PIK3CA mutations represent the most frequent oncogenic driver lesion found across all human cancers. Given that single PIK3CA mutations are a predictive biomarker for response to PI3K inhibition, and that these clinical benefits are small, we hypothesized that additional genomic factors may cooperate with single PIK3CA mutations in oncogenesis and response to PI3K inhibitors. We analyzed several large pan-cancer datasets and have discovered a phenomenon of dual PIK3CA mutations in 15% of all PIK3CA-mutant cancers, including breast cancer. Dual PIK3CA mutations are clonal, are found in both primary untreated and metastatic tumors, and are enriched at conserved amino acid positions. We have proved that the majority of dual PIK3CA mutations—including the most frequent dual PIK3CA mutant combinations in breast cancer—are in cis compound mutations (i.e., on the same allele, resulting in a protein molecule with two mutations) in patient samples and cell lines, as shown through multiple sequencing techniques including long-range single-molecule real-time sequencing (SMRT-seq). Compound PIK3CA mutations increase PI3K pathway signaling and growth proliferation in nontransformed cells and cancer cells in vitro and in vivo. Biochemical experiments using recombinant PI3K complexes reveal a mechanism where compound mutants increase PI3K complex thermal instability, resulting in increased kinase activity and liposome binding as compared to single mutants. Compound PIK3CA mutations render cells more sensitive to the PI3Kα inhibitors BYL719 and GDC-0077 than single PIK3CA mutations. These data translate to the clinic, where patients with dual PIK3CA-mutant metastatic breast cancer exhibit more durable responses to PI3K inhibition versus patients with single PIK3CA-mutant breast tumors. Our data support a novel mutational dose-response model for oncogene activation, where compound mutations amplify PI3K signaling and growth to a greater degree than single mutants, resulting in increased sensitivity to PI3Kα inhibitor targeted therapy. These findings also have therapeutic relevance, where compound PIK3CA mutations may be a superior predictive biomarker for response to PI3Kα inhibitors than single PIK3CA mutations, across PIK3CA-mutant cancers. Citation Format: Neil Vasan, Jared Johnson, Hong Shao, Pedram Razavi, Alexander Gorelick, Erik Ladewig, Alesia Antoine, Hardik Shah, Eneda Toska, Guotai Xu, Abiha Kazmi, Barry Taylor, Komal Jhaveri, Maura Dickler, Elisa de Stanchina, Eduard Reznik, Raul Rabadan, Melissa Smith, Robert Sebra, Lewis Cantley, Maurizio Scaltriti, Jose Baselga. Compound PIK3CA mutations support a mutational dose-response model for oncogene activation and response to PI3K inhibitor targeted therapy in breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A21.


A new method for measuring nasal resistance is presented by which it is possible to record reproducible and consistent data on nasal flow and resistance. This method was applied to a double blind trial of 2% solution of sodium cromoglycate. Ten adult patients with allergic rhinitis due to grass pollen were assessed during the winter. One nostril was challenged 1 hr after the administration of sodium cromoglycate or placebo given in random order. Eight patients showed significant protection with sodium cromoglycate.


Caregivers may engage in benefit finding, that is, an increase in perceived positive growth, as a cognitive strategy for coping with stress. The Building Resources in Caregivers study will compare effects of a brief benefit finding writing intervention with a control intervention. Caregivers of people with mental and physical disabilities will be randomised into either a benefit-writing group or a neutral writing group. Caregivers will complete measures relating to themselves and care-recipients (e.g. sociodemographics and illness type) and psychometric measures of benefit finding, distress and quality of life at three time points. Additionally, qualitative commentary on participation experiences will be gathered.


This study aimed to examine the relationship between ethnic group affiliation (EGA) and Willingness to Communicate (WTC) in English among the undergraduates in a public university in Malaysia. The three ethnic groups involved in the study were Malays, Chinese, and Indians. An EGA questionnaire was adapted from Phinney (1992), Magid (2004), and Gatbonton and Trofimovich (2008), while a WTC questionnaire was adapted from McCroskey (1992), Fishman (1972), and Granhemat (2015). The questionnaires were distributed to 39 participants representing the three major races. The analysis showed that the level of EGA for the Malays was the highest with 83% as compared to the Chinese with 73% and the Indians with 81%. Meanwhile, the level of WTC of the Chinese received the highest score of 75%, while the Malays and the Indians were at 63%. Results of the Pearson Correlation, r= -0.323, p= 0.045, indicated a significantly weak and negative association between EGA and WTC. This implicated that high levels of EGA would result in low levels of WTC. Hence, in addressing that, attention needs to be given to the aspect of EGA in language learning and teaching approaches in order to achieve better language proficiency among the English language learners in Malaysia.


Online social media play a major role in shaping public discourse and opinion, especially during political events. We present the first public multi-platform dataset of Italian-language political conversations, focused on the 2022 Italian general election taking place on September 25th. Leveraging public APIs and a keyword-based search, we collected millions of posts published by users, pages and groups on Facebook, Instagram and Twitter, along with metadata of TikTok and YouTube videos shared on these platforms, over a period of four months. We augmented the dataset with a collection of political ads sponsored on Meta platforms, and a list of social media handles associated with political representatives. Our data resource will allow researchers and academics to further our understanding of the role of social media in the democratic process.


First came the financial and debt crisis in Greece, then government financing difficulties and rescue programs in Ireland in 2010 and Portugal in 2011. Before long, Italy and Spain were engulfed by financial contagion as well. Finally in 2012, the European Central Bank pledged to do "whatever it takes" to preserve the euro area with purchases of government bonds, a step that achieved impressive results, according to William R. Cline in this important new book. One of the world's leading experts on fiscal and debt issues, Cline mobilizes meticulously researched and forceful arguments to trace the history of the euro area debt crisis and makes projections of future debt sustainability. He argues that euro area leaders made the right decision to keep the euro from breaking apart but warns against complacency about the future. Cline contends that troubled European economies should continue their fiscal consolidation but that further debt restructurings for most countries are not called for. Greece is a special case and may need some further debt relief contingent on continued progress on fiscal and structural reform, however. In this landmark study, Cline offers a detailed analysis of the mistakes, successes, and options for Europe as it struggles to overcome its worst economic disaster since World War II.


AIMS
To examine country differences in reasons for abstaining including the association of reasons with country abstaining rate and drinking pattern.

PARTICIPANTS
Samples of men and women from eight countries participating in the GENACIS (Gender Alcohol and Culture: an International Study) project.

METHODS
Surveys were conducted with 3338 life-time abstainers and 3105 former drinkers. Respondents selected all applicable reasons for not drinking from a provided list. Analyses included two-level hierarchical linear modelling (HLM) regression.

FINDINGS
Reasons for abstaining differed significantly for life-time abstainers compared to former drinkers, by gender and age, and by country-level abstaining rate and frequency of drinking. Life-time abstainers were more likely than former drinkers to endorse 'no interest', 'religion' and 'upbringing' and more reasons overall. Gender differences, especially among former drinkers, suggested that norms restricting drinking may influence reasons that women abstain ('no interest', 'not liking taste') while drinking experiences may be more important considerations for men ('afraid of alcohol problems', 'bad effect on activities'). Younger age was associated with normative reasons ('no interest', 'taste', 'waste of money') and possibly bad experiences ('afraid of problems'). Reasons such as 'religion', 'waste of money' and 'afraid of alcohol problems' were associated with higher country-level rates of abstaining. Higher endorsement of 'drinking is bad for health' and 'taste' were associated with a country pattern of less frequent drinking while 'not liking effects' was associated with higher drinking frequency.

CONCLUSIONS
Reasons for abstaining depend on type of abstainer, gender, age and country drinking norms and patterns.


The nursery industry in Broward County, Fla., had to choose between partaking in the resolution needed to achieve 10 ppb total phosphorus discharged to the Everglades or face regulation. The industry decided to pursue the proactive route and implement best management practices (BMPs). Teams of industry personnel were formed to develop the content of the Florida Container Nursery BMP Guide that contained the following chapters: 1) nursery layout, 2) container substrate and planting practices, 3) fertilization management, 4) container substrate nutrient monitoring, 5) irrigation water quality, 6) irrigation application, 7) irrigation uniformity, 8) erosion control and runoff water management, 9) pesticide management, and 10) waste management. Each team was to determine the content of their chapter, based on cultural practices producers were currently using, or could be using, which would minimize or reduce surface water movement of phosphorus from the nursery to adjacent water. Cultural practices, brought forth after a consensus was achieved by each team in concert with governmental agencies, associations, and allied industries, were meshed with research information, or the "best" information available from academic sources to ensure that the resolutions or BMPs that were written would contribute to resolving the confl ict (i.e., elevated total phosphorus in canal waters). Consensus development is a new challenge for most academicians but it is important because unbiased and science-based knowledge is needed to assist in BMP development. Furthermore, consensus of those directly and indirectly involved in the nursery industry helps facilitate the use of BMPs. Once the Florida Container Nursery BMP Guide is adopted by rule under the statutory authority of the Florida Department of Agriculture and Consumer Services, nursery operators voluntarily using the BMPs and keeping appropriate records will receive a waiver of liability from cleanup costs associated with contaminated ground or surface water, and be presumed to be in compliance with state water quality standards.


Explores the extent and patterns of age discrimination within a changing workplace context, and specifically focuses on how employment flexibility may be used to the mutual advantage of employers and older workers. Results are presented from two large‐scale national surveys conducted with the Institute of Personnel Management (1994, n = 1,700) and the Institute of Management (1995, n = 1,665). Case study research conducted with Ford/XR Associates, J. Sainsbury and the UK National Health Service is also reported. Research shows that although age discrimination in employment remains extensive, an innovative approach to the recruitment, utilization and retention of older workers may bring a series of positive joint gains.


Purpose
Promoting sustainable behavior is an elusive task as it is not an innate and natural response of individuals. While a conducive environment that promotes sustainability arguably plays a prominent role in influencing individuals' belief structure and norms, not much has been done to examine the interplay between environmental, personal and behavioral domains in sustainable consumption. Drawing on the theoretical perspectives of the social cognitive theory (SCT) and value–beliefs–norms (VBN), this study aims to contribute to the literature by proposing an integrated framework that examines sustainable consumption.

Design/methodology/approach
This study uses a partial least squares structural equation modeling model based on 313 young consumer responses from an eco-friendly institution in Malaysia.

Findings
The findings from this study advance sustainable literature by establishing the multidimensionality concept of the personal domain of SCT. Interestingly, an enabling environment that promotes sustainability was found to be more influential in determining young consumers' beliefs and norms, as opposed to their competencies. This is demonstrated by the sequential mediation of attribution of responsibility and personal norms on the relationship between campus advertisements and pro-environmental behaviors.

Originality/value
Previous research has investigated SCT and VBN as two separate streams of research in examining green behaviors. To the best of our knowledge, this is the first study that integrates SCT and VBN by examining the multidimensionality aspect of the personal construct to provide a more holistic perspective of examining sustainable behaviors.


Highly lanthanum doped lead titanate ceramics exhibit relaxor properties and undergo on cooling a subsequent spontaneous macroscopic phase transition. The dielectric response is strongly affected by chemical (copper) doping and is found to become independent of the applied ac field for temperatures lower than the phase transition one.


This study was aimed to explore the expression level of the unknown cgi-100 gene in human leukemia K562 cells treated with matrine, and to investigate effect of cgi-100 on proliferation of K562 cells. The expression level of cgi-100 was detected by RT-PCR in K562 cells before and after being treated with matrine; pIRES2-EGFP/cgi-100 eukaryotic expression vector was constructed by DNA recombinant technique and was introduced into K562 cells by liposome-mediated DNA transfection. The cgi-100 gene expression level, growth-curve, and cell cycle of the modified K562-cgi-100 cells were detected by RT-PCR, Trypan blue staining and FCM. Morphological changes were observed under the optical and electron microscopes. The results indicated that the expression level of cgi-100 decreased in K562 cells treated with matrine. Heterochromatin decreased, euchromatin and the proportion of S phase in K562-cgi-100 cells increased, and cell proliferation enhanced. It is concluded that the expression of cgi-100 mRNA decreased in a dose- and time-dependent manner in the K562 cells treated with matrine and over-expression of cgi-100 elevates the proliferation and the immaturity level of K562-cgi-100 cells.


A solitary fibrous tumour of the pleura (SFTP) is a rare pathology, frequently benign in nature, and is usually diagnosed incidentally on imaging. We herein describe the case of a previously fit and well, 35-year-old Caucasian lady, who presented to us with a history of progressively worsening shortness of breath. Her chest X-ray showed a near-complete opacification of the right hemithorax, with displacement of the mediastinum towards the left. This study was supplemented by a computed tomography (CT), which demonstrated a well-circumscribed, non-homogenous mass, occupying the entirety of the right hemithorax. A large, smooth, encapsulated tumour was surgically resected via a posterolateral thoracotomy, measuring approximately 23.1 cm x 21.0 cm x 11.5 cm and weighing 3640 grams. Histopathology confirmed the diagnosis of a benign SFTP with an intermediate malignant potential. At six months, a follow-up CT scan demonstrated no evidence of disease recurrence.


Availability of soil copper (Cu) to plants is dependent on the release into the soil solution of Cu from the solid phases. To ascertain the pattern of Cu release and the soil characteristics affecting it, the kinetics of Cu release by diethylenetriaminepentaacetic acid (DTPA) from 14 calcareous soils of northern Iran was investigated using six kinetic models. The release pattern was generally characterised by an initial fast reaction followed by a slower reaction that continued up to 192 h. The kinetic data were best described by the power function equation as evidenced by relatively high values of the coefficient of determination (R2) and relatively low values of the standard error of the estimate. The Cu release pattern based on the parabolic diffusion equation suggested the possible involvement of two different mechanisms. Conformity of the shell progressive particle diffusion equation to kinetic data may indicate that the release rate is controlled by diffusion of Cu and/or DTPA molecules through a reacted soil particle or aggregate rather than diffusion through the film surrounding soil particles. Rate constants for the power function equation (a and b), the parabolic diffusion equation (k′p), and the initial release rate (ab) were closely associated with cation exchange capacity (CEC). From results reported herein, CEC seems to be the most important influencing factor in controlling Cu release from calcareous soils of northern Iran.


IBM's Jazz initiative offers a state-of-the-art collaborative development environment (CDE) facilitating developer interactions around interdependent units of work. In this paper, we analyze development data across two versions of a major IBM product developed on the Jazz platform, covering in total 19 months of development activity, including 17,000+ work items and 61,000+ comments made by more than 190 developers in 35 locations. By examining the relation between developer talk and work, we find evidence that developers maintain a reasonably high level of connectivity with peer developers with whom they share work dependencies, but the span of a developer's communication goes much beyond the known dependencies of his/her work items. Using multiple linear regression models, we find that the number of defects owned by a developer is impacted by the number of other developers (s)he is connected through talk, his/her interpersonal influence in the network of work dependencies, the number of work items (s)he comments on, and the number work items (s)he owns. These effects are maintained even after controlling for workload, role, work dependency, and connection related factors. We discuss the implications of our results for collaborative software development and project governance.


This letter considers the problem of piecewise affine abstraction with polytopic partitions of nonlinear systems, i.e., the over-approximation of nonlinear dynamics by a pair of piecewise affine functions over polytopic subdomains/partitions in the sense of the inclusion of all possible trajectories. Specifically, to tackle the "boundary effect" that may make the over-approximation incorrect for polytopic partitions, we propose two mesh-based affine abstraction approaches based on expanding the partitions to simultaneously find the polytopic partitions and the pair of piecewise functions over the partitions. The effectiveness of the proposed approaches are compared with existing methods using hyperrectangular partitions, and demonstrated by computing abstractions of swarm dynamics and applying them for swarm intent identification.


This paper deals with the Taiwanese sports under the KMT's ruling era from 1945 to 1971. In this time, the aim is to build an anti-communism country actively, in order to maintain the last lifeblood of country's office regime. By the Chiang Kai-shek's ideal of anti-communism idea, the fundamental principle of state is in order that to revive of the legitimacy of its reign and against the mainland China controlled by the Communist Party, demand that the importance of its dictatorship quo by one party and privilege the national defense as its basis way of getting legitimacy. For that purpose, overall inwards, are in charge of with steady to everything particular, emphasizes on smoothing its countrymen, then to impel the stable society as the first thing, and improve their livelihood. By this way, it counterfeit the situation that what the consequences such as make people go bankrupt, and being damaged suffered, brought by the ruling of Communist party in China meanwhile. On the contrary, the Republic of China emphasizes on defending international organization membership and friendly feelings of deepening the anti-communism friendly nation and striving for the overseas Chinese to approve foreign countries at the same time. Sport is one of important anti-communism stronghold that could be a way of running a country. It not only tempers the patriotic consciousness of anti-communism, but also cultivates national spirit, approving the recognition of national leader, building up civil and militant youth to protect the country, so that it can reinforce the effect of people's sense of national defense. Besides, it can also cultivate the spirit of diligence, strengthening the ability of body's performance and its endurance, so that it may offer good workers in the labor market, then promote the function of economic development. As a result, the administration regards it as an important policy to promote sports to be one of the methods to manage Taiwan. Research shows that, the goal, the strategy and the practice of Taiwan's sports was fiercely influenced by the idea of anti-communism stronghold. Thus, the promotion of sports becomes a part of socially inner control. What all the educational systems, social sports organization, CYC and boy scouts' federation were controlled by KMT's government, especially the military system which has the most budget and resources was included. However, Chiang and his son, the real decision maker, had the idea of respecting all the aspect of specificity. So that it makes all the executer of each organization equipped with their professional idea. By the economic prosperity and enhancing people's intelligence in Taiwan, its sports get rid of the shadow of its being prepared for war and the physical training gradually. Nowadays, it towards to be two axis of its development: for health and for competition.


It is currently fashionable to believe that patients with chronic diseases can be managed safely, effectively and more cheaply, entirely in the community. In the UK, current commissioning and financial models encourage the development of services to provide continuing care as well as to replace acute care traditionally provided by hospitals. For some patients, this may be appropriate, but there is a danger of taking it too far and for patients to be denied appropriate input from specialists.

In the late 1990s, home care services to manage exacerbations of chronic obstructive pulmonary disease (COPD) were introduced in the UK, largely as a way of reducing the strain on the National Health Service's (NHS) resources caused by the number of patients admitted during the winter months.1 It is now well recognised that some patients with exacerbations of COPD2 3 can be managed safely at home, and in fact this model of care fits into a model of intermediate care for older patients which has been evolving for several decades.4 Intermediate care has been seen as a way of overcoming the loss of independence and disruption of informal and formal patterns of support in the community that can occur on admission to hospital. In some cases, transferring care to the community also has a political dimension and has been seen as a way of reducing the influence of secondary care in determining priorities within local healthcare communities. Although home care or early assisted discharge may minimise the loss of independence that accompanies hospitalisation, patients at home often struggle because they are frail and they may take longer to recover because they miss out on the reablement services available in hospital.

Intermediate care is, however, undoubtedly a suitable way of managing exacerbations for some patients with COPD—but not all. In …


Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, resting, and hyperemia following intrarenal dopamine (30 μg/kg). Changes in perfusion pressure were expressed as delta mean arterial pressure, changes in flow as percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. A total of 18 patients with median age 57 years (range 27-85), 61% male with successful measurements were included. During static handgrip renal arterial pressure increased by 15.2 mmHg (range 4.2-53.0), while flow decreased by 11.2%, but with large variation between individuals (range -13.4-49.8). Intraglomerular pressure increased with 4.2 mmHg (range -3.9-22.1). Flow velocity under resting conditions remained stable with median 100.6% (range 82.3-114.6) compared to baseline. During hyperemia, maximal flow was 180% (range 111-281), while intraglomerular pressure decreased to 33.0 mmHg [IQR 26.7-39.8]. Changes in renal pressure and flow during handgrip exercise were correlated (rho=-0.68; p=0.002). Measurement of renal arterial pressure and flow velocity during handgrip exercise allows identification of patients with higher and lower sympathetic control of renal perfusion. This suggests that hemodynamic measurements may be useful to assess the response to therapeutic interventions aimed at altering renal sympathetic control.


When the subject of the meeting of this society in Leeds was named recently by some of its ardent friends, the desire was also expressed that some papers should be brought forward with reference to the staples of the town and neighbourhood, rather than upon purely scientific details, which could find other channels. As I had recently seen most of the best plans for preparing flax in Ireland, &c., I thought an account of some new chemical processes might call the attention, and deserve the discussion, of those who wish manufacturing skill and scientific truth and advantage to be united.

With this view the subject is brought forward, and the specimens will show that means have been taken to make it as practical as a paper may be, where trade processes are alluded to; and yet with no wish to advance into prominence any individual or plans, except so far as they conduce to the general bearings of the subject.

Before men so conversant with flax, and with such ample endowments for manufacturing appliances, I may give for general purposes a short account of flax and its processes, before I solicit their attention to any special points.

The flax plant, growing so extensively as it does, and in so many climes, has a name in the earliest histories, and even the "figures upon the wall" of the Egyptians show that the processes for obtaining the fibre were very similar to those employed even in Great Britain at recent periods; and ...


Background Health inequalities from the first stages of life onwards have consequences for children's health status and for their future development. Children's health is profoundly affected by the socioeconomic position (SEP) of their parents. The situation is even more disruptive in children with medically complex (CMC) conditions. The aim of this study is to describe the characteristics and related pathologies of CMC in Catalonia, and to assess the presence of socioeconomic inequalities.Methods Cross-sectional study and cluster analysis of the diseases in the CMC population under the age of 15 in Catalonia in 2016 using administrative data. Each pathology cluster obtained was described and its association with socioeconomic position (SEP) determined. The Adjusted Morbidity Groups (Catalan acronym GMA) classification system was used to identify the CMC. Main outcome measures: SEP, GMA score, sex, and age distribution were recorded in both populations (CMC and non-CMC) and in each of the clusters identified.Results 71% of the CMC population have at least one parent with no employment or an annual income of less than €18,000. Four comorbidity clusters were identified in CMC: respiratory (47%), neurodevelopmental (18%), hemato-oncological (12%), and perinatal disorders (23%). CMC experience higher levels of poverty and social disadvantage in all clusters. SES-cluster association results were: in the respiratory OR, 2.1 in boys and 2.1 in girls; in the neurodevelopmental disease, OR 2.0 in boys and 1.8 in girls; in the hemato-oncology OR, 1.7 in boys and 1.8 in girls; and in the perinatal OR, 1.7 in boys and 1.8 in girls.Conclusions There are socioeconomic health inequalities in childhood across a broad spectrum of health outcomes. Children with lower SEP are more likely to have CMC conditions. All clusters showed SEP inequalities and respiratory and neurodevelopment clusters are the most prevalent.


Education at a Glance is the annual result of a long collaboration between governments of OECD countries, experts, and institutions that participate in the Indicators of Education Systems program of the Organization for Economic Cooperation and Development (OECD). This article is an respond to the article on "Taking a Closer Look at the OECD Tertiary Statistics" by Arthur Hauptman. The following topics are covered in this article: International students and enrollment ratio, indicators to interpret the results, private funding and R&D, relationship between criteria and outcomes, and strategies for investing in expanding education systems.


Maternal obesity during pregnancy may influence fetal development and possibly predispose offspring to cardiovascular disease. The aim of the present study was to evaluate the relationship between maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy, and newborn birth weight, with lipid profile, high-sensitivity C-reactive protein (hs-CRP) and leukocyte in newborns. We performed a cross-sectional study of 245 mothers and their children. Blood was collected from the umbilical vein and assayed for lipid profile, hs-CRP and leukocyte count. Newborns average weight was 3241 g, total cholesterol 53.9 mg/dl, high-density lipoprotein cholesterol (HDL-c) 21.9 mg/dl, low-density lipoprotein cholesterol (LDL-c) 26.2 mg/dl, triglyceride 29.5 mg/dl and leukocytes 13,777/mm3. There was a direct correlation of pre-pregnancy BMI of overweight mothers with total cholesterol (r=0.220, P=0.037) and LDL-c (r=0.268, P=0.011) of newborns. Total cholesterol, LDL-c and HDL-c were higher in pre-term newborns (66.3±19.7, 35.9±14.6 and 25.2±7.7 mg/dl, respectively) that in full-term (52.4±13.1, 25.0±8.7 and 21.5±6.0 mg/dl), with P=0.001, 0.001 and 0.003, respectively. Leukocyte counts were higher in full-term newborns (14,268±3982/mm3) compared with pre-term (9792±2836/mm3, P<0.0001). There was a direct correlation between birth weight and leukocyte counts of newborns (r=0.282, P<0.0001). These results suggest the possible interaction of maternal weight and fetal growth with lipid metabolism and leukocyte count in the newborn, which may be linked to programming of the immune system.


We report new U-Pb detrital zircon sensitive high-resolution ion microprobe (SHRIMP) age data (702 grains) from 13 samples collected from Miocene to Holocene sedimentary deposits in the western Snake River Plain region. These samples effectively show that modern stream sediments of the Snake River system reliably and repeatedly record the detrital zircon age populations that are present as sources in their drainage basins across the Cordilleran thrust belt and Basin and Range Province. We use this framework and the provenance of Neogene sedimentary rocks in the region to test the effect of the migrating Yellowstone hotspot on regional drainage patterns in southern Idaho since the middle Miocene. Our results indicate that Neogene paleodrainages were fi rst directed radially away from the tumescent Yellowstone highland, then subsequently reversed their fl ow toward the subsiding Snake River Plain basin. This occurred in east-progressing time-constrained intervals starting at 16 Ma. In northern Nevada, the drainage divide is represented by a northeast-trending, southeast-migrating crest of high topography. Specifi cally, middle to late Miocene (16‐ 10 Ma) sedimentary deposits of the western Snake River Plain and Oregon-Idaho graben contain early to middle Eocene (52‐42 Ma) detrital zircon populations sourced in Challis magmatic rocks north of the Snake River Plain. Middle Jurassic (160 Ma) and middle to late Eocene (42‐35 Ma) detrital zircons, sourced from rocks in northern Nevada, are not present. Late Eocene detrital zircons from Nevada are present in two younger than 7 Ma sedimentary units of the Idaho Group along the Oregon-Idaho border. This indicates that by the late Miocene, southeastward headward erosion of the paleo‐Owyhee River into the Owyhee Plateau had captured drainage from north-central Nevada and directed it northwestward toward the subsiding western Snake River Plain. The modern Owyhee Plateau is still a topographic high, in contrast to the modern Snake River Plain, suggesting that lowering of the regional Snake River Plain base level, rather than crustal subsidence, drove stream capture. By the late Pliocene (3 Ma), Middle Jurassic detrital zircons are recorded in the Glenns Ferry Formation and Tuana Gravel of the central Snake River Plain, suggesting that surface subsidence reversed the fl ow direction of paleo‐Salmon Falls Creek from southward into Nevada to northward toward Idaho. Miocene strata of the western Snake River Plain lack recycled Proterozoic detrital zircons that are ubiquitous in sedimentary rocks of the central and southeast Idaho thrust belts. Such detrital zircons appear on the central and western Snake River Plain in early Pliocene to Holocene (4‐0 Ma) deposits. This records capture of drainage from the eastern Snake River Plain. The Yellowstone hotspot controlled the east-migrating continental divide, in the wake of which formed the western-draining, and progressively eastward-collecting, Snake River system.


Since Global Positioning System technologies cannot be used indoors, a significant amount of research focuses on developing radio-frequency-based alternatives for indoor localization. Unfortunately, most of the suggested solutions for indoor localization consist of theoretical work or have been evaluated in non-industrial environments, typically office spaces. To evaluate the influence of industrial environments on localization accuracy, in this paper, a time-of-arrival (ToA) approach was used to determine the stationary locations of a robot inside the w-iLab.t II testbed, an open industrial-like environment containing several metal obstacles. The ToA method utilizes the measured propagation time of a radio wave between a sender and receiver to estimate their corresponding distance. This paper evaluates several industrial-related deployment aspects that influence location accuracy and describes how their negative impact can be reduced, resulting in an almost 50% accuracy improvement in industrial environments.


The collision of a primordial black hole with a neutron star results in the black hole eventually consuming the entire neutron star. However, if the black hole is magnetically charged, and therefore stable against decay by Hawking radiation, the consequences can be quite different. Upon colliding with a neutron star, a magnetic black hole very rapidly comes to a stop. For large enough magnetic charge, we show that this collision can be detected as a sudden change in the rotation period of the neutron star, a glitch or anti-glitch.We argue that the magnetic primordial black hole, which then settles to the core of the neutron star, does not necessarily devour the entire neutron star; the system can instead reach a long-lived, quasi-stable equilibrium. Because the black hole is microscopic compared to the neutron star, most stellar properties remain unchanged compared to before the collision. However, the neutron star will heat up and its surface magnetic field could potentially change, both effects potentially observable.


As organizations increase their adoption of database systems as one of their key data management technologies for the daily operations and decision makings, the security of data managed by these systems becomes crucial. Damage and misuse of data affect not only a single user or application, but may have effect the entire organization. The recent rapid proliferations of web-based applications with database at its backend have further increased the risk of database exposure to the outside world. There are many recent reports on intrusion from external hackers which compromised the database system. However, there are also insiders who abuse their privileges and access the database system for many intentions. For that reason, it is imperative for us to secure database system from both external and internal attacks. This paper describes on database security threats and the existing works that had been done to mitigate these problems. One of possible solutions is by using Intrusion Detection System (IDS). For that reason, this study proposed a novel SQL Injections and Insider Misuse Detection System (SIIMDS) to provide higher level of security for database system.


This article deals with the main elements of competitiveness, defines essence of its practical significance, analyses the CPC of Ukraine novelties, connected with competitiveness, in particular, the definition of the party in criminal proceedings in the national legislation is researched, its comparison with definitions, fixed in the criminal procedure codes of the other countries is made.


Objective To determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture. Design Retrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through a central venous or arterial catheter and peripheral venipuncture. Setting Tertiary-care, university-affiliated medical center. Patients Two hundred seventy-one patients hospitalized on a surgical and a cardiothoracic intensive care unit between November 1994 and August 1997. Interventions None. Measurements and Main Results Blinded assessments of culture results done by two physicians were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from catheters and culture of blood from peripheral venipuncture. Of 499 observations, 426 were catheter-negative/venipuncture-negative, 19 were catheter-positive/venipuncture-positive, 18 were catheter-negative/venipuncture-positive, and 36 were catheter-positive/venipuncture-negative pairs. For catheter draws compared with peripheral venipuncture, sensitivity was 78% (confidence interval [CI], 65% to 90%) and 65% (CI, 50% to 79%) (p = .2), specificity was 95% (CI, 94% to 97%) and 98% (CI, 97% to 99%) (p = .002), positive predictive value was 63% (CI, 51% to 76%) and 78% (CI, 64% to 91%) (p = .1) and negative predictive value was 98% (CI, 96% to 99%) and 97% (CI, 95% to 98%) (p = .3). When central venous specimens as differentiated from arterial catheter specimens were compared with peripheral venipuncture, the difference between positive predictive values reached statistical significance (61% and 82%;p = .04). Conclusions In critically ill surgical patients, cultures of blood drawn through a catheter are less specific than those obtained from a peripheral venipuncture. Both types of cultures have an excellent negative predictive value. Positive predictive value of cultures of blood drawn through a catheter is low and, when obtained from a central line, statistically less than from a peripheral venipuncture. Additional cultures seem to be necessary for the proper interpretation of a positive culture drawn through a catheter in critical care patients.


OBJECTIVE
To evaluate effectiveness therapeutic regimens for obstructive sleep apnea hypopnea syndrome (OSAHS) children at an acceptable cost.

METHOD
This study was performed at Yuying Children's Hospital of Wenzhou Medical University from Mar. 2008 to Dec. 2010. Prospective random number table method was used for the analysis; 60 children with mild OSAHS were divided into Mild OSAHS Montelukast Treatment (MM) group and Mild OSAHS Adenotonsillectomy Treatment (MAT) group. 32 children in MM group were treated with leukotriene receptor antagonists (LTRAs), while 28 children in MAT group were treated with adenotonsillectomy. Also, 58 children with moderate and severe OSAHS were divided into severe OSAHS Montelukast Treatment (SM) group and severe OSAHS Adenotonsillectomy Treatmen (SAT) group. Twenty-two children in SM group were treated with LTRAs, while 36 children in SAT group were treated with adenotonsillectomy. All selected children were evaluated by polysomnography (PSG) and Obstructive Sleep Apnea-18 (OSA-18) items before and after a six-month treatment. Both records were taken and analyzed, surgical complications and the reason for non-remission after operation were also analyzed. Two therapies were compared based on economic consideration and therapeutic effect. Result (1) PSG: A significant change of a significant change of Apnea Hypopnea Index (AHI) was observed in MM group after the treatment (before receiving the treatment 4.56 ± 1. 26, and after receiving the treatment 3. 48 ± 1. 52, t =3. 50, P <0. 05). But for oxygen desaturation Index (ODI) (MM group 2. 18 ± 2. 19, and MAT group 1. 80 ± 2. 34) and Lowest Oxygen satuation (LSaO2) (MM group 91. 66 ± 2. 34, and MAT group 92. 79 ± 2. 18), there was no significant difference in MM group and MAT group after the treatment (ODI, t =0. 65, and LSaO2 t = - 1. 93, P >0. 05). (2) OSA-18 scores: Significant differences were found in sleeping disorder (before 14. 81 ± 6. 28, and after 10. 56 ± 3. 57), the degree of familial stress (before 13. 56 ± 3. 54, and after 8. 97 ± 2. 96), and OSA-18 total scores (before 52. 66 ± 1. 11, and after 42. 56 6. 48) in MM group after the treatment (sleeping disorder Z - 3. 14, the degree of familial stress Z = -4. 50, and OSA-18 total scores Z= -4. 01, P <0. 05). (3) In addition to the cost of drugs, groups with surgical treatment had a larger economic burden than those with LTRAs treatment. (4) Treatment was totally effective for 28 children (88%) in MM group, and 28 children (100%) in MAT group. Meanwhile, treatment also achieved an obvious effect on 2 children (9%) in SM group, and in 35 children (97%) in SAT group. In MAT group, 3 children improved (11%). And in SAT group, 7 children improved (19%), but treatment was found to be ineffective in 1 case (3%). Among those effective and ineffective cases in groups with surgical treatment, there were 9 children with nasal diseases.

CONCLUSION
(1) Surgical treatment is recommended as the first choice for children with moderate and severe OSAHS. And for those who also suffer from nasal diseases, treatment combining drugs with surgery is necessary. (2) LTRAs therapy has a good effect for mild OSAHS. Surgery is also recommended when drugs could not achieve any obvious improvement in clinical symptoms of children with mild OSAHS.


Many rural communities across Canada are experiencing or anticipating climate change effects. Our study, a contribution to the limited social science research on adaptation in rural regions in this country, focused on a rural, forest-dependent, francophone region of New Brunswick on unceded Wolastoqiyik territory. In collaboration with a regional governance organization, we developed and administered a survey to gather the perspectives and experiences of rural community leaders on climate change adaptation. The study results are intended to provide a basis for discussion to support regional adaptation planning. They may also be used as a baseline for measuring future advances in climate adaptation efforts. Theories of new social movements, Indigenous resurgence, and organizational leadership informed our investigation and analysis. Our study focuses on three themes identified in the literature review critical to supporting environmental action: leadership, communication processes, and relationships. Our core research question is: To what extent are community leaders in the rural study region engaging in these functions? We conclude with reflections on how climate change adaptation is occurring in this rural region and the role of regional governance in this process.

Keywords: rural, climate, adaptation, leadership, Wolastoq


In previous communications' we have discussed the procedures used and the results obtained in a probability determination of the magnitude of the volume and the radius of the cell "sensitive volume" which appears to be associated with mutation at the white locus in Drosophila melanogaster. It has been indicated that the result may be tentatively considered as the minimum limiting value for the size of the gene. Partly as a test of the method, and partly because of the wealth of interesting results which it has given, we have recently extended the scope of the investigation to include (1) an evaluation of the mutation rate-dosage relationship as a function of temperature of the irradiated material, using a single wave-length of x-rays, (2) an evaluation of the same relationship at


DNA methylation is a fundamental epigenetic mechanism in regulating the expression of genes controlling crucial cell functions in cancer development. Gene silencing via CpG island methylation/demethylation in the promoter region is one of the mechanisms by which different genes are inactivated/activated in human cancers. Tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to antagonize matrix metalloproteinase (MMP) activity and to suppress tumor growth, angiogenesis, invasion, and metastasis. TIMP-2 expression has been found to be both upregulated and downregulated in various cancers. The inconsistent TIMP-2 expression and unclear epigenetic regulation lead us to investigate its role in colorectal cancer in the presence of a methylating agent. Highly invasive human colorectal cells SW-620 were treated with the methyl donor S-adenosylmethionine (SAM) and its effect was evaluated by cell proliferation, cell cycle, invasion and migration assay. The ability of SAM to down regulate a panel of activated prometastatic, angiogenesis and growth- and cell cycle-regulatory genes was evaluated using end-point and real-time PCR. Treatment of SW-620 with SAM diminished cell proliferation and altered cell cycle kinetic G2/M phase cell cycle arrest. An in vitro matrigel invasion assay of SAM-treated cells showed a significant reduction in the invasive potential compared to untreated SW-620 cells. Treatment of SW-620 cells with SAM resulted in activation of TIMP-2 and inhibition of the expression of genes such as MMP (MMP-2, MT1-MMP), urokinase plasminogen activator, and vascular endothelial growth factors. The level of expression of tumor suppressor and apoptotic genes was not significantly higher compared to the untreated control. No changes in the levels of expression of genes (growth and cell cycle regulator), such as TGF-β, Smad2, Smad4, and p21 were observed. Our data support the hypothesis that TIMP-2, along with other prometastatic genes, is hypomethylated and expressed differently in colorectal cancer. Further in-depth analysis is warranted to confirm the promoter region CpG methylation pattern of the TIMP-2 gene.


137 CT-angiograms of arterial celiac-mesenterial vessels were pro- and retrospectively analyzed in 120 patients. Radiological data was compared with intraoperative anatomy during standard and extended pancreatoduodenal resections. The analysis showed a considerable variability in architecture of celiac and superior mesenteric artery branches: hereby, a classical arterial anatomy was found only on 55% of the analyzed CT-scans. Intraoperative revision confirmed CT-data in all cases. CT-angiography is a prompt and reliable method of celiac-mesenterial arterial anatomy determination, making surgical treatment of patients with liver and pancreas diseases safer.


2 We address wide-area coverage for hand-held portables using an on-board signal processing satellite in geostationary (GEO) orbit at minimum payload cost. A GEO link, being power-limited, di ers from terrestrial mobile communications systems that use direct radiating antennas by requiring a focal-fed parabolic re ector, which acts as a xed analog beamformer. We propose to cascade a high-gain parabolic re ector and a digital maximum signal-to-interference-plus-noise ratio (SINR) multi-beamformer for spatial multi-user interference suppression to achieve coverage extension. This involves on-board antenna array signal processing of multiple feeds. It is shown that nearly uniform coverage of an area the size of Canada can be provided using only ve parbolic re ector apertures. Compared to conventional focussed multibeam system, link margins are typically increased from a minimum requirement of 5.25 dB to 7.5 dB in border areas. The more uniform coverage reduces dynamic power control requirements.


In the first clinical study on GM-CSF in acute leukemias continuous infusion of the growth factor is given to patients in aplasia and at high risk of early death due to age over 65 years and/or intensive chemotherapy for resistance or relapse. Among 6 patients (4 AML, 2 ALL) receiving a total of 7 courses two died too early to contributing adequate data. Three patients and 4 courses showed earlier neutrophil recovery than related control groups and a fourth patient with secondary AML showed a neutrophil recovery time in the normal range, but much shorter than her platelet and reticulocyte recovery. No evidence was obtained so far for leukemic regrowth in these patients including blood and bone marrow cytology, monitoring of DNA aneuploidy by flow cytometry and clonogenic cells by colony assays. Thus, GM-CSF may be useful for rescue after intensive chemotherapy of AML and ALL and may not necessarily increase the risk of leukemia progression.


Liquidity management has proved to be difficult in India after financial liberalisation in 1991. This paper studies the liquidity management in India from 1998 to 2010 and analyses the determinants of liquidity in India. The focus is on the liquidity in banks and nonbanking financial institutions. The finding indicates that the average increase in liquidity of banks was 2.77% per quarter from 1998 to 2010. The average increase in liquidity in non banking financial institutions from 1998 to 2010 was observed to be 1.13% per quarter. In all cases for banks, periods of liquidity decline were followed by periods of increase in liquidity but it was not the same with nonbanking financial institutions which suffered a cumulative liquidity decline of 27.7% between 2007 and 2010. Nonbanking financial institutions were affected more in terms of liquidity decline during global financial crisis as compared to banks in India. Discount rates and SLR have a negative influence on liquidity for banks while an increase in cash reserve ratio has a positive influence on liquidity of banks. In regard to liquidity in non banking financial institutions it is observed that determining factors are only discount rates and cash reserve ratio.


The article is of a scientific and research nature and it is aimed primarily at outlining the legal status of animals and to what extent legal regulations governing this status determine the level of humane protection of animals in Poland. To achieve this goal, first of all, the concept of "animal" needed to be made more specific, the principle of dereification discussed and its normative scope outlined, and the characteristics of an animal as a specific tangible good needed to be presented. The need to address the issue is determined primarily by the awareness that the way of human life and human attitude to animals has been changing with the development of civilisation. In any case, the changes that have taken place in this area in recent decades make the title issue topical and conducive to verify previous findings. It is assumed that the research carried out will contribute to the development of an optimal model of legal protection of animals and to the development of legal science. The very dissemination of the results is to raise the social awareness of the legal status of animals, which is one of the conditions of further progress of civilisation.


Cluster analysis was performed on a diverse group of 69 non-clinical grievers whose loved ones died between 12–40 months prior to the study. Based on psychometric measures of both bereavement distress and growth, three distinct clusters emerged: High Grief (high distress—low growth; n = 16); High Growth (low distress—high growth; n = 32); and Low Impact (low distress—low growth; n = 21). Discriminant function analyses showed that the High Grief cluster differed robustly from the other two groups on several measures of grief adaptation and coping; the differences between the High Growth and Low Impact clusters were less pronounced. High Grief participants sought grief counseling significantly more often whereas the Low Impact grievers preferred medicinal help for symptoms if they sought any professional assistance at all. When High Growth participants sought counseling, they seemed to focus on growth-oriented dimensions rather than mere symptom relief. Of the 11 participants who sought grief counseling for their loss, 10 (91%) found the experience to be helpful. Findings are discussed in the context of meta-analytic studies of the effectiveness of grief counseling.


ABSTRACT Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion and migration. However, the mechanism by which PTP-PEST is regulated in response to oncogenic signaling to dephosphorylate its substrates remains unclear. Here, we demonstrate that activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells. These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression.


Depletion of acetylcholine in the central nervous system (CNS) is responsible for memory loss and cognition deficit. Enzyme acetylcholinesterase (AChE) is responsible for destruction of acetylcholine (Ach) in the brain. Many herbal plant extracts have been investigated for their potential use in the treatment of Alzheimer's disease (AD) by inhibiting AChE and upregulating the levels of Ach. The current study investigated the anti-acetylcholinesterase (AChE) activity of an aqueous extract of Unicaria tomentosa bark which has not been reported so far in the literature. The in vitro study of an aqueous extract of U. tomentosa showed maximum inhibition of 76.2±0.002 % at 0.4mg/ml of final concentration with an IC50 = 0.112 mg/ml. The mechanism of inhibition was elucidated by kinetic study which showed mixed type of inhibition, this might be due to the presence of various phytoconstituents such as oxindole alkaloids present in an aqueous extract. Based on molecular structure of phytoconstituents obtained from U. tomentosa known from the relevant literature, in-silico molecular docking study was performed against AChE protein to validate the results.


When collecting information, local differential privacy (LDP) alleviates privacy concerns of users because their private information is randomized before being sent it to the central aggregator. LDP imposes large amount of noise as each user executes the randomization independently. To address this issue, recent work introduced an intermediate server with the assumption that this intermediate server does not collude with the aggregator. Under this assumption, less noise can be added to achieve the same privacy guarantee as LDP, thus improving utility for the data collection task. This paper investigates this multiple-party setting of LDP. We analyze the system model and identify potential adversaries. We then make two improvements: a new algorithm that achieves a better privacy-utility tradeoff; and a novel protocol that provides better protection against various attacks. Finally, we perform experiments to compare different methods and demonstrate the benefits of using our proposed method.


Importance
Bone marrow or peripheral blood from unrelated donors may be used for hematopoietic cell transplantation. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them.

Objective
To compare patient-reported outcomes between patients randomized to receive 1 of 2 graft types for unrelated donor transplantation.

Design, Setting, and Participants
This follow-up of a randomized clinical trial included English- or Spanish-speaking patients 16 years or older participating in a multicenter randomized clinical trial of unrelated donor bone marrow (BM) vs peripheral blood (PB) (N = 551) in hematopoietic cell transplantation for hematologic neoplasms. Patient-reported outcomes were collected from patients at enrollment and 0.5, 1, 2, and 5 years after transplantation.

Interventions
Unrelated donor BM or PB hematopoietic cell transplantation.

Main Outcomes and Measures
Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Mental Health Inventory, occupational functioning, Lee Chronic Graft-vs-Host Disease Symptom Scale.

Results
At 5 years after transplantation, 102 BM and 93 PB participants were alive and eligible for assessment (age ≥40 years or older: 104 [53.5%] male: 101 [51.8%]). The mean (SE) Mental Health Inventory Psychological Well-Being scores (78.9 [1.7] vs 72.2 [1.9]; P = .01; higher better) and Lee chronic graft-vs-host disease symptom scores (13.1 [1.5] vs 19.3 [1.6]; P = .004; lower better) were significantly better for BM recipients, adjusting for baseline scores and missing data. Recipients of BM were also more likely to be working full or part-time than recipients of PB (odds ratio, 1.5; 95% CI, 1.2-2.0; P = .002), adjusting for work status before transplantation. With a median follow-up of 73 months (range, 30-121 months) for survivors, no differences in survival (40% vs 39%; P = .84), relapse (32% vs 29%; P = .47), or treatment-related mortality (29% vs 32%; P = .44) between BM and PB were observed.

Conclusions and Relevance
Recipients of unrelated donor BM had better psychological well-being, less burdensome chronic GVHD symptoms, and were more likely to return to work than recipients of PB at 5 years after transplantation. Bone marrow should be the standard of care for these types of transplant procedures.

Trial Registration
clinicaltrials.gov Identifier: NCT00075816.


Using an anti‐Tn monoclonal antibody, the Tn antigen was detected immunohistochemically in prenatal and early postnatal central nervous tissues. On embryonic day 9 (E9), the antigen was distributed throughout the single neuroepithelial layer in the neocortex and then became more prominent in the preplate than in the ventricular zone along with formation of the preplate. Following division of the preplate and concomitant formation of the cortical plate, distinct labeling of the neocortex occurred in the marginal, subplate and intermediate zones, whereas in the cortical plate and ventricular zone were virtually not immunostained. It is notable that thalamocortical afferent fibers were also immunostained specifically on E14. After birth, the localization of the antigen became less noticeable and by 3 weeks after birth, the antigen had substantially disappeared. In the developing cerebellum, prominent labeling was also observed in the molecular layer and outskirts of the cerebellar nuclei on early postnatal days. To characterize the glycoprotein bearing the Tn antigen biochemically, immunoblot analysis was performed. The glycoprotein, most of which was extracted with a salt solution, migrated as a broad smeared band corresponding to a molecular weight of about 250 kDa on SDS‐PAGE. Among the various tissues examined, this glycoprotein was only detected in the brain and its amount increased until an early postnatal stage with a peak on postnatal day 3 (P3), and then decreased gradually with age. This spatially and developmentally regulated expression of the Tn antigen suggests that this antigen plays a significant role in brain development. J. Neurosci. Res. 65:595–603, 2001. © 2001 Wiley‐Liss, Inc.


We estimate the causal effects of infants' exposure to opioids in utero on their health at birth and on the likelihood that their parents will be the subjects of subsequent reports to child protective services. We use administrative data on 259,723 infants born to 176,224 mothers enrolled in Medicaid between 2010 and 2019. Results suggest that an infant experiencing withdrawal symptoms after birth or needing admission to intensive care is strongly associated with prenatal opioid exposure, and that this effect is concentrated among those whose mothers used illicit opioids or were undergoing medication-assisted opioid treatments in their first and third trimesters. Prenatal opioid exposure is also associated with referrals of parents to child protective services and with being born preterm, low birthweight, or small for gestational age. We find smaller effects among infants exposed to prescription opioids, but these effects are not trivial, supporting current recommendations to balance the potential for infant adverse effects with the benefits of pain management during pregnancy.


The planetary boundary layer (PBL) provides an important link between the scales and processes resolved by global atmospheric sampling/modeling and site-based flux measurements. The PBL is in direct contact with the land surface, both driving and responding to ecosystem processes. Measurements within the PBL (e.g., by radiosondes, aircraft profiles, and flask measurements) have a footprint, and thus an integrating scale, on the order of 1-100 km. We use the coupled atmosphere-biosphere model (CAB) and a Bayesian data assimilation framework to investigate the amount of biosphere process information that can be inferred from PBL measurements. We investigate the information content of PBL measurements in a two-stage study. First, we demonstrate consistency between the coupled model (CAB) and measurements, by comparing the model to eddy covariance flux tower measurements (i.e., water and carbon fluxes) and also PBL scalar profile measurements (i.e., water, carbon dioxide, and temperature) from Canadian boreal forest. Second, we use the CAB model in a set of Bayesian inversions experiments using synthetic data for a single day. In the synthetic experiment, leaf area and respiration were relatively well constrained, whereas surface albedo and plant hydraulic conductance were only moderately constrained. Finally, the abilities of the PBL profiles and the eddy covariance data to constrain the parameters were largely similar and only slightly lower than the combination of both observations.


Adaptive e-Learning systems are the newest paradigm in modern learning approaches. Nowadays, adaptive e-Learning systems are accountable for selecting learning materials or contents according to the learners' style, profile, interest, previous knowledge level, goal, pedagogical method, etc., all in order to provide highly personalized learning sessions. A number of researches have been conducted in the area of adaptive learning and different adaptive learning methods have been proposed. Due to similarity between learning objects graph and the formalism of Petri Nets, an approach based on Petri Nets for controlling the learning path among learning activities has brought many improvements to the paradigm of adaptive e-Learning systems. A model based on High-Level Petri Nets (HLPN) for modeling and generating behavioral pattern of students has been presented recently, bringing numerous advantages, but also a lot of open issues that need to be resolved. This paper exposes the fundamental characteristics of adaptive e-Learning systems, as well as the students' behavior, such as learning styles and levels of knowledge, thus providing a basis for a novel modeling framework for performance analysis of such systems, as our main goal in future research.


The assessment of knowledge, skills, and behaviors related to innovation is a challenging task. Current assessment approaches rely on idea generation tasks, surveys, or project deliverables each of which have limitations. In this paper, we present an alternative novel approach for assessing individual understanding of innovation process that we argue should be a learning outcome of any innovation education program or curricula. Our method, called the Innovation Process Mapping Protocol provides individualized assessment of knowledge and skills and takes about 30 minutes to complete. The data collected in the form of Innovation Process Maps are evaluated in two ways: using the innovation process mapping rubric and in the form of a Markov chain. We present results from two students and discuss how this instrument can be used in research studies and discuss its' potential for use as a preand post-test to evaluate growth.


In order to realize energy saving in discrete manufactures, a manufacturing process optimization system was designed and implemented based on energy consumption. Firstly energy flow and energy information flow in manufacturing enterprises were analyzed aiming at dispersive energy consumption and the problem of product energy consumption calculation. Secondly the architecture and function structure were designed, and the program language adopted and database management technology were analyzed. Thirdly some key technologies adopted in the system were introduced to realize manufacturing information interaction and ensure security, stability, and interoperability of the information. Feasibility and effectiveness of the system were verified by a case of enterprise application.


It is currently not known if repeating fast radio bursts (FRBs) are fundamentally different from those that have not been seen to repeat. One striking difference between repeaters and apparent non-repeaters in the CHIME sample is that the once-off events are typically shorter in duration than sources that have been detected two or more times. We offer a simple explanation for this discrepancy based on a selection effect due to beamed emission, in which highly-beamed FRBs are less easily observed to repeat, but are abundant enough to detect often as once-off events. The explanation predicts that there is a continuous distribution of burst duration---not a bimodal one---with a correlation between repetition rate and width. Pulse width and opening angle may be related by relativistic effects in shocks, where short-duration bursts have small solid angles due to a large common Lorentz factor. Alternatively, the relationship could be a geometric effect where narrow beams sweep past the observer more quickly, as with pulsars. Our model has implications for the FRB emission mechanism and energy scale, volumetric event rates, and the application of FRBs to cosmology. It also provides a way of predicting which sources could be seen to repeat in the future.


Hawthorn (Crataegus species) is distributed widely in Asia, North America and Europe. The fruits and leaves of hawthorn have been used to treat many health conditions. Many in vivo and in vitro studies have been carried out for its biomedical applications. Hawthorn extract possesses a range of different activities including, antioxidant, antibacterial, anti-inflammatory, anticataract, hypolipidemic, hypotensive, and anticancer activities. The present review aims to give a detailed understanding of the morphology, chemical composition, pharmacological and biomedical activities of Hawthorn. Phytochemicals like flavonoids, procyanidins, catecholamines, polysaccharides, triterpenes, have been identified evaluated for biological activities. In addition, this review discusses the clinical trials of various Crataegus plants along with the scope for future research in this aspect.


USA Government wiretapping activities is a very controversial issue. Undoubtedly this technology can assist law enforced authority to detect / identify unlawful or hostile activities; however, this task raises severe privacy concerns. In this paper, we have discussed this complex information technology issue of governmental wiretapping and how it effects both public and private liberties. Legislation has had a major impact on the uses and the stigma of wiretapping for the war on terrorism. This paper also analyzes the ethical and legal concerns inherent when discussing the benefits and concerns of wiretapping. The analysis has concluded with the effects of wiretapping laws as they relate to future government actions in their fight against terrorists.


We study the low temperature static and dynamical properties of the classical bond-disordered antiferromagnetic Heisenberg model on the kagome lattice. This model has recently been shown to host a new type of spin liquid exhibiting an exponentially large number of discrete ground states. Surprisingly, despite the rigidity of the groundstates, we establish the vanishing of the corresponding spin stiffness. Locally, the low-lying eigenvectors of the Hessian appear to exhibit a fractal inverse participation ratio. Its spin dynamics resembles that of Coulomb Heisenberg spin liquids, but exhibits a new low-temperature dynamically arrested regime, which however gets squeezed out with increasing system size. We also probe the properties of the energy landscape underpinning this behaviour, and find energy barriers between distinct ground states vanishing with system size. In turn the local minima appear highly connected and the system tends to lose memory of its inital state in an accumulation of soft directions.


Hybrid capacitive deionization (HCDI) is a derivative of capacitive deionization (CDI) method for water desalination, in which one carbon electrode is replaced with a redox-active intercalation electrode, resulting in substantial improvements in ion removal capacity over traditional CDI. The search for high-performing intercalation host compounds is ongoing. In this study, two-layered manganese oxides (LMOs), with sodium (Na-birnessite) and magnesium (Mg-buserite) ions stabilizing the interlayer region, were for the first time evaluated as HCDI electrodes for the removal of ions from NaCl and MgCl2 solutions to understand structural/compositional dynamics and electrochemical stability of LMO electrodes over extended cycling. Both materials demonstrated excellent initial ion removal performance with the highest capacities of 37.2 mg g-1 (637 μmol g-1) exhibited by Mg-buserite in NaCl solution and 50.2 mg g-1 (527 μmol g-1) exhibited by Na-birnessite in MgCl2 solution. The performance decay observed over the course of 200 ion adsorption/ion release cycles was attributed to two major phenomena: oxidation of carbon electrode and evolution of the structure/composition of LMO electrodes. The latter involves disorder in stacking of Mn-O layers and changes in the interlayer spacing/interlayer ions reflecting the composition of the solution being desalinated. This work highlights the importance of understanding the interactions between the HCDI electrodes and solutions containing different ions and the structural analysis of redox-active material in intercalation electrodes over the course of operation for gaining insight into the fundamental processes governing desalination performance and developing next-generation HCDI systems with long-term electrochemical stability.


Over the past 12 years, as directed by federal and provincial regulations, Canadian pipeline companies have been formally developing and implementing Integrity Management Programs (IMPs). Since 1999, IMPs have been a requirement in the Canadian consensus industry standard CSA Z662. Furthermore, since the release of CSA Z662 Annex N in 2005, both the BC OGC and the Alberta Energy Resources Conservation Board (ERCB) (Canadian provincial regulators) have made CSA Z662 Annex N mandatory for their regulated companies. Annex N incorporates key management system (MS) elements such as a company's policy and commitment, responsibilities, competency, planning, management of change, review and evaluation.This paper presents the findings of IMP audits conducted by the NEB and BC OGC regulators during the period of 2001–2011. This paper also includes the findings of NEB's analysis of pipeline incidents that occurred between 2005 and 2009 and how these incident findings correlate to the audit findings.This paper is structured as follows:• Integrity management regulatory frameworks• IMP and MS elements and their interconnection• Audit findings from the NEB and the BC OGC• Incident findings from the NEB• Analysis of the audit findings and their correlation to incidents• Trends on IMP and MS audit and incident findingsThe paper provides a general understanding of the findings and their trends on pipeline integrity management and on incidents in terms of IMP/MS elements as described in Table 1. The results from this study may help stakeholders to determine strategies to increase the adequacy, implementation and effectiveness of pipeline integrity management. This paper does not include any company-specific information nor results and conclusions from any particular audit report or incident.Copyright © 2012 by ASME


This article attempts to respond to a simple question: What are the factors which caused the December crisis and whether or not they have been defused since president Duhalde came to power? The answer, by contrast, does not appear to be so straightforward. After analyzing a broad range of causes, some of which were thought of as harbingers of democratic breakdown and some which are considered driving forces of the current instability, this article points out two combined causes in the Argentinean crisis: the fragmentation of the politico-institutional system and the extreme dependency of its economy on foreign credit. Given the fact that both reasons cannot be fully understood simply in terms of historical precedent, the article also looks at what is new in this case.


ABSTRACT This paper provides the first study of an untitled, large-scale painting, which the author refers to as The Creation of Mole (1946), by Mexican artist Carlos González. Commissioned for Café de Tacuba, one of Mexico City's oldest and most well-known restaurants, this painting was part of an aggressive rebranding campaign for the café, which sought to legitimize claims of Mexican culinary authenticity through evocations of Pueblan colonial heritage, including the fictive legend of the invention of Mexico's national dish, mole poblano. The paper demonstrates how and to what ends The Creation of Mole, which has been precluded from scholarly inquiry due to its commercial status, engages in meaning making at the nexus of national identity and aspirational modernity. It is argued that the labor rendered invisible in The Creation of Mole nonetheless amplifies an important kind of civic "making" present in, and perpetuated by, the painting. The confluence of mole poblano's popularized mythic invention coupled with the colonial historicity of Café de Tacuba encodes mole poblano, and Café de Tacuba's menu writ large, as foodstuffs of a collective Mexican mestizaje—an invisible but powerful phenomenon that could be consumed, absorbed, and digested.


Both the functionalist and the "reproductive" radical paradigms of formal education, though rooted in divergent ideologies, proclaim that the system of education helps to legitimate the socio-political status quo. We noted, however, that the assumption by both paradigms that students passively internalize the dominant norms and values which the school teaches is not invariably tenable. Alternatively, it was suggested that students quite often only selectively internalize from various diverse cues pertaining to the dominant norms and values presented by educators along with other agents of socialization. Therefore, it was argued that the factor of "selective internalization" coupled with the social axiom of the discord between reality (what is) and ideal (what ought to be) conduce to crisis. The body of evidence demonstrates that, in addition to its role as an agent of legitimation the system of education (the primary emphasis is on higher education) mediates the dialectical relationship between legitimation and crisis.


Abstract
Sukuk restructuring primarily aims at offering a debtor more latitude, in form and time, to settle his obligations. To meet Shari'ah requirements of transferring assets to Sukuk holders in asset-based Sukuk, the originator usually transfers the beneficial ownership to the issuer special purpose vehicles (SPV). However, in asset-backed Sukuk, the originator sells the underlying asset to an SPV and Sukuk holders do not have recourse to the originator in the event of defaults. Among some key unresolved Shari'ah issues in this regard is whether a change of contract necessitates entering a new contract. Other related issues that conflict with the tenets of Shari'ah are: (1) Sukuk structuring on tangible assets and debts; (2) receiving the full title by the Sukuk holders to the underlying assets in the event of default in case of securities that are publicized as asset backed; (3) Sukuk's similarity with interest bearing conventional bonds: (a) capital guarantee by the originator or third party, (b) the originators' promise to repurchase Sukuk at face value upon their redemption, and (c) providing internal and external credit enhancement. The Shari'ah-compliance of the above-mentioned clauses and structures of Sukuk remain debated among the Shari'ah scholars. Based on some specific cases, this study examines the Shari'ah viewpoint on sukuk restructuring and potential solutions to these unresolved Shari'ah issues in light of the past and recent declaration of some Sukuk defaults as non-Shari'ah complaints. Undoubtedly, resolution of these and other unresolved issues pertaining to Sukuk defaults can help strengthen the confidence of investors in Islamic capital market structures.


We have developed a code that semi-analytically calculates the radio footprint (intensity and polarization) of an extensive air shower subject to atmospheric electric fields. This can be used to reconstruct the height dependence of atmospheric electric field from the measured radio footprint. The various parameterizations of the spatial extent of the induced currents are based on the results of Monte-Carlo shower simulations. The calculated radio footprints agree well with microscopic CoREAS simulations.


Background Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits. Methods and Results We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six previously unreported loci at genome-wide significance (P < 5 × 10−8), three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for one or more neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity. Conclusions We discovered six novel variants individually associated with both lipids and coronary artery disease.


The structure systems with non-rigid member were classified by the composition type of line and surface members. As a result of the classification, there are 1-way cable structure, cable net and radial cable net structure in the line member system. And there are pneumatic structure and suspension membrane structure in surface member system. In addition, when the line and surface members are composed together, there is the hybrid membrane system which are divided into hanging type and supported type. In this paper, the Korean terms of structure systems with non-rigid member are recommended through this classification.


The various isomers including stable structures, carbenes, and diradicals on the C3H4 surface have been investigated. The two carbenes propenylidene and cyclopropylidene have been found to have singlet ground states. Vinylmethylene is predicted to have a triplet ground state with a planar diradical type of structure. The syn and anti forms of this state are degenerate. This is in agreement with the observation of two triplet states in the electron spin resonance (ESR) spectra. The π electrons are found to be delocalized over the three carbons. The singlet diradical structures are found to be more stable than the carbene structures, which retain the CH2 (DOUBLE BOND) CH allylic structures. The orbital compositions of the frontier orbitals of all systems have been determined to examine the nature of these orbitals. © 1996 John Wiley & Sons, Inc.


We construct an approximate Riemann solver for the isentropic Baer-Nunziato two-phase flow model, that is able to cope with arbitrarily small values of the statistical phase fractions. The solver relies on a relaxation approximation of the model for which the Riemann problem is exactly solved for subsonic relative speeds. In an original manner, the Riemann solutions to the linearly degenerate relaxation system are allowed to dissipate the total energy in the vanishing phase regimes, thereby enforcing the robustness and stability of the method in the limits of small phase fractions. The scheme is proved to satisfy a discrete entropy inequality and to preserve positive values of the statistical fractions and densities. The numerical simulations show a much higher precision and a more reduced computational cost (for comparable accuracy) than standard numerical schemes used in the nuclear industry. Finally, two test-cases assess the good behavior of the scheme when approximating vanishing phase solutions.


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

The purpose of this study was to determine the expression of envelope (env) genes from five Human Endogenous Retrovirus (HERV) family members in Endometrial Carcinomas (EnCa) and correlate with CpG-methylation of the 5′LTR HERV-W in EnCa and prestages compared to matched control tissues.

Over 85% of all EnCa are classified as endometrioid expressing steroid hormone receptors and involve prior stages, like hyperplasia. HERV families embody over 8% of the human genome and are derived from ancestral germ line retroviral infections. Sixteen different functional HERV-env genes are essential for cytotrophoblast cell-cell fusion during placentogenesis, but are also implicated in tumorigenesis. Aberrant methylation and hypomethylation are hallmarks of tumorigenesis. Hypomethylated 5′ LTRs of HERVs correlating with an increased expression have been shown for HERV-K and HERV-W (ovary) in different human carcinomas. Previously, we demonstrated a significant step-wise increase of the Syncytin-1 HERV-W env gene at both mRNA and protein levels for EnCa and prestages compared to controls. A pivotal role for Syncytin-1 in EnCa cell-cell fusions and cellular proliferation was shown using RNAi technology after treatment of cell lines with cAMP analogs or steroid hormones and tamoxifen, respectively. Tamoxifen also activated phosphorylation of AKT (Thr308) and ERα (Ser118) leading to Syncytin-1 induction via non-genomic ER signalling.

We have established methods for absolute quantification real time PCR (qPCR) for five different HERV-env genes and methylation-specific-PCR (MSP) using bisulfite treated genomic DNA. Methylated CpGs were verified by cloning and sequencing.

Gene expression results of benign and malignant tissues (EnCa n=44, polyps n=21, hyperplasia n=12) compared to control postmenopausal endometrium (n=33) showed that the HERV-env genes Syncytin-1, HERV-K, ERV-3, HERV-P(b) and Syncytin-2 were significantly up-regulated. We observed that in control endometrium the highest expressed env was ERV3; whereas in hyperplasia and EnCa Syncytin-1 was the most prominent. Methylation studies of the Syncytin-1 5′ LTR identified 20 potential CpGs where many correlated with protein binding sites, e.g. for ERα, AP-1, GATA1-3 and MeCP2. MSP results showed that the 5′LTR region was hypomethylated in tumors compared to matched controls. Cloning and sequencing of PCR fragments showed that 3-4 CpGs corresponding with protein binding sites were hypomethylated in tumors (n=10) compared to matched controls. Studies using 5′Aza-2′Cytidine treatment of EnCa cell lines resulted in a 2.5-fold increase of Syncytin-1.

In conclusion, up-regulation of Syncytin-1 in EnCa is due to specific hypomethylation of the 5′ LTR. Understanding epigenetic regulation of HERV-env genes will contribute to the molecular etiology in EnCa and stepwise induction from benign prestages but also other carcinomas.

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 4894.


The contrast with classical expectations is one of the most intriguing features of quantum mechanics. It can be illustrated by playing a classic "guessing game" with quantum rules. In this case, the answer to one question will depend on the other questions being asked and the order chosen. This dependence on the context does not conform to our everyday experience, but we may have to live with it, as theorists have shown that we can't just assume that there exists a hidden answer sheet that is unaffected by the choice of questions. However, designing a generic test of quantum contextuality in the lab has been difficult, so far. Writing in Physical Review Letters, Chong Zu of Tsinghua University in Beijing, China, and his colleagues have shown that context does matter in a three-level photon system generated by a simple but elegant linear-optics setup [1].


The Spatially Modulated (SM) photodetector and Double Photodetector (DPD) are designed in 0.5 μ m standard CMOS technology. Spice models of them are accomplished in SPECTRE environment based on analysis of its physical model. Two kinds of photodetectors and the compatible design monolithic optoelectronic integrated circuit (OEIC) with preamplifier are successfully fabricated in 0.5μm standard CMOS technology. At 850nm the measured responsivity of SM photodetector is 80mA/W at deffered terminal and 89mA/W at immediate terminal, while DPD is 40mA/W. Work frequency of SM OEIC and DPD OEIC reaches to 1.25GHz and 50MHz.


In this study, the authors propose a control structure for a class of linear time-invariant (LTI) systems with Lipschitz non-linearity and unknown time-varying input delay. This scheme considers the worst-case scenario in control design with truncated prediction feedback approach, and takes into account the information of the lower bound of delay in the stability analysis. A finite-dimensional controller is constructed, requiring neither the non-linear function nor the exact delay function. The truncated prediction deviation is minimised by employing the delay range, and then bounded by integral construction and related techniques. Within the framework of Lyapunov–Krasovskii functionals, sufficient delay–range-dependent conditions are derived for the closed-loop system to guarantee the global stability. Two numerical examples are given to validate the proposed control design.


We present analog experiments on dike propagation, followed by a numerical model of horizontal and vertical growth, which is partially analytical and partially based on empirical observations. Experimental results show that the growth rates are similar until buoyancy becomes significant and, afterward, vertical growth dominates. The numerical model is defined for different conditions in a homogeneous medium: (a) constant flux, fracture‐limited propagation; (b) constant flux, viscous‐limited propagation; and (c) variable flux dependent on the driving pressure and dike dimensions. These conditions distinguish between cases when the influx depends on the deeper source of magma (e.g., a conduit, independent of the dike geometry) and when it depends on the dike, so the influx can change as it grows. In all cases, the ratio of vertical to horizontal propagation is proportional to the ratio of buoyancy pressure to source pressure, in which buoyancy drives vertical propagation. We test the numerical model on dikes observed at Piton de la Fournaise, in which the dimensions were estimated using geodetic and seismic data. The results show that the final dimensions can be reproduced using magma‐crust density differences of 50–300 kg/m3, viscosities of 30–300 Pa·s, influxes of 50–750 m3/s and shear moduli of ∼10 GPa. The modeled magma and host rock parameters agree with previous studies of the volcano, while the flux is higher than what is typically observed during eruption. This implies a variable injection condition, in which the flux peaks during propagation and diminishes by the onset of eruption.


Some applications of Bayesian neural networks (BNN) in the high energy physics experiments are described in the present paper. They are the applications of BNN to particle identification in the second generation of BEijing Spectrometer experiment (BESII), event identification and event reconstruction in reactor neutrino experiments and supernova location in scintillator detector experiments, respectively. Compared to traditional method, better results are obtained in those experiments using BNN. So we believe that BNN can be also well applied to other fields in other experiments for the high energy physics.


Flow control techniques for turbulent drag reduction in internal flows are typically evaluated under two alternative flow conditions, i.e. at constant mass flow rate or constant pressure gradient. Succesfull control leads to reduction of drag and pumping power at constant mass flow rate, whereas constant pressure gradient leads to an increase of the mass flow rate and pumping power. In practical applications, however, a compromise between the energy consumption and the corresponding convenience (flow rate) achieved with that amount of energy has to be reached so as to accomplish a goal which in general depends on the specific application. Based on this idea, we describe the derivation of two dimensionless parameters which quantify the total energy consumption and the required time (convenience) for transporting a given volume of fluid through a given duct. Performances of existing drag reduction strategies are re-evaluated within the present framework.


The process of receiving and scheduling residency interviews for otolaryngology–head and neck surgery positions is chaotic, inducing unnecessary anxiety for applicants and introducing inefficiencies for programs. With incomplete information, applicants often accept all invitations they receive, resulting in interview hoarding and late cancellations. Various specialties have attempted to improve the interview offer and scheduling process through standardization of interview offer dates. In this commentary, we propose that otolaryngology programs adopt a uniform interview offer and scheduling date. We also advise programs commit to limiting the number of interview invitations to the number of interview slots available, and we review best practices to optimize the interview offer and scheduling process for both applicants and programs.


Question: What is the role of the relative rates of fatty acid delivery from lypolysis and of mitochondrial oxidative phosphorylation in explaining variations in intramyocellular lipid content and insulin resistance? Population: Insulin-resistant subjects (three men and 11 women) and insulin-sensitive controls (five men and seven women) who were young [26 (±7) and 28 (±7) years, respectively], lean [body mass index (BMI) of 23 (±2) and 21 (±2) kg/m2, respectively], sedentary and in general good health were studied. Insulin resistance was defined as an insulin sensitivity index1 <4.0, and a family history of type 2 diabetes (DM); insulin-sensitive controls had to have an insulin sensitivity index >6.3. Design and methods: Between 2001 and 2003, 150 individuals were screened through questionnaires and an oral glucose tolerance test (OGTT) to select subjects at extremes of insulin resistance and insulin sensitivity. 1H magnetic resonance spectroscopy (MRS) was performed to assess intracellular triglyceride content within liver and muscle cells. Subjects then either underwent (i) 31P MRS, to assess mitochondrial phosphorylation rates (a proxy of muscle ATP synthesis rates) and the ratio of inorganic phosphate-to-creatine phosphate (which reflects the ratio of oxidative to glycolytic muscle fibers); or (ii) a hyperinsulinemic-euglycemic clamp, to assess the glucose infusion required to respond to a constant insulin influx (a measure of the body's responsiveness to insulin). Two of the insulin-sensitive controls were excluded after they were found to be insulin resistant by the clamp study. Whole body energy expenditure, and fat and glucose oxidation were measured through indirect calorimetry. In vivo lipolysis was assessed through microdialysis probes. Subjects were instructed to maintain regular diets with adequate carbohydrate intake (> 150 g per day) and refrain from exercise, other than routine walking, for the 3 days before the clinic visit. Women were examined during the follicular phase to avoid the potential impact of ovarian hormones on glucose metabolism. Results: (i) Oral glucose tolerance test: levels of glucose at baseline and during the OGTT were within the normal range for both insulin-resistant and insulin-sensitive subjects, but were consistently higher in the former group. Both groups had similar levels of plasma fatty acids and glucagon. (ii) Hyperinsulinemic-euglycemic clamp: a60% lower glucose infusion rate was required in insulin-resistant subjects to maintain a euglycemic state relative to insulin-sensitive subjects, largely due to a 70% reduction in non-oxidative glucose clearance in the former group. No difference was found between groups in the rate of glucose or fat oxidation; however, the basal metabolic rate was lower in insulin-resistant subjects relative to insulin-sensitive subjects. (iii) Intracellular triglyceride content: an80% increase in intramyocellular but not intrahepatic triglyceride content was found in insulin-resistant subjects relative to insulin-sensitive subjects. (iv) Mitochondrial phosphorylation rates were decreased by 30% and the ratio of inorganic phosphate-to-creatine phosphate was decreased by 20% among insulin-resistant subjects relative to insulin-sensitive subjects. (v) Similar levels of glycosylated hemoglobin, adiponectin, tumor necrosis factor α, interleukin-6, and resistin were found in both groups. Conclusion: Insulin-resistant subjects have a marked elevation in intramyocellular lipid levels perhaps due to an inherited defect in mitochondrial oxidative phosphorylation rates.


The rheumatoid vaskulitis (RV) strikes about a quarter of patients with rheumatoid arthritis, causing defeat of visceral bodies and systems, a cachexy and progressing of articulate destruction. Therefore RV treatment - an actual problem of modern rheumatology.

Aim: To study microcirculation at sick RV and possibility of its improvement the pentoxifyllini.

Materials and methods: Research included women, patients rheumatoid artritis (n=69). Middle age - 55,54±3,22 years. Having positive antibodies to cyclic citrullined peptide (ACCP) and a positive rheumatoid factor in blood. All patients received DMARD-therapy. Microcirculation was investigated by a method of a laser Doppler flowmetri on forearm skin. Two groups of patients - intact (n=39), not receiving a preparation and research (n=30), receiving a preparation are allocated. Pentoxifyllin was entered in an average dose of 800 milligrams per day.Research was conducted within two weeks. Statistical processing carried out by means of Mann-Whitney methods.

Results: Microcirculation in the first group made 14,28±5,21 perfusion units. In the second group - 19,24±2,65 perfusion units that made statistically significant difference (p=0,00032). Clinically patients of intact group had no dynamics. The patients receiving in addition to DMARD therapy pentoxifyllin (the second group) had positive clinical dynamics of articulate and visceral syndromes. Moreover, statistically significantly lower CRP levels (p=0,0043).

Conclusion: Pentoxifyllin inclusion in a dose of 800 mg per day leads to positive clinical and laboratory dynamics at patients rheumatoid vaskulitis and can be a new target for therapy.