Background Both testosterone (T) and methotrexate (MTX) seem to exert negative effects on cell growth that might partially explain some of their antiproliferative/antiinflammatory effects exerted in rheumatoid arthritis (RA).1,2 Objectives Therefore, we evaluated the T and MTX effects on cell apoptosis (apo) in cultured human myeloid monocytic cells (THP-1) differentiating into macrophages (M) and in cultured synovial M obtained from RA patients. Since extracellular adenosine increase seems implicated in the MTX action, we evaluated also the enzyme adenosine deaminase (ADA) levels. ADA is involved in adenosine metabolism. Methods Synovial RA M as well as the THP-1 cells induced to differentiate into M (IFN gamma 500U), were cultured in presence of T (10–8M) and 17-beta estradiol (E2,10–8M) alone. The cells were also treated with the MTX concentrations present in vivo during RA therapy (= 50 microg/ml) again alone, or in association with T plus MTX or E2 plus MTX. After 24 h early and late apo were evaluated by immunofluorescence (annexin V and propidium iodide assay, respectively). ADA was evaluated on supernatants by spectrophotometry. Results By considering the THP-1 cells, a significant induction of the late apo in T (17%) (p less 0.05), MTX (80%) alone, and T (72%), E2 (74%) plus MTX-treated cells was observed (all p < 0.001). No significant differences were observed during the early apo for all the treatments during the 24 hr. By evaluating the RA synovial M, a significant (p < 0.001) induction of the late apo (50%) was observed in the T plus MTX-treated M when compared with the alone MTX- or E2-treated M. The treatment of RA M with T alone was found to induce an evident cell apo (30%) (although non significant). ADA levels increased only in the supernatants from all the MTX-treated cells vs MTX-untreated controls, mainly in THP-1 cells. Conclusion The T and MTX-induced apoptotic effects were more evident in cultured THP-1 cells than in cultured RA M. Therefore, immature differentiating monocytes (i.e. infiltrating monocytes) seem more sensible to the pharmacologic effects of MTX than differentiated cells (i.e. resident M). The significant increase of ADA levels found only in MTX-treated cells, might support the already suggested implication of adenosine level increase as part of the pharmacologic effects exerted by MTX. References Cutolo M, Wilder R. Rheum Dis Clin North Am. 2000;26:825 Cutolo M, et al. J Rheumatol. 2000;27:2551


The two fundamental approaches to studying human evolution are those of using data relating to the past itself (i.e., archaeology, palaeontology), and those of establishing comparative frameworks, usually based on the study of extant related species. Work with primates has been important in establishing comparisons of social structure, frameworks of subsistence, and base levels of intelligence, and has recently been used to generate ideas about the origins of language. This chapter examines how archaeology can be used to address critically the application of comparative ideas, especially those which are based on the concept of 'Machiavellian intelligence', linking group size and neocortex ratio. Archaeology is able to map out the communication of cultural information in a number of ways. Its direct evidence establishes that early Homo had far greater ranges than those of living apes. Technology used across these ranges had to pay for itself in energetic terms. It is argued that such factors may be as important as group size in accounting for evolutionary change.


In quantum field theory the creation and annihilation operators that are located at the points in 3-momentum space have commutation relations that are conserved under the action of a $U({\infty})$ group. Here it is shown how to define an appropriate $U_q({\infty})$ which then leads to deformed commutation relations. A formalism that was previously defined for quantum group symmetric quantum mechanics can be applied by imposing simple adjustments. The simplest example of a free scalar $q$-bosonic field is discussed. The deformation occurs as a multi-particle effect, which introduces a kinetic energy (i.e. $({\vec{p}})^2$) - ordering of the involved particles.


Abstract Mung bean is highly susceptible to insect attack during storage. Hermetic storage is an effective technique to control insect damage. This study investigated the potential of the hermetic SuperGrain bag (SGB) for controlling bruchids during storage. The dry samples were packed in SGB infested with adult bruchids (SGB-I), SGB natural field infested (SGB-N), woven polypropylene bags (WPP-I and WPP-N) and kept at room temperature for 180 days. Oxygen (O2) and carbon dioxide (CO2) concentrations were measured at 15 days intervals. Moisture content, infestation level, seed damage and weight loss were determined at 60 days intervals. Seed colour, hardness, crude protein and fat contents were analysed before and after storage. The O2 level decreased to 10.09%, whereas the CO2 level increased to 8.87% in both SGB-I and SGB-N treatments. The moisture content of mung bean was maintained as onset storage in both SGB-N and SGB-I treatments, whereas reduced in WPP-N (9.26% db) and WPP-I (9.21% db). In SGB treatments, no significant bruchids were detected, but they increased drastically in WPP-N (52 ± 9) and WPP-I (377 ± 14). Seed damage (2–3%) and weight loss (0.8–1.0%) were recorded in both SGB-N and SGB-I. Conversely, seed damage reached 26.67 and 54.17%, corresponding to weight losses of 12.33 and 20.82% in WPP-N and WPP-I, respectively. Seed colour, hardness, crude protein and fat contents in SGBs showed no significant changes than in the WPP bags. The study illustrated that the SGB is an efficient hermetic device in protecting mung beans against bruchids attacks compared to the WPP bags.


Effects of ischemia and nitroglycerin on systolic time intervals in the segmental myocardial length were studied in anesthetized open-chest dogs. Two strain-gauges were sutured on the surface of the left ventricular wall; one was in the central area perfused by the left circumflex coronary artery (LCX) and the other was in the area perfused by the left anterior descending coronary artery. LCX was partially occluded with a screw type constrictor to the degree at which reactive hyperemia after the transient total coronary occlusion almost disappeared. After the hemodynamics stabilized nitroglycerin (20 microgram/kg) was injected into the femoral vein. In the ischemic area, contraction time was shortened and precontraction time was prolonged in association with an elongation of end-systolic and early systolic segment-length, respectively. The systolic time intervals in the ischemic segment were improved as a result of the recovery in the segment-length toward the control. The results suggest the usefulness of analyzing the segmental myocardial systolic time intervals for verifying the asynchronous contraction of the ventricle and the favourable effects of nitroglycerin on segmental myocardial function in the ischemic area.


As enterprises extend internal systems and applications to external users, it is important to ensure that the user experience operates seamlessly between disparate organizations. To meet this challenge, Federated Identity Management (FIM, also single sign-on) provides an economically efficient and convenient way of providing connectivity to customers, partners, suppliers, and others. FIM is a topic of widespread discussion with rapid growth predicted for almost ten years. This growth has not happened. This prescriptive study identifies some key factors contributing to the slow adoption of FIM technology, including technological complexities, lack of trust between partners, and the complications and expenditures involved in establishing and maintaining contractual agreements between partners.


These are commentaries of a Cochrane review, published in this issue of EBCH, first published as: Zehetner AA, Orr N, Buckmaster A, Williams K, Wheeler DM. Iron supplementation for breath-holding attacks in children. Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008132. DOI: 10.1002/14651858.CD008132.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration


Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) are chronic, progressive, and age-associated neurological disorders characterized by neuronal deterioration in specific brain regions. Although the specific pathological mechanisms underlying these disorders have remained elusive, ion channel dysfunction has become increasingly accepted as a potential mechanism for neurodegenerative diseases. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by the HCN1-4 gene family and conduct the hyperpolarization-activated current (Ih). These channels play important roles in modulating cellular excitability, rhythmic activity, dendritic integration, and synaptic transmission. In the present review, we first provide a comprehensive picture of the role of HCN channels in PD by summarizing their role in the regulation of neuronal activity in PD-related brain regions. Dysfunction of Ih may participate in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity and represent a pathogenic mechanism in PD. Given current reports of the critical role of HCN channels in neuroinflammation and depression, we also discussed the putative contribution of HCN channels in inflammatory processes and non-motor symptoms in PD. In the second section, we summarize how HCN channels regulate the formation of β-amyloid peptide in AD and the role of these channels in learning and memory. Finally, we briefly discuss the effects of HCN channels in ALS and SMA based on existing discoveries.


[1] Factors controlling the selection of deformation modes during continental extension are investigated using analytical and numerical methods. We view the lithosphere as a laminate and examine a simple system with a uniform plastic layer overlying a uniform linear viscous layer. The rate of energy dissipation is analyzed for pure shear (PS), symmetric plug (SP), and asymmetric plug (AP) extension modes, and the analysis reveals that the primary control is the relative rate of dissipation in the two layers. A basic difference is that the plastic layer yield strength is independent of the strain rate, whereas the viscous stress depends on strain rate; therefore dissipation scales linearly and quadratically with extension velocity for these respective layers. When other parameters, e.g., extension velocity, and properties are held constant, minimum dissipation predicts that the modes AP, SP, and PS will be selected in this order with increasing viscosity of the lower layer. Transition viscosities between modes, ηT1 and ηT2 are 4 × 1021 Pa s and 8 × 1022 Pa s, respectively, for our parameters values. Numerical models confirm the analysis results, inferred mode controls, and order of mode selection when strain softening of the plastic layer occurs during extension. Implications for lithosphere that acts as a bonded plastic/viscous laminate include the following (1) asymmetric extension (AP mode) is preferred when the extension rate and/or effective viscosity is low or the viscous region temperature is high, (2) symmetric (SP mode) extension is preferred for intermediate combinations of parameters, and (3) overall pure shear (PS mode) may occur for opposite end-member parameter combinations.


Abstract: Global health crises impose considerable strain in health care systems worldwide that create mental health challenges among medical practitioners. Greater challenges are experienced by doctors practicing in rural areas of developing countries such as the Philippines that have weak healthcare infrastructures and meager resources for health services. Thus, this study sought to explore doctors' experiences of working in rural areas during the COVID-19 pandemic and to identify contextual factors contributing to their mental health. Interpretative phenomenological analysis was used in gathering and analyzing data from semistructured interviews with 12 doctors who worked in rural areas in Eastern Visayas, a region that has very few doctors and that experienced a rise in COVID-19 cases at the time of the study. The findings revealed challenges to doctors' mental health that include fear of exposure, burnout, scarcity of supplies, and patient-related challenges that reflected contextual realities in the area. The results also described coping strategies utilized by the rural doctors, e.g., communing with nature, diskarte (resourcefulness), social support from family and coworkers, and bayanihan (observed in this study as mutual support among doctors in the rural community to achieve collective goals). The findings highlight policy implications and other forms of support that will sustain rural doctors' mental health amid a pandemic.


The fault current levels gradually increase with becoming widespread of distributed generation units, expansion of power systems, increased current levels, and power demand. High fault currents can cause damage to the power system components or shorten their life. This can bring about serious economic costs and affect the reliability of the system. In this study, three different fault current limiting methods such as current limiting series reactor, high impedance transformer and controlled series reactor (solid-state) fault current limiter that is applied in the IEEE 9-bus system are analyzed for three-phase fault and their effects to the system are discussed for normal operating conditions. The power system and current limiters are modeled in PSCAD/ EMTDC.


Super‐ and hypersonic rarefied gas flow over blunt bodies is investigated by using asymptotically correct viscous shock layer (VSL) model with effective boundary conditions and thin viscous shock layer model. Correct shock and wall conditions for VSL are proposed with taking into account terms due to the curvature which are significant at low Reynolds number. These conditions improve original Davis's VSL model [1]. Numerical calculation of Krook equation [2] is carried out to verify continuum results. Continuum numerical and asymptotic solutions are compared with kinetic solution, free‐molecule flow solution and with DSMC solutions [3, 4, 5] over a wide range of free‐stream Knudsen number Kn∞. It is shown that taking into account terms with shock and surface curvatures have a pronounced effect on skin friction and heat‐transfer in transitional flow regime. Using the asymptotically correct VSL model with effective boundary conditions significantly extends the range of its applicability to higher Kn∞ numbers.


The own-race bias in face recognition is one of the most replicated findings in cognitive psychology; however, it has been shown to be affected by gaze direction. The current study explored the effect of gaze direction on different race faces using a facial recognition task. Participants were 30 Han males and 32 Han women. The facial recognition task involved presentation of 40 faces with manipulated eye gaze direction; then, participants were shown the same 40 faces randomly mixed with 40 new faces, and were asked to point out which faces they had seen previously as quickly and as accurately as possible. The results showed that hit rates, false alarm rates, and response bias (C) were influenced by gaze direction. Furthermore, gaze direction and race had a significant interaction effect on C. Under the averted-gaze condition, the C for the Han face images was higher than that for the minority faces images, while there was no significant difference in C under the direct-gaze condition. These findings indicate that the influence of other-race faces exposure on C was mediated by the averted-gaze direction.


Implantation of a pregnancy within a cesarean delivery scar is considered to be the rarest form of ectopic pregnancy, with a high morbidity and mortality. Pregnancy in a cesarean delivery scar may cause catastrophic complications which may result in hysterectomy and compromise the reproductive future of a woman. We report an ectopic pregnancy in cesarean scar case in a 28-year old pregnant woman that was treated with success with the association between three treatment modalities (methotrexate, uterine artery embolization and curettage) and preserve her fertility.


In this work, we demonstrate that a functional modeling the self-aggregation of stochastically distributed lipid molecules can be obtained as the $\Gamma$-limit of a family of discrete energies driven by a sequence of independent and identically distributed random variables. These random variables are intended to describe the asymptotic behavior of lipid molecules that satisfy an incompressibility condition. The discrete energy keeps into account the interactions between particles. We resort to transportation maps to compare functionals defined on discrete and continuous domains, and we prove that, under suitable conditions on the scaling of these maps as the number of random variables increases, the limit functional features an interfacial term with a Wasserstein-type penalization.


Volleyball is a dynamic physical game that does not have a definite match duration but is based on high tempo, quickness, strength, flexibility, endurance and jumping. The aim of this study is to research the relationship between isokinetic knee strength and jumping height in young male volleyball players. 8 male volleyball players aged between 18-22 participated in the research voluntarily. In the study, the physical characteristics of the subjects (body height, body weight, body mass index) were determined, vertical jump heights were measured and at low (60 0 /sec) and high (300 0 /sec) speeds, the right and left knee flexion/extension concentric isokinetic strength test was applied. Data was analyzed with paired sample t-test and Spearman correlation coefficient test was used to determine the relationship between vertical jump and isokinetic strength (p<0.05). The right and left knees peak torque of the athletes were compared at low and high angular speeds and no significant difference was found. A significant positive correlation was detected between the jumping height and the right knee peak torque at low angular speed (r =.817, p<0.05). This result can be explained by the fact that quadriceps femoris, which is the biggest muscle of the lower extremity, is in the foreground during the jumps that volleyball players perform frequently. It may be advisable to give importance to leg strength training to increase the jump height.


Ribonucleases (RNases) are small molecules which are highly cytotoxic in nature. They catalyse the degradation of RNA into smaller molecules rapidly in an unprotected environment. The cytotoxic properties of RNases include degradation of RNA leading to blockage of protein synthesis in malignant cells and inducing the apoptosis response. Cytotoxicity of RNases is determined by catalytic activity, stability, non-selective nature of inhibitors, positive charge on molecule and internalization. Onconase, BS-RNase and other RNases exert cytotoxic activity on cancer cells selectively by involving different cellular pathways and/ or enhance the cytotoxicity by mutation. A general mechanism of the cytotoxic activity of RNases includes the interaction of the enzyme with the cellular membrane by non-specific interactions mediated by Coulombic forces, internalization by endocytosis, translocation to the cytosol, degradation of ribonucleic acid and subsequent cell death by activation of caspase-dependent mechanisms, low molecular weight compounds or alteration in protein and NF-κB signal pathway. But still it is unclear that which of these mechanisms is most potent, common and causes cell death in cancerous cells. The problem related to ribonuclease inhibitor (RI) has not fully elucidated. This article looks at the cellular pathways of RNases and mechanism of their cytotoxicity towards the malignant cells which makes RNase as a strong candidate to be considered as chemotherapeutic or antitumor drug. Some of the prominent approaches to exploit RNase molecule as an anticancer therapeutic agent have been discussed.


The objective of this study was to analyse the level of pedigree and genomic inbreeding in a herd of the Norik of Muran horses. The pedigree file included 1374 animals (603 stallions and 771 mares), while the reference population consisted of animals that were genotyped by using 70k SNP platform (n = 25). The trend of pedigree inbreeding was expressed as the probability that an animal has two identical alleles by descent according to classical formulas. The trend of genomic inbreeding was derived from the distribution of runs of homozygosity (ROHs) with various length in the genome based on the assumption that these regions reflect the autozygosity originated from past generations of ancestors. A maximum of 19 generations was found in pedigree file. As expected, the highest level of pedigree completeness was found in first five generations. Subsequent quality control of genomic data resulted in totally 54432 SNP markers covering 2.242 Mb of the autosomal genome. The pedigree analysis showed that in current generation can be expected the pedigree inbreeding at level 0.23 % (ΔFPEDi  =  0.19  ±  1.17%). Comparable results was obtained also by the genomic analysis, when the inbreeding in current generation reached level 0.11%. Thus, in term of genetic diversity both analyses reflected sufficient level of variability across analysed population of Norik of Muran horses.


The electrochemical and mechanical properties of welded high-strength steel were investigated using the slow strain rate test method with a constant applied cathodic potential. No correlations were found with the maximum tensile strength, yield strength, stress at failure, or hydrogen embrittlement. However, the elongation, time-to-fracture, and strain-to-failure ratio decreased as the potential became more negative. These parameters were greatest when the potential was -770mV, regardless of the post-weld heat treatment conditions. The elongation and time-to-fracture increased with PWHT.


This study was conducted to analyze the profitability of banana farming in some selected areas of Tangail district of Bangladesh during 2015. A total of 60 samples (16 small, 19 medium and 25 large farmers) were directly interviewed using a structured questionnaire for achieving the purpose. Apart from the descriptive analysis of the socio-economic variables of the selected respondents, the benefit-cost and functional profitability analysis of banana farming were also performed. The Cobb-Douglas production function was chosen to determine the effects of various inputs on the profitability of banana. The finding of costbenefit analysis reveals that banana farming is a profitable activity in Bangladesh as the estimated cost of production was lower than the return in the selected study areas. However, the profitability differs among different farmers' group and large farmers are more profitable in banana farming than small and medium farmers. In addition, the functional analysis identifies four inputs such as the cost of human labor, manure, fertilizer and irrigation as the significant determinants of profitability of banana farming in the study area. In this study, resource use efficiency was also measured to show the efficient resource allocation to attain the goal of profit maximization which showed that human labor, seedling, manure, fertilizer, insecticides, irrigation and bamboo has inefficient use of the resources, and farmers should limit the use of these inputs. The researcher suggested some recommendations to improve the present production situation so that banana farming could be more viable and attractive commercial enterprise.


In this paper, fractional differential equations in the sense of Caputo-Fabrizio derivative are transformed into integral equations. Then a high order numerical method for the integral equation is investigated by approximating the integrand with a piece-wise quadratic interpolant. The scheme is capable of handling both linear and nonlinear fractional differential equations. A detailed error analysis and stability region of the numerical scheme is rigorously established.


Spare parts is one of the production support components which plays an important role for the survival of gas production in the gas processing facility owned by SKN JOB Pertamina Talisman Jambi Merang. The high inventory level increased the high inventory cost for the industry which get the benefit from the efficiency of processes and resources. This research involved consumable spare parts for Solar Turbine engine as much as 25 SKUs with demand character patterned lumpy demand and Poisson distribution. The implementation of policies using Periodic Review (R, s, S) with Power Approximation approach in the inventory system capable to generate a lower total cost inventory by pressing the backorder volume, the booking volume and the inventory levels in a balanced manner. Calculation of Periodic Review (R, s, S) with Power Approximation approach resulted inventory parameter which was able to press the total cost of inventory at 8.54% lower and increase the service level by 1.11%.


This case report is about an 85‐year‐old woman with bicuspid aortic stenosis (AS). Although preoperative multimodality imaging showed challenging anatomical aspects, transcatheter aortic valve replacement (TAVR) was selected to be performed as a less invasive alternative treatment approach, owing to her comorbidity. Postoperative transesophageal echocardiography and multidetector‐row computed tomography revealed the presence of "locked‐in leaflet" caused by stent distortion due to pinching by calcified native leaflets, with nodular calcification preventing the full expansion of the valve, which resulted in moderate perivalvular leakage. This is the first reported case of bicuspid AS treated with TAVR that eventually resulted in "locked‐in leaflet."


The literature was systematically reviewed to determine if children with spina bifida have lower self‐concept compared with their peers with typical development. Relevant trials were identified by searching electronic databases, supplemented by citation tracking. Of 803 papers initially identified, 15 met the inclusion criteria. Meta‐analysis revealed children with spina bifida scored significantly lower than children with typical development for the domains of global self‐worth (d=−0.39, 95% confidence interval [CI] −0.65 to −0.12); physical appearance (d=−0.26, 95% CI −0.46 to −0.06); athletic competence (d=−0.45, 95% CI −0.67 to −0.22); social acceptance (d=−0.33, 95% CI −0.55 to −0.11); and scholastic competence (d=−0.43, 95% CI −0.66 to −0.21). There was no difference between the groups for the behavioural conduct domain. Children with spina bifida on average have a lower self‐concept than their peers with typical development. Clinicians need to take account of this information in planning the assessment and treatment of this group.


This paper deals in general terms with social change in India between the second decade of the nineteenth century when the British emerged completely dominant in the subcontinent through to the 1870s when the railways, the growth of export trades and new political associations were palpably transforming the Indian Empire. Some suggestions about comparable developments injava will be made at the end of the paper.


Background: Pegylated liposomal doxorubicin (PLD) has a unique pharmacokinetic profile and is widely used to treat a variety of malignancies, alone or in combination with other agents. Case Report: A 57-year-old female patient with metastatic breast cancer developed dural metastases to the brain and underwent craniotomy and whole-brain radiation. She continued to receive chemotherapy with carboplatin without any serious complications. Four months later, there was evidence of progression leading to the institution of PLD. During the first course of PLD, there was evidence of acute encephalopathy which resolved after 18 h with discontinuation of this agent. Interestingly, she did well when she was rechallenged with conventional doxorubicin in the following cycles. Conclusion: We hereby report, to the best of our knowledge, the first case of acute transient encephalopathy induced by PLD. We postulate that partial disruption of the blood-brain barrier may have been responsible for PLD-induced encephalopathy.


Although Vertisols have been highly documented owing to technological breakthroughs, numerous aspects are still not fully understood such as implication of geochemistry on source area-weathering, provenance, tectonic setting and sedimentary processes as well as problems of classification and management. This work aims to highlight the geochemical characteristics of Vertisols formed on alluvial deposits in the Benue Basin of North Cameroon and to highlight their source area-weathering, sedimentary processes, tectonic setting, taxonomic level and possible management strategies. The work was done in the field and in the Laboratory. The main results showed that smectite is the predominant clay mineral. Chemical composition revealed high Si, Al and Fe contents. Heavy minerals contents are of plutonic (augite, aegerine and aegerinic augerinic augite), metamorphic (kyanite, sillimanite and andalusite) and volcanic (tourmaline) origin. This agrees with the Al2O3/TiO2 ratio of 8.72 to 30.40 reflecting sediments from felsic rocks and minor mafic rocks. The CIA (chemical index of alteration: 70 to 85), PIA (plagioclase index of alteration: 66 to 82) and Ruxton's index (SiO2/Al2O3: 2.27 to 3.55) suggest a warm and humid climate during moderate to intense chemical weathering probably prevailing during a more humid pre-depositional period. The K2O/Na2O ratio <1 suggests high sediments chemical maturity. The predominance of angular quartz grains suggests short fluvial transport distance and low sorting. The tectonic setting discrimination ternary diagram indicates that alluvial sediments, parent material of Vertisols, originate from an Active Continental Margin while the discriminant function-based multidimensional tectonic diagram indicates an arc-collisional setting suggesting that parent materials are from the Pan-African basement of the Central African Fold Belt. The Vertisols are classified as Ustic Haplusterts Clayey Isohyperthermic (United States Department of Agriculture) and as Gleyic Stagnic Vertisols (Pellic, Hypereutric, Clayic) (World Reference Base for Soil Classification).


Nanotechnology covers a wide variety of fields of research, including chemistry, physics, biology and medicine, with extensive applications in cancer, ranging from accurate, early detection of malignant lesions to minimizing metastasis. Continued development of cancer‐targeted therapy has promising advantages: maximizing the effectiveness of anticancer drugs while decreasing the harmful systemic effects; tumor destruction via heating that takes advantage of magnetic nanoparticles' size, magnetization and biocompatibility; novel drug‐delivery systems; and gene therapy functions to facilitate controlled drug loading and release inside the cytoplasm. These and other nanotechnology applications can contribute essential new knowledge in the fight against cancer. Copyright © 2011 John Wiley & Sons, Ltd.


Background Tamoxifen (TAM) has been commonly used as a selective estrogen receptor modulator for the treatment and prevention of breast cancer. Although this drug is effective in many patients, some develop resistant and eventually relapse. Recent studies suggest that the cancer recurrence could possibly be due to changes in drug metabolism. TAM is metabolized by the cytochrome P450 enzyme pathway into several metabolites including 4-hydroxy-tamoxifen (4-OH), N-desmethyl-tamoxifen (DMT) and N-desmethyl-4-hydroxy-tamoxifen (endoxifen). These metabolites have variable potencies in suppressing estrogen-dependent breast cancer. Differences in metabolism may contribute to the clinical inter-individual variability in TAM response. The aim of our study was to provide a comprehensive evaluation of TAM and its metabolites through quantitative measurement in breast cancer patients to help better understand the pharmacological effects of TAM therapy. In the past, most methods used to measure the levels of TAM and its metabolites were in plasma or fresh/frozen tissue samples. These samples are typically not available retrospectively, and their long-term storage is expensive and laborious. Methods : We therefore explored the possibility to utilize formalin-fixed and paraffin-embedded (FFPE) tissues archived post breast surgery for quantification of TAM and its metabolites. Our laboratory has developed a rapid, sensitive and specific analytical method using liquid chromatography and tandem mass spectrometry (LC-MS/MS) for the measurement of TAM and its metabolites in FFPE tissues. The FFPE tissues were thin sectioned and deparaffinized by incubating twice with xylene for 10 min at room temperature. Sample clean-up was carried out subsequently using C2 solid-phase extraction, and detection was performed in the multiple-reaction monitoring mode with a triple quadrupole mass spectrometer. This method allows simultaneous quantification of TAM and three metabolites in FFPE tissues with a run time of 12 min. Results : The assay had good inter- and intra-assay precisions (2-6 %CV), and was linear over the range of 0.01-5 ng/g for 4-OH and endoxifen, and 0.1-50 ng/g for TAM and DMT. The extraction recoveries were between 83–88%. The validated method was successfully applied to analyze the FFPE tissues obtained from two groups of breast cancer patients. Patients were categorized into those with tumor recurrence (R) and those without recurrence (NR) after at least 2 months of 20 mg/d TAM treatment. Levels of TAM, 4-OH, DMT and endoxifen in FFPE tissues were compared between the two groups. Our preliminary data show that the ratio of DMT/TAM was significantly higher in the R (6.7, n = 13) than the NR patients (14.2, n = 9) (p Discussion : The assay described here not only allows accurate quantification of TAM and metabolites in FFPE tissues, but also opens up an incredible opportunity and new challenges for researchers to excavate precious information from FFPE tissues, especially when these archival samples represent the only source of biomaterial available. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-12-03.


Retinoic acid (RA), a bioactive chemical compound synthesized from dietary derived vitamin A, has been successfully used as a chemopreventive and chemotherapeutic agent through the regulation of cell proliferation, differentiation, and apoptosis acting via the retinoic acid receptors. Despite two decades of research on the function of retinoic acid, the physiological role of RA in mammary gland development is still not well characterized. In this report, we demonstrate that RA is required for proper morphogenesis of mouse mammary gland in a novel transgenic mouse model system. It was found that inhibition of RA signaling in vivo leads to excessive mammary ductal morphogenesis through upregulation of cyclin D1 and MMP‐3 expression. Furthermore, we show that the transgene‐induced excessive branching morphogenesis could be reversed by treatment with RA, demonstrating the direct physiological effect of RA signaling in vivo. In addition, we demonstrate that excessive branching morphogenesis in the transgenic mammary gland are cell‐autonomous and do not require stromal signals within the transgenic mammary gland. Finally, we provide evidence suggesting that retinoic acid signaling is required for appropriate mammary gland differentiation. Collectively, our data indicate for the first time that retinoic acid signaling is required to maintain the homeostasis of mammary gland morphogenesis. Developmental Dynamics 234:892–899, 2005. © 2005 Wiley‐Liss, Inc.


Aims: Real-time quantitative polymerase chain reaction (RT-qPCR) is the standard assay used for revealing the gene expression characteristics. However, the RT-qPCR studies all need reference genes for normalization to make the results comparable, which should hold a high expression stability during all experimental datasets. So far, there was no optimal set of reference genes identified in mice left ventricles (LV) across embryonic and postnatal stages. The objective of our research was to identify the appropriate reference genes in mice LV from different developmental stages.Methods and Results: we investigated the gene expressions of common 21 candidate housekeeping genes in mice LV from 7 different developmental stages, almost throughout the whole period of the mouse lifespan. The expression of some candidate reference genes, such as 18S and Actb, apparently fluctuated. The stability of potential reference genes was evaluated by a number of methods, such as GeNorm, NormFinder, BestKeeper, Delta-Ct and RefFinder method. we identified a set of optimal reference genes that can be reliably used for normalization of RT-qPCR experiments in different developmental stages of mice LV. Our results showed that following genes should not be used as reference genes in mice LV development studies: 18S, Hmbs, Ubc, Psmb4, Tfrc and Actb. And the Rplp0 appeared to represent a good choice. Conclusions: Our study provides the expression stability of the commonly used reference genes in process of LV development and maturation. We also identified a set of optimal reference genes under different conditions. Our findings may be helpful in future studies to investigate the gene expression patterns and mechanism of mammalian heart development.


Examination of sperm morphology is an essential criterion for evaluating male fertility. This examination can be done by staining sperm cells with various techniques to facilitate the visualization of sperm cells. Several other methods that can be used to evaluate sperm morphology are Eosin-nigrosin, AgNO3 staining, Papanicolaou, Diff Quick and Giemsa. However, using these synthetic dyes can harm the environment and water sources because they prefer to decompose. The natural dye derived from environmentally friendly plants expected to minimize hazardous waste. This study aimed to identify and compare the potency of several natural dyes derived from purple cabbage, sappan wood and beetroot, which have not been studied in sperm studies. Sperm obtained from 30 men in the campus area and underwent 3-5 days of abstinence from intercourse in preparation for sampling. The sperm stained with natural dye, and their quality compared with WHO standard Papanicolaou. Extracts of sappan wood, purple cabbage and beetroot are made with various mordant alum, ethanol and acetic acid compositions. The study's results showed that the presence of mordant increased the staining quality of sperm with sappan wood and purple cabbage extracts. The use of acid improves the quality of sperm staining with beet extract. There was no different between dyeing with beetroot extract in various solvent compositions and dyeing with Papanicolaou to color all sperm components (p> 0.05). The results showed that beetroot extract has a high potential to evaluate sperm morphology.


Background: The presence of an Epidermal Growth Factor Receptor (EGFR) activating mutation guide treatment selection in advanced Non-Small Cell Lung Cancer (NSCLC), whereas (BRAF) mutations play a role in metastatic melanoma. We aimed to determine the feasibility of routine multigene mutation analysis for EGFR, KRAS, BRAF and PI3KCA in EndoBronchial UltraSound-guided (EBUS) TransBronchial Needle Aspiration (TBNA) in patients with NSCLC and melanoma.

Methods: Data was prospectively collected from patients undergoing EBUS-TBNA from March 2011 until September 2012. Smears were studied after using Papanicolaou and May-Grunwald Giemsa stains. Genetic mutations were analyzed in metastatic lymph nodes diagnosed by EBUS TBNA in 40 patients with NSCLC and 1 melanoma patient. PCR and direct sequencing of EGFR exons 18 to 21, KRAS exon 2, BRAF exon 15 and PI3KCA exons 9 and 20 were performed.

Results : Multigene mutation analysis was completed for samples from 40 patients (97,6%). Mutations were detected in 11 patients (26,8%) : 3 (7,3%) EGFR exon 19 deletion, 6 (14,6%) KRAS mutation, 1 (2,4%) BRAF, and 1 (2,4%) PI3KCA mutation. Only one sample could not be processed for the detection of KRAS mutation. All the samples were adequate for the other mutations detection. Molecular biology analyses were performed both on cytological samples and biopsy samples in 7 patients (17,1%), with a perfect correlation between these.

Conclusions: Mutations of the EGFR, KRAS, BRAF and PI3KCA genes can be detected in cytological samples routinely obtained with EBUS TBNA.


This study examined engagement in treatment in substance abuse treatment programs that treated primarily either African American or White clients. Findings showed higher levels of engagement in White programs; however, engagement of African Americans in White programs was similar to that of Whites and was greater than Whites in African American programs. No significant differences emerged when a mixed model analysis considered additional variables of staff consensus (regarding treatment elements), treatment climate, acceptance of Medicaid clients, the proportion mandated to treatment, and the quality of the physical space. Although African American programs may show poorer levels of engagement than White programs, attribution of engagement in treatment to client level race/ethnicity should be made with caution.


Addition of theophylline to primary cultures of rat hepatocytes in which tyrosine aminotransferase had been preinduced with dexamethasone caused a further increase in specific activity of the enzyme. This increase was due in part to a reduction in the rate of tyrosine aminotransferase degradation that began about 2 hr after theophylline was added. The level of cGMP also increased with a similar time lag following the addition of theophylline. The concentration of theophylline which produced the above effects (1 mM) did not alter the rate of general protein degradation in hepatocytes. Addition of 8‐bromo‐cGMP (0.5 mM) resulted in an immediate reduction in the rate of tyrosine aminotransferase degradation and in an increase in the activity of the enzyme. Treating hepatocytes with MnCl2 (0.9 mM) caused an elevation of cGMP and a concomitant slowing of tyrosine aminotransferase degradation without changing the level of cAMP significantly. These results suggest an inverse relationship between the level of cGMP and the rate of tyrosine aminotransferase degradation in hepatocytes.


In this paper the problem of distillation sequence synthesis with heat integration is formulated and solved as a mixed integer linear superstructure optimization problem. Allowing both conventional and multieffect distillation, two alternatives for generating a superstructure are shown, then a formulation is presented which approximates the synthesis problem as a mixed integer linear programming (MILP) problem. Examples illustrate the method. Reported computer times suggest that earlier algorithmic methods for discovering the better sequences among those allowed by the problem formulation, and without the option of multieffecting, are an order of magnitude slower than this approach.


Background: Early initiation of breastfeeding (EIBF) is defined as starting breastfeeding within the first hour of birth. It has clinical importance to reduce neonatal morbidity and mortality. Previously studies have been conducted in Ethiopia to identify factors associated with EIBF. However, those studies hadn't investigated the variation of factors within rural versus urban populations. Therefore, this study is aimed to investigate the differences in factors associated with the early initiation of breastfeeding in rural-urban populations.Methods: This study was used Ethiopian Demographic and Health Survey data, 2016. A total of 3662 children aged less than 24 months were included in the study. Thus,2897 children were disaggregated into rural and the rest 765 of them were into urban. A multivariable logistic regression model was fitted to identify the determinant of EIBF. Finally, a statistically significant association was declared at a p-value of ≤0.05.Results: In rural populations, the study found that the age of mothers 15-24 years (AOR=1.50, 95%CI: 1.13,2.00), mothers not working (AOR=1.38,95%CI: 1.12,1.69), large birth size (AOR=1.44,95%CI:1.12,1.85), and participation of mothers in making health care decisions (AOR=1.43, 95%CI: 1.17,1.75) were positively associated with EIBF. Rural mothers having ≤2 children(AOR=0.55,95%CI: 0.45,0.67), living in larger to center regions (AOR=0.13,95%CI: 0.06, 0.27), and small peripheral regions (AOR=0.12,95%CI:0.06, 0.24) were negatively associated with EIBF. Irrespective of residence, the odds of EIBF were higher in vaginal delivery (RuralAOR= 4.38,95%CI:1.81,10.59; urban AOR= 3.19,95%CI:1.86, 5.48 ).In the urban population, having frequent ANC follow-ups was associated with a higher odds of EIBF.Conclusions: The study concludes that the age of mothers, working status of mothers, birth sizes, mothers participation in making health care decisions, numbers of children in the households, living in large to center regions and small peripheral regions were determinants of early initiation of breastfeeding, only rural residence. Mode of delivery was associated with EIBF, Irrespective of the residence. In the urban population, having frequent ANC follow-ups was associated with a higher odds of EIBF. Special emphases to mothers living in rural large to center and small peripheral regions should be given. Regardless of the residence, appropriate guidance and supports should be given for babies delivered through cesarean section.


This study aims to improve the vocabulary mastery of VII grade students of SMP Negeri 4 Taniwel, West Seram, Mollucas, through the use of picture cards.
This research was classroom action research. The research subjects were grade VII students of SMP Negeri 4 Taniwel, West Seram, Mollucas, consisting of 24 students, which was selected because they were the poorest of the three classes in vocabulary mastery. The techniques for collecting the data were observation and interview, whereas the instruments for collecting data were observation checklist, field notes, and test. The data analysis used the qualitative analysis and quantitative analysis. The qualitative analysis was related to the result analysis of the observation, interview, field notes and the observation checklist, while the quantitative analysis was related to the analysis process of simple statistic from the students' test result.
The result of the research indicates that the use of picture cards can improve the students' vocabulary mastery, as shown by the students' test result that improved at the first cycle, and then achieved the indicator of success at the second cycle. The students' vocabulary mastery was said "improved" if their percentage of completeness overall achieved the indicator of success ≥85%. In the first cycle, the percentage of the students' completeness overall improved to 75% with the average score of 74.1, which is at the good level. But, the percentage of the students' completeness overall did not achieve the indicator of success, which indicated that the students' vocabulary mastery has not improved. Therefore the cycle was repeated in the second cycle with some improvements. At the second cycle, the percentage of the students' completeness overall achieved the indicator of success 91.6% or ≥85% with the average score of 84.5, which is at the very good level. It meant that the students' vocabulary mastery has improved in the second cycle, and the cycle was ended. Besides that, the students' motivation and enthusiasm in the learning activity also improved as indicated by their enthusiastic participation in the learning process of each cycle.


We present a strategy for resolving multiple hypotheses of a robot's state during global localization. The strategy operates in two stages. In the first stage a unique direction of the motion is sought that resolves or eliminates maximum number of hypotheses. In the second stage, among the frontier areas arising from the multiple hypotheses states, that frontier is chosen which resolves the maximum number of the hypotheses. The two stages are alternated till a unique hypothesis emerges. Simulation and experimental results verify the efficacy of this method. A comparison with other methods based on entropy minimization, and minimum distance travel portrays the advantage of the current methodology. A convergence proof for the algorithm is also presented.


We study distributed stochastic gradient (D-SG) method and its accelerated variant (D-ASG) for solving decentralized strongly convex stochastic optimization problems where the objective function is distributed over several computational units, lying on a fixed but arbitrary connected communication graph, subject to local communication constraints where noisy estimates of the gradients are available. We develop a framework which allows to choose the stepsize and the momentum parameters of these algorithms in a way to optimize performance by systematically trading off the bias, variance, robustness to gradient noise and dependence to network effects. When gradients do not contain noise, we also prove that distributed accelerated methods can \emph{achieve acceleration}, requiring $\mathcal{O}(\kappa \log(1/\varepsilon))$ gradient evaluations and $\mathcal{O}(\kappa \log(1/\varepsilon))$ communications to converge to the same fixed point with the non-accelerated variant where $\kappa$ is the condition number and $\varepsilon$ is the target accuracy. To our knowledge, this is the first acceleration result where the iteration complexity scales with the square root of the condition number in the context of \emph{primal} distributed inexact first-order methods. For quadratic functions, we also provide finer performance bounds that are tight with respect to bias and variance terms. Finally, we study a multistage version of D-ASG with parameters carefully varied over stages to ensure exact $\mathcal{O}(-k/\sqrt{\kappa})$ linear decay in the bias term as well as optimal $\mathcal{O}(\sigma^2/k)$ in the variance term. We illustrate through numerical experiments that our approach results in practical algorithms that are robust to gradient noise and that can outperform existing methods.


Objective: To evaluate the efficacy and safety of ospemifene, a novel selective oestrogen receptor modulator, in the treatment of vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA). Study design: A 12 week, multicentre, randomised, double-blind, parallel-group phase III study of women (40–80 years) with VVA and self-reported vaginal dryness as their most bothersome symptom. Main outcome measures: The co-primary efficacy endpoints were the change from baseline to Week 12 in (1) percentage of parabasal cells in the maturation index (MI), (2) percentage of superficial cells in the MI, (3) vaginal pH, and (4) severity of vaginal dryness. Safety assessments included physical examination, cervical Papanicolaou test and clinical laboratory analyses. Endometrial thickness and histology was also assessed. Results: A total of 314 women were randomised to once-daily ospemifene 60 mg/day (n = 160) or placebo (n = 154). Significant improvements in the percentages of parabasal and superficial cells in the MI and vaginal pH were observed with ospemifene compared with placebo (p < 0.001 for all parameters). The mean change from baseline in severity score of vaginal dryness reported by women receiving ospemifene compared with those receiving placebo approached statistical significance (p = 0.080). Improvements in each of the four co-primary endpoints with ospemifene were statistically significant compared to placebo in the per protocol population. The majority of treatment-emergent adverse events were considered mild to moderate in severity. Conclusions: Once-daily oral ospemifene 60 mg was effective for the treatment of VVA in postmenopausal women with vaginal dryness. © 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC


Abstract Over the past 100 years, hydrogeology has played a role in most military operations undertaken by the USA. The first significant application by US forces took place during World War I, on the Western Front. America's entry into World War II highlighted the need for military hydrogeologists once again, and a combination of civilian and uniformed hydrogeologists provided valuable support to the war effort, notably by terrain analysis. During the Cold War, the United States Geological Survey Military Geology Branch conducted military hydrogeological studies, and in 1985 the US Army Corps of Engineers created the Water Detection Response Team (WDRT) to provide hydrogeological expertise to military well-drilling units. During the Persian Gulf War of 1990–1991, groundwater was important for sustaining troops living in the northern Saudi Arabian desert. Operations in Bosnia and Kosovo later in that decade required the assistance of the WDRT in obtaining adequate groundwater supplies for base camps. Current military operations in Afghanistan rely on groundwater as a significant source for most US bases. In combination, uniformed and civilian geologists serving in a variety of roles to support American troops have located water supplies essential to the success of US military operations around the globe.


Very little work have been reported on the computational methods for non-Newtonian fluid turbulent flows. This is due to nonlinear system of elliptic partial differential equations that makes the solution very difficult. Another concern is the meshing of flow domain that accounts for complications in solving most problems. In this work we present standard Galerkin finite element method for the steady incompressible non Newtonian fluid flow in a convergingdiverging nozzle. The flow is fully three-dimensional with turbulent characteristics. The main aim is to study the velocity and shear stress profiles. Shock profiles are noted for specific pressure boundary conditions. Moreover the plotted results shows variations of velocity components, pressure and turbulence energy dissipation. It is observed that for non-Newtonian fluid flow the mass flow rate and pressure loss effects are significant in diverging part of nozzle.


In the last few years, the operating modes of Gunn oscillators for frequencies above 60 GHz have been discussed controversially. In this context, a general theoretical circuit model for oscillators operating in the fundamental and in the second-harmonic modes is studied. The model employs a simple cubic I - V characteristic of the active element and separate embedding circuits for the fundamental and second-harmonic frequencies. The current and voltage waveforms of both modes are contrasted. The oscillator source impedances and the external Q of the second-harmonic mode oscillator are calculated.


Electroreflectrance (ER) spectra of GaAs and GaP, taken with the Schottky-barrier method, exhibit to 27 eV the strong structural enchancement and high resolution characteristic of similar measurements below 6 eV. Above 20 eV, a new set of critical points is observed between the flat valence bands derived from the Ga 3d core levels and the local extrema of the sp3 conduction bands. The attained resolution, of the order of 100 meV, enables us to resolve clearly the spin-orbit splitting of 0.45 eV of the 3d-derived valence bands. The following critical-point energies have been determined in GaAs and GaP, respectively. sp3 valence conduction: E1′, 6.63 ± 0.05 eV, and 6.80 ± 0.05 eV; E1′+Δ1′, 6.97 ± 0.05 eV (GaAs only); E0''(Γv15→Γc12), 10.53 eV, and 9.38 ± 0.1 eV; E0'''(Γv15→Γc1), 8.33 ± 0.1 eV, and 10.27 ± 0.1 eV, E1'', 9.5 ± 0.2 eV, and 10.7 ± 0.2 eV. E5, E6, and E7 structures are observed at 15.1, 16.7, and 17.9 eV in GaAs, and at 14.7, 16.1, and 18.6 eV in GaP. Relative values of 3d core to sp3 conduction-band matrix elements are estimated for several states and show that the lowest 3d core-level ER structures arise from transitions terminating at the Xc1conductionband minimum. We calculate an exciton or core-hole interaction shift of 150 meV for GaP and 200 meV for GaAs, which indicates that core-hole effects are probably small for these materials. Spectral features with initial structure less than 100 meV in width are observed above 20 eV, showing that broadening effects are much smaller in this energy range than previously believed.


The Service is required to be part of the hospital in implementing the documentation of nursing care using computerization. Patients in hospitals often feel dissatisfied with services because nurses take too long to search for patient history data and nurses feel dissatisfied in paper-based documentation which makes the workload increase. The purpose of this study was to design a nursing care documentation design in the 2000s SDKI, SLKI, SIKI (3S) in hospital management information systems on nurse satisfaction. The research method used a research and development design as well as descriptive observational cross sectional with a total sampling technique of 74 nursing respondents at Dian Harapan Jayapura Hospital and analyzed using simple regression analysis. The results showed that 73% of the 3-S nursing care documentation design in SIMRS was in the good category and 77% of nurses were satisfied with the 2000s nursing care documentation design in SIMRS and a significant p-value (0.000) which means that there is an effect of 30.8 % between the design of the 3S nursing care documentation in SIMRS and the satisfaction of nurses at Dian Harapan Jayapura Hospital. It can be said that by increasing the resulting information system, the satisfaction of nurses as users is getting better. It is recommended to hold socialization, training and policy realization for nurses documenting 3S nursing care in SIMRS.


In a series of experiments, the consequences of a single and double social conflict on various behaviours and body weight in rats were studied. Animals were subjected to social defeat by placing them into the territory of an aggressive male conspecific for one hour, either once, or twice at the same time on two consecutive days. To assess the consequences of social defeat, three experiments were performed with independent groups of rats. In the first experiment, an open field test was performed two days after the last conflict. Locomotor activity was strongly reduced after social defeat. There were no differences between the single and double defeat group. To assess the effects of social defeat on subsequent social behaviour, a second experiment was performed in which experimental animals were confronted with an unfamiliar non-aggressive rat two days after a single or double conflict. Social defeat resulted in a reduction of social contact with the unfamiliar conspecific. There was no difference between the single and double conflict group. In the third experiment, the effects of social conflict on food intake, body weight and saccharine preference were measured. Food intake was not affected after a single conflict, but in the double conflict group food intake was decreased for several days. Body weight gain was decreased after both single and double social defeat. The decrease was stronger in the double conflict group. Water intake and saccharine preference were not significantly affected. This study revealed that social defeat in rats causes pronounced changes in various behaviours and body weight. Different aspects of behaviour are differentially affected by defeat with respect to the magnitude and time course of the changes induced. Moreover, different behavioural parameters are differentially sensitive to repetition of the stressor.


GPI-anchored proteins, glycosphingolipids, and sphingomyelin are all enriched in the detergent-insoluble complex which has been suggested to be purified caveolae. I studied the relationship of the molecules with caveolae in cultured cells by immunocytochemical methods. In cells reacted with antibodies to various membrane proteins and lipids on ice and fixed before applying secondary antibodies, labeling did not show concentration in caveolae. In contrast, when cells were incubated with the primary and secondary antibodies on ice and then transferred to 37 degrees C without fixation, labeled Thy-1.2, beta 2-microglobulin, lactosyl ceramide, ceramide tetrahexose, Forssman antigen, and sphingomyelin became concentrated in caveolae, whereas labeled transferrin receptor did not. Thy-1.2 and sphingolipids formed common patches and were sequestered in the same caveolae when crosslinked with two primary antibodies simultaneously. On the other hand, when either Thy-1.2 alone or lactosyl ceramide alone was crosslinked and sequestered to caveolae, the other antigen remained evenly distributed. Caveolar sequestration of the antigens occurred in the presence of cytochalasin D, nocodazole, or a mixture of the two reagents. The results show that not only GPI-anchored proteins but also glycosphingolipids and sphingomyelin are sequestered in caveolae only after crosslinking, and that the sequestration does not require the intact cytoskeleton.


Incubation under sublethal high pressure (50 MPa) allowed the isolation of a piezotolerant mutant of Lactobacillus sanfranciscensis. Compared to the wild type this strain showed faster growth at 50 MPa and an altered temperature-dependent growth at ambient pressure. Additionally, an altered antibiotic resistance pattern was detected. To address the molecular basis of the mutation the genotypic characterisation was focused on alterations of ribosomal components. Northern analysis using ssrA (transfer mRNA) as probe revealed a constitutive overexpression in the mutant. A 2.2 fold induction after pressure shock and increased pressure sensitivity of a ssrA-insertional mutant of L. sanfranciscensis indicate the tmRNA as genetic determinant of a piezotolerance response in the wild type. Thus, we propose trans-translation and peptide tagging, processes that promote recycling of stalled ribosomes and prevent accumulation of abortively synthesised polypeptides to be involved in combating high-pressure damage and conferring moderate piezotolerance.


Results are presented that show the damage thresholds of e-beam deposited multi- layer HfO2/SiO2 thin films can be permanently increased by a factor of 2 to 3 by illumination with subthreshold fluences of laser light. This sub-threshold illumination procedure is referred to as "laser conditioning". The films used in this study were prepared by three different physical-vapor-deposition techniques: ion-beam sputtering, plasma plating and e- beam evaporation. Only the e-beam deposited films showed consistent and significant improvement with laser conditioning. Of the material pairs examined (Hf02/Si02, ZrO2/SiO2 and TiO2/SiO2), Hf02/Si02 gave the greatest and most consistent damage improvement with conditioning. The number of layers and the reflective or transmissive characteristics of the HfO2/SiO2 films were found to have little` impact on laser conditioning of the film. The results show that the damage thresholds of a wide range of e-beam deposited coatings (e.g. HR's, polarizers, etc.) can be improved by laser conditioning. Several possible conditioning mechanisms are examined.


This paper proposes a linear predictive (LP) analysis method where sample autocorrelations are estimated from the spectral envelope of a speech signal on the basis of the spectral autocorrelation. The spectral autocorrelation is defined as discrete quantities of speech spectrum with spectral resolution identical to the discrete Fourier transform (DFT) used to obtain the speech spectrum. From analytical and empirical derivation of its properties, we can estimate the fundamental frequency and the maximally correlated frequency for voiced and unvoiced speech, respectively, and then obtain the spectral envelope by sampling at a rate of the estimated frequency. A frequency normalization can be applied to the estimated spectral envelope because the number of samples of the spectral envelope usually differs from frame to frame. The spectral envelope is warped into the mel-frequency scale and the inverse DFT is applied to extract the estimate of sample autocorrelations. From the result of LP analysis on the sample autocorrelations, we finally obtain the spectral envelope cepstral coefficients (SECC). Hidden Markov model (HMM) recognition experiments show that SECC significantly improves the performance of a recognizer at low signal-to-noise ratios (SNRs) over several other representations.


By JOHN C. BROCKLEHURST, M.D. Pp. xiii + 19I, with 62 illustrations. Edinburgh: E. & S. Livingstone. 195 1. 30s. This monograph is based on a most comprehensive study of 412 senile patients incontinent of urine or faeces or both, found in the general and mental wards of five Glasgow hospitals. Aged incontinents present a sociological and clinical problem, the magnitude of which is better appreciated when it is realized that i per cent. of patients in general wards are found to suffer from this distressing and disabling condition, and that 26 per cent. of these cases occupy a bed for periods from six months to two years. The book is divided into three parts:Part i reviews the literature on the subject and discusses at length the anatomical and physiological considerations of micturition and defaecation with perhaps slight lack of accuracy in describing the nerve supply to the urethral sphincter. Part 2 discusses the aetiology of incontinence in old people. Three important chapters are devoted to cystometric and rectometric study in a large number of cases, and many graphic illustrations are presented. Three precipitating factors are (a) cerebro-vascular accidents, (b) becoming bedfast, and (c) increasing mental confusion. It is surprising to note that enlargement of the prostate plays only a minor part in this condition. Part 3 presents the management of incontinence in old people. In this section present methods of treatment are discussed and new ways are presented in which management of these difficult cases may be facilitated. The volume is, indeed, well worth studying by all engaged in the care of the aged sick.


Different formalisms used in the perturbative approach to Thermal Field Theory (TFT) are briefly reviewed. The rate of production of a virtual photon in a quark-gluon plasma is then discussed to illustrate some features of TFT before introducing the Hard Thermal Loop resummation which improves the behaviour of the theory in the infrared sector. Some of the successes of this appraoch are described before turning to the problems associated to the undamped transverse gluon oscillations and the light-cone singularities arising when on-shell and/or massless particles are involved.


The mathematical model for melt spinning of Doufas et al. [Doufas, A. K. et al., J. Rheol. 43, 85–109 (1999); J. Non-Newtonian Fluid. Mech. 92, 27–66 (2000); 92, 81–103 (2000)] coupling the polymer microstructure (molecular orientation, chain extension, and crystallinity) with the macroscopic velocity/stress and temperature fields is tested against low- and high-speed spinline experimental data of PET melts. The model includes the combined effects of flow-induced crystallization (FIC), viscoelasticity, filament cooling, air drag, inertia, surface tension, and gravity and simulates melt spinning from the spinneret down to the take-up roll device (below the freeze point). As is the case with nylon systems, model fits and predictions are shown to be in very good quantitative agreement with spinline data for the fiber velocity, diameter, and temperature fields at both low- and high-speed conditions, and, with flow birefringence data available for high speeds. Our model captures the necking phenomenon for PET quantitatively and the associated extensional softening which is shown to be related to nonlinear viscoelastic effects and not to the release of latent heat of crystallization. Although crystallization is quite slow under low-speed spinning conditions, the model captures the occurrence of the freeze point naturally, and is thus a significant improvement over existing melt spinning models that enforce the freeze point at the glass transition temperature. In this article we demonstrate the robustness of our microstructural FIC model to melt spinning of quite slow crystallizers in the quiescent state, while the robustness for faster crystallizers was shown previously [Doufas, A. K. et al., J. Non-Newtonian Fluid. Mech. 92, 27–66 (2000); 92, 81–103 (2000)].The mathematical model for melt spinning of Doufas et al. [Doufas, A. K. et al., J. Rheol. 43, 85–109 (1999); J. Non-Newtonian Fluid. Mech. 92, 27–66 (2000); 92, 81–103 (2000)] coupling the polymer microstructure (molecular orientation, chain extension, and crystallinity) with the macroscopic velocity/stress and temperature fields is tested against low- and high-speed spinline experimental data of PET melts. The model includes the combined effects of flow-induced crystallization (FIC), viscoelasticity, filament cooling, air drag, inertia, surface tension, and gravity and simulates melt spinning from the spinneret down to the take-up roll device (below the freeze point). As is the case with nylon systems, model fits and predictions are shown to be in very good quantitative agreement with spinline data for the fiber velocity, diameter, and temperature fields at both low- and high-speed conditions, and, with flow birefringence data available for high speeds. Our model captures the necking phenomenon for PET ...


The act of programming can be traced back to the 19th century and Ada Lovelace. In the context of history, the idea to combine programming with mathematics and technology is not strange. Today programming is a much more widespread phenomenon. But the relevance of programming in mathematics and technology is still very obvious. However, with the mandatory addition of programming in K-12 setting a debate has been sparked concerning the impact on teaching activities. The aim of this study was to analyse and discuss possible obstacles and opportunities in integrating programming in K-12 settings from a teacher perspective. The two important main questions to answer were: 1) which are teachers' perceived obstacles and opportunities in the integration of programming in K-12 setting? 2) which are the differences and similarities in expectation between teachers with and without earlier programming experience? This study was carried out inspired of action research with the objective of improving an existing programming course for mathematic and technology teachers. Action research is a strategy that do not only strive to generate new knowledge but also has the aim to improve real world phenomena. Authors in this study had the double roles of being teachers and researchers, with the idea of establishing a cyclical process where course participants feedback should lead to extensions of the future course versions. Data were collected in the teacher training course and consist of 44 submitted essay answers on the question: In which aspects might programming be a positive and/or negative enhancement of you daily teaching? Collected data were grouped into categories with the use of content analysis. Results indicate that there are both perceived opportunities and perceived obstacles among teachers concerning integrating programming in mathematics and technology. An obvious finding was the mix of positive and negative attitudes in the vast majority of essays. In the category of obstacles many teachers brought up the risk of time trouble in both their professional development and in their teaching activities. In the category of opportunities several teachers mentioned the potential of programming as a new and motivating learning tool in their subjects. Finally, it seems important for the participants to get concreate takeaways from the course that could be used in their daily teaching activities.


Porroca is a lethal disease of coconut (Cocos nucifera) emerging in Central America. Previously known only from Colombia, it has spread rapidly across the Isthmus of Panama in the last decade. Porroca is characterized by the production of stiff, dwarfed leaves, usually followed by the death of the palms within 2 years. We describe the long-distance spread of the disease as determined from regular censuses of more than 200,000 coconut palms in the indigenous Comarca of Kuna Yala and the Republic of Panama. Spread is temporally and spatially variable, with the disease moving across the landscape as much as 40 km per year. Porroca may represent a significant new threat to coconut production in the Caribbean Region.


ELF magnetic field has many advantages, in addition to being a non-ionizing radiation, it is also able to penetrate almost any material. Several research results prove that exposure to ELF magnetic field can trigger the growth of tomato plants Ranti (Sari et al, 2015) and large chili plants (Handoko et al, 2017). The underlying mechanism for this is that exposure to ELF magnets can increase intracellular calcium, which can lead to increased cell proliferation. Excess magnetic field ELF is expected to be an alternative solution to the problems faced by tobacco farmers, which is the decline of the production of tobacco. Simple and inexpensive solutions need to be sought. Therefore, this study proves the effect of ELF magnetic field on increasing the leaf mass of tobacco. The sample of this research is tobacco seed exposed to ELF magnetic field after soaked in water for 24 hours. The variations in the intensity of the ELF magnetic field used in this study were 300μT, 500μT and 700μT and variations of 45 minutes and 60 minutes of exposure time. The results of One Way Anova analysis of this research data proves that exposure to the ELF magnetic field significantly increases the wet mass of leaf tobacco production. The highest wet mass of tobacco leaf was obtained in the group exposed to the magnetic field ELF 500μT for 60 minutes. In conclusion, that exposure to ELF magnetic field has an effect on increasing wet mass of leaf tobacco production. Extremely Low Frequency, Leaf Mass, Length of Exposure


The origins of Nur Bânu, first consort of Selim II and mother of Murad III, have been a subject of many speculations and much confusion. Modern historiography produced two contrasting versions about the early life of this influential personality: whereas most scholars have regarded her as a Venetian patrician, she is considered as Corfiote in Greece. A reconsideration of the question, supported by archival documents, though not leading to a definite solution, presents the Greek version as more plausible, while analyzing the various factors which may explain the elusiveness characterizing Nur Bânu's identity.


Abstract : This paper describes a prototype system for quickly developing joint military courses of action. The system, SOCAP (System for Operations Crisis Action Planning), combines a newly extended version of an AI planning system, SIPE-2 (System for Interactive Planning and Execution), with a color map display and applies this technology to military operations planning. This paper describes the Socap problem domain, how SIPE-2 was used to address this problem, and the strengths and weaknesses of our approach.


This paper reviews social science research on the antecedents and consequences of voluntary sterilization. The major conclusions are that socioeconomic status has little impact on the decision to be sterilized and that sterilizations are rare among those without sons and among male non-whites. Significant others are important sources of encouragement and information, and good marital relations increase the likelihood of having the procedure performed. Most acceptors experience no change in sexual activity, quality of marital relationships, or work-related behavior, and few regret their choice. Negative consequences are more likely among those in India, those coerced into having a sterilization, those who did not understand the consequences of the procedure, those with health complications after sterilization, and those couples who have unstable marriages or who disagree about sterilization.


This experimental investigation focuses on the turbulence features of weak hydraulic jumps in rectangular channels for two different approach flow lengths. The turbulent kinetic energy equation includes the turbulence production and dissipation terms, two advection and two turbulent transport terms and the pressure transport term, which could not be measured, however. For jumps with a limited approach flow length, the turbulence production is mostly confined to the shear layer, while for jumps with a longer approach flow length, an additional peak turbulence production region is observed at the near-wall region due to boundary layer separation. The turbulent energy is then transported by the mean flow both towards the free surface and into the downstream direction and is diffused by turbulent processes away from the energetic shear layer towards less energetic regions. Dissipation occurs mostly in the shear layer along the upstream portion of the jump and over most of the flow depth further downstream.


The flavor volatile compounds of dried red cashew flowers, cashew leaf-buds, cashew leaves and licorice roots as well as flavored herb teas were analyzed by gas chromatography-mass spectrophotometry (GC-MS). It was found that terpenes, including α-pinene, α-phellandrene and β-phellandrene were the main volatiles in the cashew leaf-buds and leaves. The major volatile compounds of the red cashew flowers were 3-butyn-1-ol, acetic acid, benzyl alcohol and β-caryophyllene. The contents of 2-propanol,1,1'-oxybis and pentanedioic acid of the traydried flowers were higher than in the freeze-dried flowers, whereas (Z)-3-hexan-1-ol, ethanone, benzyl nitrile and benzyl tiglate were presented at highest concentrations in the freeze-dried flowers. 3-Butyn-1-ol was the main component in dried licorice roots. Flavored cashew tea formula A (a mixture of 70% freeze-dried cashew flowers, 12.5% cashew leaf-buds, 12.5% cashew leaves and 5% licorice roots) contained total volatile contents higher than tea formula B (a mixture of 70% tray-dried cashew flowers, 12.5% cashew leaf-buds, 12.5% cashew leaves and 5% licorice roots). However, 2-propen-1-ol, 3-phenyl was not found in tea formula A, while benzyl tiglate was not detected in tea formula B. Tea formula A contained more volatiles in the alcohol, ketone and ester classes than tea formula B. The classification of two formula flavored herb teas was presented. There are some differences in the signal response of each sensor for two grade flavored herb teas. Two grades of flavored herb tea were discriminated using electronic tongue (e-tongue). The results of discrimination function analysis (DFA) and principal component analysis (PCA) displayed that the grades of tea samples were discriminated.


Selective radical generation in conjugated oligomeric o-aryleneethynylenes initiates an intramolecular cascade which involves five fast radical cyclizations followed by aromatization via a 1,5-H shift with a >93% yield per step. This radical cascade transformation opens a new avenue for the systematic and controlled preparation of functionalized graphene nanoribbons where, potentially, each of the peripheral aromatic rings can be different.


This paper presents a hybrid fuzzy logic proportional plus conventional integral-derivative controller (FP+ID) for the speed control of a permanent magnet brushless DC (PMBLDC) motor. Though PID controllers are commonly used in practice, they have failed to perform satisfactory under nonlinearity, load disturbances, parameter variation, etc. In this paper, the performance of the permanent magnet brushless DC motor drive is examined with a hybrid controller which is a combination of fuzzy logic and conventional controller. This controller shows improved performance compared to PID speed controller.


Inverse kinematics greatly simplifies the animation of models: positioning the hand alone will position the entire arm. In some dance styles, the position of the feet, together with which foot the weight is on, determines much of the bending and rotation of the legs, hips, rib cage, shoulders and arms. Cuban motion is a highly stylized example of this, used in several dances such as Salsa, Rumba, and Cha-cha. The principles covering Cuban motion, when combined with normal rigging constraints, allow a wide variety of dances and dance moves to be synthesized rapidly with minimal input. Only the timing of the weight changes (usually fixed for each dance), and the placement of the feet (usually fixed for each dance move), need be specified. In this talk we outline the principles of Cuban motion, and demonstrate how natural looking dance moves can be procedurally generated. We have found that the code for dance moves can be simplified enough to resemble the instructions given in dance guidebooks.


42 Soil bioturbation activity affects soil texture, bulk density, soil water content and redistribution of 43 nutrients. All of these parameters influences sediment redistribution, which shapes the earth surface. 44 Hence it is important to include bioturbation into erosion models. However, up to present, the inclusion 45 of bioturbation into erosion models was limited. This is because to realistically include bioturbation into 46 the modelling, the interplay between bioturbation, sediment redistribution and environmental parameters 47 is not understood. 48 Here, we included bioturbation into a soil erosion model and interpreted the impacts of bioturbation on 49 sediment redistribution. To do this, we measured the needed soil properties and location of burrows 50 created by bioturbating animals in four research sites located along the Chilean climate gradient. Then, 51 we parametrized a semi-empirical erosion model by applying machine learning algorithms to upscale 52 soil properties and burrow distribution. We ran the model for a time period of 6 years under two 53 conditions: With and without bioturbation. We validated the model using several sediment fences in the 54 field. We estimated the modelled sediment redistribution and surface runoff in all climate zones. Lastly, 55 we identified environmental parameters determining the positive or negative impact of bioturbation on 56 sediment redistribution. 57 We found that the model with integrated bioturbation performed much better (R 2 = 0.71, RMSE = 0.63) 58 than the model without integrated bioturbation (R 2 = 0.17, RMSE = 1.18), meaning that model runs which 59 considered bioturbation predicted the sediment redistribution more realistically. Furthermore, 60 bioturbation increased sediment redistribution in all but the humid climate zone, especially in the 61 Mediterranean zone. The quantity of sediment redistributed due to bioturbation was reliant on an 62 interplay between elevation, slope, surface roughness and sink connectivity. Overall, bioturbation 63 enhances sediment erosion in areas where more erosion is expected, and enhances sediment 64 accumulation in areas which are more prone to accumulate sediment. In other words, considering 65 bioturbation when studying earth surface evolution means an amplification of existing tendencies in 66 sediment redistribution, and leads to a faster hillslope relief equalisation.


Background: Honeybees produced by Apis mellifera is well-known of its nutritional and therapeutic effectiveness since ancient times. However, its properties vary according to the vegetation cover in each area, which requires scientific verification. Methods: Two samples of natural jujube honey, from northcentral and southwestern Saudi Arabia, from Buraidah and Najran, respectively, was screened using disc dif¬fusion test against seven referenced bacterial strains. Results: both samples showed significant antibacterial activity on gram-positive bacteria and weak or no activity on gram-negative bacteria. Although, honey sample from Buraidah exhibited higher antibacterial efficacy. Conclusion: According the current study, the antibacterial characteristics of honey may have affected by the area from which it was collected and the tested honey samples could have a potential effect against diseases caused by gram-positive bacteria.


Background Liver transplantations have been widely performed with good outcome for patients with end-stage liver disease. However, complications associated with vascular reconstruction might result to graft liver failure and negatively impact on the outcome. These complications more frequently occur using a reduced-size graft such as a living donor because of an intrinsic short pedicle or a size mismatch of the graft vessel. Percutaneous transhepatic portal vein angioplasty (PTPA) is an alternative except for a surgical revision for the treatment of portal vein stricture. The aim of this study is to evaluate efficacy of PTPA for portal vein stricture after living donor liver transplantation (LDLT). Patients and Methods We have performed 303 LDLTs since June 1990 and experienced 35 cases (11.6%) of portal vein complications. Out of them, 11 recipients who underwent PTPA for portal vein stricture that occurred after LDLT were included in this study. The diagnosis of portal vein stricture was obtained based on the findings of contrast-enhanced CT and/or magnetic resonance imaging, in addition to symptoms arising from portal hypertension. PTPA was performed using the ultra-sonography-guided percutaneous transhepatic method. We inserted a catheter into a portal vein and placed a balloon catheter into the anastomotic stricture. After measuring the portal vein pressure, we dilated the stricture using balloons, starting from small diameter and then extending step by step till vanishing a notch, without inserting a vascular stent. We retrospectively evaluated the outcome and complications associated with this procedure. Results Eleven recipients aged from 5 months to 49 years old (median 18 years old) at the time of LDLT, had obtained a diagnosis of portal vein stricture median 3.4 years after LDLT. Portal vein pressure decreased and symptoms arising from portal hypertension improved via PTPAs in all recipients excluding one required stenting and another underwent revision of anastomosis after PTPA. Vascular patency was maintained during the follow-up period ranging from 1 month to 22.3 years (median 7.9 years) after PTPA. Complication associated with PTPA occurred in one recipient with portal vein thrombus (grade II); no recipients had complications over grade III in the Clavien-Dindo classification. All recipients are still alive except one dying of chronic rejection. The 10 and 20 year patient survival rates in 11 recipients were comparative to those in 268 recipients without portal complications (90% each vs 93.2% and 86.7%, p>0.1). Conclusion PTPA for portal vein stricture after LDLT was effective because of safety and long vascular patency.


Optical coatings applied to one-half of thin film magnetic rings allow real-time readout of the chirality of the vortex state of micro- and nanomagnetic structures by breaking the symmetry of the optical signal. We use this technique to demonstrate data storage, operation of a NOT gate that uses exchange interactions between slightly overlapping rings, and to investigate the use of chains of rings as connecting wires for linking gates.


Percutaneous nephroureterolithotripsy was performed a total of 309 times in 225 renal units of 209 patients with upper urinary tract calculi, a mean of 1.37 times per kidney. Residual calculi, 5 mm or greater in diameter, were observed in 3 of 100 kidneys (3%) with single calculi, 12 of 102 kidneys (11.8%) with multiple calculi, and 8 of 23 kidneys (34.8%) with staghorn calculi. The number of sessions, duration of nephrostomy, and the frequency of residual calculi were significantly higher in problem calculi, such as multiple, large and staghorn calculi, than in other calculus types. A combination of percutaneous nephroureterolithotripsy and extracorporeal shock wave lithotripsy was considered to be necessary to improve the efficiency of lithotripsy. Complications included a transient fever, bleeding requiring transfusion and perforation of the renal pelvis in a small number of cases, but these were all mild and could be managed by conservative treatment, alone.


In this chapter, we first discuss the role that pragmatics has played in the development of (im)politeness theory, and the recent move towards a middle ground that integrates classic and discursive approaches to (im)politeness. We outline the key tenets of integrative pragmatics that afford such a move, before illustrating how these can be implemented through a case study focusing on an incident in Big Brother UK where the (ostensibly) jocular use of a racial slur by a contestant caused offence and the subsequent removal of that contestant from the show. Our analyses draw from multiple methods, including those of interactional pragmatics and corpus pragmatics. In this way, we aim to both highlight the fundamentally pragmatic basis of (im)politeness, as well as the need for a nuanced and complex theorisation that integrates multiple perspectives and methods of analysis.


Several useful software engineering techniques, disciplines and perspectives are related to typical software development problems in design automation. Specific examples from recent experience illustrate both beneficial and undesirable practices. Oriented toward managers and practicing software engineers, the tutorial discusses system structure, control and data structures, programming guidelines, work habits, testing, documentation and operational maintenance.


Background Results of the OAK study demonstrated that atezolizumab improved median overall survival and progression-free survival of patients with advanced non-small cell lung cancer (NSCLC). Purpose Evaluate the efficacy and safety of atezolizumab treatment in patients with metastasic or advanced NSCLC in second and successive lines. Material and methods Retrospective observational study in which patients with NSCLC were included who started treatment with atezolizumab in the second or successive line, during the period from April to September 2018. Data were collected on demographic variables (age and sex) and clinical variables (ECOG, smoking habit, previous chemotherapy, dose, number of cycles and adverse reactions) through clinical history (Selene) and the oncological prescription program (Farmatools). The descriptive statistical analysis was carried out through the SPSS vs22.0 program. Efficacy was evaluated in terms of progression-free survival (PFS) and overall survival (OS), calculated by the Kaplan–Meier method. To assess safety, the severity of adverse events (AA) was measured according to CTCAEv4.0 Results We analysed 14 patients, 9 males and 5 females. Ninety-three per cent were smokers or ex-smokers, and 7% had never smoked. Eleven patients had ECOG 0–1 and three ECOG 2% and 93% had metastases at the start of treatment with atezolizumab. All patients had received prior platinum-based chemotherapy as first-line treatment. The dose administered was 1200 mg every 3 weeks and the average of cycles was four. The median of PFS was 4.8 months (95% CI: 1.0 to 8.6) and the average of OS 4.5 months (95% CI: 3.6 to 5.4). 57.14% of the patients presented some AA of any degree and only 12.5% were grade 3–4. The most frequent were renal failure (37.5%), diarrhoea (25%), rash (25%), hypersensitivity (12.5%), thrombocytopaenia (12.5%), lung infection (12.5%), oedema (12.5%), emésis (12.5%) and decreased appetite (12.5%) Conclusion The efficacy in terms of OS obtained was lower than that of the OAK study (13.8 months). However, when the PFS was analysed in our study, it was superior to that of the OAK study (PFS 2.8 months). In general, atezolizumab presents an acceptable safety profile, the most frequent AEs coincide with those described in the literature. References and/or acknowledgements No conflict of interest.


ABSTRACT Objectives: The purpose of this study was to develop an individually tailored, non-pharmacological treatment model, the Cognitive Model for Behavioral Interventions (CoMBI), for patients with Behavioral and Psychological Symptoms of Dementia (BPSD) and comorbid maladaptive personality traits (CMPT), and to explore its feasibility and effectiveness. Methods: CoMBI was developed and implemented in two geriatric psychiatric inpatient wards in the Netherlands. In this single-group pretest-posttest, feasibility study, 40 patients with BPSD and CMPT (M = 73.8, SD = 8.5) were treated with CoMBI. BPSD and CMPT were assessed using informant-based questionnaires. Wilcoxon signed-rank tests and effect size calculations were conducted to determine differences. Results: Wilcoxon signed-rank tests demonstrated a significant decrease of BPSD with medium (r = 0.45) to large (r = 0.56) effect sizes. CoMBI demonstrated high acceptability and compliance by health-care professionals and family members. Conclusions: CoMBI is a feasible treatment model for challenging behavior in patients with BPSD and CMPT. CoMBI is associated with a significant decrease in challenging behaviors regardless of etiology. Clinical implications: Focusing on personality and associated core needs could have a key role in the non-pharmacological treatment of the elderly with BPSD.