We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with Trypanosoma cruzi, identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. T. cruzi-infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls. CCC(+) and CCC(++) hosts exhibited decreased frequencies of monocytes, NK and NKT-cell subsets in both compartments, and increased frequencies of activated CD8+ T-cells and GranA+/GranB+ cells. While a balanced cytokine profile (TNF/IL-10) was observed in peripheral blood of CCC(-) macaques, a predominant pro-inflammatory profile (increased levels of TNF and IFN/IL-10) was observed in both CCC(+) and CCC(++) subgroups. Our data demonstrated that cardiac histopathological features of T. cruzi-infected cynomolgus macaques are associated with perturbations of the immune system similarly to those observed in chagasic humans. These results provide further support for the validity of the cynomolgus macaque model for pre-clinical research on Chagas disease, and provide insights pertaining to the underlying immunological mechanisms involved in the progression of cardiac Chagas disease.


An alkali-soluble, photocrosslinkable polymer was synthesized by esterification of OH groups of acrylic phenolic resin with maleic anhydride. The OH groups were formed by the ring-opening reaction of epoxy groups of epoxy phenolic resin with acrylic acid. The esterification conditions were studied. The results showed that it is better to use tetramethyl ammonium bromide as catalyst than N,N-dimethylbenzylamine. The conversion of maleic anhydride in acetone can reach about 80% at 56°C for 4 h. The purified product was characterized by IR, DSC, and TGA. The product containing acrylate and maleic acid monoester groups, above a certain content, can be dissolved in 1% Na2CO3 solution. The photocrosslinkable properties of the product were investigated through selection of photoinitiator, accelarator, crosslinkable diluent monomer, etc. The acrylate and maleic acid monoester group-containing phenolic resin exhibited very good photocrosslinking behavior, since it contains double bonds from both acrylate groups and maleic acid monoester groups. The activity of photoinitiator decreases in the order: isopropylthioanthraquinone > benzoin ethyl ether (BE) > anthraquinone (AQ) > benzophenone > Michel ketone (MK) > 2,2-diethoxyacetophenone. The combination of some photoinitiators showed synergistic effects. The order of increasing activity for the accelerator is as follows: MK > ethyl p-(dimethylamino)benzoate > N,N-dimethylaniline > triethanolamine. The optimum diluent monomer is trimethylolpropane trimethacrylate. The gel content of the mixture of the resin and trimethylolpropane trimethacrylate could reach 85% using the combined photoinitiators of BE and AQ under UV exposure for 120 s. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1607–1614, 2005


Context. GRB 111209A, one of the longest gamma-ray bursts (GRBs) ever observed, is linked to SN 2011kl, which is the most luminous GRB supernova (SN) detected so far. Several lines of evidence indicate that this GRB-SN is powered by a magnetar central engine.
Aims. We place SN 2011kl into the context of large samples of SNe, addressing in more detail the question of whether this GRB-SN could be radioactively powered, and whether it represents an extreme version of a GRB-SN or an underluminous superluminous SN (SLSN).
Methods. We modelled SN 2011kl using SN 1998bw as a template and derived a bolometric light curve including near-infrared data. We compared the properties of SN 2011kl to literature results on stripped-envelope and SLSNe.
Results. A comparison in the k, s context, i.e. comparing SN 2011kl to SN 1998bw templates in terms of luminosity and light-curve stretch, clearly shows SN 2011kl is the most luminous GRB-SN to date and is spectrally very dissimilar to other events because it is significantly bluer/hotter. Although SN 2011kl does not reach the classical luminosity threshold of SLSNe and evolves faster than any of these objects, it resembles SLSNe more than the classical GRB-associated broad-lined Type Ic SNe in several aspects.
Conclusions. GRB 111209A was a very energetic event, both at early (prompt emission) and at very late (SN) times. We show in a companion publication that with the exception of the extreme duration, the GRB and afterglow parameters are in agreement with the known distributions for these parameters. SN 2011kl, on the other hand, is exceptional both in luminosity and spectral characteristics, indicating that GRB 111209A was likely not powered by a standard-model collapsar central engine, further supporting our earlier conclusions. Instead, it reveals the possibility of a direct link between GRBs and SLSNe.


Abstract UVB exposure penetrates deeply into the dermis to alter skin barrier function, which is a primary factor in skin photoaging. We previously reported that dalteparin and protamine nanoparticles (D/P NPs) are effective carriers of FGF-2. This study aimed to examine the ability of FGF-2-containing D/P NPs (FGF-2&D/P NPs) to ameliorate UVB-induced skin photoaging in hairless mice. Dorsal skin of HR-1 hairless mice were exposed to UVB irradiation 5 days/week for 8 weeks (UV (+): final total, 2700 mJ/cm2). Mice were divided into four groups: Non-UVB (UV (−)) + saline, UV (+) + saline, UV (+) + FGF-2&D/P NPs, UV (+) + FGF-2, and UV (+) + D/P NPs, and following UVB irradiation, FGF-2&D/P NPs, FGF-2, and D/P NPs were applied to the groups of mice just after each UVB irradiation. Each group was subjected to evaluation of skin changes (elasticity), and histological examination using hematoxylin & eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. UVB irradiation of mice significantly induced a decline in elasticity and acanthosis, which was alleviated by application of FGF-2&D/P NPs. Furthermore, TUNEL-staining showed the proportions of apoptotic dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) in the UV (+) + FGF-2&D/P NPs group were significantly lower than those in the UV (+) + saline, UV (+) + FGF-2, and UV (+) + D/P NPs groups. Thus, FGF-2&D/P NPs may be effective in preventing skin photoaging accelerated by UVB irradiation such as declining elasticity, acanthosis, and apoptosis of DFCs and EKCs.


Over the past twenty years, magnetic resonance imaging (MRI) has become one of the most important imaging modalities available to clinical medicine. It offers great technical flexibility, and is free of the hazards associated with ionizing radiation. In addition to its role as a routine imaging technique with a growing range of clinical applications, the pace of development in MRI methodology remains high, and new ideas with significant potential emerge on a regular basis. MRI is a prime example of the spin-off benefits of basic science, and is an area of medicine in which physical science continues to play a major role, both in supporting clinical applications and in developing new techniques. This article presents a brief history of MRI and an overview of the underlying physics, followed by a short survey of current and emerging clinical applications.


Bronchial challenge tests were performed in 16 asthmatic subjects. Eight developed an immediate and eight a dual asthmatic response. In all patients serial blood samples were analysed for plasma recalcification time and Factor XII activation rate. In all instances a profound shortening of the recalcification time was found, but only in patients with a dual response could an increased activation rate of Factor XII be detected. A positive correlation, although weak, was found between the time for maximum shortening of recalcification time and the time of onset of the late reaction. The study suggests a relationship between activation of blood coagulation factors and the type of asthmatic response elicited after challenge test.


We determined the status of vascular kallikrein in rats with severe hypertension caused by treatment with deoxycorticosterone acetate (DOCA) and drinking of 1% Nad for 6 weeks. We assayed active and total kininogenase (kallikrein) activity in the perfusate and in arterial and venous tissue. DOCA-salt rats had higher systolic blood pressure at 6 weeks (214±5 mm Hg) than rats drinking tap water (135±4 mm Hg) or saline (145±8 mm Hg). Kininogenase in the perfusate (nanograms bradykinin per minute per kilogram body weight) increased significantly at 2 weeks, from 5.8±2.1 to 8.9±1.4 for active kallikrein and from 28.7±0.4 to 48.7±2.9 for total kallikrein. Total kallikrein returned to control values at 4 weeks, whereas it was significantly reduced at 6 weeks (20.9±0.7). Active kallikrein was significantly depressed at 4 and 6 weeks (1.08±0.1 and 0.85±0.1, respectively [P<.05]). Active kallikrein in arterial tissue (picograms bradykinin per milligram per minute) showed a small but significant increase at 2 weeks, from 156±7 to 201 ±10 (P<.05), finally decreasing significantly by 6 weeks to 64±3; however, total kallikrein showed a significant decrease only at 6 weeks, from 844±17 to All±21. Both active and total kallikrein in the veins were higher than control values at 2 weeks, changing from 437±7 to 541±19 and from 1619±17 to 2062±86, respectively. Venous kallikrein remained elevated until the end of the experiment. These findings suggest that mineralocorticoids increase vascular kallikrein and that established hypertension lowers both arterial kallikrein and kallikrein released by the vasculature, whereas venous kallikrein is under a different regulatory control. The vascular kallikrein-kinin system may help counteract the elevation of vascular resistance in the earliest stages of DOCA-salt hypertension.


BACKGROUND
Our objective was to examine the knowledge and treatment decision practice patterns of Canadian surgeons who treat patients with rectal cancer.

METHODS
A mail survey with 6 questions on staging investigations, management of low rectal cancer, lymph node harvest, surgical margins and use of adjuvant therapies was sent to all general surgeons in Canada. Appropriate responses to survey questions were defined a priori. We compared survey responses according to surgeon training (colorectal/surgical oncology v. others) and geographic region (Atlantic, Central, West).

RESULTS
The survey was sent to 2143 general surgeons; of the 1312 respondents, 703 treat patients with rectal cancer. Most surgeons responded appropriately to the questions regarding staging investigations (88%) and management of low rectal cancer (88%). Only 55% of surgeons correctly identified the recommended lymph node harvest as 12 or more nodes, 45% identified 5 cm as the recommended distal margin for upper rectal cancer, and 70% appropriately identified which patients should be referred for adjuvant therapy. Surgeons with subspecialty training were significantly more likely to provide correct responses to all of the survey questions than other surgeons. There was limited variation in responses according to geographic region. Subspecialty-trained surgeons and recent graduates were more likely to answer all of the survey questions correctly than other surgeons.

CONCLUSION
Initiatives are needed to ensure that all surgeons who treat patients with rectal cancer, regardless of training, maintain a thorough and accurate knowledge of rectal cancer treatment issues.


Since Ancient Greece, a guiding principle of Western medicine has been paternalism—the idea that doctors have intrinsically superior insights, patients should defer to their edicts, and this asymmetry is a desirable state of affairs. In the 20th century, new medical knowledge and technologies accumulated at an unprecedented rate, and medical paternalism arguably reached its zenith. Now, however, new technologies are eroding the doctor's privileged role by deconstructing, digitizing, and democratizing medical knowledge. Digital technologies and other breakthroughs offer unprecedented opportunities to save lives and cut costs. Along with self-interest, however, selective strains of risk aversion, technophobia, and egalitarianism among physicians are generating resistance to the new reality. This article catalogs the motives for and impact of medical paternalism, the reasons for its decline, and potential policy responses that would ease the transition.


Thermal conductivity analysis of insulation materials is of great importance for determining the critical temperature of structures. The magnitude of this thermal property has a significant influence on the analysis of temperature distribution and heat flow which depends essentially on the thermal properties of the protection material. The most common method for obtaining the required fire resistance is through passive fire protection materials, such as the calcium silicate boards. By using this material, it is possible to slow down the temperature increase on the structural elements surface during a fire situation. Knowing accurate information about the effects of high temperatures on thermal conductivity is certainly an important prerequisite for running a high-performance design involving safety in buildings. Therefore, an investigation of two different calcium silicate boards has been performed to demonstrate how the thermal conductivity is highly affected when exposed to high temperatures. A set of experimental tests is presented. They were conducted in different techniques such as: the transient plane source (TPS) and the guarded hot plate.


Using a model system of single, isolated carbon nanotubes loaded with high-capacitance metal-oxide films, we have quantitatively investigated electrochemical composites on the single-nanotube scale. Electrochemical charging and discharging of a model MnO2 storage material was used to probe interfacial charge transfer and surface impedances at the nanotube interface. We found that one single-walled carbon nanotube has an apparent surface resistivity of 30 mΩ cm(2), approximately 4 times smaller than for a multiwalled carbon nanotube and 50 times smaller than the 1.5 Ω cm(2) resistivity of Pt or graphite films. The improvement originates in the electrochemical-transport properties of microelectrodes shrunk to a nanotube's dimensions rather than any unique nanotube property like curvature, bandstructure, or surface chemistry. In explaining the enhanced performance of certain nanotube-containing composites, the results overturn widely held assumptions about nanotubes' roles while also providing guidelines for optimizing effective composites.


The North American Muslim population is growing rapidly, but little research has been conducted to help social workers interact with members of this population in a culturally sensitive manner. To assist social workers engage with Muslims in an ethical and effective manner, this qualitative study sought to answer the following questions: how do Muslims experience interactions with non-Muslims and what have they learned from their encounters that might facilitate positive interactions? To answer these two questions, we used narrative inquiry with a sample of 10 Muslim social work students and recent alumni. The findings suggest that Muslims may be treated either positively or negatively by non-Muslims in interactions in various contexts, that they are frequently unable to voice their religious perspectives, and that their religious difference is often portrayed in single-sided or negative ways as well as prioritized against their wishes while ignoring other aspects of their social identities. As a result, many tend to avoid interactions with non-Muslims. The paper offers strategies to foster more respectful interactions with Muslims, such as attending to how much their religious difference is prioritized, and providing opportunities to share their perspectives.


A novel approach for the allylic alkylation of anilines, hydrazides and indole derivatives by the direct use of allylic alcohols is described under very mild conditions, such as room temperature and using sustainable deep eutectic solvents (DESs). The search of the optimum DES to be used in the reaction reveals that a simple mixture of choline chloride (ChCl) and lactic acid provides excellent results for a wide substrate scope and with high isolated yields. This methodology represents a great improvement compared to other procedures described in literature, for which high temperatures, stronger reaction conditions or metal catalysts are usually required. In some cases, this protocol affords to the first examples of trapping allylic carbocations with indole derivatives. All these features make this procedure an appealing and green alternative in comparison with other examples reported in literature on alkylation of amines by allylic alcohols. Preliminary mechanistic studies using unsymmetrically substituted alcohols support that the reaction should proceed by an S N 1 pathway.Introduction.


BACKGROUND: Primary bone cancer comprises three major histological subtypes: osteosarcoma (OS), Ewing sarcoma (ES) and chondrosarcoma (CS). The most frequent subtype, OS, primarily occurs in adolescence, but has a second peak at the oldest ages, usually attributed to late effects of radiotherapy and chemotherapy, and Paget9s disease. The adolescent age distribution of ES resembles that of OS, suggesting a link between the onset of puberty and these subtypes of bone cancer. CS is rare in childhood, and incidence rates, unlike those of OS and ES, increase fairly uniformly with age. Given the limited knowledge about the etiology of primary bone cancer, and the unusual age-incidence distribution for OS and ES, we undertook an APC analysis to determine whether incidence varied by birth cohort or calendar period. For other cancers, such as testis and breast, the identification of cohort patterns has generated new hypotheses regarding environmental risk factors. METHODS: We fit an APC model to incidence data among U.S. whites for OS, ES and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results (SEER) program, which covers about 10% of the U.S. population, 1976-2005. The purpose was to examine the temporal development of each bone cancer subtype, with an aim to providing etiologic clues as to the role of birth cohort-related changes. RESULTS: Incidence of OS decreased between 1976 and 2005 among those 60 years and older, and rates declined among cohorts born 1905-34. The risk of CS doubled among females 20-69 years, with rates increasing among consecutive birth cohorts born 1925-54, whereas those of males were unaltered. For both sexes, ES incidence rates tended to be stable. CONCLUSIONS: The risk reduction in OS at older ages was most likely due to improved radiotherapy and more effective chemotherapy. The CS risk increase in females corresponds to birth cohorts who were increasingly exposed to estrogens, both in terms of contraceptives (from 1960 onwards), and hormone replacement therapy (from 1950 onwards). In support of our hypothesis that estrogens are involved in the increase in CS among women over time, in vitro studies show that the estrogen signaling pathway stimulates proliferation of both normal and malignant chondrocytes. Further studies are warranted to pursue the possible etiological significance of estrogen exposure in CS risk. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1822.


95% N-15 enriched ribotetranucleotide GGCUp was prepared. Its aqueous solution gives three imino-proton resonances at 10.6, 12.0 and 13.6 ppm. The peak at 10.6 ppm split by N-15 into a doublet with coupling constant 90 Hz. On the preirradiation at this peak, the intensity of the 12.0 ppm peak decreased and the peak at 13.6 ppm remained unchanged. Therefore the 10.6 ppm peak was unambiguously assigned to the G imino proton and the 12.0 ppm peak to the U imino proton in the G:U base pair. By raising temperature the former two peaks coalesced at around 25 degrees C, while the signal of the G imino proton in the G:C pair was observed up to 35 degrees C. The G:U base pair seems to be disrupted first, then the break of the G:C pair is followed. Temperature dependences of the CH proton, N-15 and P-31 nuclei resonances were also measured.


The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.


Researchers are calling on practitioners to use more robust mixed-method approaches in program and product evaluations in the global development sector. Using qualitative and quantitative research methods from both experimental engineering and applied anthropology fields can provide more holistic and accurate information regarding potential impact and application of a product or program in its actual usage context.
 This paper presents a mixed-method approach for the evaluation of a new water treatment technology, the InStove Water Purifier. A combination of technical and ethnographic methods are used to estimate the product's efficacy in a high-school dormitory in Mbale, a city in Eastern Uganda. Methods include participant observation, focal follow, time allocation and data collection of system parameters including fuel usage, flowrate, and temperature. Additionally, a holistic approach to water treatment implementation is applied by experimentally evaluating water storage treatment methods to prevent recontamination of water before its point-of-use.
 This study highlights the importance of method triangulation and, more specifically, the value of ethnographic methods to evaluate engineering solutions. While two methods concluded statistically insignificant results (time allocation and fuel usage) due to limited sample size and duration of the study, this work emphasizes the value that comes from working closely with end-users in an uncontrolled experimental environment.
 Informal interviewing during participant observation combined with time allocation and fuel usage data show a high potential for user acceptance due to the Purifier's time and fuel savings (42% and 67% savings; respectively), increased water capacity, and reduction of emissions. Potential barriers to user adoption of the Purifier, identified in this study, include the trust required by users, lack of water outlet temperature control, and a size change of fuel wood. These findings have been reported to InStove, the manufacturer of the product, to begin design modifications to improve its potential impact to users.
 Ultimately, this paper aims to encourage engineering practitioners to become more comfortable performing ethnographic methods and integrating qualitative data to more accurately evaluate their projects in the field and provide design changes that increase user adoption and sustained impact.


Truck transportation has become very important to the North Dakota grain industry. Identification of the costs and characteristics of exempt motor carriers allowed evaluation of the performance of the industry. Average mileage per vehicle was about 88,000 per year. Firms larger than four trucks achieved higher annual mileage as well as larger percent of return trip that was loaded (59 percent compared to 25 percent for the smaller firms). Seventy-eight of the firms had been in business five years or more. Costs per operating mile appeared to be about 92 cents for the industry. Larger firms had a four cent per mile advantage over smaller firms. Three conclusions were: The industry has become more mature and stable in the past five years after experiencing a significant influx in 1966-76 period. Larger firms have increased in importance and have a competitive advantage over small firms. Variable costs per mile are an important part of total costs.


The interaction of organometallic compounds with biological systems, generally called bioorganometallic chemistry, is receiving increasing interest. We present the first part of our studies concerning the biological activity of organometallic compounds. Several alkyne‐cobalt carbonyl complexes inhibited the growth of human melanoma and lung carcinoma cell lines. They are more active than uncomplexed dicobalt octacarbonyl, cobalt chloride, or the free ligand. A significant difference in potency towards the lung carcinoma cell line was observed among the cobalt complexes, indicating that the complexed ligand may influence cytotoxic activity. These results suggest that further exploratory work with such cobalt‐alkyne complexes is warranted.


Nanoindentation has become a popular tool for the exploration of mechanical properties of materials at the nanoscale. However, calibration and traceability issues are often neglected, making the direct comparison of results between different instruments difficult. The direct calibration of the sensors is challenging and requires dedicated instruments leaving indirect calibration as the only option to ordinary users. However, indirect calibration compares only the resulting hardness or modulus of the reference sample and the measured sample. Therefore, it cannot distinguish the source of errors, such as errors in the depth and load sensors, errors in the reference sample properties, contamination of the tip or sample, wear of tip and others. In this contribution we explore the possibility of using measurements of indents by atomic force microscopy for the verification of the depth sensor. Measurements for different nanoindentation devices are presented and compared with a focus on the uncertainties of the method.


This guide will provide students with access to resources in forensic psychology. This includes information on courts, law enforcement, criminal justice, national security, prisons, social services agencies, child welfare agencies, and treatment facilitie


PURPOSE
To investigate the feasibility of obtaining expert consensus on the prosthodontic principles to be followed when constructing complete dentures, so that any modifications to materials and methods would not sacrifice those principles--a philosophy known as "appropriatech." These principles would then comprise a Minimum Acceptable Protocol (MAP) for complete dentures.

MATERIALS AND METHODS
A Delphi survey technique was used that requested yes/no answers to a variety of statements describing the different stages in the construction of complete dentures. Respondents could also provide comments on any aspect of the questionnaire. The statements were then modified in light of the responses and comments received, and recirculated. Three rounds of questionnaires were used, and only statements achieving a 90% or greater consensus were included in the MAP. The respondents were randomly selected by country from the 2004 membership e-mail list of the International College of Prosthodontists.

RESULTS
Forty-one respondents answered the first questionnaire, 39 the second, and 36 the third. The 75 statements in the first questionnaire were gradually reduced as consensus was reached, and eventually 18 statements remained with 90% or greater agreement.

CONCLUSION
Even though expert opinion is regarded as the lowest level of evidence, there are no other methods available to derive such a protocol, and the Delphi technique was useful in obtaining the consensus. This MAP could now be used to help assess clinical techniques that attempt to reduce time and costs while producing a quality service-in other words, which will conform to the philosophy of appropriatech.


One of the reasons for promoting sustainable consumption is that it may give rise to greater happiness for a greater number, at least in the long run. In this paper I explore the strength of that moral account. I take stock of the assumed effects of sustainable consumption on happiness and then review the empirical evidence for such effects on the present generation. I make also educated guesses about the consequences for the happiness of generations to come. The evidence suggests that a shift to sustainable consumption involve a minor reduction in happiness, at least temporarily, but that we can live quite happily with less luxury. Sustainable consumption by the present generation will only add to the happiness of future generations if it prevents major ecological disasters or if exhaustion of resources will reduce future generations to poverty. Moral justification of sustainable consumption can better appeal to the inherent value of the things it aims to sustain than to human happiness.


Polyarteritis Nodosa (PAN) is a multisystem, necrotizing vasculitis of small and medium-sized muscular arteries. Sometimes PAN is detected at cholecystectomy or appendectomy in the absence of other disease manifestations. In such cases, surgical removal of the involved organ may be curative. Here we presented a case of poly arteritis nodosa, the process of diagnosis and explained the pathophysiology of the disorder and currently available treatments DOI: http://dx.doi.org/10.3329/pulse.v5i1.20188 Pulse Vol.5 January 2011 p.35-38


The presence of multinucleate giant cells in the sublabial salivary gland tissue in Sj6gren's syndrome is an unusual phenomenon which can give rise to differential diagnostic problems. We found in 4 cases of 55 patients with Sj6gren's syndrome multinucleate giant cells. In 2 of these 4 patients epimyoepithelial islands were also present. The combination of both multinucleate giant cells as epimyoepithelial islands can mimic the histological picture of a non-caseating granulomatous disease. To discriminate between an epimyoepithelial island and an epithelioid granuloma the immunoperoxidase technique with antibodies directed against muramidase appeared an useful tool. The epithelioid cells contain muramidase whereas the cells in the epimyoepithelial island do not contain this enzyme. Thus, multinucleate giant cells are a rare phenomenon in Sj6gren's syndrome, therefore restricting its diagnostic significance. When they occur in Sj6gren's syndrome staining for muramidase can be of help to avoid a false positive diagnosis of diseases in which non-caseating granulomatous inflammation occur, such as in sarcoidosis.


A classic filter problem is the construction of minimumphase transfer functions which simultaneously possess linear phase in the passband and steep amplitude selectivity. This paper presents a detailed quantitative treatment of this problem for lossless transducers, and it is shown that the bandwidth for linear phase is strictly constrained independent of the complexity of the transducer once the amplitude selectivity is prescribed. Prototype, but nonrational, physically realizable transfer functions are constructed which satisfy the bandwidth constraints, and polynomials which approximate the prototypes are then calculated to yield physical LC linear phase ladder networks. The resultant structures, though minimum phase, can have respectable selectivity and phase properties. For example, an 8-element ladder is synthesized which realizes flat delay to ± 2.5 percent over 80 percent of the passband, with 60 dB of loss at twice cutoff, and 3-dB passband tolerance. Finally, the paper shows how to further improve amplitude selectivity at the price of small amounts of nonlinear phase distortion, and quantitative measures of this improvement are presented.


Architectural innovation has telescoped the HPC community from the commodity (Beowulf) cluster in a machine room, i.e., a multi-node system with Ethernet interconnect, to a commodity cluster on a chip, i.e., multicore CPU with an on-die interconnect. We project that this notion of "telescoping architecture" will apply more broadly to heterogeneous computing, namely from heterogeneous clusters like Tianhe-2 in a machine room to on a chip. To that end, we present an experimental studythat extends the notion of telescoping architectures to identify the ideal mixture of compute engines (CEs) and the number of such CEs on a chip to create a heterogeneous "cluster on a chip" (CoC). Specifically, we experiment with heterogeneous architectures that contain single or multiple instances of CPUs, GPUs, Intel MICs, and FPGAs to demonstrate their performance efficacy given continuing advances in hardware technology, software, tools, and run-time support.


Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.


Liposomes represent suitable tools for the diagnosis and treatment of a variety of diseases, including cancers. To study the role of the human epidermal growth factor receptor 2 (HER2) as target in cancer imaging and image-guided deliveries, liposomes were encapsulated with an intrinsically quenched concentration of a near-infrared fluorescent dye in their aqueous interior. This resulted in quenched liposomes (termed LipQ), that were fluorescent exclusively upon degradation, dye release, and activation. The liposomes carried an always-on green fluorescent phospholipid in the lipid layer to enable tracking of intact liposomes. Additionally, they were functionalized with single-chain antibody fragments directed to fibroblast activation protein (FAP), a marker of stromal fibroblasts of most epithelial cancers, and to HER2, whose overexpression in 20–30% of all breast cancers and many other cancer types is associated with a poor treatment outcome and relapse. We show that both monospecific (HER2-IL) and bispecific (Bi-FAP/HER2-IL) formulations are quenched and undergo HER2-dependent rapid uptake and cargo release in cultured target cells and tumor models in mice. Thereby, tumor fluorescence was retained in whole-body NIRF imaging for 32–48 h post-injection. Opposed to cell culture studies, Bi-FAP/HER2-IL-based live confocal microscopy of a high HER2-expressing tumor revealed nuclear delivery of the encapsulated dye. Thus, the liposomes have potentials for image-guided nuclear delivery of therapeutics, and also for intraoperative delineation of tumors, metastasis, and tumor margins.


Two determinants of scale response—the denotative meaning of the adjective labels used and the location of the labels in relation to scale endpoints—were investigated. On the basis of the procedures used, both label and location were found to have an impact on subject response. Estimation of a mixing parameter for the two factors permits comparison of their relative effects across different scales.


We hypothesized that age-linked changes in the composition and elastic properties of the arterial wall occur earlier in hypertensive than in normotensive rats. We evaluated the consequences of hypertension and aging on aortic mechanics, geometry, and composition in 3-, 9-, and 15-month-old awake Wistar-Kyoto rats (WKY) (normotensive) and spontaneously hypertensive rats (SHR) (hypertensive). The elastic modulus of the thoracic aorta, calculated from aortic pulse wave velocity and geometry, was higher in young and adult SHR than in age-matched WKY, as was wall stress; however, isobaric pulse wave velocity and pulse wave velocity-pressure curves were similar. Elastic modulus, isobaric pulse wave velocity, and the slope of the pulse wave velocity-pressure curve dramatically increased in old SHR compared with age-matched WKY; there was no further elevation of blood pressure or wall thickness. Fibrosis did not develop with age in SHR, and the ratio of elastin to collagen decreased in a similar fashion with aging in both strains. In conclusion, although elastic properties of the aortic wall are not intrinsically modified in young and adult SHR in comparison to age-matched WKY, aging is associated with a dramatic stiffening of the aortic wall in old SHR but not in WKY. Changes in blood pressure, aortic wall geometry, or scleroprotein composition do not appear to explain this age-linked aortic stiffening in SHR, suggesting that other mechanisms of disorganization of the media may be involved.


A unified energy expression for Einstein-Gauss-Bonnet gravity, valid about the model's two distinct vacua, is obtained. It reduces to the usual Einstein form about a flat background, but about an anti-de Sitter vacuum it becomes that appropriate to a ghost Einstein theory with a cosmological term. Linearisation instability about the latter and general stability about the former are deduced by energy considerations, in agreement with previous results.


SigrafW is Windows‐compatible software developed using the Microsoft® Visual Basic Studio program that uses the simplified Hill equation for fitting kinetic data from allosteric and Michaelian enzymes. SigrafW uses a modified Fibonacci search to calculate maximal velocity (V), the Hill coefficient (n), and the enzyme‐substrate apparent dissociation constant (K). The estimation of V, K, and the sum of the squares of residuals is performed using a Wilkinson nonlinear regression at any Hill coefficient (n). In contrast to many currently available kinetic analysis programs, SigrafW shows several advantages for the determination of kinetic parameters of both hyperbolic and nonhyperbolic saturation curves. No initial estimates of the kinetic parameters are required, a measure of the goodness‐of‐the‐fit for each calculation performed is provided, the nonlinear regression used for calculations eliminates the statistical bias inherent in linear transformations, and the software can be used for enzyme kinetic simulations either for educational or research purposes.


In this issue of the Journal of Hospital Medicine, Lee et al.1 describe a randomized trial to assess the effectiveness of four different approaches to teaching handoffs with the goal of improving process measures related to interns' handoffs. The Society of Hospital Medicine (SHM), The Joint Commission (TJC), Accreditation Council for Graduate Medical Education (ACGME), and others have all emphasized the importance of high-quality handoffs as an essential component of safe patient care.2-4 The ACGME specifically requires that all institutions that sponsor ACGME-accredited programs provide both structure and monitoring, and the SHM complements this with evidence-based guidelines for handoffs. Lee's team trained 4 groups of residents in handoffs using 4 different hour-long sessions, each with a different focus and educational format. A control group received a 1-hour didactic, which they had already heard; an I-PASS–based training group included role plays; and Policy Mandate and PDSA (Plan, Do, Study, Act) groups included group discussions. The prioritization of content in the sessions varied considerably among the groups, and the results should be interpreted within the context of the variation in both delivery and content. Consistent with the focus of each intervention, the I-PASS–based training group had the greatest improvement in transfer of patient information, the policy mandate training group (focused on specific tasks) had the greatest improvement in task accountability, and the PDSA-training group (focused on intern-driven improvements) had the greatest improvement in personal responsibility. The control 60-minute didactic group did not show significant improvement in any domains. The lack of improvement in the control group doesn't imply that the content wasn't valuable, just that repetition didn't add anything to baseline. One takeaway from the primary results of this study is that residents are likely to practice and improve what they are taught, and therefore, faculty should teach them purposefully. If residents aren't taught handoff skills, they are unlikely to master them. The interventions used in this study are neither mutually exclusive nor duplicative. In the final conclusions, the authors described the potential for a curriculum that includes elements from all 3 interventions. One could certainly imagine a handoff training program that includes elements of the I-PASS handoff bundle including role plays, additional emphasis on personal responsibility for specific tasks, as well as a focus on PDSA cycles of improvement for handoff processes. This likely could be accomplished with efficiency and might add only an hour to the 1-hour trainings. Evidence from the I-PASS study5 suggests that improving handoffs can decrease medical errors by 21% and adverse events by 30%; this certainly seems worth the time. Checklist-based observation tools can provide valuable data to assess handoffs.6 Lee's study used a checklist based on TJC recommendations, and the 17 checklist elements overlapped somewhat with the SHM guidelines,2 providing some evidence for content validity. The dependent variable was total number of checklist items included in handoffs, a methodology that assumes that all handoff elements are equally important (eg, gender is weighted equally to if-then plans). This checklist also has a large proportion of items related to 2-way and closed-loop communication and therefore, places heavy weight on this component of handoffs. Adapting this checklist into an assessment tool would require additional validity evidence but could make it a very useful tool for completing handoff assessments and providing meaningful feedback. The ideal data collection instrument would also include outcome measures, in addition to process measures. Improvements in outcome measures such as medical errors and adverse events, are more difficult to document but also provide more valuable data about the impact of curricula. In designing new hybrid curricula, it will be extremely important to focus on those outcomes that reflect the greatest impact on patient safety. Finally, this study reminds us that the delivery modes of curricula are important factors in learning. The control group received an exclusively didactic presentation that they had heard before, while the other 3 groups had interactive components including role plays and group discussions. The improvements in different domains with different training formats provide evidence for the complementary nature. Interactive curricula involving role plays, simulations, and small-group discussions are more resource-intense than simple didactics, but they are also likely to be more impactful. Teaching and assessing the quality of handoffs is critical to the safe practice of medicine. New ACGME duty hour *Address for correspondence and reprint requests: Glenn Rosenbluth, MD, Department of Pediatrics, 550 16th Street, 5th floor, San Francisco, CA 94143-0110; Telephone: 415-476-9180; Fax: 415-476-4009; E-mail: glenn. firstname.lastname@example.com


Nowadays, even apps for corporate management are respectable. Manager app portals complement such "run-a-business" apps with apps that make managers' business life easier. The right mix of apps makes the difference. Accommodating the user perspective, the objective of this article is to examine which apps disproportionately influence managers' perception regarding the usefulness of information systems (IS). Applying the Kano model and considering both "analyst-" and "consumer-type" managers, we employ findings from a manager focus group survey to discuss the strongest differentiators: (1) Offer collaboration bars and push notifications for analyst managers. Get consumer managers "online" with news tickers. (2) Make core reports more interactive with drill downs and filters for manager self-service. (3) Take "fun and enjoyment" into account when accommodating managers' business life. (4) Consider that tablets create their own manager use case as a "first-stop information shop."


Genetic overlap involving rare disrupting mutations may contribute to high comorbidity rates between autism spectrum disorders and epilepsy. Despite their polygenic nature, genome-wide association studies have not reported a significant contribution of common genetic variation to comorbidity between both conditions. Analysis of common genetic variation affecting specific shared pathways such as miRNA dysregulation could help to elucidate the polygenic mechanisms underlying comorbidity between autism spectrum disorders and epilepsy. We evaluated here the role of common predisposing variation to autism spectrum disorders and epilepsy across target genes of 14 miRNAs selected through bibliographic research as being dysregulated in both disorders. We considered 4,581 target genes from various in silico sources. We described negative genetic correlation between autism spectrum disorders and epilepsy across variants located within target genes of the 14 miRNAs selected (p = 0.0228). Moreover, polygenic transmission disequilibrium test on an independent cohort of autism spectrum disorders trios (N = 233) revealed an under-transmission of autism spectrum disorders predisposing alleles within miRNAs' target genes across autism spectrum disorders trios without comorbid epilepsy, thus reinforcing the negative relationship at the common genetic variation between both traits. Our study provides evidence of a negative relationship between autism spectrum disorders and epilepsy at the common genetic variation level that becomes more evident when focusing on the miRNA regulatory networks, which contrasts with observed clinical comorbidity and results from rare variation studies. Our findings may help to conceptualize the genetic heterogeneity and the comorbidity with epilepsy in autism spectrum disorders.


Structure of RbdA, a Regulator of Biofilm Dispersal of Pseudomonas aeruginosa Understanding how proteins containing tandem GGDEF-EAL domains control c-diGMP concentration is crucial for deciphering the mechanism of c-di-GMP signaling. Liu et al. (e00515-17) determined the crystal structure of the PAS-GGDEF-EAL portion of RbdA, a bifunctional protein that regulates dispersal of Pseudomonas aeruginosa biofilms. Together with biochemical data, the crystal structure points towards a highly flexible protein that undergoes dramatic structural rearrangements to control the activity of its GGDEF and EAL domains for c-di-GMP synthesis and degradation. This work sets the stage for a better understanding of the highly dynamic regulatory mechanism that underpins the biological functions of GGDEF-EAL-containing proteins.


Although Nonlinear Time Series is the only part of the title to appear on the spine of this new book by Fan and Yao, the word "nonparametric" in the subtitle really deserves top billing. There are hints here and there that the authors follow the viewpoint emphasized by Tong (1990), that there is a true underlying nonlinear dynamic law generating the time series data. Nonparametric methods can help uncover this dynamic law. But the book also works from a purely pragmatic standpoint; nonparametric estimation methods are useful in constructing effective forecasting algorithms, whatever the true dynamic law. The standard time series modeling paradigm for building a forecast algorithm reduces an observed series to approximate stationarity through removal of trend and seasonal components, identifies the covariance structure and possible parametric models through the estimated autocovariance function of the resulting series, selects among competing estimated models through order-selection criteria (such as the Akaike information criterion) and residual diagnostics, and then computes optimal predictors for future values of the series. Autoregressive moving average (ARMA) models form a broad class of linear models that can approximate quite general autocovariance structures arbitrarily closely. Dependence outside the second-order moment structure, on the other hand, may require nonlinear models. Nonparametric methods have a long history in time series analysis and appear throughout the standard modeling paradigm, particularly in estimation of trend and seasonal components for nonstationary time series and in estimation of spectral density functions and marginal probability densities for stationary time series. The authors hope to extend the use of nonparametric tools for identifying and estimating nonlinear time series models. These models may have flexible nonparametric specifications, or the nonparametric analysis may suggest parametric nonlinear models. Nonparametric methods are also useful in constructing predictors for nonlinear processes. The authors provide considerable background material on both time series and nonparametrics. Introductory chapters on characteristics of time series (Chap. 2) and ARMA modeling and forecasting (Chap. 3) borrow heavily from texts by Brockwell and Davis (1991, 2002) and associated ITSM software. Subsequent chapters review important classes of parametric nonlinear time series models [threshold, generalized autoregressive conditional heteroscedastic (GARCH), and bilinear; Chap 4] and introduce nonparametric methods through density estimation (Chap. 5) and spectral density estimation (Chap. 7). The subjects of main interest—those that really set this book apart—are concentrated in later chapters: smoothing with dependent data (Chap. 6), nonparametric time series models (Chap. 8), model validation (Chap. 9), and nonlinear prediction (Chap. 10). The broad range of topics covered in this book makes for a large and awkward load. It is like coming home from the grocery store and trying to get all of the bags into the house in one trip; losing a few things on the way up the steps, crushing a few more while pushing through the door, and cracking one or two eggs when dropping the bags on the counter. Everything in the bags must be examined carefully for scratches, bruises, and breaks, and some items are lost altogether. This book has scratches scattered throughout, in the form of abundant errors and inconsistencies in the technical typesetting. There are quite a few bruises as well: incorrect figure references, typos in formulas, garbled phrases, and terms used before they are defined. Some breaks are noticeable, especially the proof of Theorem 7.4. The maximum periodogram ordinate for an iid non-Gaussian sequence, suitably normalized, does indeed converge in distribution to the standard Gumbel distribution. The authors' argument makes this result appear trivial, but the key approximation they use is incorrect. (See Davis and Mikosch 1999 for a valid proof, which relies on a Gaussian approximation technique for sums of independent random vectors.) Elsewhere, there are cracks in the exposition, with statements that are not quite right, like the claim on page 420 that point transformations of weakly stationary series are weakly stationary. After taking stock of the damage, we might ask whether anything is missing. One omission is suggested by the authors' comments on page 16 that "the validity of a parametric model for a large real data set over a long time span is always questionable," and that this, among other factors, has "led to a rapid development of computationally intensive methodologies. . . that are designed to identify complicated data structures by exploring local lower-dimensional structures." These comments seem to ignore the possibility of parametric hierarchical models, which often take the form of parameter-driven generalized state-space models in the time series context. Such models can capture a variety of nonstationary and nonlinear behaviors (e.g., Kitagawa 1987; Harvey 1989; Durbin and Koopman 2001). The hierarchical model specifies dynamics of observations given time-dependent "local parameters" (or states) and dynamics of local parameters given time-invariant "global parameters" (or hyperparameters). Such hierarchical models can often successfully describe real datasets over long time spans by allowing the local parameters to change smoothly over time, suggesting that this parametric methodology has some relationship with nonparametric methods. Indeed, certain smoothing splines can be computed using the Kalman recursions, because they are the optimal fixed-interval smoothers for an integrated random walk plus noise, a simple hierarchical time series (see, e.g., Durbin and Koopman 2001 and references therein). Some mention of this relationship, and perhaps some discussion of the authors' perspective on the use of nonparametric methods in the identification of hierarchical models, would have been nice to see. Despite these problems, this book has much that is interesting and useful. The discussions of ergodicity in Section 2.1.4 and of mixing conditions in Section 2.6 are handy. The presentation of ARCH and GARCH models in Section 4.2 is a concise introduction to this vast literature from a statistics standpoint, and Chapter 5 gives a nice overview of nonparametric density estimation, with particular emphasis on results and references for density estimation with dependent data. In fact, most chapters end with extensive bibliographical notes. These will certainly be valuable resources for researchers, particularly in the later chapters that describe evolving areas. These later chapters, notably Chapters 6 and 8–10, constitute the book's main contribution—topics not found in typical time series or nonparametrics texts. Chapter 6 covers smoothing with dependent data, in both the time domain (a standard topic in traditional time series analysis) and the state domain (not so standard). Chapter 8, on nonparametric time series models, includes functional coefficient autoregressions, additive autoregressions, and index models, among others. Model validation, in Chapter 9, focuses on generalized likelihood ratios for testing against nonparametric alternatives (for which the nonparametric maximum likelihood estimator may not exist or may be too constrained to be of use). Chapter 10 covers nonlinear prediction, including point predictors, minimum-length prediction intervals, and predictive distributions. Many of the interesting ideas presented in these chapters are highlighted through examples worked out in detail. These include both classic datasets (Canadian lynx and Wolf's sunspots, naturally), and new examples. Chapter 8 provides some informative examples of financial applications (a technical trading rule applied to pound/dollar exchange rates, and a value-at-risk analysis for the Standard and Poor's 500 index). The material presented in these chapters includes techniques that anyone with a solid background in time series analysis could appreciate and could implement immediately with standard software. Even so, as the authors point out, there are plenty of open questions about these techniques. This makes the material in these chapters appealing to practitioners and researchers alike, although the practitioner would need to pick through lots of technical detail to extract the useful applied bits. Nonlinear Time Series: Nonparametric and Parametric Methods is best suited as a stimulating research monograph. It is not a textbook (in particular, it has no exercises), but it has sufficient breadth that it could serve as the focus of a graduate reading course or as a source of supplemental teaching materials for an advanced time series class.


Asynchronous motors represent a large percentage of motors used in the electrical industry. Suitable predictive maintenance techniques are strongly required when these motors are critical in their operations. Continuous non-invasive monitoring techniques can be investigated to avoid the disconnection of the motors under test and service interruption. This paper proposes an innovative predictive monitoring system based on the online sweep frequency response analysis (SFRA) technique. The testing system applies variable frequency sinusoidal signals to the motors and then acquires and processes the applied and response signals in the frequency domain. In the literature, SFRA has been applied to power transformers and electric motors switched off and disconnected from the main grid. The approach described in this work is innovative. Coupling circuits allow for the injection and acquisition of the signals, while grids feed the motors. A comparison between the transfer functions (TFs) of healthy motors and those with slight damage was performed with a batch of 1.5 kW, four-pole induction motors to investigate the technique's performance. The results show that the online SFRA could be of interest for monitoring induction motors' health conditions, especially for mission-critical and safety-critical applications. The overall cost of the whole testing system, including the coupling filters and cables, is less than EUR 400.


An independent set in a graph G is a set of vertices no two of which are joined by an edge. A vertex-weighted graph associates a weight with every vertex in the graph. A vertex-weighted graph G is called a unique independence vertex-weighted graph if it has a unique independent set with maximum sum of weights. Although, in this paper we observe that the problem of recognizing unique independence vertex-weighted graphs is NP-hard in general and therefore no efficient characterization can be expected in general; we give, however, some combinatorial characterizations of unique independence vertex-weighted graphs. This paper introduces a motivating application of this problem in the area of combinatorial auctions, as well.


The purpose of this research was to determine the effect of the application of an Integrating Instructional Strategy for Reading Comprehension (EIICL), implemented in a virtual context and designed to develop comprehension text skills on social sciences and administration of second semester students of Public Accounting and Administration Bachelor's Degree, in a Higher Education Institution. The research was conducted with a correlational design, applied to an experimental group and a control group, with before and after measurements of applying the EIICL. The results confirm that, there are significative differences between the students that made the text reading in a virtual environment with the application of EIICL, from the students that made the reading without the application of such strategy.


Systems of systems that collaborate for a common purpose are called cooperating systems. Typical examples of novel cooperating systems are electronic health systems and electronic money transfer systems but also critical infrastructures, such as future vehicular ad hoc networks and distributed air traffic management systems. Business processes and technical workflows control the cooperation of the networked systems. Important safety and security goals of the applications, business goals, and external compliance requirements create security obligations for such processes. These processes must not only be secure, they must be demonstrably so. To support this, we present an approach for security compliance tracking of processes in networked cooperating systems using an advanced method of predictive security analysis at runtime. At that, operational models are utilized for: (a) tracking conformance of process behavior with respect to the specification, (b) detection of behavior anomalies which indicate possible attacks, (c) tracking compliance of process behavior with respect to safety and security requirements, and (d) prediction of possible violations of safety and security policies in the near future. We provide an extensive background analysis, introduce the model-based conformance tracking and uncertainty management algorithm, and describe security compliance tracking and model-based behavior prediction. We demonstrate the implementation of the proposed approach on a critical infrastructure scenario from a European research project.


A therapeutic group for clients with acute mental health problems is described using a case study research design. The setting of the group is a British community mental health centre. Theoretical and research approaches to brief therapeutic work with clients are discussed. Results include qualitative descriptions of the group from the perspective of various respondents and quantitative descriptions of client attendance. The group was evaluated positively by respondents and high attendance rates indicated that the group met clients' needs. The group was primarily utilized by professionals as an addition to present services rather than as an alternative to in-patient hospitalization. However, in practice many of the clients needed some degree of professional support after ceasing to attend the group. In this study, the establishment of a therapeutic group for clients with acute mental health problems improved inter-professional relations. The ability to facilitate therapeutic groups is an important competence for mental health nurses.


Study design: This was a cross-sectional, population-based and descriptive study. Study objective: To describe the clinical and epidemiological profile of hypertensive patients at the primary health care of Alagoas state. Methods: This study was carried out in the Basic Health Units of 12 cities of Alagoas, between 2014 and 2015, with hypertensive individuals between 20 and 60 years, of both gender. Socioeconomic, demographic, clinical, lifestyle, anthropometric and biochemical data were collected. Data were analyzed using descriptive statistics by Epi-Info version 7. Results: We evaluated 645 individuals. Of these, 86.2% were women, 62.3% had uncontrolled blood pressure, 41.9% had low educational level, 11.1% were smokers, 26.3% were alcohol users, 64.7% were sedentary, 48.4% were obese, 73.6% had high cardiovascular risk, according to waist circumference; 54.4% and 47.2% had elevated total cholesterol and triglycerides, respectively. Conclusion: Since hypertension is an important public health problem that has serious consequences, the knowledge of the hypertensive population profile of Alagoas will facilitate the treatment for the health of patients with this condition.


In the long run, your data matters more than your code. It's worth investing some effort to keep your data in good shape for years to come. Data is at the heart of science. A scientist is expected to be able to back up all published conclusions with data. Data management should thus be a priority in science. Scientists can't afford to lose data, be uncertain of what it means, or not know where it came from. In the experimental sciences, there's a long tradition of writing down all experimental setups, parameters, and results meticulously in a lab notebook. Unfortunately, computational science is much less rigorous about data handling, although there are clear signs of improvement. Here, we'll consider what you can do to better prepare and manage your data.


Abstract The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. The present research was aimed to evaluate expression of various molecules associated with adipocyte differentiation and maturation in the epididymal fat of ERαKO mouse at several postnatal ages by using quantitative real-time polymerase chain reaction. The highest transcript levels of all molecules were detected at 12 months of postnatal age, except leptin which the mRNA level was increased at 5 months of age and was unchanged until 12 months of age. The expression levels of CCAAT enhancer binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were decreased at 5 months of age but increased at about 8 months of age. The mRNA levels of Cebp gamma and sterol regulatory element binding transcription factor 1 remained steady until 8 months of age. Continuous increases of transcript levels during postnatal period were found in Cebp beta, estrogen receptor (ER) beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1. The increases of peroxisome proliferator-activated receptor gamma and adiponectin mRNA levels were detected as early as 8 months of age. The levels of fatty acid synthase and resistin transcript at 5 and 8 months of age were lower than that at 2 months of age. These findings show the aberrant expression patterns of genes related to adipocyte differentiation and maturation in the postnatal epididymal fat pad by the disruption of ER alpha function.


Switzerland is one of the few countries with long-term experience on the payout decisions made by retirees in fully-funded pension plans. Switzerland is also atypical in its unusually high annuitization rates: A majority of retirees covered by mandatory occupational pension plans choose an annuity. This paper will shed light on this extraordinary aspect. It revisits the historical role of occupational pension plans in the provision of old age income, and examines the role of regulation in the payout phase of the scheme. Recent developments in both market conditions and regulations are used to assess the impact of certain determinants of the annuitization decision, such as money's worth ratios (MWR), means-tested benefits and behavioral factors.


In the present study, we have evaluated the anti-cellular and immunomodulatory potential of aqueous extract of Rhodiola imbricata rhizome (RAE). Rhodiola extract inhibited the proliferation of human T cell lymphoma cell line EL-4 and erythroleukemic cell line HL-60. Furthermore, treatment of human peripheral blood mononuclear cells (hPBMCs) with lipopolysaccharide (LPS) and RAE suppressed regulated upon activation, normal T cell expressed and secreted (RANTES) production. However, number of TNF-α spots was increased in RAE treated hPBMCs. The reverse transcriptase polymerase chain reaction (RT-PCR) analysis of RAE treated rat splenocytes confirmed the up regulation of TLR-4 mRNA expression. Therefore, the present study concludes that RAE has potent immune boosting activity which might be useful in immunocompromised individuals.


A challenging issue for HCI is the development of usable mobile interfaces for interactions with a complex pervasive environment. We consider a need for interfaces which automatically adapt their interaction and presentation capabilities on the user's situational needs and expectations to decrease the complexity of the environment and increase the usability of the system. Therefore, a rule-set is required which gives knowledge on the mobile interface's adaptations as a consequence on a user's situations within the environment. This rule-set iteratively emerges within a user-centred development process by considering and testing each contextual situation of the user when interacting with the mobile interface. In this paper we describe an approach of a usage model for specifying each context of the user and the environment as well as the user's goals and mental model. Moreover, we describe our used user-centred process to develop the usage model and rule-set, practical experience in development of mobile interfaces, some guidelines and our planned future work.


Background. Although several epidemiological studies have found increases in the percentages of people who have made a suicide attempt, few cohort comparisons have been conducted to determine changes within this population over time. The purpose of this investigation was to determine if there have been changes in the clinical profile of suicide attempters in recent decades. Method. Comparisons between a sample of 258 suicide attempters evaluated between 1970 and 1973 and a second sample of 179 suicide attempters evaluated between 1999 and 2002 were made on depression, hopelessness, suicide intent, drug use, history of suicide attempts and subsequent suicide attempts. Results. Present-day suicide attempters were found to exhibit greater levels of depression (p=0·031), hopelessness (p=0·008), suicide intent (p<0·001), and had much higher rates of illicit drug use (p<0·001). Almost twice as many of the present-day suicide attempters had histories of four or more suicide attempts (p<0·001), and the present-day suicide attempters made subsequent suicide attempts at close to four times the rate in the year following the index attempt (p<0·001). Conclusions. The present-day suicide attempters exhibited greater levels of psychopathology on every major variable assessed. Replication is necessary and public health implications are discussed.


Purpose. The isolation of hepatocytes from intact liver involves collagenase digestion of the tissue, resulting in loss of cell polarization and functional vectorial excretion. These studies examined repolarization, localization of P-glycoprotein (P-gp) to the canalicular domain of the hepatocyte, and re-establishment of vectorial transport in sandwich-cultured (SC) rat and human primary hepatocytes. Methods. Protein localization and expression were determined in SC hepatocytes by confocal microscopy and Western blotting, respectively. T ransporter f unction w as e valuated b y m easuring [D-penicillamine 2,5 ]enkephalin ( 3 H-DPDPE) and 5 (and 6)-carboxy2,7-dichlorofluorescein (CDF) biliary excretion in SC hepatocytes. Results. P-gp and the canalicular marker protein dipeptidyl peptidase IV (DPPIV) co-localized by Day 3 and Day 6 in SC rat hepatocytes and SC human hepatocytes, respectively, consistent with canalicular network formation visualized by light microscopy. Co-localization of multidrug resistance associated protein 2 (MRP2) and P-gp in SC human hepatocytes was observed on Day 6 in culture. Expression levels of P-gp increased slightly in both species over days in culture; similar expression was observed for MRP2 in SC human hepatocytes. Oatp1a1 expression in SC rat hepatocytes was maintained over days in culture, whereas Oatp1a4 expression decreased. OATP1B1 expression decreased slightly on Day 3 in SC human hepatocytes. OATP1B3 expression was constant in SC human hepatocytes. In vitro biliary excretion of the opioid peptide 3 H-DPDPE correlated with the proper localization of canalicular proteins in both species. Excretion of CDF in SC human hepatocytes confirmed network formation and MRP2 function. Conclusions. These studies indicate that SC hepatocytes repolarize and traffic functional canalicular transport proteins to the appropriate cellular domain.


In this paper the researchers developed a training programme for state prosecutors working with sexually abused children during court procedures. The study commenced with a literature study focusing on: (a) the person-centred approach as a scientific foundation for the study, (b) the long-term effects of sexual abuse, and c) the revictimization of sexually abused children during forensic procedures. The empirical study was a combined qualitative-quantitative study. The researchers started with the qualitative study, where prosecutors dealing with sexual abuse cases were interviewed to determine their training needs in this field of service delivery. After training needs were determined, a training programme was compiled. This training programme formed part of the quantitative study and was implemented during a training session for prosecutors at the Justice College in Pretoria. The programme was evaluated using pre- and post-test questionnaires


Purpose Most patients, even some urologists, assume that prostate volume is the most important prognostic factor for lower urinary tract symptoms (LUTS). In some cases, however, prostatic inflammation is a more important factor in LUTS than is prostate volume. For this reason, comparison of the impact on LUTS of inflammation and prostate volume is an attractive issue. Materials and Methods From January 2000 to May 2009, 1,065 men aged between 47 and 91 years (who underwent transrectal ultrasound-guided prostate needle biopsy and transurethral prostatectomy) were retrospectively investigated. Components such as age, serum prostate-specific antigen (PSA) level, prostate volume, and the presence of prostatitis were investigated through independent-sample t-tests, chi-square tests, and univariate and multivariate analyses. Results Chi-square tests between prostatitis, prostate volume, serum PSA, and severe LUTS showed that prostate volume (R=0.173; p=0.041) and prostatitis (R=0.148; p<0.001) were related to LUTS. In particular, for a prostate volume under 50 ml, prostatitis was a stronger risk factor than was prostate volume. Among the multivariate predictors, prostatitis (odds ratio [OR]: 1.945; p<0.001) and prostate volume (OR, 1.029; p<0.001) were found to be aggravating factors of LUTS. Conclusions For patients with prostate volume less than 50 ml, prostatitis was found to be a more vulnerable factor for LUTS. For those with prostate volume over 50 ml, on the other hand, the volume itself was a more significant risk factor than was prostatitis. In conclusion, the presence of prostatitis is one of the risk factors for LUTS with increased prostate volume.


Abstract: Aim: Bisphosphonates are potent inhibitors of osteoclastic activity and are used in the treatment of multiple myeloma (MM) in combination with chemotherapy. The effect of pamidronate on markers of bone resorption [cross‐linked N‐telopeptides of type I collagen (NTx)], markers of bone formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)], interleukin‐6 (IL‐6), β2‐microglobulin, CRP, paraprotein and disease‐related pain and skeletal events has been evaluated in 62 newly diagnosed patients with MM. Patients and methods: The patients were randomly assigned to two groups: the first included 32 patients under chemotherapy and pamidronate (group I) and the second 30 patients on chemotherapy only (group II). Pamidronate was administered at a monthly dose of 90 mg iv, and the above parameters were evaluated at the beginning of this study and after 1, 3, 6, 9, 12 and 14 months of treatment. Results: The addition of pamidronate to chemotherapy resulted in a significant reduction of NTx, IL‐6 and paraprotein from the 3rd month and of β2‐microglobulin, CRP and pain from the 6th month of treatment. No changes of NTx, IL‐6, β2‐microglobulin, CRP or skeletal events were observed in patients of group II, while paraprotein was significantly reduced after 6 months of treatment. The differences in NTx, IL‐6, paraprotein and β2‐microglobulin were statistically significant between the two groups. Multivariate analysis revealed a significant correlation between changes of NTx, changes of IL‐6 in both groups and reduction of pain and paraprotein in group I. Conclusions: These results suggest that pamidronate may have a synergistic action with chemotherapy in decreasing osteoclastic activity, in reducing markers of myeloma activity and myeloma related pain and in improving the quality of life in patients with MM.


We derived one-fluid equations based on a relativistic two-fluid approximation of e± pair plasma and electron–ion plasma to reveal the specific relativistic nature of their behavior. Assuming simple condition on the relativistic one-fluid equations, we propose generalized relativistic magnetohydrodynamic (RMHD) equations which satisfy causality. We show the linear analyses of these equations regarding various plasma waves to show the validity of the generalized RMHD equations derived here and to reveal the distinct properties of the pair plasma and electron–ion plasma. The distinct properties relate to (1) the inertia effect of electric charge, (2) the momentum of electric current, (3) the relativistic Hall effect, (4) the thermal electromotive force, and (5) the thermalized energy exchange between the two fluids. Using the generalized RMHD equations, we also clarify the condition that we can use standard RMHD equations and that we need the distinct RMHD equations of pair and electron–ion plasmas. The standard RMHD is available only when the relative velocity of the two fluids is nonrelativistic, a difference of the enthalpy densities of the two fluids is much smaller than the total enthalpy density, and the above distinct properties of the pair/electron–ion plasma are negligible. We discuss a general relativistic version of the equations applicable to the pair and electron–ion plasmas in black hole magnetospheres. We find the effective resistivity due to the shear of frame dragging around a rotating black hole.


Background

Health literacy, as a social determinant of health, has a decisive role in providing different populations with healthcare services in an equal manner. Our aim in this study was to investigate the contribution of socio-demographic factors to functional health literacy (FHL) in a population of Iranian adults and identify differences in the contribution of these factors across genders.
Methods

This community-based cross-sectional study was conducted in 2015 to 2016 in Sanandaj, Iran. Multistage cluster sampling was employed to recruit 1000 people older than 18 (response rate = 89.2%) from 35 urban and 10 rural health care centers. Test of functional health literacy in adults (TOFHLA) was used to assess FHL. In order to measure inequality in FHL, concentration index decomposition was used.
Results

In total, 869 respondents (response rate: 86.9%) with a mean age (standard deviation; SD) of 33.68 (13.0) completed TOFHLA questionnaire. More than half of participants were women (57.5%). Participants demonstrated an average TOFHLA score of 51.9. Women demonstrated slightly higher TOFHLA scores (52.2 [SD: 0.46]) compared to men (50.7 [SD: 0.4]). However, the concentration index for gender was 10.9% suggesting gender contributed only moderately to TOFHLA scores. Comparatively, 54.3% of TOFHLA differences were attributed to geographic location. Among women, place of residence, monthly income, age, education level and being head of household contributed to 43%, 32%, 13%, 11.5% and 11% of FHL inequality, respectively. Among men, however, place of residence (45.2%), size of household (15.1%) and monthly income (13.5%) contributed most to inequality in FHL.
Conclusions

Although gender was not the strongest contributing factor for FHL inequalities, poor FHL was mostly concentrated among men. Different factors were attributed to FHL inequality by gender, as discussed inside. Understanding these differences may assist in identifying and targeting interventions towards men and women with low levels of FHL. Our findings shed light the critical role of social determinants of health (SDH) in promoting the health literacy of populations, particularly in developing countries like Iran.


ABSTRACT The search to identify Mycobacterium tuberculosis antigens capable of conferring protective immunity against tuberculosis has received a boost owing to the resurgence of tuberculosis over the past two decades. It has long been recognized that lymphoid cells are required for protection against M. tuberculosis. While traditionally the CD4+ populations of T cells were believed to predominantly serve this protective function, a pivotal role for CD8+ T cells in this task has been increasingly appreciated. We show that the 50- to 55-kDa Apa protein, specified by the Rv1860 gene of M. tuberculosis, can elicit both lymphoproliferative response and gamma interferon (IFN-γ) production from peripheral blood mononuclear cells (PBMC) of purified protein derivative (PPD)-positive individuals, with significant differences recorded in the levels of responsiveness between PPD-positive healthy controls and pulmonary tuberculosis patients. Flow cytometric analysis of whole blood stimulated with the recombinant Apa protein revealed a sizeable proportion of CD8+ T cells in addition to CD4+ T cells contributing to IFN-γ secretion. PBMC responding to the Apa protein produced no interleukin-4, revealing a Th1 phenotype. A DNA vaccine and a poxvirus recombinant expressing the Apa protein were constructed and tested for their ability to protect immunized guinea pigs against a challenge dose of virulent M. tuberculosis. Although the DNA vaccine afforded little protection, the poxvirus recombinant boost after DNA vaccine priming conferred a significant level of protective immunity, bringing about a considerable reduction in mycobacterial counts from the challenge bacilli in spleens of immunized guinea pigs, a result comparable to that achieved by BCG vaccination.


Quantifying sources and sinks of climatological relevant trace gases as well as understanding their exchange between atmosphere and land surface have become essential research topics in atmospheric sciences during the last years. Modeling of the net CO2 uptake by vegetation via photosynthesis (Net Primary Productivity, NPP, and Net Ecosystem Productivity, NEP) has become an important tool to study the mechanisms of CO2 exchange and to quantify the magnitude of terrestrial sinks and sources. For Europe not many studies exist regarding NPP and NEP of the whole continent. Veroustraete et al. [1] used the C-Fix model, a Monteith type parametric model driven by temperature, radiation and fraction of Absorbed Photosynthetically Active Radiation (fAPAR). These type of models are based on the idea to estimate plant productivity by using the light use efficiency and the amount of absorbed photosynthetically active radiation. In order to make a comparison with the results of Veroustraete et al. simulations with a more complex model are presented for improving the fundamental knowledge of geographical distribution of European carbon sinks and sources.


Skeletal mineralization is initiated in utero and continues throughout childhood and adolescence. During these key periods of the life cycle, calcium retention must increase significantly to provide sufficient mineral for bone deposition and skeletal growth. Stable calcium isotopes have served as a fundamental tool to non‐invasively characterize the dynamic changes in calcium physiology that occur from infancy through adolescence. These approaches have helped define the dynamics of calcium absorption and utilization in healthy children and in children with chronic diseases. As data in this area have accumulated, new areas of emphasis are beginning to characterize the determinants of variability in mineral retention, the genetic determinants of bone turnover and calcium flux and the impact of the gut microbiome on whole body and niche specific calcium dynamics. Advances in these areas will help define calcium utilization in paediatric populations and provide information that may be useful in maximizing bone acquisition across this critical phase of the life cycle.


Web search results clustering is the navigator for users to find relevant results quickly. Through combining the advantages of vector space model (VSM) and suffix tree clustering (STC) document models, this paper puts forward a more effective Web snippets clustering algorithm. It can take into account the semantic information of candidate label phrases, and offer descriptive, readable and conceptual topic labels for the final documents groups. Evaluation of results demonstrates that clustering Web snippets based on the improved suffix tree algorithm has better performance in making search engine results easy to browse and helping users quickly find Web pages that they are interested in.


Production system design (PSD) is a key process at the beginning of any manufacturing effort. It can be regarded as an initial planning task that involve a set of decisions that play an important role in the implementation of core Lean concepts, such as pull production, batch size, takt time. Despite its importance, very little attention is usually given to PSD in construction projects, and its relationship with the implementation of the Last Planner System (LPS). This article reports the experience of a construction company that has implemented PSD and the LPS, as part of the development of an improvement program in production management based on the Lean Philosophy. This company is based in Chile, and its core business is the development and construction of residential building projects. The implementation of PSD, and the LPS were the means for the adoption of a number of Lean principles and concepts, including pull production, takt time, work-in-progress control, reduction of batch size, and process transparency. Six main benefits of implementing PSD have been identified: (i) formalizing and making explicit planning decisions; (ii) reduction in uncertainty; (iii) improving planning accuracy; (iv) facilitating the adoption of cycle times and takt time control; (v) increasing the engagements of stakeholders; (vi) improving production stability. A set of practices were proposed for implementing PSD and these were classified according to decision categories.


ABSTRACT This study explored to what extent personal and environmental factors, as defined by the ecological model of aging, help us to understand length of stay in assisted living (AL). A convenience sample (N = 218) of administrative records of AL residents admitted between the years 2006 and 2011 was collected and included AL residents' demographic and healthcare information as well as dates of admission and discharge. Cox regression was used to determine which personal and environmental factors influenced length of stay in three AL programs. Number of medical diagnoses, level of care score, and facility were found to be significant predictors of length of stay. The analyses identified a median survival time of 32 months as well as critical periods for discharge from AL. Implications for future research and social work practice are presented.


The banana weevil borer (Cosmopolites sordidus) is the main pest of banana crops, causing significant losses in productivity, being recommended control by chemical insecticides which cause several environmental impacts. On the other hand, entomopathogenic nematodes can be an alternative to the pest control, mainly because of their habits. Thus, this study aimed at evaluating isolated entomopathogenic nematodes under laboratory conditions and also their interaction with a chemical insecticide (carbofuran), aiming at their use for the weevil borer control. Sixteen Sterinernematidae and Heterorhabditidae isolates were evaluated, applied over the banana tree pseudo stem (100 JIs/cm 2 ) and they were compared to one another concerning mortality caused in adults individual of C. sordidus. The most infective isolates were subjected to in vivo multiplication at the host Galleria mellonella and interaction with the insecticide carbofuran, including in this case, viability and infectivity analysis of the entomopathogenic nematodes exposed to the product, as well as the effect of the insecticide on the symbiotic bacteria of the entomopathogenic nematodes. The experiments at this stage were conducted in completely randomized design and the data were subjected to ANOVA, with application of the Tukey test (p < 0.05). The most virulent isolates were IBCBn24 and IBCBn40 (respectively 33.3% and 36.7% of confirmed mortality), which also showed high multiplication in corpses. The insecticide did not affect the viability of the isolate, but it really harmed its infectivity, although it did not affect the development of the symbiotic bacterium.


Introduction: Delivery of a nanoparticle payload to a specific cellular compartment is a prized goal of cancer nanomedicine. The well-known SELEX (systematic evolution of ligands by exponential enrichment) process is often used to identify aptamers that localize to target cellular compartments, but such aptamers cannot be guaranteed to traffic an attached payload nanoparticle to the target as well. We hypothesized that to find an aptamer capable of trafficking a nanoparticle to a specific cellular compartment, the screened library must consist of aptamer-nanoparticle conjugates. We therefore designed a screening procedure we call "Conjugate-SELEX". In this process, the aptamer library is conjugated to liposomal nanoparticles, creating a nanoparticle-aptamer conjugate library for screening. At each round of Conjugate-SELEX, aptamers recovered from the desired cellular compartment are amplified, and used to create the conjugate library for the next round of Conjugate-SELEX. Negative screens against off-target cells (e.g. hepatocytes, unwanted uptake in which, causes many of the toxicities associated with nanoparticle therapeutics) facilitate the identification of an aptamer that efficiently transports payload into target cells while minimizing the uptake in off-target cells. Using fluorescently tagged particles, imaging the cells at each stage verifies the successful transport of the payload particles into the cytosol. Methods: We used conjugate-SELEX to screen for aptamers that carried an attached nanoparticle payload to the cytosol of UM-SCC-22A oral cancer cell line, while not being taken up by THLE-3 hepatocytes. IonTorrent sequencing of the remaining aptamers after each round demonstrated convergence to a small family of sequences with only one base difference between members. Mass spectrometric proteomics identified the surface receptor bound by these sequences as the neuroblast differentiation-associated protein AHNAK (desmoyokin) a ubiquitous intracellular protein with surface expression exclusively in certain epithelial cell types. Uptake studies with concertedly synthesized hit aptamer sequences showed enhanced uptake of targeted nanoparticles over controls, and increased cytotoxicity of doxorubicin in the nanoparticles over controls. Conclusions: Conjugate-SELEX is an excellent means of identifying aptamers with the ability to transport attached nanoparticle payloads to targeted cellular compartments, while minimizing off target effects. The technique also lends itself to the identification of surface receptors mediating the trafficking.[D.G., A.A., and N.V. contributed equally to this work.] Citation Format: Qingshan Mu, Akshaya Annapragada, Mayank Srivastava, Varatharasa Thiviyanathan, Xin Li, David Gorenstein, Annanth Annapragada, Nadarajah Vigneswaran. Conjugate-SELEX, a novel screening method, identifies aptamers that deliver payload to the cytosol of target cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3913.


The MYC family (c-, L-, and N-MYC) is one of the most important groups of proteins in human cancer. More than 50% of all malignancies overexpress at least one MYC family member, and estimates suggest that upwards of 100,000 Americans die from cancer every year as a result of inappropriate MYC expression or activity. Preclinical mouse models have demonstrated that perturbing MYC function in preexisting cancers promotes frank tumor regression, establishing MYC proteins as bonafide and high-value targets for discovery of broadly effective anti-cancer therapies. Despite the potential of MYC inhibitors to impact cancer therapy, efforts to discover MYC inhibitors are stymied by numerous factors, including an absence of MYC interaction partners with characteristics that make them amenable to drug discovery efforts. The best understood MYC interaction partner, MAX, is required for MYC to assemble a competent DNA-binding module and would theoretically be a superb target for anti-MYC therapies. The MYC–MAX interaction, however, encompasses more that 1800 A2 of buried protein surface, making it difficult to effectively disrupt by a small molecule with drug-like properties. Breaking the stalemate in drugging MYC requires a fresh perspective on how MYC functions and where the vulnerabilities in its molecular mechanisms of action lie. Structure-function studies have delineated a potent activation domain at the amino-terminus of MYC and a DNA-binding domain at the carboxy-terminus, but the central portion between these domains has not been studied in detail. To rectify this deficit, we recently initiated screens to identify proteins that bind to the central portion of MYC, with the idea that these proteins would reveal new aspects of MYC regulation or function; some of which may expose new ways to target MYC activity. One novel MYC-interaction partner to emerge from this screen was WDR5. WDR5 is a chromatin-associated protein that co-binds with MYC at a majority of its target genes. MYC binds weakly to WDR5 by engaging a structured hydrophobic cleft on one side of the WDR5 protein. Mutations in MYC that disrupt interaction with WDR5 block the ability of MYC to bind chromatin and disable its tumorigenic properties in mice, demonstrating that WDR5 is a critical co-factor for MYC. These studies led to a revised model for target gene recognition by MYC in which WDR5 facilitates the recruitment of MYC/MAX complexes to chromatin, and revealed that the MYC–WDR5 interface is a tractable surface for small molecule inhibition. In collaboration with the laboratory of Dr. Stephen Fesik we seek to discover and validate drug-like molecules that disrupt the MYC–WDR5 interaction and explore their utility in cell and animal-based models of cancer. Citation Format: William Tansey. Novel approaches for targeting MYC. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA15.


Horizon Scan reports provide brief summaries of information regarding new and emerging health technologies; Heath Technology Update articles typically focus on a single device or intervention.
These technologies are identified through the CADTH Horizon Scanning Service as topics of potential interest to health care decision-makers in Canada.
This Horizon Scan summarizes the available information regarding an emerging technology, artificial intelligence algorithms, for the prediction of sepsis in adults.


This study takes a fresh look at the nature of financial and real business cycles in OECD countries using annual data series and shorter quarterly economic indicators. It first analyses whether the last cycle has been different compared to previous cycles in terms of length, amplitude, asymmetry and changes of these parameters during expansions and contractions. We also study the degree of economic and financial cycle synchronization between OECD countries but also of economic and financial variables within a given country and gauge the extent to which cycle synchronization changed over time. We next describe the connection between the great moderation and the last cycle. Finally, the study discusses the synchronization between the real economy and the financial sector and provides some new evidence on the banking sector's pro-cyclicality by using aggregate and bank level. The main findings show that the amplitude of the real business cycle was becoming smaller during the great moderation, but asset price cycles were becoming more volatile. In part, this was linked to developments in the banking sector which tended to accentuate pro-cyclical behaviour. Greater synchronization of cycles may help explain the severity of the crisis.