immune activation, metastasis, and dendritic cell infiltration in cancer cells. We then modeled two myeloma cell lines using available genomics information as proxy for myeloma patient cancer. Finally, we predicted these two representative patient classes would vary in response to PD-L1/PD-1 inhibitors. We validated our prediction that bio-markers contribute to the immunotherapy response.

Methods : Predictive computational simulation models of myeloma cell lines, human myeloid dendritic cells, and myeloma cell + dendritic cell co-cultures were developed and used to predict extracellular (IL6, IL10, TGFB1, VEGFA) and cell-associated (CD47, FASLG, IDO1, PD-L1) biomarker readouts in an automated high-throughput system. Results were validated with myeloma cell lines MM.IS and U266B1 cultivated with and without dendritic cells in Transwell 12-well polystyrene plates. At 24 hours, IL6, IL10, TGFB1, and VEGFA concentrations in tissue culture media were determined using Millipore immunoassays. CD47, FASLG, IDO1, and PD-L1 concentrations in cell lysates were determined by ELISA and IHC. One-way fixed-effects ANOVA models were fit to log-transformed concentrations. Pairwise group comparisons were conducted using Tukey's Honest Significant Differences (JMP10, Version 10.0, SAS, Cary, NC) at a 0.05 level of significance.

Results : Predictive simulation and experimental results were highly correlated. Predicted IL10, TGFβ1, IDO1, CD47, FASLG, IL6, VEGFA, and PD-L1 responses differed among MM.IS and U266B1 patient models and were similar to those observed in cell culture supernatants and cell lysates.

Simulation models also predicted myeloma cell effects on dendritic cell biomarker responses. Twenty-three myeloma cell lines had high, moderate, and low expression effects on 19 dendritic cell biomarker readout responses. Experimental results using MM.IS and U266B1 cell lines + dendritic cell co-cultures confirmed these effects also occur in cell co-culture. Predicted IL10, TGFβ1, IDO1, CD47, FASLG, IL6, VEGFA, and PD-L1 responses were similar to that observed in cell culture supernatants and cell lysates.

Conclusion : The ability to predict which patients respond to PD-L1/PD-1 inhibitors and adjuvant combinations of existing drugs will improve response rates and meet current needs. Here we show a novel predictive simulation based approach with a myeloma example to leverage patient genomics information for predicting non-responders. This approach predicts the immunotherapy index of a patient, which is correlated experimentally. We show that U266B1 has higher PD-L1 expression because of patient genomics. While correlation at the bio-marker level is important, future work will focus on predicting and confirming the response to PD-L1 inhibitors.

Disclosures Brogden: Cellworks Group Inc.: Research Funding. Fischer: Cellworks Group Inc.: Research Funding. Bates: Cellworks Group Inc.: Research Funding. Lanzel: Cellworks Group Inc.: Research Funding. Gomez Hernandez: Cellworks Group Inc.: Research Funding. Treinen: Cellworks Group Inc.: Research Funding. Recker: Cellworks Group Inc.: Research Funding. Nair: Cellworks Group Inc.: Employment. Sundara: Cellworks Group Inc.: Employment. Joseph: Cellworks Group Inc.: Employment. Abbasi: Cellworks Group, Inc.: Employment, Equity Ownership. Vali: Cellworks Group, Inc.: Employment, Equity Ownership.


Pharmaceutics Research Group, Pharmacy Department, University of Aston in Birmingham, Gosta Green, Birmingham B4 7ET, U.K. The prediction of three-dimensional configuration from analysis of a two-dimensional section would be useful in determining the structure of a compact. Relations can be predicted by stereology in the presence of random distributions. In a preliminary attempt to apply this technique to pharmaceutical systems it was necessary to prepare two-dimensional sections and test the systems for randomness. Compacts were prepared of sodium chloride, copper powder, magnesium carbonate, limestone and potassium permanganate using a hydraulic press. The compacts were sectioned using a microtome and embedded in resin, or first embedded in resin and cut by a band-saw. Random dispersions of particles in resin were prepared by simple mixture. In preliminary experiments, an epoxy resin casting system was used, but later this was replaced by a styrene polyester resin owing to partial dissolution of one of the materials investigated (sodium chloride) by the epoxy resin. The specimens were examined microscopically and photomicrographs were obtained using the light microscope and also the scanning electron microscope. Some preliminary examination of the samples was carried out by the Quantimet 720. In order to obtain resin penetration of the compacts the original material had to be of suitable particle size (e.g. for sodium chloride, 420-600 pm) and also a low pressure of compaction (about 1 MNm-2) was desirable. High porosity by itself did not ensure resin penetration as was found with limestone (36%) and magnesium carbonate (39%). Satisfactory examination by the Quantimet demanded good contrast between particles and resin because the instrument is intended for black and white specimens only. Black, white and red pigments were used in the resin casting systems to improve the contrast. To overcome the difficulty caused by the transparency of sodium chloride crystals, an etching technique was used, the surface layers of crystals being dissolved by water and the cavities filled by a thick paste of plaster of Paris. The photographic evidence obtained shows that this technique of embedment can be applied to compacts and dispersions under certain conditions. Provided randomness in these systems can be established it should be possible to predict various features of compacts by means of stereological relation. R. A. CRAWFORD


Abstract : The protest process is a means of ensuring that the Government conducts procurements in accordance with statutory and regulatory procedures. Additionally, protests serve a vital role in assuring full and open competition in the federal acquisition process. Protests can be costly in many aspects, including the direct costs of taking the action as well as more indirect costs such as program delays and damaged business relationships. The Government recognizes the negative impact protests have on the procurement process and has enacted several laws and regulations in an effort to reduce protest frequency and streamline procurement procedures. While it appears that the Government has made substantial efforts aimed at reducing protests, it becomes necessary to ask whether they were successful in their efforts. This study examined one such piece of legislation, the Federal Acquisition Streamlining Act of 1994 (FASA), and found that there was an impact on particular contracting practices. Additionally, the findings of this study indicate that protest frequency within the Air Force has decreased since FASA's implementation. This correlation suggests that FASA did have an impact on reducing the frequency of protests.


Abstract In 2015, Germany experienced a record high influx of refugees – and received international praise for its 'welcome culture'. At the same time, however, attacks on refugees rose to an alarming level. This article describes the distribution of these attacks and probes their causes, using detailed socioeconomic and political data while modelling a hierarchical data structure. Controlling for further relevant factors taken from the extant literature, the analysis first tests whether the strength of extreme right political parties plays a role and, second, it models a contagion effect, taking into account spatial as well as temporal proximity. The findings suggest that the strength of right-wing parties in a district considerably boosts the probability of attacks on refugees in that area. They also corroborate the idea of behavioural contagion. The set of social-structural variables employed as controls yielded only limited explanatory power.


This paper presents the effect of high strain rate loading to tensile strength for mild steel by using Hopkinson bar technique. The behavior of material at high strain rates is important for application such as structural impact, automotive safety engineering and metalworking. In automotive industries, mild steel has been used as material in some of component. Due to dynamic condition occurrence during vehicle crash it is important to analyze the strength of component. Split Hopkinson Pressure Bar (SPHB) is the most common method for determining material properties at high strain rates, it consist of two long slender bar that sandwich a short cylindrical specimen between them. A striker bar impacts the incident bar, producing in it elastic wave pulse that travels through the incident bar and then reaches specimen. Upon arrival at the specimen, the wave partially reflects back towards the impact end and the remainder of the wave transmits through the specimen into the second bar. By capturing the wave pulse at the Hopkinson Bar apparatus a stress-strain relationship on the specimen can be calculated. It is found that the tensile strength on the stress-strain diagram increase significantly compared to a static test.


In this study, we propose an approach to generate spatially correlated seismic ground‐motion fields for loss assessment and risk analysis. Differently from the majority of spatial correlation models, usually calibrated on within‐earthquake residuals, we use the sum of the source‐, site‐, and path‐systematic effects (namely corrective terms) of the ground‐motion model (GMM), obtained relaxing the ergodic assumption. In this way, we build a scenario‐related spatial correlation model of the corrective terms by which adjusting the median predictions of ground motion and the associated variability. We show a case study focused on the Po Plain area in northern Italy, presenting a series of peculiar features (i.e., availability of a dense dataset of seismic records with uniform soil classification and very large plain with variable thickness of the sedimentary cover) that make its study particularly suitable for the purpose of developing and validating the proposed approach.
 The study exploits the repeatable corrective terms, estimated by Lanzano et al. (2017) in northern Italy, using a local GMM (Lanzano et al., 2016), which predicts the geometric mean of horizontal response spectral accelerations in the 0.01–4 s period range. Our results show that the implementation of a spatially correlated model of the systematic terms provides reliable shaking fields at various periods and spatial patterns compliant with the deepest geomorphology of the area, which is an aspect not accounted by the GMM model. The possibility to define a priori fields of systematic effects depending on local characteristics could be usefully adopted either to simulate future ground‐motion scenarios or to reconstruct past events.


According to legend, the fall of Troy was accomplished by a clever ruse. After 10 years of unsuccessfully dashing themselves against the impregnable walls of Troy, the Greeks pretended to give up and sail away from the besieged City, leaving behind a giant, hollow wooden horse. The Trojans, considering the wooden horse to be symbolic of their hard‐earned victory, demolished the walls that had protected them for so long and triumphantly wheeled the horse inside their city. Only a handful of the jubilant Trojans suspected that there might be something wrong. One of them, supposedly the high priest, is said to have muttered the memorable phrase as the horse was pushed and dragged into Troy, "Whatever that thing is, I fear the Greeks bearing gifts." Fateful and prescient words. That night, as the reveling Trojans slept, Greek soldiers poured out of the hollow wooden horse and the fall of Troy was at long last accomplished. The modern world has its counterpart to the lesson of Troy: money laundering. And the results can be equally as devastating to the modern business person: loss of reputation, draconian fines, bankruptcy, imprisonment. Once let a money launderer, the modern equivalent of the Trojan Horse, into a business without heeding the warning to "fear the Greeks bearing gifts" and this can be the result. It is not so long ago that money laundering was relatively easy to recognize. It involved scruffy looking characters delivering hordes of cash in cardboard boxes, paper shopping bags, duffel bags, suitcases and the like. More often than not, the delivery persons had not even counted the hundreds of thousands of dollars in cash they were delivering. Receipts never were expected. A classic example is the Miami bank in which over $242 million in cash was deposited into one checking account in one branch in the space of eight months, all in cash and all delivered to the bank in precisely the manner just described. In that case, the cash poured in so quickly that the bank itself limited the amount of cash it would accept ‐ to no more than $2 million per day.


The effects of carbon on the magnetic properties of steel have been of great interest over the years both because of the great commercial importance of steel and because it is known that carbon is the most important single factor affecting the magnetic properties of steel. Slight changes in the amount and distribution of the carbon content can completely mask any changes due to grain size, stress, and the effects of other impurities. The magnetic properties of several specimens of steel in which the carbon content has been deliberately reduced are investigated so that the more subtle effects on magnetic properties caused by these other factors can be determined. The results presented include magnetic Barkhausen measurements, magnetoacoustic emission measurements, and magnetization data. The grain structure of each specimen was closely monitored and the resulting magnetization data correlated with the microstructure.


The brain-derived neurotrophic factor (BDNF) is a neurotrophin recognized to play a major role in neuroplastic modifications associated to drug abuse, being involved in various behavioral changes found in drug use disorders, such as drug sensitization, craving and relapses. These neuroplastic changes were shown to affect the prefrontal cortex functions, which can be briefly measured through cognitive tests such as the Frontal Assessment Battery (FAB). In this study we investigated the BDNF mRNA expression in peripheral blood lymphocytes of crack-cocaine use disorder (CUD) and alcohol use disorder (AUD) patients, after drug detoxification treatment, using a real-time PCR approach and examining its association to FAB performance. BDNF mRNA expression was found to be higher by 2.25-fold in CUD patients and by 2-fold in the AUD patients when normalized to controls, and these values were found to be associated with FAB scores. This preliminary study evaluates, for the first time, BDNF mRNA expression in leukocytes and its relationship to FAB scores in crack-cocaine and alcohol use disorder patients.


Indonesia is the largest social media market in Southeast Asia with approximately 79 million active users. Since 2015, government agencies have been actively using social media as one of their communication channels. This study aims to analyse whether the advent of communication technologies of social media has made Indonesia government to perform a long-term two-way communication with the citizens. The social network analysis (SNA) method was used to analyse four types of government-citizens' conversations on social media: daily communication, campaign communication, crisis, and emergency communication. Two Indonesian government agencies' social media accounts at the national level were selected as samples. One was a policy-based government agency and the other was a service-based agency. This study found that a two-way communication happened in a limited way, which was mainly in the daily conversation. The policy-based agency used social media as a channel to disseminate information, thus they had a low number of interactions. Although the agency allows comments from every follower on Facebook page, there was no interaction between the agency and the public. The agency apparently was more active to reply messages via Twitter. The high number of fake followers and political buzzer on Twitter support the finding that the only interest for the agency to be on Twitter was to disseminate information. Lack of interaction happened in the campaign communication, also in crisis and emergency communication — types of communication that are urgent and important. Keywords : SNA, Indonesia, government social media , symmetrical communication, interaction .


This research is concerned with the barriers and opportunities experienced by working class British Pakistani women who aspired to higher education and to obtaining professional jobs. It examines the career trajectories of nine second generation British Pakistani women who were born in a working class area of a former textile town in the north of England. These women pursued educational qualifications as the means to acquire new knowledge and experiences and in order to secure higher status jobs. This is in marked contrast to the traditional trajectory which they saw other British Pakistani women following, of marrying and having children soon after leaving school. My informants viewed a career outside the home as affording advantages in terms of personal and social development, family pride and economic rewards. While, at the time of the research, some of them were still caught up in 'making themselves' in terms of their careers, others had already secured professional jobs. The women in this study reflect on changing ideas about British Pakistani womanhood, their educational routes to social mobility, and the effects of problematic perceptions of Pakistani Muslims in schools and workplaces. In this thesis I explore the kinds of cultural capital relevant to their careers, the obstacles they faced, and how they negotiated these. I conducted in-depth biographical interviews using a qualitative approach that was designed to be culturally sensitive, revealing how relationships with parents, siblings, peers, neighbours, teachers and colleagues, as well as local contexts and opportunities, feature in informants' lives. The study is a contribution to the small but growing literature that sets out to understand social mobility through qualitative research methods, exploring the processes involved. It also illuminates the life stories of a specific group of British Pakistani women at a particular time in their community's history.


When the Jazz Man played, Zeke thought about nothing else but the wonderful music that drifted from the bright yellow room scross the courtyard. He did not think about how his mother crept up and down five long flights of stairs every day to go to work. He did not think about the jobs he knew his father must work. He thought about just of the dreamy blues adding color to his drab world. How long will Zeke's dreams last when the Jazz Man leaves?


The ocurrence of 0+-aged fish was observed during 1992 in different habitats of the Lower River Rhine (km 815-856) and in two gravel-pit lakes connected with the main stream. In both waters successful reproduction was established by early developmental stages of a large number of resident fish species. The species composition in both riverine and lake habitats was similar. In the gravel-pit lakes, fry of all species was much more abundant than in the River Rhine. Thus, the lentic waters of gravel-pit lakes connected with the River Rhine represent highly productive spawning and nursery areas even for rheophilous species of fish, so that they may be of great importance for the recruitment of the River Rhine' s fish populations.


The purpose of this thesis is to examine the radiation from high-temperature superconducting mesas of Bi 2 Sr 2 CaCu 2 O 8+ δ (BSCCO). This is motivated by the need for coherent sources of continuous wave terahertz (THz) emission capable of radiating practically in the THz frequency band. As BSCCO has been shown to be tunable from 0.5–2.4 THz (i.e., through the entire so-called terahertz gap centered about 1 THz), and has a higher peak operating temperature near 1 THz than most alternative sources, it is a good candidate for imaging and spectroscopy device applications [1]. When a static DC voltage is applied to a BSCCO mesa, the stack of Josephson junctions intrinsic to this type-II layered superconductor synchronously radiate. Adjustment of the bath temperature and applied voltage allows for the high degree of tunability observed for such an emitter [2]. To determine the angular dependence of radiation from BSCCO mesas, the dual source model from antenna theory is employed, and Love's equivalence principle is used to simplify this framework. The total emission power obtained in this manner for the pie-shaped wedge is then fit to experimental results for a thin isosceles triangular mesa using the method of least squares, resulting in a standard deviation of σ = 0 . 4657 . Additionally, symmetry is shown to play a significant role in the emissions for the transverse magnetic (TM) cavity modes of the equilateral triangular mesa. When the full group symmetry is imposed, the density of allowed modes is heavily diminished, and the original first excited even mode becomes the C 3 v symmetric ground state. These results for the equilateral triangle suggest, along with earlier experiments on the regular pentagonal mesa [3], that symmetry breaking effects can be used for purposes of tuning the characteristic frequency and angular dependence of the power radiated from BSCCO mesas with a high degree of symmetry.


The essay, based on interviews with eight people, deals with name changes from a foreign-sounding name to Swedish-sounding name. The aim is to investigate the reasons behind the name change and whether experiences of ethnic discrimination were among these reasons. Furthermore, I explore the consequences of the name change, and whether the name change was an effective strategy to avoid ethnic discrimination. The study employs qualitative method; I carry out eight interviews with four women and four men, and analyze the empirical material by means of post-colonial theory in which categorizing, otherness and passing are significant terms. The results show that the name change takes place primarily to reduce a sense of otherness, and the discursively locked positions a foreign-sounding name creates. The name change helps the individual to avoid being questioned as much as before, making the individual more likely to pass. The name change facilitates social interaction with others and leads to a greater sense of inclusion, creating more favorable conditions of work and career development. The subject can thus pass from a position of stranger to a more familiar or ambiguous body.


OBJECTIVES
Recent research has suggested that bipolar disorder, when defined to include milder variants such as bipolar II disorder and bipolar disorder not otherwise specified (NOS), is more prevalent than had been previously reported and often underrecognized. Recommendations for improving the detection of bipolar disorder have included careful clinical evaluations inquiring about a history of mania and hypomania and the use of screening questionnaires. The Bipolar Spectrum Diagnostic Scale (BSDS) was designed to be particularly sensitive to the milder variants of bipolar disorder. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the operating characteristics of the BSDS in a large sample of psychiatric outpatients presenting for treatment.

METHODS
A total of 1,100 psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV and asked to complete the BSDS. Missing data on the BSDS reduced the sample size to 961, approximately 10% (n = 90) of whom were diagnosed with bipolar disorder.

RESULTS
The sensitivity of the BSDS was similar for bipolar I disorder, bipolar II disorder, and bipolar disorder NOS/cyclothymia. A receiver operating curve (ROC) analysis indicated that cutoffs of 11 and 12 maximized the sum of sensitivity and specificity for the entire group of patients with bipolar disorder (area under curve = 0.80, p < 0.001). The cutoff point associated with 90% sensitivity for the entire sample of patients with bipolar disorder was 8. At this cutoff the specificity of the scale was 51.1% and positive predictive value was 16.0%. We compared the patients with and without bipolar disorder on each of the BSDS symptom items. The odds ratios were higher for the items assessing hypomanic/manic symptoms than items assessing depressive symptoms. We therefore examined the performance of a subscale composed only of the hypomania/mania items. The area under the curve in the ROC analysis was nearly identical to that of the entire scale (0.81, p < 0.001).

CONCLUSIONS
With its high negative predictive value, the BSDS was excellent at ruling out a diagnosis of bipolar disorder; however, the low positive predictive value indicates that it is not good at ruling in the diagnosis. These data raise questions about the use of the BSDS as a screening measure in routine clinical psychiatric practice.


Adult spinal deformity (ASD) is a complex disease comprised of different deformity types that often involve the entire spine. Accurate assessment of ASD requires a thorough radiographic evaluation of both the spine and pelvis, including concomitant assessment of the cervical, thoracic, and lumbar spine, as well as the femoral heads and pelvis. Radiographic measurements should include assessment of regional alignment (including lumbar lordosis, thoracic kyphosis, C2–C7 lordosis), global alignment (including C7 SVA, C2–C7 SVA, and T1 pelvic angle), and measures of pelvic compensation and morphology (pelvic tilt, pelvic incidence, T1 slope, and C2-pelvic tilt). Together these radiographic parameters provide important information regarding how the ASD patient maintains upright posture and correlate with the patient's pain and disability. ASD surgical planning must integrate regional, global, and pelvic compensatory/morphologic parameters to adequately correct deformity and thereby provide pain relief and improve function. Radiographic classifications for cervical and thoracolumbar deformities have been developed that utilize the regional and global measures of spinal deformity that are most predictive of patient-reported pain and function. These classifications are aimed to standardize the assessment of ASD to aid in clinical management and to facilitate future research on the evaluation and treatment of ASD.


ABSTRACT Terms such as "gender-based violence" are connected with a range of evolving discourses that are not merely descriptive, but interpretive and political in nature. Yet, what makes violence "gender-based" is often implicit rather than explicit. In this Debates we argue that there needs to be greater specificity about what is gendered about gender-based violence, while allowing for the continued elasticity of the concept for application across diverse contexts and forms of violence. Drawing on international scholarship and key insights from the evolving sociology of gender, we outline a framework for locating and defining the "gender" in "gender-based violence". This framework, we suggest, makes for a clearer starting point for mapping the connections between gender and violence, by examining these connections at the three levels of identity, interaction and structure. As such, it invites a more comprehensive picture of gender-based violence, one that includes women, men, and non-binary people while still accounting for the ways gender-based violence disproportionately affects women. We argue that the rich contextually-specific scholarship being produced in South Africa and elsewhere in the global South reflects gender as operating at these three levels, and adds further layers and complexity with a genuine attention to intersectionality that is often lacking from international scholarship.


The authors report twenty-eight cases of superior vena cava thrombosis. They try to establish a correlation between the radiological features of thrombosis and the etiology. The etiology was Behçet's disease in 64% of cases, lung cancers in 14%, the mediastinal tuberculosis in 14%, systemic lupus erythematosus in 3.5% and undetermined origin in 7%. A normal meiastinal appearance slight widening of the superior mediastinum is noted in Behçet's disease, systemic lupus erythematosus and tuberculous mediastinal fibrosis. Superior vena cava thrombosis is extensive in Behçet's disease involving the subclavian vein and the azygos vein. An obvious widening of the mediastin is noted in lung cancers and tuberculous mediastinal lymphadenopathy.


Cell migration is essential for the development of multicellular organisms; with disruptions in this process contributing to diseases such as cancer, neurological disorders and musculoskeletal diseases. The LINC (Linker of Nucleoskeleton and Cytoskeleton) complex is an evolutionary conserved proteinaceous structure, critical for maintaining proper cellular migration. This multifunctional complex provides a physical connection between the nuclear interior and the cytoskeleton, with disruptions stimulating loss of directed cell migration, compromised nuclear structure and abnormal cellular signalling. As it is also noted that the nucleus in many cells is the stiffest cellular component, it is suggested that LINC complex disruptions may be key in increasing the migration potential of cells through both in vivo and in vitro 3D environments.

This project aimed to investigate the roles of LINC complex disruptions on keratinocyte morphological and migratory behaviours in 2D, and both non-restrictive and space-restrictive 3D culture environments, through the application of dominant negative SUN1 mutants. Through extensive analysis, it was identified that these mutants exhibited altered cell-cell and cell-substratum attachment phenotypes, alongside increased nuclear heights. It was also demonstrated that the LINC disrupted mutants displayed a migration advantage in space-restricted 3D environments, which was attributed to a decrease in nuclear stiffness. Through fibroblast incorporation to the 3D scaffolds used, it was further shown that LINC disrupted keratinocytes displayed increased levels of differentiation markers, alongside increased cellular stacking phenotypes across scaffolds surface regions, potentially attributed to alterations in Hippo pathway signalling.

The migratory phenotypes observed in DN mutants closely resemble that of high-grade cancer cells, able to migrate through space-restrictive environments during metastasis. Comprehensive protein expression and localisation analysis across a range of breast cancer cell lines and tissues suggested that several LINC complex components display altered expression levels closely linked to cancer progression, most significantly a down-regulation of lower nesprin-1/-2 isoforms was identified. As following investigations later suggested Nup88 as an upstream regulator of nesprin-2, able to bind C-terminal regions, it's suggested that these phenotypes link closely to that observed in high-grade cancers.

Together, the data presented suggests that LINC complex disruptions increase migration potential of cells through restrictive 3D environments due to a decrease in nuclear stiffness, comparable to that observed across high-grade breast cancer cell lines.


In this letter, a novel wide-beam circularly polarized (CP) antenna is presented for satellite digital audio radio service (SDARS) band (2320-2345 MHz), intended for application in portable terminals. This new antenna is comprised of four independent radiation units that are axial symmetrical around the center. The radiation unit is miniaturized by using a distributed capacitive load and a short point in its configuration. The antenna is excited by a compact four-way, quadrifilar power splitter, which is implemented by using microstrip phase shifter and couplers. Simulation results match well with the experimental ones, demonstrating a half-power beamwidth (HPBW) of 120°, a 3-dB axial-ratio beamwidth of 180°, and a good match at 2100-2400 MHz. The developed antenna is based on low-cost printed circuit board (PCB) technique and can be easily integrated with other microwave circuits.


The current knowledge economy has brought several challenges to contemporary organisations. There is need for flexibility on the part of key players, namely individual employees as well as organisations as a whole; this flexibility arises from the innovation in both products and services. The complexity of knowledge requires an education that enhances softer skills. The intellectual capacity, creativity, and adaptability of individuals gives rise to greater flexibility. This strengthens the fact that there is a change of paradigm in the way human capital is viewed. Through the human-oriented perspective, knowledge is seen as collective sense making and social practice. The objective of this chapter lies in this context of complexity, change, and adaptation within an economic and social reality based on knowledge. Therefore, the chapter aims to reflect upon Knowledge Management in companies such as universities where tacit knowledge is stored as intellectual capital in the minds of both lecturers and students and to highlight the need to instill the new paradigm which fosters knowledge creation and sharing in universities.


PURPOSE
Positron emission tomography (PET) is an important imaging technique for the diagnosis and staging of patients with non-small cell lung cancer (NSCLC). In this study, we evaluated the standardized uptake values (SUV) of PET in NSCLC patients to determine whether there was a cut-off value for predicting response to treatment and survival.

METHODS
We retrospectively analyzed 149 patients with locally advanced NSCLC. All the patients were staged by PET-computerized tomography (CT) after diagnosis. 18fluoro-2-deoxyribose (FDG) was used as the PET tracer. Univariate and multivariate analyses were performed to detect whether any prognostic factors were related to response to treatment.

RESULTS
The median patient age was 60 years and the median follow-up time 10.3 months. One-year progression-free survival (PFS) and overall survival (OS) rates were 31% and 58.7%, respectively. The median OS was 15.4 months. Stage, sex and response to treatment were important factors for OS and PFS. We defined a cut-off value for SUVmax (the highest standardized uptake value for all cross sectional areas) as 10.8 by using ROC analysis. Multivariate analysis identified response to treatment as the most significant (p<0.05) prognostic factor for OS. Logistic regression analysis showed that SUVmax and weight loss were important for response to treatment.

CONCLUSION
Multivariate analysis indicated that whilst response to treatment was an important factor for predicting survival, the SUVmax was also significant for determining response to therapy and a cut-off value for SUVmax was defined as 10.8.


Background
Colorectal cancer is the third most common cause of cancer deaths in Poland. Free prophylactic colonoscopy performed in Poland since 2000 as part of the National Program for Combating Cancer Diseases, is characterized by low reporting rates. Therefore, a study was carried out to understand the medical circumstances immediately preceding the diagnosis of colorectal cancer in the Katowice agglomeration, with particular emphasis on the role of screening colonoscopy.

Material and methods
The questionnaire study included 96 patients with colorectal cancer. The socio-economic status, knowledge about prophylaxis, individual disease history, including diagnostic procedures, and participation in the population screening program were assessed.

Results
In the case of patients hospitalized in the Katowice agglomeration in 2019-2022, the diagnosis of colorectal cancer occurred most often as a result of the patient visiting a doctor due to disturbing gastrointestinal symptoms (56.3% of cases). 36.4% of cases were diagnosed by a physician during a visit for reasons other than suspicion of cancer. Participation in the free screening program (colonoscopy) accounted for 6.3% of the circumstances in which the disease was detected.

Conclusions
The most common diagnosis of colorectal cancer was performed by the patient visiting a doctor due to disturbing symptoms from the digestive system. The mean age of the patients diagnosed with the disease as a result of reporting to a physician due to alarming symptoms was 3 years greater than the age of patients diagnosed during the screening colonoscopy.


The relevance of the article is determined by the increasing role of the Arctic transport system in the economy of the Russian Federation: involvement of territories of the Arctic zone of the country in economic activities, an increase in their social and economic potential. The development of the northern territories is directly related to existing and future capabilities of the Arctic transport system, for successful functioning of which it is necessary to provide it with feeder transport network.The objective of the work is to determine the scenarios according to which development of these feeder roads can be carried out. When writing the article, the methods of systemic, comparative, and statistical analysis were particularly used.The paper clarifies the definition of the Arctic transport system. It is noted that scenarios for development of feeder routes to it should be linked to its general development, as well as to the development of the Arctic zone of the Russian Federation. The European and Ural Arctic subregion is highlighted, where development of feeder routes is most important in connection with the growth of economic activity on Yamal Peninsula. With reference to the works of domestic and foreign authors, strategic planning documents of the Russian Federation, it is assumed that according to the degree of achievement of target indicators of traffic volumes along the Northern Sea Route, optimistic and pessimistic scenarios for formation of feeder network can be activated. The final implementation of one of those scenarios is determined by political, natural, and other risks.When developing scenarios for formation of transport feeder network to the Arctic transport system, the emergence of new modes of transport should be considered. New modes of transport can provide linking of remote objects to the trunk transport networks or eliminate the gaps emerging in them.The use of new modes of transport in the Russian Arctic should be carried out only after testing at specialized test sites, where their safety for transportation of passengers and goods, as well as for the environment, will be determined.The work was carried out within the framework of the comprehensive program of fundamental scientific research of the Ural Branch of the Russian Academy of Sciences for 2018–2020 and is associated with the need to increase the capacity of the main ports of the European and Ural Arctic and the volume of traffic along the Northern Sea Route.