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Few studies have examined atopic dermatitis (AD) prevalence among Asian American and Pacific Islander (AAPI) children. Moreover, the atopic march (e.g., AD-asthma association) is under-explored in the AAPI population. We examined AD prevalence and AD-asthma association among AAPI ethnic groups.

Innate lymphoid cells (ILCs) play an important role in regulating immune responses at mucosal surfaces. The transcription factor T-bet is crucial for the function of ILC1s and NCR+ILC3s and constitutive deletion of T-bet prevents the development of these subsets. Lack of T-bet in the absence of an adaptive immune system causes microbiota-dependent colitis to occur due to aberrant ILC3 responses. Thus, T-bet expression in the innate immune system has been considered to dampen pathogenic immune responses. Here, we show that T-bet plays an unexpected role in negatively regulating innate type 2 responses, in the context of an otherwise intact immune system. Selective loss of T-bet in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally important impact on mucosal immunity, including enhanced protection from Trichinella spiralisinfection and inflammatory colitis. Mechanistically, we show that T-bet controls the intestinal ILC pool through regulation of IL-7 receptor signalling. These data demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic vs. protective mucosal immune responses, which has significant implications for the understanding of the pathogenesis of inflammatory bowel diseases and intestinal infections.

Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study is to assess the performances of a new eight channel steering‐DBS lead and compare this with a conventional cylindrical contact (CC) lead. The two leads were evaluated in a finite element electric field model combined with multicompartment neuron and axon models, representing the internal capsule (IC) fibers and subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as the configuration that activated the highest percentage of STN cells, without activating any IC fibers. With this criterion, we compared monopolar stimulation using a single contact of the steering‐DBS lead and CC lead, on three locations and four orientations of the lead. In addition, we performed a current steering test case by dividing the current over two contacts with the steering‐DBS lead in its worst‐case orientation. In most cases, the steering‐DBS lead is able to stimulate a significantly higher percentage of STN cells compared to the CC lead using single contact stimulation or using a two contact current steering protocol when there is approximately a 1 mm displacement of the CC lead. The results also show that correct placement and orientation of the lead in the target remains an important aspect in achieving the optimal stimulation outcome. Currently, clinical trials are set up in Europe with a similar design as the steering‐DBS lead. Our results illustrate the importance of the orientation of the new steering‐DBS lead in avoiding side effects induced by stimulation of IC fibers. Therefore, in clinical trials sufficient attention should be paid to implanting the steering DBS‐lead in the most effective orientation.

Redistribution layer (RDL) is one key enabling technology for advanced packaging. RDL is usually fabricated at wafer level by a photolithography process. An alternative approach for implementing RDL by additive manufacturing (AM) method is proposed in this study. This allows RDL to be fabricated on a singulated chip. Nanosilver (nano-Ag) ink is printed on the silicon chip to form routing traces and bond pads. However, the Ag pad may be consumed by the solder quickly if the reflow process is not properly controlled. The mechanical integrity of the solder joint was evaluated by both solder ball shear and die shear tests. A high temperature storage test and humidity test were carried out to evaluate the solder joint reliability. Experiment results showed that the Ag pad fabricated by AM is compatible with surface mount technology (SMT). Reliable solder joints on the Ag pad were achieved. There was no significant change in the Ag3Sn intermetallic compound (IMC) layer thickness and mechanical strength after aging at high temperature and high humidity conditions. There was no early solder joint failure observed. The finding of the present study will serve as a very useful reference for the future practice of forming solder joints on sintered nano-Ag pads.

AbstractExpert judgement is frequently used within general insurance. It tends to be a method of last resort and used where data is sparse, non-existent or non-applicable to the problem under consideration. Whilst such judgements can significantly influence the end results, their quality is highly variable. The use of the term “expert judgement” itself can lend a generous impression of credibility to what may be a little more than a guess. Despite the increased emphasis placed on the importance of robust expert judgements in regulation, actuarial research to date has focussed on the more technical or data-driven methods, with less emphasis on how to use and incorporate softer information or how best to elicit judgements from others in a way that reduces cognitive biases. This paper highlights the research that the Getting Better Judgement Working Party has conducted in this area. Specifically, it covers the variable quality of expert judgement, both within and outside the regulatory context, and presents methods that may be applied to improve its formation. The aim of this paper is to arm the insurance practitioner with tools to distinguish between low-quality and high-quality judgements and improve the robustness of judgements accordingly, particularly for highly material circumstances.

The primary aim of this study was to assess whether parents’ own anxiety and their perception of their child’s dental fear and child’s general fear can predict preoperatively their child’s behaviour during dental treatment under oral sedation. The secondary aim was to assess whether the child’s age, gender and ASA classification grade are associated with a child’s behaviour under oral sedation. Cross-sectional prospective study. The Corah’s Dental Anxiety Scale (DAS), Children’s Fear Survey Schedule Dental-Subscale (CFSS-DS) and Children’s Fear Survey Schedule Short-Form (CFSS-SF) questionnaires were completed by parents of children undergoing dental treatment with oral midazolam. Behaviour was rated by a single clinician using the overall behaviour section of the Houpt-Scale and scores dichotomised into acceptable or unacceptable behaviour. Data were analysed using χ2, ttest and logistic regression analysis. In total 404 children (215 girls, 53 %) were included, with the mean age of 4.57 years, SD = 1.9. Behaviour was scored as acceptable in 336 (83 %) and unacceptable in 68 (17 %) children. The level of a child’s dental fear, as perceived by their parent, was significantly associated with the behaviour outcome (p= 0.001). Logistic regression analysis revealed that if the parentally perceived child’s dental fear (CFSS-DS) rating was high, the odds of the child exhibiting unacceptable behaviour under oral sedation was two times greater than if their parents scored them a low dental fear rating (OR 2.27, 95 % CI 1.33–3.88, p= 0.003). CFSS-DS may be used preoperatively to help predict behaviour outcome when children are treated under oral sedation and facilitate treatment planning.

Sustained activation of nuclear factor-κB (NF-κB) in cancer cells has been shown to promote inflammation, expansion of cancer stem cell (CSC) population, and tumor development. In contrast, recent studies reveal that CSCs exhibit increased inflammation due to constitutive NF-κB activation; however, the underlying molecular mechanism remains unclear. In the present study, the analysis of microarray data revealed upregulation of NF-κB-regulated pro-inflammatory genes and downregulation of copper metabolism MURR1 domain-containing 1 (COMMD1) during the enrichment for stemness in SAS head and neck squamous-cell carcinoma (HNSCC) cells. The 3′-UTR of COMMD1 mRNA contains microRNA (miR)-205 target site. Parallel studies with HNSCC and NSCLC cells indicated that miR-205 is upregulated upon NF-κB activation and suppresses COMMD1 expression in stemness-enriched cancer cells. COMMD1 negatively regulates the inflammatory responses induced by TLR agonists, IL-1β, and TNF-α by targeting RelA for degradation. The shRNA-mediated downregulation of COMMD1 in cancer cells enhanced inflammatory response, generating favorable conditions for macrophage recruitment. In addition, genes associated with stemness were also upregulated in these cells, which exhibited increased potential for anchorage-independent growth. Furthermore, COMMD1 downregulation promoted in vivo tumorigenesis and tumor growth, and tumors derived from COMMD1-knockdown cells displayed elevated level of NF-κB activation, increased expression of inflammatory- and stemness-associated genes, and contain expanded population of tumor-associated leukocytes and stemness-enriched cancer cells. These results suggest that COMMD1 downregulation by miR-205 promotes tumor development by modulating a positive feedback loop that amplifies inflammatory- and stemness-associated properties of cancer cells.

The aim of this study was to investigate whether directional steering through a novel 32-contact electrode is safe and can modulate the thresholds for beneficial and side effects of stimulation.

BACKGROUND Myoclonus-dystonia is an autosomal dominantly inherited movement disorder clinically characterized by myoclonic jerks and dystonic postures or movements of the upper body. Functional imaging studies in other, mainly heterogeneous groups of dystonia do agree on dysfunction of the striato-pallido-thalamo-cortical circuit. OBJECTIVE To study cerebral activation patterns with functional magnetic resonance imaging in a genetically defined homogeneous group of patients with dystonia. DESIGN, SETTING, AND PATIENTS Thirteen clinically affected SGCE mutation carriers and 11 control subjects were studied in a case-control study. INTERVENTION A finger-tapping motor task was performed in a block design using 3.0-T magnetic resonance imaging. MAIN OUTCOME MEASURES Blood oxygenation level–dependent signals were compared between groups. RESULTS In SGCE mutation carriers, we observed significant hyperresponsiveness in contralateral inferior parietal cortical areas, ipsilateral premotor and primary somatosensory cortex, and ipsilateral cerebellum during the motor task compared with healthy control subjects. CONCLUSIONS The cortical activation patterns in SGCE mutation carriers during this motor task point to a disorganized sensorimotor integration in this uniform group of patients with dystonia and are consistent with functional neuroimaging studies in other types of (hereditary) dystonia.Arch Neurol. 2010;67(4):469-474--

This paper proposes a non-contacted CCD to replace contacted displacement sensors in a two-dimensional (2D) pneumatic arm control system. The CCD is used to capture images which are then transformed to X-Ycoordinates that are used as feedback signals. Since the measuring process requires considerable computational effort a self-organizing sliding mode fuzzy controller is proposed to simplify the fuzzy rules and reduce the computer load. The proposed learning mechanism can be used to optimize the fuzzy rules online and improve the control performance. Experimental data is provided on the trajectory tracking performances of the CCD-based and encoder-based 2D pneumatic arms.

The influence of spatial confinement on the structure and spectra of the Rydberg HeH molecule is analysed at the level of the variational full configuration interaction approach. The confining potential is assumed to have cylindrical symmetry, with the symmetry axis of the potential overlapping with the molecular bond. In the direction perpendicular to the axis quadratic dependence of the potential on the electron coordinates is assumed. The influence of the confining potential on the form of the potential energy curves (in particular on the bond lengths), on the electronic spectra and on the ionization due to the confinement is studied in detail.

This article discusses the benchmarking of supply chain performance in the textile and clothing industry. With the elimination of quotas from January 2005, supply chain performance has become more important than ever before. Colombia and China benefit from the recent change in trade regulations and are said to be important production bases for textile and garment imports to the U.S. market. A major challenge for the companies in the textile and garment industries after the elimination of the international apparel quotas is to improve making sourcing decisions which account for all parameters which affect profitability and customer satisfaction.

The first published results of the geodetic GPS analysis of the data from the base stations that comprise Land Victoria's GPSnet are presented. Nineteen GPS base stations distributed across the state of Victoria (Australia) make up the network, whose principal purpose aims to reduce the reliance for positioning across the state on ground marks, and satisfy the ever increasing number of GPS users desiring access to GPS base stations. This paper provides zero order ITRF2000 coordinates for the base stations and details the method used in their computation and subsequent transformation to GDA94, for use by surveyors and for reference for future geodetic studies such as deformation monitoring. Three weeks of data were analysed from April 2003, plus a supplementary one week of data from June 2002, with day-to-day coordinate repeatabilities of 1-2mm in the horizontal components and <6mm in height from both data sets. After transformation of both the mean April 2003 and June 2002 ITRF2000 coordinates to GDA94, coordinate differences were sub-centimetre for both horizontal and vertical components for all twelve stations present in both data sets, demonstrating the high quality of the data from the GPSnet base stations and the stability of the network. The potential of the GPSnet stations for atmospheric research and GPS meteorology is also demonstrated.

Ab initiopotential energy curves of the Rydberg NeH molecule in the presence of cylindrical spatial confinement were computed by the method of multi-reference configuration interaction with extended basis sets. The influence of the applied potential to the structures and spectra of the ground and excited states of NeH was analysed in terms of perturbation theory. In addition, the phenomenon of field-induced ionization was discussed.

ABSTRACTWe compared the clinical and laboratory features of human immunodeficiency virus (HIV)- and non-HIV-infected patients with penicilliosis marneffei. HIV-infected patients had a higher incidence of fungemia. A total of 85.7% of the HIV-negative patients had underlying diseases including hematologic malignancies or had received therapy with corticosteroids or cytotoxic agents. By aPenicillium marneffei-specific mannoprotein Mp1p enzyme-linked immunosorbent assay, serum antigen titers were found to be higher in HIV-positive patients, whereas serum antibody levels were found to be higher in HIV-negative patients.

Microfabricated capillary array electrophoresis (μCAE) microchannel plates are the next generation of bioanalytical separation devices. To fully exploit the capabilities of μCAE devices, supporting technology such as robotic sample loading, gel loading, microplate washing, and data analysis must be developed. Here, we describe a device for loading gel into radial capillary array electrophoresis microplates and for plate washing and drying. The microplates are locked into a loading module, and high-pressure helium is used to drive aqueous separation media or wash solutions into the microchannels through fixtures connected to the central anode reservoir. Microplates are rapidly (30 s to 5 min) loaded with separation media, such as 3%–4.8% linear polyacrylamide or 0.7%–3.0% hydroxyethyl cellulose, for electrophoresis. The effective and rapid gel-filling and plate-cleaning methods together with short electrophoretic analysis times (2–30 min) make μCAE systems versatile and powerful nucleic acid analysis platforms.

Escherichia coli ClpA and ClpX are ATP-dependent protein unfoldases that each interact with the protease, ClpP, to promote specific protein degradation. We have used limited proteolysis and deletion analysis to probe the conformations of ClpA and ClpX and their interactions with ClpP and substrates. ATP gamma S binding stabilized ClpA and ClpX such that that cleavage by lysylendopeptidase C occurred at only two sites. Both proteins were cleaved within in a loop preceding an alpha-helix-rich C-terminal domain. Although the loop varies in size and composition in Clp ATPases, cleavage occurred within and around a conserved triad, IG(F/L). Binding of ClpP blocked this cleavage, and prior cleavage at this site rendered both ClpA and ClpX defective in binding and activating ClpP, suggesting that this site is involved in interactions with ClpP. ClpA was also cut at a site near the junction of the two ATPase domains, whereas the second cleavage site in ClpX lay between its N-terminal and ATPase domains. ClpP did not block cleavage at these other sites. The N-terminal domain of ClpX dissociated upon cleavage, and the remaining ClpXDeltaN remained as a hexamer, associated with ClpP, and expressed ATPase, chaperone, and proteolytic activity. A truncated mutant of ClpA lacking its N-terminal 153 amino acids also formed a hexamer, associated with ClpP, and expressed these activities. We propose that the N-terminal domains of ClpX and ClpA lie on the outside ring surface of the holoenzyme complexes where they contribute to substrate binding or perform a gating function affecting substrate access to other binding sites and that a loop on the opposite face of the ATPase rings stabilizes interactions with ClpP and is involved in promoting ClpP proteolytic activity.

Extensive development of the structure−activity relationships of a screening lead determined three important pharmacophores for gonadotropin-releasing hormone (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N-4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5-trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1) as a potent antagonist of the GnRH receptor. A 10⁴-fold increase in in vitro binding affinity is observed for the GnRH receptor as compared to the initial screening lead. Compound 1 exhibits nanomolar binding activity and functional antagonism at the human receptor and is 7-fold less active at the rhesus receptor. Intravenous administration of compound 1 to rhesus monkeys results in a significant decrease of the serum levels of downstream hormones, luteinizing hormone (79% decrease in area under the curve) and testosterone (92% decrease in area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl antagonist for the human GnRH receptor that is efficacious for the suppression of luteinizing hormone and testosterone in primates.

ABSTRACTNinety-one ampicillin-resistant Shigella flexneristrains from Hong Kong and Shanghai were studied for production of β-lactamases. TEM-1-like and OXA-1-like enzymes were identified in 21 and 79% of the strains, respectively, by isoelectric focusing (IEF). No difference in the pattern of β-lactamase production was found between strains from Hong Kong and Shanghai. Four ribotypes were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1-like strains harbored a plasmid which hybridized positively with theblaTEMprobe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel. The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned, sequenced, and found to differ from blaOXA-1at codon 131 (AGA→GGA; Arg to Gly), resulting in the novel designation OXA-30. The predominance of OXA-type enzymes in ampicillin-resistantS. flexnerisuggests host preference for specific β-lactamases.

Ninety-one ampicillin-resistant Shigella flexneri strains from Hong Kong and Shanghai were studied for production of beta-lactamases. TEM-1-like and OXA-1-like enzymes were identified in 21 and 79% of the strains, respectively, by isoelectric focusing (IEF). No difference in the pattern of beta-lactamase production was found between strains from Hong Kong and Shanghai. Four ribotypes were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1-like strains harbored a plasmid which hybridized positively with the bla(TEM) probe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel. The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned, sequenced, and found to differ from bla(OXA-1) at codon 131 (AGA-->GGA; Arg to Gly), resulting in the novel designation OXA-30. The predominance of OXA-type enzymes in ampicillin-resistant S. flexneri suggests host preference for specific beta-lactamases.

Bacteria possessing TEM‐1‐like β‐lactamases are generally regarded as susceptible to ampicillin‐sulbactam (SAM), while those harboring OXA‐1 enzymes are considered resistant. The current study was undertaken to compare susceptibility testing using various combinations of ampicillin and sulbactam to improve clinical correlation. Members of the Enterobaeteriaceaefamily harboring TEM‐1, SHV‐1 or OXA‐1‐like β‐lactamases were tested using the agar dilution method. A substantial proportion of strains harboring OXA‐1‐like β‐lactamases showed false susceptibility to SAM at the 1:1 ratio or fixed sulbactam concentration of 8 μg/ml. At a fixed sulbactam concentration of 4 μg/ml, the activity of ampicillin‐sulbactam appeared to be reduced, with large numbers of TEM‐1 producers becoming frankly resistant. Results obtained with the 2:1 ratio exhibited the closest correlation with that obtained by the currently recommended disk diffusion test. However, very major errors were still found between the disk diffusion test and agar dilution test, suggesting the necessity for consideration of a change in criteria for interpretation of disk diffusion test results. In conclusion, SAM susceptibility testing by agar dilution using other than a 2:1 ratio is not recommended and results should be interpreted with caution.

Correlation between in vitrosusceptibility results for amoxicillin‐clavulanate (AMC) and ampicillin‐sulbactam (SAM) was studied using 136 clinical and control strains of Enterobacteriaceaeharboring TEM‐1, SHV‐1 or OXA‐1‐like β‐lactamases. Determination of minimal inhibitory concentration of antibiotics was performed by agar dilution. The β‐lactamases were initially characterized using isoelectric focusing. Further identification was done by DNA hybridization with or without prior PCR amplification. All strains sensitive to SAM were found to be sensitive also to AMC. In contrast, among those susceptible to AMC, only 50% were sensitive to SAM while 36% gave intermediate results and 14% were resistant. Major differences were found solely among SHV‐producers while minor differences occurred mostly among TEM‐producers. This phenomenon is probably related to the differential activities of clavulanate and sulbactam against various β‐lactamases. In conclusion, testing of Enterobacteriaceaeisolates for susceptibility to AMC and SAM should be performed and reported individually to avoid erroneous designation of susceptibility.