Experiences of coercion to sterilize and forced sterilization among women living with HIV in Latin America.

PubMed

Kendall, Tamil; Albert, Claire

2015-01-01

Forced and coerced sterilization is an internationally recognized human rights violation reported by women living with HIV (WLHIV) around the globe. Forced sterilization occurs when a person is sterilized without her knowledge or informed consent. Coerced sterilization occurs when misinformation, intimidation tactics, financial incentives or access to health services or employment are used to compel individuals to accept the procedure. Drawing on community-based research with 285 WLHIV from four Latin American countries (El Salvador, Honduras, Mexico and Nicaragua), we conduct thematic qualitative analysis of reports of how and when healthcare providers pressured women to sterilize and multivariate logistic regression to assess whether social and economic characteristics and fertility history were associated with pressure to sterilize. A quarter (23%) of the participant WLHIV experienced pressure to sterilize post-diagnosis. WLHIV who had a pregnancy during which they (and their healthcare providers) knew their HIV diagnosis were almost six times more likely to experience coercive or forced sterilization than WLHIV who did not have a pregnancy with a known diagnosis (OR 5.66 CI 95% 2.35-13.58 p≤0.001). WLHIV reported that healthcare providers told them that living with HIV annulled their right to choose the number and spacing of their children and their contraceptive method, employed misinformation about the consequences of a subsequent pregnancy for women's and children's health, and denied medical services needed to prevent vertical (mother-to-child) HIV transmission to coerce women into accepting sterilization. Forced sterilization was practiced during caesarean delivery. The experiences of WLHIV indicate that HIV-related stigma and discrimination by healthcare providers is a primary driver of coercive and forced sterilization. WLHIV are particularly vulnerable when seeking maternal health services. Health worker training on HIV and reproductive rights, improving counselling on HIV and sexual and reproductive health for WLHIV, providing State mechanisms to investigate and sanction coercive and forced sterilization, and strengthening civil society to increase WLHIV's capacity to resist coercion to sterilize can contribute to preventing coercive and forced sterilization. Improved access to judicial and non-judicial mechanisms to procure justice for women who have experienced reproductive rights violations is also needed.

Fabrication of CoFe2O4 ferrite nanowire arrays in porous silicon template and their local magnetic properties

NASA Astrophysics Data System (ADS)

Hui, Zheng; Man-Gui, Han; Long-Jiang, Deng

2016-02-01

CoFe2O4 ferrite nanowire arrays are fabricated in porous silicon templates. The porous silicon templates are prepared via metal-assisted chemical etching with gold (Au) nanoparticles as the catalyst. Subsequently, CoFe2O4 ferrite nanowires are successfully synthesized into porous silicon templates by the sol-gel method. The magnetic hysteresis loop of nanowire array shows an isotropic feature of magnetic properties. The coercivity and squareness ratio (Mr/Ms) of ensemble nanowires are found to be 630 Oe (1 Oe, = 79.5775 A·m-1 and 0.4 respectively. However, the first-order reversal curve (FORC) is adopted to reveal the probability density function of local magnetostatic properties (i.e., interwire interaction field and coercivity). The FORC diagram shows an obvious distribution feature for interaction field and coercivity. The local coercivity with a value of about 1000 Oe is found to have the highest probability. Project supported by the National Natural Science Foundation of China (Grant No. 61271039), the Scientific Projects of Sichuan Province, China (Grant No. 2015HH0016), and the Natural Science Foundations of Zhejiang Province, China (Grant Nos. LQ12E02001 and Y107255).

Developing high coercivity in large diameter cobalt nanowire arrays

NASA Astrophysics Data System (ADS)

Montazer, A. H.; Ramazani, A.; Almasi Kashi, M.; Zavašnik, J.

2016-11-01

Regardless of the synthetic method, developing high magnetic coercivity in ferromagnetic nanowires (NWs) with large diameters has been a challenge over the past two decades. Here, we report on the synthesis of highly coercive cobalt NW arrays with diameters of 65 and 80 nm, which are embedded in porous anodic alumina templates with high-aspect-ratio pores. Using a modified electrochemical deposition method enabled us to reach room temperature coercivity and remanent ratio up to 3000 Oe and 0.70, respectively, for highly crystalline as-synthesized hcp cobalt NW arrays with a length of 8 μm. The first-order reversal curve (FORC) analysis showed the presence of both soft and hard magnetic phases along the length of the resulting NWs. To develop higher coercive fields, the length of the NWs was then gradually reduced in order from bottom to top, thereby reaching NW sections governed by the hard phase. Consequently, this resulted in record high coercivities of 4200 and 3850 Oe at NW diameters of 65 and 80 nm, respectively. In this case, the FORC diagrams confirmed a significant reduction in interactions between the magnetic phases of the remaining sections of NWs. At this stage, x-ray diffraction (XRD) and dark-field transmission electron microscopy analyses indicated the formation of highly crystalline bamboo-like sections along the [0 0 2] direction during a progressive pulse-controlled electrochemical growth of NW arrays under optimized parameters. Our results both provide new insights into the growth process, crystalline characteristics and magnetic phases along the length of large diameter NW arrays and, furthermore, develop the performance of pure 3d transition magnetic NWs.

Magnetic properties enhancement of melt spun CoZrB ribbons by elemental substitutions

NASA Astrophysics Data System (ADS)

Chang, H. W.; Tsai, C. F.; Hsieh, C. C.; Shih, C. W.; Chang, W. C.; Shaw, C. C.

2013-11-01

Effect of elemental substitution of M (M=C, Cu, Ga, Al and Si) for Zr on the magnetic properties, phase evolution, and microstructure of melt spun Co80Zr18-xMxB2 (x=0-2) ribbons have been investigated. The x-ray diffraction (XRD) and thermal magnetic analysis (TMA) results showed that two magnetically soft phases, namely fcc-Co and Co23Zr6, coexisted with hard phase Co5Zr in Co80Zr17M1B2 ribbons with M=Cu, Ga, Al and Si, while an extra unknown magnetic phase was present in ribbons with M=C. The ribbons with M=C and Si were found to improve the remanence (σr) of the Co80Zr17M1B2 ribbons. However, only M=Si could improve the whole magnetic properties, including Br, intrinsic coercivity (iHc) and energy product ((BH)max) of the above ribbons. The optimal magnetic properties of Br=5.2 kG, iHc=4.5 kOe, and (BH)max=5.3 MGOe were obtained in Co80Zr17Si1B2 ribbons, which possessed Co5Zr and minor fcc-Co phases with much finer grain size (10-30 nm) in comparison with its counterpart Co80Zr18B2 (20-60 nm).

How are Inner Hair Cells Stimulated? Evidence for multiple mechanical drives

PubMed Central

Guinan, John J.

2013-01-01

Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz. PMID:22959529

Experiences of coercion to sterilize and forced sterilization among women living with HIV in Latin America

PubMed Central

Kendall, Tamil; Albert, Claire

2015-01-01

Introduction Forced and coerced sterilization is an internationally recognized human rights violation reported by women living with HIV (WLHIV) around the globe. Forced sterilization occurs when a person is sterilized without her knowledge or informed consent. Coerced sterilization occurs when misinformation, intimidation tactics, financial incentives or access to health services or employment are used to compel individuals to accept the procedure. Methods Drawing on community-based research with 285 WLHIV from four Latin American countries (El Salvador, Honduras, Mexico and Nicaragua), we conduct thematic qualitative analysis of reports of how and when healthcare providers pressured women to sterilize and multivariate logistic regression to assess whether social and economic characteristics and fertility history were associated with pressure to sterilize. Results A quarter (23%) of the participant WLHIV experienced pressure to sterilize post-diagnosis. WLHIV who had a pregnancy during which they (and their healthcare providers) knew their HIV diagnosis were almost six times more likely to experience coercive or forced sterilization than WLHIV who did not have a pregnancy with a known diagnosis (OR 5.66 CI 95% 2.35–13.58 p≤0.001). WLHIV reported that healthcare providers told them that living with HIV annulled their right to choose the number and spacing of their children and their contraceptive method, employed misinformation about the consequences of a subsequent pregnancy for women's and children's health, and denied medical services needed to prevent vertical (mother-to-child) HIV transmission to coerce women into accepting sterilization. Forced sterilization was practiced during caesarean delivery. Conclusions The experiences of WLHIV indicate that HIV-related stigma and discrimination by healthcare providers is a primary driver of coercive and forced sterilization. WLHIV are particularly vulnerable when seeking maternal health services. Health worker training on HIV and reproductive rights, improving counselling on HIV and sexual and reproductive health for WLHIV, providing State mechanisms to investigate and sanction coercive and forced sterilization, and strengthening civil society to increase WLHIV's capacity to resist coercion to sterilize can contribute to preventing coercive and forced sterilization. Improved access to judicial and non-judicial mechanisms to procure justice for women who have experienced reproductive rights violations is also needed. PMID:25808633

Determining the effect of grain size and maximum induction upon coercive field of electrical steels

NASA Astrophysics Data System (ADS)

Landgraf, Fernando José Gomes; da Silveira, João Ricardo Filipini; Rodrigues-Jr., Daniel

2011-10-01

Although theoretical models have already been proposed, experimental data is still lacking to quantify the influence of grain size upon coercivity of electrical steels. Some authors consider a linear inverse proportionality, while others suggest a square root inverse proportionality. Results also differ with regard to the slope of the reciprocal of grain size-coercive field relation for a given material. This paper discusses two aspects of the problem: the maximum induction used for determining coercive force and the possible effect of lurking variables such as the grain size distribution breadth and crystallographic texture. Electrical steel sheets containing 0.7% Si, 0.3% Al and 24 ppm C were cold-rolled and annealed in order to produce different grain sizes (ranging from 20 to 150 μm). Coercive field was measured along the rolling direction and found to depend linearly on reciprocal of grain size with a slope of approximately 0.9 (A/m)mm at 1.0 T induction. A general relation for coercive field as a function of grain size and maximum induction was established, yielding an average absolute error below 4%. Through measurement of B50 and image analysis of micrographs, the effects of crystallographic texture and grain size distribution breadth were qualitatively discussed.

Men pressured and forced into sexual experience.

PubMed

Struckman-Johnson, C; Struckman-Johnson, D

1994-02-01

A predominantly heterosexual sample of 204 college men were asked to report incidents of pressured or forced sexual touch or intercourse since age 16. About 34% indicated they had received coercive sexual contact: 24% from women, 4% from men, and 6% from both sexes. Contact involved only sexual touching for 12% and intercourse for 22%. Sexual contact was pressured in 88% of the 81 reported incidents by tactics of persuasion, intoxication, threat of love withdrawal, and bribery. In 12% of the incidents, sexual contact was forced through physical restraint, physical intimidation, threat of harm, or harm. Contact was initiated by an acquaintance or intimate in 77% of incidents. The negative emotional impact of male contact was rated significantly higher than the impact of female contact. Men with and without coercion experience did not differ, however, for scale scores on sexual esteem, depression, and preoccupation. Interviews with 10 subjects revealed complex reactions to coercive male and female contact, including doubts about one's sexuality, resentment of unexpected or forceful contact, and fear of telling others about the event.

High-coercivity, thermally stable and low unblocking temperature magnetic phase: Implications for Archeomagnetic studies

NASA Astrophysics Data System (ADS)

Hartmann, G. A.; Gallet, Y.; Trindade, R. I.; Genevey, A.; Berquo, T. S.; Neumann, R.; Le Goff, M.

2013-05-01

The thermoremanent magnetization in baked clay archeological materials provide very useful information on the time evolution of the Earth's magnetic field over the past few millennia. In these materials, a thermally stable magnetic phase characterized by high coercivities (>400 mT) and low unblocking temperatures (~200 degrees Celsius) has recently been recognized in European bricks, tiles, kilns and hearth samples. Both the identification and the origin of this phase remain, however, poorly constrained. The very same high-coercivity, thermally stable, low unblocking temperature (HCSLT) magnetic phase has been identified in Brazilian bricks fragments dated of the past five centuries. We report here a large set of measurements on a selected collection of samples showing variable contributions of the HCSLT phase. These measurements include low-field magnetic susceptibility vs. temperature curves, hysteresis loops, isothermal remanent magnetization (IRM) acquisition, thermal demagnetization of the three-axis IRM, first order reversal curves (FORC), low-temperature magnetization experiments (remanent magnetization curves and alternating current susceptibility), Mössbauer spectroscopy and X-ray diffraction. Results show the coexistence of low-coercivity magnetic minerals (magnetite and titanomagnetite) and high-coercivity minerals (hematite, HCSLT phase and, in some cases, goethite). We note that the HCSLT magnetic phase is always found in association with hematite. We further observe that the Mössbauer spectroscopy, X-ray diffraction spectra, and the FORC diagrams are also very similar to results previously obtained from annealed clays in which nontronite or iron-rich montmorillonite was transformed into Al-substituted hematite by heating. The HCSLT magnetic phase is thus confidently identified as being hematite with Al substitution. Moreover, considering the abundance of montmorillonite in clay mining settings, we suggest that the widespread occurrence of HCSLT in archeological materials predominantly originates from the transformation of iron-rich montmorillonite during the manufacturing (heating) process.

Discrimination of Thermal versus Mechanical Effects of Shock on Rock Magnetic Properties of Spherically Shocked up to 10-160 GPa Basalt and Diabase

NASA Astrophysics Data System (ADS)

Bezaeva, N. S.; Swanson-Hysell, N.; Tikoo, S.; Badyukov, D. D.; Kars, M. A. C.; Egli, R.; Chareev, D. A.; Fairchild, L. M.

2016-12-01

Understanding how shock waves generated during hypervelocity impacts affect rock magnetic properties is key for interpreting the paleomagnetic records of lunar rocks, meteorites, and cratered planetary surfaces. Laboratory simulations of impacts show that ultra-high shocks may induce substantial post-shock heating of the target material. At high pressures (>10 GPa), shock heating occurs in tandem with mechanical effects, such as grain fracturing and creation of crystallographic defects and dislocations within magnetic grains. This makes it difficult to conclude whether shock-induced changes in the rock magnetic properties of target materials are primarily associated with mechanical or thermal effects. Here we present novel experimental methods to discriminate between mechanical and thermal effects of shock on magnetic properties and illustrate it with two examples of spherically shocked terrestrial basalt and diabase [1], which were shocked to pressures of 10 to >160 GPa, and investigate possible explanations for the observed shock-induced magnetic hardening (i.e., increase in remanent coercivity Bcr). The methods consist of i) conducting extra heating experiments at temperatures resembling those experienced during high-pressure shock events on untreated equivalents of shocked rocks (with further comparison of Bcr of shocked and heated samples) and ii) quantitative comparison of high-resolution first-order reversal curve (FORC) diagrams (field step: 0.5-0.7 mT) for shocked, heated and untreated specimens. Using this approach, we demonstrated that the shock-induced coercivity hardening in our samples is predominantly due to solid-state, mechanical effects of shock rather than alteration associated with shock heating. Indeed, heating-induced changes in Bcr in the post-shock temperature range were minor. Visual inspection of FORC contours (in addition to detailed analyses) reveals a stretching of the FORC distribution of shocked sample towards higher coercivities, consistent with shock-induced hardening. However, shock does not alter the intrinsic shape of coercivity and the shape of FORC contours (apart from field scaling) while heating does, which is seen as a significant alteration of FORC contours. Reference: [1] Swanson-Hysell N. L. et al. 2014. G3 15:2039-2047.

Simultaneous magnetic investigations of Cu precipitation and recovery in thermally aged Fe-Cu alloy by first-order-reversal-curves

NASA Astrophysics Data System (ADS)

Kobayashi, Satoru; Kawagoe, Riko; Murakami, Hiroaki

2018-05-01

We have measured first-order reversal curves (FORCs) for Fe-1wt%Cu alloy thermally aged at 753 K up to 20000 min. While hardness exhibits a maximum at around 1000 min, reflecting the formation and growth of Cu precipitates, major-loop coercivity monotonically decreases and becomes almost constant above 100 min.; an increase of coercivity associated with Cu precipitation is masked by a large decrease due to recovery. On the other hand, FORC diagrams exhibit two distribution peaks at low and high switching fields after aging. While the former shifts towards a lower switching field after aging, reflecting recovery, the latter shows up after aging up to ˜1000 min, possibly due to the formation of Cu precipitates. These observations demonstrate that FORCs are useful to separately evaluate competing microstructural changes in thermally aged Fe-Cu alloy where recovery and Cu precipitation take place simultaneously.

Spontaneous activity of cochlear hair cells triggered by fluid secretion mechanism in adjacent support cells

PubMed Central

Wang, Han Chin; Lin, Chun-Chieh; Cheung, Rocky; Zhang-Hooks, YingXin; Agarwal, Amit; Ellis-Davies, Graham; Rock, Jason; Bergles, Dwight E.

2015-01-01

Summary Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl− efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl− channels. Release of Cl− from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea, and prevents ATP-dependent shrinkage of supporting cells. These results indicate that support cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells. PMID:26627734

Roughness-Induced Magnetic Domain in Fe Thin Films on Land-and-Groove Structures Studied by Spin-Polarized Secondary Electron Microscopy

NASA Astrophysics Data System (ADS)

Ueda, Shigenori; Iwasaki, Yoh; Ushioda, Sukekatsu

2003-10-01

The magnetic domain structures of Fe thin films on two-dimensionally arranged land-and-groove structures have been studied by spin-polarized secondary electron microscopy (SP-SEM) under an applied dc field. The coercive force on the land area was found to be higher than that on the groove area under magnetization reversal. The surface roughness measured by atomic force microscopy (AFM) was greater on the land area than on the groove area. The roughness-induced high-coercivity on the land prevented the reversed magnetic domain on the groove from spreading over the land in the initial magnetization reversal. This result indicates that surface roughness is an important factor in domain size control of thin magnetic films.

Nonlinear geometric scaling of coercivity in a three-dimensional nanoscale analog of spin ice

NASA Astrophysics Data System (ADS)

Shishkin, I. S.; Mistonov, A. A.; Dubitskiy, I. S.; Grigoryeva, N. A.; Menzel, D.; Grigoriev, S. V.

2016-08-01

Magnetization hysteresis loops of a three-dimensional nanoscale analog of spin ice based on the nickel inverse opal-like structure (IOLS) have been studied at room temperature. The samples are produced by filling nickel into the voids of artificial opal-like films. The spin ice behavior is induced by tetrahedral elements within the IOLS, which have the same arrangement of magnetic moments as a spin ice. The thickness of the films vary from a two-dimensional, i.e., single-layered, antidot array to a three-dimensional, i.e., multilayered, structure. The coercive force, the saturation, and the irreversibility field have been measured in dependence of the thickness of the IOLS for in-plane and out-of-plane applied fields. The irreversibility and saturation fields change abruptly from the antidot array to the three-dimensional IOLS and remain constant upon further increase of the number of layers n . The coercive force Hc seems to increase logarithmically with increasing n as Hc=Hc 0+α ln(n +1 ) . The logarithmic law implies the avalanchelike remagnetization of anisotropic structural elements connecting tetrahedral and cubic nodes in the IOLS. We conclude that the "ice rule" is the base of mechanism regulating this process.

Magnetic Force Microscopy Investigation of Magnetic Domains in Nd2Fe14B

NASA Astrophysics Data System (ADS)

Talari, Mahesh Kumar; Markandeyulu, G.; Rao, K. Prasad

2010-07-01

Remenance and coercivity in Nd2Fe14B materials are strongly dependent on the microstructural aspects like phases morphology and grain size. The coercivity (Hc) of a magnetic material varies inversely with the grain size (D) and there is a critical size below which Hc∝D6. Domain wall pinning by grain boundaries and foreign phases is the important mechanism in explaining the improvement in coercivity and remenance. Nd2Fe14B intermetallic compound with stochiometric composition was prepared from pure elements (Nd -99.5%, Fe—99.95%, B -99.99%) by arc melting in argon atmosphere. Magnetic Force Microscope (MFM) gives high-resolution magnetic domain structural information of ferromagnetic samples. DI-3100 Scanning Probe Microscope with MESP probes was used For MFM characterization of the samples. Magnetic domains observed in cast ingots were very long (up to 40 μm were observed) and approximately 1-5 μm wide due to high anisotropy of the compounds. Magnetic domains have displayed different image contrast and morphologies at different locations of the samples. The domain morphologies and image contrast obtained in this analysis were explained in this paper.

Gender differences in patterns of experienced sexual coercion and associated vulnerability factors among young people in the Netherlands.

PubMed

Kuyper, Lisette; de Wit, John; Smolenski, Derek; Adam, Philippe; Woertman, Liesbeth; van Berlo, Willy

2013-11-01

The development of effective policies and programs to prevent sexual coercion among young people requires thorough understanding of the diversity of coercive sexual experiences, patterns in such types of experiences, and similarities and differences between subgroups, especially by gender, in patterns of coercive sexual experiences and associations with potential vulnerability factors. The present online self-report study assessed a wide range of coercive sexual experiences and potential vulnerability factors among a sociodemographically diverse sample of 1,319 young people (16-25 years old) in The Netherlands. Findings confirm that sexual coercion comprises a diversity of experiences, with rates differing substantially across types of coercion. Latent class analysis revealed distinct patterns of coercive sexual experiences for young women and young men. Among young men, three patterns of experiences were found: no coercive sexual experiences, experience with verbal pressure, and experience with verbal pressure as well as coercion related to alcohol intoxication. Among young women, four patterns of coercive experiences were identified. In addition to the three patterns observed among young men, a fourth pattern encompassed experiences with verbal pressure as well as the use of force or violence. Higher numbers of sexual partners, lower levels of sexual refusal skills, and higher levels of token resistance were consistently associated with increased vulnerability. Findings illustrate the importance of communication skills and suggest that sexual communication training should be an integral part of sexuality education.

Subjective experience of coercion in psychiatric care: a study comparing the attitudes of patients and healthy volunteers towards coercive methods and their justification.

PubMed

Mielau, J; Altunbay, J; Gallinat, J; Heinz, A; Bermpohl, F; Lehmann, A; Montag, C

2016-06-01

Under certain conditions, coercive interventions in psychotic patients can help to regain insight and alleviate symptoms, but can also traumatize subjects. This study explored attitudes towards psychiatric coercive interventions in healthy individuals and persons suffering from schizophrenia, schizoaffective or bipolar disorder. The impact of personal history of coercive treatment on preferences concerning clinical management of patients unable to consent was investigated. Six case vignettes depicting scenarios of ethical dilemmas and demanding decisions in favour of or against coercive interventions were presented to 60 healthy volunteers and 90 patients. Structured interviews focusing on experienced coercion were performed in conjunction with the Coercion Experience Scale and the Admission Experience Survey. Symptom severity, psychosocial functioning and insight into illness were assessed as influencing variables. Student's t tests compared patients' and controls' judgments, followed by regression analyses to define the predictive value of symptoms and measures of coercion on judgments regarding the total patient sample and patients with experience of fixation. Patients and non-psychiatric controls showed no significant difference in their attitudes towards involuntary admission and forced medication. Conversely, patients more than controls significantly disapproved of mechanical restraint. Subjective experience of coercive interventions played an important role for the justification of treatment against an individual's "natural will". Factors influencing judgments on coercion were overall functioning and personal experience of treatment effectiveness and fairness. Qualitative and quantitative aspects of perceived coercion, in addition to insight into illness, predicted judgments of previously fixated patients. Results underline the importance of the quality of practical implementation and care, if coercive interventions cannot be avoided.

Systematic impact of institutional pressures on safety climate in the construction industry.

PubMed

He, Qinghua; Dong, Shuang; Rose, Timothy; Li, Heng; Yin, Qin; Cao, Dongping

2016-08-01

This paper explores how three types of institutional pressure (i.e., coercive, mimetic and normative pressures) systematically impact on the safety climate of construction projects. These impacts are empirically tested by survey data collected from 186 questionnaires of construction companies operating in Shanghai, China. The results, obtained by partial least squares analysis, show that organizational management commitment to safety and employee involvement is positively related to all three institutional pressures, while the perception of responsibility for safety and health is significantly influenced by coercive and mimetic pressure. However, coercive and normative pressures have no significant effect on the applicability of safety rules and work practices, revealing the importance of external organizational pressures in improving project safety climate from a systematic view. The findings also provide insights into the use of institutional forces to facilitate the improvement of safety climate in the construction industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spin reorientation transition and hard magnetic properties of MnBi intermetallic compound

NASA Astrophysics Data System (ADS)

Suzuki, K.; Wu, X.; Ly, V.; Shoji, T.; Kato, A.; Manabe, A.

2012-04-01

The effects of mechanical grinding (MG) on the crystallite size, the spin reorientation transition temperature (TSR) and the hard magnetic properties in melt-spun low temperature phase (LTP) MnBi have been investigated in order to understand the origin of magnetic hardening induced by MG. The room-temperature coercive field (μ0Hcj) is enhanced dramatically from 0.08 T before MG to 1.5 T after MG for 43.2 ks while TSR is concurrently suppressed from 110 to 38 K. The coercive force exhibits positive temperature dependence approximately 50-60 K above TSR and the lowered TSR after MG could result in magnetic hardening at room temperature. The room-temperature coercive force of LTP-MnBi is highly dependent on the crystallite size (D) and is found to be described phenomenologically by the following relationship: μ0Hcj = μ0Ha(δ/D)n, where μ0Ha is ˜ 4 T, the Bloch wall width δ is 7 nm, and the exponent n is approximately 0.7. Our results suggest that the grain refinement is the primary origin of the hardening effect induced by MG with a possible minor hardening effect due to the suppression of the spin reorientation transition temperature.

Irreversible evolution of angular-dependent coercivity in Fe80Ni20 nanowire arrays: Detection of a single vortex state

NASA Astrophysics Data System (ADS)

Alikhani, M.; Ramazani, A.; Almasi Kashi, M.; Samanifar, S.; Montazer, A. H.

2016-09-01

The irreversible evolution of magnetic coercivity in arrays of 75 nm diameter Fe80Ni20 nanowires (NWs) has been explored by means of first-order reversal curve (FORC) analysis as a function of the angle between the magnetic field and the NW axis (0°≤θ≤90°). The Fe80Ni20 NWs with lengths up to 60 μm were fabricated using a pulsed electrodeposition method into hard-anodic aluminum oxide templates with an interpore distance of 275 nm. Investigating the interwire and intrawire magnetostatic interactions, the angular FORC (AFORC) diagrams indicated enhanced intrawire interactions with increasing length and θ (<90°), induced by a magnetization reversal through vortex domain wall (VDW) propagation. Intriguingly, in addition to the VDW mode, a single vortex state with broad irreversible switching of nucleation and annihilation fields was detected at θ=83° for 60 μm long NWs. At θ=90°, the NWs reversed magnetization through transverse domain wall, involving a reversible component by a fraction of 95%. Furthermore, the transition angle between the reversal modes was found to decrease with increasing aspect ratio from 200 to 800. The irreversible angular-dependent coercivity (HcIrrev(θ)) of Fe80Ni20 NWs was extracted from the AFORC measurements and compared with the major angular dependence of coercivity (HcMajor(θ)) obtained from the conventional hysteresis loop measurements. While HcMajor(θ) showed a non-monotonic behavior, HcIrrev(θ) constantly increased with increasing θ (<90°). On the other hand, using analytical models, a 93% agreement was obtained between the theoretical angular-dependent nucleation field and experimental HcIrrev(θ) for irreversible switching of VDW when 0°≤θ≤86°.

Decomposition of Sources of Errors in Seasonal Streamflow Forecasts in a Rainfall-Runoff Dominated Basin

NASA Astrophysics Data System (ADS)

Sinha, T.; Arumugam, S.

2012-12-01

Seasonal streamflow forecasts contingent on climate forecasts can be effectively utilized in updating water management plans and optimize generation of hydroelectric power. Streamflow in the rainfall-runoff dominated basins critically depend on forecasted precipitation in contrast to snow dominated basins, where initial hydrological conditions (IHCs) are more important. Since precipitation forecasts from Atmosphere-Ocean-General Circulation Models are available at coarse scale (~2.8° by 2.8°), spatial and temporal downscaling of such forecasts are required to implement land surface models, which typically runs on finer spatial and temporal scales. Consequently, multiple sources are introduced at various stages in predicting seasonal streamflow. Therefore, in this study, we addresses the following science questions: 1) How do we attribute the errors in monthly streamflow forecasts to various sources - (i) model errors, (ii) spatio-temporal downscaling, (iii) imprecise initial conditions, iv) no forecasts, and (iv) imprecise forecasts? and 2) How does monthly streamflow forecast errors propagate with different lead time over various seasons? In this study, the Variable Infiltration Capacity (VIC) model is calibrated over Apalachicola River at Chattahoochee, FL in the southeastern US and implemented with observed 1/8° daily forcings to estimate reference streamflow during 1981 to 2010. The VIC model is then forced with different schemes under updated IHCs prior to forecasting period to estimate relative mean square errors due to: a) temporally disaggregation, b) spatial downscaling, c) Reverse Ensemble Streamflow Prediction (imprecise IHCs), d) ESP (no forecasts), and e) ECHAM4.5 precipitation forecasts. Finally, error propagation under different schemes are analyzed with different lead time over different seasons.

Angular dependence of coercivity derived from alignment dependence of coercivity in Nd-Fe-B sintered magnets

NASA Astrophysics Data System (ADS)

Matsuura, Yutaka; Nakamura, Tetsuya; Sumitani, Kazushi; Kajiwara, Kentaro; Tamura, Ryuji; Osamura, Kozo

2018-01-01

Experimental results of the alignment dependence of the coercivity in Nd-Fe-B sintered magnets showed that the angle of magnetization reversal for anisotropically aligned magnets was bigger than that obtained from the theoretical results calculated using the postulation that every grain independently reverses its magnetization direction following the 1/cos θ law. The angles of reversed magnetization (θ1) for Nd13.48Co0.55B5.76Febal. with alignment α=0.95 and for Nd12.75Dy0.84B5.81Co0.55Febal. with α=0.96 were 30° and 36°, respectively, which were very similar to that of an ideal magnet with a Gaussian distribution (σ=31° and 44°, respectively) of the grain alignment. In this model, we postulated that every grain independently reversed according to the 1/cos θ law. The calculation results for the angular dependence of the coercivity using the values θ1=ω1(0°)=30°, σ=31° and θ1=ω1(0°)=36°, σ=44° could qualitatively and convincingly explain the observed angular dependence of the coercivity of Nd14.2B6.2Co1.0Febal. and Nd14.2Dy0.3B6.2Co1.0Febal.. It is speculated that the magnetic domain wall is pinned at grains tilted away from the easy magnetization direction, and when the magnetic domain wall de-pins from the tilted grains, the magnetic domain wall jumps through several grains. We suggest that the coercive force of the aligned magnet behaves like a low-aligned magnet owing to the magnetization reversal of the crust of the grains induced by the pinning and subsequent jumping of the magnetic domain wall.

Searching for solutions to alcohol and other drug abuse during pregnancy: ethics, values, and constitutional principles.

PubMed

Andrews, A B; Patterson, E G

1995-01-01

Recent efforts to develop legal mechanisms to detect prenatal substance abuse and force pregnant women into drug-free conditions have precipitated ethical struggles for social workers. This article reviews relevant social work values and ethical issues, particularly the need to balance obligations to promote client self-determination, privacy, and access to chosen services with professional values that support coercive intervention to aid vulnerable people and to protect life. The constitutional principles that most affect coercive interventions--due process and equal protection--are reviewed. Recommendations are offered to guide ethical and legal social work for case interventions and policy development.

MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice.

PubMed

Kluk, Michael J; Ho, Caleb; Yu, Hongbo; Chen, Benjamin J; Neuberg, Donna S; Dal Cin, Paola; Woda, Bruce A; Pinkus, Geraldine S; Rodig, Scott J

2016-02-01

Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number. Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Legality of Nuclear Weapons Employment under the International Humanitarian Law of Coercion Control.

DTIC Science & Technology

1987-01-01

fm$0 TELMT OF NUICLEMR IdERPONiS EMPLOYMENT UNDERTH 1/ I INTERNRTIOSEL NUIfI.. (U) AIR FORCE INST OF TECH I NRIONT-PATTERSON AFI ON R R PRICE 1967...Coercion Control c. Rank: Major d. Service: United States Air Force e. Date: 1987 I . Number of pages: 106 g. Degree awarded: Master ot Laws (LL.M.) in...33 A. Sources of International Humanitarian Law ............ 33 B. Use of Coercive Force Under International Law ..... 34 C. Basis Principles

Development of Optimum Theoretical Warhead Design Criteria

DTIC Science & Technology

1976-12-01

d11 iipl 7(I d Ld TheeC ~ desity veocityl metail Lqa tin rqiStec. ~~i~i~ f’Iqain5t tl-G IHC e( j Ut io ti T cnhe relorittenquateioin now tbevoimbes: a...cvelopment arid Education Conmmand, Quantico Mobility Support Division, Major Thorp (1) Waj (aiecs Division, Mai ine Coips Landing Forc 1)cvelopment

"Treat me with respect". A systematic review and thematic analysis of psychiatric patients' reported perceptions of the situations associated with the process of coercion.

PubMed

Tingleff, E B; Bradley, S K; Gildberg, F A; Munksgaard, G; Hounsgaard, L

2017-11-01

WHAT IS KNOWN ON THE SUBJECT?: Psychiatric patients have generally negative experiences of being exposed to coercive measures. Existing research has generally not investigated coercion as a process; that is, it does not address issues that arise before, during and after exposure to coercion. A part of existing research within the area does not clarify and define the type of coercive measure(s) investigated. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Patients place great significance on the link between the positive and negative perceived impact of a coercive situation and the professionals' ability and willingness to interact and communicate respectfully. Psychiatric patients associate the use of seclusion, physical restraint/holding, mechanical restraint and forced medication with strong negative perceptions and wish to be treated with respect by professionals, rather than being subjected to the professionals' control. What patients perceive as moderating factors in regard to the use of coercive measures is currently under-researched. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Increased sensitivity to the patient's views of the situation at each point in the coercive process would help professionals to respond to the patients' individual needs. Professionals need to articulate concern and empathy towards patients and to improve communication skills before, during and after a coercive incident. Greater emphasis should be placed on de-escalation and the use of non-coercive strategies or coping skills before the initiation of coercive measures. Introduction There is a lack of research into psychiatric patients' perceptions of coercion that discriminates between different types of coercive measures, while also investigating patients' perceptions of undergoing coercion as a process. This knowledge is required to improve our understanding and provide a foundation for improving clinical practice. Aims To review existing research literature in order to investigate adult psychiatric patients' reported perceptions of situations before, during and after specific and defined types of coercive measures, and to investigate what patients perceive as moderating factors, in regard to the use of these coercive measures. Method A systematic review and thematic analysis of 26 peer-reviewed studies was undertaken. Results The analysis identified six themes and additional subthemes, where "interactions with professionals" and "communication" were predominant themes across the timeline of coercion. Altogether, themes were associated with either "positive or negative patient-perceived impact." Implications for practice Increased sensitivity to patients' views of the situation at each point in the process is desirable in order to respond to the patients' individual needs. Professionals also need to articulate concern and empathy towards the patient and to improve communication skills before, during and after a coercive incident. Use of de-escalation and noncoercive strategies is required. Relevance statement Coercion within psychiatric/mental health care remains controversial, and repeated international calls have recommended a reduction of their use. This review indicates that greater attention to how patients perceive the use of coercive measures (before, during, and after incidents) needs to be considered in order to improve the evidence-based and clinical practice. © 2017 John Wiley & Sons Ltd.

Clinical utility of RT-PCR in assessing HER 2 gene expression versus traditional IHC and FISH in breast cancer patients.

PubMed

Suryavanshi, Moushumi; Mehta, Anurag; Jaipuria, Jiten; Kumar, Dushyant; Vishwakarma, Gayatri; Panigrahi, Manoj Kumar; Verma, Haristuti; Saifi, Mumtaz; Sharma, Sanjeev; Tandon, Simran; Doval, D C; Das, Bhudev C

2018-02-09

IHC and FISH are used for categorizing HER 2 status in breast cancer at the protein and DNA level, respectively. HER 2 expression at the RNA level is quantitative, cheaper, easier to standardize and free from interobserver variation. 115 consecutive patients were tested by IHC, FISH and RT-PCR (test cohort). Assuming FISH result to be the response variable, ROC curves for RT-PCR ratio were analyzed to label HER 2 negative, equivocal and positive cases as RT-PCR score 1, 2 and 3, respectively. Inter-relationships between RT-PCR, IHC and FISH were defined. 'Clinical benefit' of a test was defined as proportion of patients labeled unequivocally as HER 2 positive or negative. Population for 1 year was simulated constraint to previous reports of HER 2 positivity and IHC category distribution by a meta-analysis of previous studies that evaluated concordance between IHC and FISH to determine HER 2 status (simulation cohort). Four diagnostic pathways in the simulation cohort were defined-(1) initial IHC, followed by FISH (conventional pathway); (2) initial RT-PCR, followed by FISH; (3) initial IHC, followed by RT-PCR and then by FISH; (4) initial RT-PCR, followed by IHC and then by FISH. The clinical benefit of IHC and RT-PCR in the four pathways was analyzed and sensitivity analysis for incremental cost-effectiveness ratio and cost-benefit comapring RT-PCR against IHC, both as first-line tests and among those with IHC score 2 as a reflex second-line test was performed by the Monte Carlo technique. 115 patients comprised the study population. While none with IHC score of 0 or 1 was FISH positive for HER 2, all cases with IHC score of 3 were FISH positive. 43 cases were assigned IHC score of 2. Thus, 72 patients benefited from the initial IHC testing [clinical benefit 62.6%], with the overall concordance between IHC and FISH being 100% for those with IHC score of 0, 1 and 3 (conclusive IHC categories). For RT-PCR with 100% concordance, 15.7% (115-97 = 18) patients would have benefited from RT-PCR testing if it was used as a first-line test. If RT-PCR would have been used as a second-line test among those with IHC score 2 (n = 43), then only 6 patients would have been assigned a conclusive RT-PCR category (category 1 or 3) translating to a clinical benefit of 14% (6/43) as a second-line test. As a second-line test it had 51% probability to prove more cost-effective than the conventional pathway, provided the cost of RT-PCR was 0.4 times the cost of IHC. Also in a three-step pathway, RT-PCR upfront would have 56% probability of higher cost-benefit provided the cost of RT-PCR was 0.1 times the cost of IHC. RT-PCR results were found to be suboptimal to IHC in terms of discriminative ability and clinical benefit; thus, it is unlikely to replace IHC as a first-line test in the near future.

Coercive Diplomacy American-Style.

DTIC Science & Technology

1997-02-21

invasion force was deployed and presumably beyond the control of the distinguished negotiators ("Team Carter") on the ground. The Haitian strongman , Raoul...should have little difficulty drumming up a large amount of luke -warm support for its efforts against the communist behemoth, with the unfortunate

Insights into magmatic processes and hydrothermal alteration of in situ superfast spreading ocean crust at ODP/IODP site 1256 from a cluster analysis of rock magnetic properties

NASA Astrophysics Data System (ADS)

Dekkers, Mark J.; Heslop, David; Herrero-Bervera, Emilio; Acton, Gary; Krasa, David

2014-08-01

We analyze magnetic properties from Ocean Drilling Program (ODP)/Integrated ODP (IODP) Hole 1256D (6°44.1' N, 91°56.1' W) on the Cocos Plate in ˜15.2 Ma oceanic crust generated by superfast seafloor spreading, the only drill hole that has sampled all three oceanic crust layers in a tectonically undisturbed setting. Fuzzy c-means cluster analysis and nonlinear mapping are utilized to study down-hole trends in the ratio of the saturation remanent magnetization and the saturation magnetization, the coercive force, the ratio of the remanent coercive force and coercive force, the low-field magnetic susceptibility, and the Curie temperature, to evaluate the effects of magmatic and hydrothermal processes on magnetic properties. A statistically robust five cluster solution separates the data predominantly into three clusters that express increasing hydrothermal alteration of the lavas, which differ from two distinct clusters mainly representing the dikes and gabbros. Extensive alteration can obliterate magnetic property differences between lavas, dikes, and gabbros. The imprint of thermochemical alteration on the iron-titanium oxides is only partially related to the porosity of the rocks. Thus, the analysis complements interpretation based on electrofacies analysis. All clusters display rock magnetic characteristics compatible with an ability to retain a stable natural remanent magnetization suggesting that the entire sampled sequence of ocean crust can contribute to marine magnetic anomalies. Paleointensity determination is difficult because of the propensity of oxyexsolution during laboratory heating and/or the presence of intergrowths. The upper part of the extrusive sequence, the granoblastic dikes, and moderately altered gabbros may contain a comparatively uncontaminated thermoremanent magnetization.

CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome.

PubMed

Johnson, Jessica; Affolter, Kajsa; Boynton, Kathleen; Chen, Xinjian; Valentine, John; Peterson, Kathryn

2018-04-30

Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.

Comparison of next-generation sequencing mutation profiling with BRAF and IDH1 mutation-specific immunohistochemistry.

PubMed

Jabbar, Kausar J; Luthra, Rajalakshmi; Patel, Keyur P; Singh, Rajesh R; Goswami, Rashmi; Aldape, Ken D; Medeiros, L Jeffrey; Routbort, Mark J

2015-04-01

Mutation-specific antibodies for BRAF V600E and IDH1 R132H offer convenient immunohistochemical (IHC) assays to detect these mutations in tumors. Previous studies using these antibodies have shown high sensitivity and specificity, but use in routine diagnosis with qualitative assessment has not been well studied. In this retrospective study, we reviewed BRAF and IDH1 mutation-specific IHC results compared with separately obtained clinical next-generation sequencing results. For 67 tumors with combined IDH1 IHC and mutation data, IHC was unequivocally reported as positive or negative in all cases. Sensitivity of IHC for IDH1 R132H was 98% and specificity was 100% compared with mutation status. Four IHC-negative samples showed non-R132H IDH1 mutations including R132C, R132G, and P127T. For 128 tumors with combined BRAF IHC and mutation data, IHC was positive in 33, negative in 82, and equivocal in 13 tumors. The sensitivity of IHC was 97% and specificity was 99% when including only unequivocally positive or negative results. If equivocal IHC cases were included in the analysis as negative, sensitivity fell to 81%. If equivocal cases were classified as positive, specificity dropped to 91%. Eight IHC-negative samples showed non-V600E BRAF mutations including V600K, N581I, V600M, and K601E. We conclude that IHC for BRAF V600E and IDH1 R132H is relatively sensitive and specific, but there is a discordance rate that is not trivial. In addition, a significant proportion of patients harbor BRAF non-V600E or IDH1 non-R132H mutations not detectable by IHC, potentially limiting utility of IHC screening for BRAF and IDH1 mutations.

Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH.

PubMed

Yi, Eunhee S; Boland, Jennifer M; Maleszewski, Joseph J; Roden, Anja C; Oliveira, Andre M; Aubry, Marie-Christine; Erickson-Johnson, Michele R; Caron, Bolette L; Li, Yan; Tang, Hui; Stoddard, Shawn; Wampfler, Jason; Kulig, Kimary; Yang, Ping

2011-03-01

Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach. One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue. Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative. IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.

Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors.

PubMed

Tanino, Mishie; Sasajima, Toshio; Nanjo, Hiroshi; Akesaka, Shiori; Kagaya, Masami; Kimura, Taichi; Ishida, Yusuke; Oda, Masaya; Takahashi, Masataka; Sugawara, Taku; Yoshioka, Toshiaki; Nishihara, Hiroshi; Akagami, Yoichi; Goto, Akiteru; Minamiya, Yoshihiro; Tanaka, Shinya

2015-01-01

Rapid immunohistochemistry (R-IHC) can contribute to the intraoperative diagnosis of central nervous system (CNS) tumors. We have recently developed a new IHC method based on an alternating current electric field to facilitate the antigen-antibody reaction. To ensure the requirement of R-IHC for intraoperative diagnosis, 183 cases of CNS tumors were reviewed regarding the accuracy rate of diagnosis without R-IHC. The diagnostic accuracy was 90.7 % (166/183 cases) [corrected] in which definitive diagnoses were not provided in 17 cases because of the failure of glioma grading and differential diagnosis of lymphoma and glioma. To establish the clinicopathological application, R-IHC for frozen specimens was compared with standard IHC for permanent specimens. 33 gliomas were analyzed, and the Ki-67/MIB-1 indices of frozen specimens by R-IHC were consistent with the grade and statistically correlated with those of permanent specimens. Thus, R-IHC provided supportive information to determine the grade of glioma. For discrimination between glioma and lymphoma, R-IHC was able to provide clear results of CD20 and Ki-67/MIB-1 in four frozen specimens of CNS lymphoma as well as standard IHC. We conclude that the R-IHC for frozen specimens can provide important information for intraoperative diagnosis of CNS tumors.

Magnetic Behavior of Ni-Fe Core-Shell and Alloy Nanowires

NASA Astrophysics Data System (ADS)

Tripathy, Jagnyaseni; Vargas, Jose; Spinu, Leonard; Wiley, John

2013-03-01

Template assisted synthesis was used to fabricate a series of Ni-Fe core-shell and alloy nanowires. By controlling reaction conditions as well as pore structure, both systems could be targeted and magnetic properties followed as a function of architectures. In the core-shell structure coercivity increases with decrease in shell thickness while for the alloys, coercivity squareness improve with increase pore diameter. Details on the systematic studies of these materials will be presented in terms of hysteretic measurements, including first order reversal curves (FORC), and FMR data. Magnetic variation as a function of structure and nanowire aspect ratios will be presented and the origins of these behaviors discussed. Advanced Material Research Institute

Integrative health care - Toward a common understanding: A mixed method study.

PubMed

Leach, Matthew J; Wiese, Marlene; Thakkar, Manisha; Agnew, Tamara

2018-02-01

To generate a multidisciplinary stakeholder-informed definition of integrative health care (IHC). A mixed-method study design was used, employing the use of focus groups/semi-structured interviews (phase-1) and document analysis (phases 2 and 3). Phase-1 recruited a purposive sample of Australian health consumers/health providers. Phase-2 interrogated websites of international IHC organisations for definitions of IHC. Phase-3 systematically searched bibliographic databases for articles defining IHC. Data were analysed using thematic analysis. Data were drawn from 54 health consumers/providers (phase-1), 23 IHC organisation webpages (phase-2) and 23 eligible articles (phase-3). Seven themes emerged from the data. Consensus was reached on a single, 65-word definition of IHC. An unambiguous definition of IHC is critical to establishing a clearer identity for IHC, as well as providing greater clarity for consumers, health providers and policy makers. In recognising the need for a clearer description, we propose a scientifically-grounded, multi-disciplinary stakeholder-informed definition of IHC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sexually coercive behavior in male youth: population survey of general and specific risk factors.

PubMed

Kjellgren, Cecilia; Priebe, Gisela; Svedin, Carl Göran; Långström, Niklas

2010-10-01

Little is known about risk/protective factors for sexually coercive behavior in general population youth. We used a Swedish school-based population survey of sexual attitudes and experiences (response rate 77%) and investigated literature-based variables across sexually coercive (SEX), non-sexual conduct problem (CP), and normal control (NC) participants to identify general and specific risk/protective factors for sexual coercion. Among 1,933 male youth, 101 (5.2%) reported sexual coercion (ever talked or forced somebody into genital, oral, or anal sex) (SEX), 132 (6.8%) were classified as CP, and the remaining 1,700 (87.9%) as NC. Of 29 tested variables, 25 were more common in both SEX and CP compared to NC youth, including minority ethnicity, separated parents, vocational study program, risk-taking, aggressiveness, depressive symptoms, substance abuse, sexual victimization, extensive sexual experiences, and sexual preoccupation. When compared to CP youth only, SEX youth more often followed academic study programs, used less drugs and were less risk-taking. Further, SEX more frequently than CP youth reported gender stereotypic and pro-rape attitudes, sexual preoccupation, prostitution, and friends using violent porn. Finally, in a multivariate logistic regression, academic study program, pro-rape attitudes, sexual preoccupation, and less risk-taking independently remained more strongly associated with SEX compared to CP offending. In conclusion, several sociodemographic, family, and individual risk/protective factors were common to non-sexual and sexually coercive antisocial behavior in late adolescence. However, pro-rape cognitions, and sexual preoccupation, were sexuality-related, specific risk factors. The findings could inform preventive efforts and the assessment and treatment of sexually coercive male youth.

Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small cell lung cancer patients and response to crizotinib.

PubMed

Xu, Chun-Wei; Wang, Wen-Xian; Chen, Yan-Ping; Chen, Yu; Liu, Wei; Zhong, Li-Hua; Chen, Fang-Fang; Zhuang, Wu; Song, Zheng-Bo; Chen, Xiao-Hui; Huang, Yun-Jian; Guan, Yan-Fang; Yi, Xin; Lv, Tang-Feng; Zhu, Wei-Feng; Lu, Jian-Ping; Wang, Xiao-Jiang; Shi, Yi; Lin, Xian-Dong; Chen, Gang; Song, Yong

2018-04-11

ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements. A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent. Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion. VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.

Immunohistochemical ATRX expression is not a surrogate for 1p19q codeletion.

PubMed

Yamamichi, Akane; Ohka, Fumiharu; Aoki, Kosuke; Suzuki, Hiromichi; Kato, Akira; Hirano, Masaki; Motomura, Kazuya; Tanahashi, Kuniaki; Chalise, Lushun; Maeda, Sachi; Wakabayashi, Toshihiko; Kato, Yukinari; Natsume, Atsushi

2018-04-01

The IDH-mutant and 1p/19q co-deletion (1p19q codel) provides significant diagnostic and prognostic value in lower-grade gliomas. As ATRX mutation and 1p19q codel are mutually exclusive, ATRX immunohistochemistry (IHC) may substitute for 1p19q codel, but this has not been comprehensively examined. In the current study, we performed ATRX-IHC in 78 gliomas whose ATRX statuses were comprehensively determined by whole exome sequencing. Among the 60 IHC-positive and 18 IHC-negative cases, 86.7 and 77.8% were ATRX-wildtype and ATRX-mutant, respectively. ATRX mutational patterns were not consistent with ATRX-IHC. If our cohort had only used IDH status and IHC-based ATRX expression for diagnosis, 78 tumors would have been subtyped as 48 oligodendroglial tumors, 16 IDH-mutant astrocytic tumors, and 14 IDH-wildtype astrocytic tumors. However, when the 1p19q codel test was performed following ATRX-IHC, 8 of 48 ATRX-IHC-positive tumors were classified as "1p19q non-codel" and 3 of 16 ATRX-IHC-negative tumors were classified as "1p19q codel"; a total of 11 tumors (14%) were incorrectly classified. In summary, we observed dissociation between ATRX-IHC and actual 1p19q codel in 11 of 64 IDH-mutant LGGs. In describing the complex IHC expression of ATRX somatic mutations, our results indicate the need for caution when using ATRX-IHC as a surrogate of 1p19q status.

Coercive Effects-based Operations Targeting Enemy Resolve: No Bang for the Buck

DTIC Science & Technology

2007-05-10

http://www.bartelby.com/65/tr/Trenchar.html (accessed 8 April 2007) 15 Pamela Feltus , The Prophets: Advocates of Strategic Bombing, Available...the Air. Washington D.C.: Office of Air Force History, 1983. Feltus , Pamela. “The Prophets: Advocates of Strategic Bombing”. http

Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma.

PubMed

Ying, J; Guo, L; Qiu, T; Shan, L; Ling, Y; Liu, X; Lu, N

2013-10-01

To evaluate the diagnostic value of a novel fully automated immunohistochemistry (IHC) assay for detection of anaplastic lymphoma kinase (ALK) fusion in a large number of ALK-positive lung adenocarcinoma (ADC) patients. We tested 196 lung ADCs for ALK rearrangement by two IHC assays (Ventana pre-diluted ALK D5F3 antibody with the Optiview DAB IHC detection kit and Optiview Amplification kit, D5F3 by Cell Signaling Technology (CST) with Ultraview DAB detection kit by Ventana), fluorescence in situ hybridization (FISH) and real-time reverse transcription-PCR (RT-PCR). CST ALK IHC was scored using the scoring scheme of 0, no staining; 1+, faint; 2+, moderate; and 3+, strong cytoplasmic reactivity in ≥ 10% of tumor cells. As for Ventana IHC, a binary scoring system (positive or negative for ALK status) was adopted for evaluating the staining results. Among 196 cases tested, 63 (32%), 65 (33%), 70 (36%), and 69 (35%) cases were ALK positive by FISH, Ventana IHC, CST IHC, and RT-PCR, respectively. The sensitivity and specificity of Ventana IHC were 100% and 98%, respectively. Two Ventana IHC-positive cases, which were also CST IHC score of 3+, showed FISH negative, but their ALK rearrangement was confirmed by RT-PCR and direct sequencing. The sensitivity and specificity of CST IHC with staining intensity score of 1+ or more were 100% and 95%, respectively. Five (25%, of 20) patients with CST IHC score of 1+ were both FISH and RT-PCR negative. The sensitivity and specificity of RT-PCR for detection of ALK fusion were 98% and 95%, respectively. The total accordance rate between ALK RT-PCR and Ventana IHC was 97%. The novel fully automated IHC assay is a reliable screening tool in routine pathologic laboratories for identification of patients with ALK rearrangement for targeted therapy in lung ADC.

Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory.

PubMed

Badve, Sunil S; Baehner, Frederick L; Gray, Robert P; Childs, Barrett H; Maddala, Tara; Liu, Mei-Lan; Rowley, Steve C; Shak, Steven; Perez, Edith A; Perez, Edith D; Shulman, Lawrence J; Martino, Silvana; Davidson, Nancy E; Sledge, George W; Goldstein, Lori J; Sparano, Joseph A

2008-05-20

Central and local laboratory concordance for hormone receptor measurement is therapeutically important. This study compares estrogen receptor (ER) and progesterone receptor (PR) measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcriptase polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay. A case-control sample of 776 breast cancer patients from Eastern Cooperative Oncology Group (ECOG) study E2197 was evaluated. Central IHC Allred score for ER and PR was obtained using tissue microarrays and 1D5 ER antibody and 636 PR antibody. Quantitative RT-PCR for ER and PR in whole sections was performed using the 21-gene assay. For ER, the concordance between local and central IHC was 90% (95% CI, 88% to 92%), between local IHC and central RT-PCR was 91% (95% CI, 89% to 93%), and between central IHC and central RT-PCR was 93% (95% CI, 91% to 95%). For PR, the concordance between local IHC and central IHC was 84% (95% CI, 82% to 87%), between local IHC and central RT-PCR was 88% (95% CI, 85% to 90%), and between central IHC and central RT-PCR was 90% (95% CI, 88% to 92%). Although concordance was high, IHC ER-negative cases that were RT-PCR positive were more common than IHC ER-positive cases that were RT-PCR negative. In ER-positive patients, ER expression by central IHC Allred score was marginally associated with recurrence (P = .091), and ER expression by central RT-PCR was significantly associated with recurrence (P = .014). However, recurrence score, which incorporates additional genes/pathways, was a highly significant predictor of recurrence (P < .0001). There is a high degree of concordance among local IHC, central IHC, and central RT-PCR by the proprietary gene assay for ER and PR status. Although ER expression is marginally associated with relapse in ER-positive patients treated with chemohormonal therapy, recurrence score is a highly significant predictor of recurrence.

Female youth who sexually coerce: prevalence, risk, and protective factors in two national high school surveys.

PubMed

Kjellgren, Cecilia; Priebe, Gisela; Svedin, Carl Göran; Mossige, Svein; Långström, Niklas

2011-12-01

Sexual coercion is recognized as a serious societal problem. Correlates and risk factors of sexually abusive behavior in females are not well known. Etiological theory and empirical study of female perpetrators of sexual coercion are usually based on small or highly selected samples. Specifically, population-based data are needed to elucidate risk/protective factors. Main outcome measures include a self-report questionnaire containing 65 items tapping socio-demographic and health conditions, social relations, sexual victimization, conduct problems and a set of normative and deviant sexual cognitions, attitudes, and behaviors. We used a 2003-2004 survey of sexual attitudes and experiences among high school students in Norway and Sweden to identify risk factors and correlates to sexually coercive behavior (response rate 80%); 4,363 females participated (Mean = 18.1 years). Thirty-seven women (0.8%) reported sexual coercion (ever talked someone into, used pressure, or forced somebody to have sex). Sexually coercive compared with non-coercive women were similar on socio-demographic variables, but reported less parental care and more parental overprotection, aggression, depressive symptoms, and substance misuse. Also, sexually coercive females reported more sexual lust, sex partners, penetrative sexual victimization, rape myths, use of violent porn, and friends more likely to use porn. When using the Swedish subsample to differentiate risk factors specific for sexual coercion from those for antisocial behavior in general, we found less cannabis use, but more sexual preoccupation, pro-rape attitudes, and friends using violent porn in sexually coercive compared with non-sex conduct problem females. Sexually coercive behavior in high school women was associated with general risk/needs factors for antisocial behavior, but also with specific sexuality-related risk factors. This differential effect has previously been overlooked, agrees with similar findings in men, and should have substantial etiological importance. © 2009 International Society for Sexual Medicine.

Markets versus Monopolies in Education: The Historical Evidence.

ERIC Educational Resources Information Center

Coulson, Andrew

1996-01-01

Historical data are presented to show that teachers and schools are affected by the financial incentives of the systems in which they operate. Economic pressures have forced schools in competitive markets to meet the needs of families, while centralized bureaucratic systems have been coercive and pedagogically stagnant. (Author/SLD)

A Theory of the Origin of the State

ERIC Educational Resources Information Center

Carneiro, Robert L.

1970-01-01

Suggests that states evolve in response to ecological or social circumscription, or resource concentration. When dense populations develop, fighting over land forces loser into political subordination or incorporation. This modification of coercive theories explain lack of state in Amazon basin and origin of Inca, Maya, Hwang Valley states.…

Female Genitalia Concealment Promotes Intimate Male Courtship in a Water Strider

PubMed Central

Han, Chang S.; Jablonski, Piotr G.

2009-01-01

Violent coercive mating initiation is typical for animals with sexual conflict over mating. In these species, the coevolutionary arms-race between female defenses against coercive mating and male counter-adaptations for increased mating success leads to coevolutionary chases of male and female traits that influence the mating. It has been controversial whether one of the sexes can evolve traits that allow them to “win” this arms race. Here, we use morphological analysis (traditional and scanning electron micrographs), laboratory experiments and comparative methods to show how females of a species characterized by typical coercive mating initiation appear to “win” a particular stage of the sexual conflict by evolving morphology to hide their genitalia from direct, forceful access by males. In an apparent response to the female morphological adaptation, males of this species added to their typically violent coercive mounting of the female new post-mounting, pre-copulatory courtship signals produced by tapping the water's surface with the mid-legs. These courtship signals are intimate in the sense that they are aimed at the female, on whom the male is already mounted. Females respond to the signals by exposing their hidden genitalia for copulatory intromission. Our results indicate that the apparent victory of coevolutionary arms race by one sex in terms of morphology may trigger evolution of a behavioral phenotype in the opposite sex. PMID:19516886

The Coercive Efficacy of Air Exclusion Zones: Myth or Reality

DTIC Science & Technology

2012-06-01

use force and such threats lacked credibility. The lack of intervention by the international community in other Arab nations may have reinforced such...those of the author. They do not reflect the official position of the US Government, Department of Defense, the United States Air Force, or Air...security. We do not seek the destruction of Iraq, its culture, or its people. Rather, we seek an Iraq that uses its great resources not to destroy, not to

Serial forced displacement in American cities, 1916-2010.

PubMed

Fullilove, Mindy Thompson; Wallace, Rodrick

2011-06-01

Serial forced displacement has been defined as the repetitive, coercive upheaval of groups. In this essay, we examine the history of serial forced displacement in American cities due to federal, state, and local government policies. We propose that serial forced displacement sets up a dynamic process that includes an increase in interpersonal and structural violence, an inability to react in a timely fashion to patterns of threat or opportunity, and a cycle of fragmentation as a result of the first two. We present the history of the policies as they affected one urban neighborhood, Pittsburgh's Hill District. We conclude by examining ways in which this problematic process might be addressed.

Mapping the phase inhomogeneity across first order spin flop transition

NASA Astrophysics Data System (ADS)

Tripathi, Malvika; Majumder, Supriyo; Choudhary, R. J.; Phase, D. M.

2018-04-01

As a consequence of spin reorientation phase transition (SRPT, TSRPT = 34K) in SmCrO3, the two phases, high temperature uncompensated anti-ferromagnetic Γ4 configuration and low temperature collinear anti-ferromagnetic phase Γ1 coexist in the vicinity of transition. The observed unexpectedly huge coercivity (Hc ˜2T) below SRPT at 25K questions on the behavior of two co-existing phases. In the present study, we have used the FORC diagrams to monitor the distribution of clusters related to different phases and to understand the nature of interaction among the clusters of distinct phases. We observed that the nature of interaction has indeed magnetic effect and the pining across phase boundaries may cause the enhancement of coercivity at 25K.

Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine. Part 3: Technical Validation of Immunohistochemistry (IHC) Assays in Clinical IHC Laboratories.

PubMed

Torlakovic, Emina E; Cheung, Carol C; D'Arrigo, Corrado; Dietel, Manfred; Francis, Glenn D; Gilks, C Blake; Hall, Jacqueline A; Hornick, Jason L; Ibrahim, Merdol; Marchetti, Antonio; Miller, Keith; van Krieken, J Han; Nielsen, Soren; Swanson, Paul E; Vyberg, Mogens; Zhou, Xiaoge; Taylor, Clive R

2017-03-01

Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Quantification of the Barkhausen noise method for the evaluation of time-dependent degradation

NASA Astrophysics Data System (ADS)

Kim, Dong-Won; Kwon, Dongil

2003-02-01

The Barkhausen noise (BN) method has long been applied to measure the bulk magnetic properties of magnetic materials. Recently, this important nondestructive testing (NDT) method has been applied to evaluate microstructure, stress distribution analysis, fatigue, creep and fracture characteristics. Until now the BN method has been used only qualitatively in evaluating the variation of BN with variations in material properties. For this reason, few NDT methods have been applied in industrial plants and laboratories. The present investigation studied the coercive force and BN while varying the microstructure of ultrafine-grained steels and SA508 cl.3 steels. This variation was carried out according to the second heat-treatment condition with rolling of ultrafine-grained steels and the simulated time-dependent degradation of SA 508 cl.3 steels. An attempt was also made to quantify BN from the relationship between the velocity of magnetic domain walls and the retarding force, using the coercive force of the domain wall movement. The microstructure variation was analyzed according to time-dependent degradation. Fracture toughness was evaluated quantitatively by measuring the BN from two intermediary parameters; grain size and distribution of nonmagnetic particles. From these measurements, the variation of microstructure and fracture toughness can be directly evaluated by the BN method as an accurate in situ NDT method.

MYC immunohistochemical and cytogenetic analysis are required for identification of clinically relevant aggressive B cell lymphoma subtypes.

PubMed

Raess, Philipp W; Moore, Stephen R; Cascio, Michael J; Dunlap, Jennifer; Fan, Guang; Gatter, Ken; Olson, Susan B; Braziel, Rita M

2018-06-01

Accurate subclassification of aggressive B cell lymphomas (ABCLs) requires integration of morphologic, immunohistochemical (IHC), and cytogenetic information. Optimal strategies have not been well defined for diagnosis of high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBLwR) and double expressor lymphomas with MYC and BCL2 protein overexpression. One hundred and eighty seven ABCLs were investigated with complete IHC and FISH analysis. Morphologic and IHC analysis was insufficient to identify clinically relevant HGBLwR. Approximately, 75% of cases classified as HGBLwR showed conventional DLBCL morphologic features. Fourteen percent of MYC-rearranged cases were negative by IHC. Conversely, 60% of cases positive for MYC by IHC did not demonstrate a MYC rearrangement. Analysis by FISH without MYC and BCL2 IHC would miss 41 cases of double expressor lymphoma. Complete IHC and FISH analysis is recommended in the evaluation of all ABCLs.

A Microfluidic Immunostaining System Enables Quality Assured and Standardized Immunohistochemical Biomarker Analysis

NASA Astrophysics Data System (ADS)

Kwon, Seyong; Cho, Chang Hyun; Kwon, Youngmee; Lee, Eun Sook; Park, Je-Kyun

2017-04-01

Immunohistochemistry (IHC) plays an important role in biomarker-driven cancer therapy. Although there has been a high demand for standardized and quality assured IHC, it has rarely been achieved due to the complexity of IHC testing and the subjective validation-based process flow of IHC quality control. We present here a microfluidic immunostaining system for the standardization of IHC by creating a microfluidic linearly graded antibody (Ab)-staining device and a reference cell microarray. Unlike conventional efforts, our system deals primarily with the screening of biomarker staining conditions for quantitative quality assurance testing in IHC. We characterized the microfluidic matching of Ab staining intensity using three HER2 Abs produced by different manufacturers. The quality of HER2 Ab was also validated using tissues of breast cancer patients, demonstrating that our system is an efficient and powerful tool for the standardization and quality assurance of IHC.

Crimes Of War And The Force Of Law

ERIC Educational Resources Information Center

Hagan, John; Levi, Ron

2005-01-01

The origin and enforcement of criminal law are central to the sociological study of crime, yet we know relatively little about how the coercive apparatus of criminalization is actualized through prosecutorial and court practices. We use Bourdieu's extension of Weber's analysis of law to develop a perspective on fields of practice, the juridical…

Conduct Disorders: Are Boot Camps Effective?

ERIC Educational Resources Information Center

Jeter, LaVaughn V.

2010-01-01

Youth diagnosed with "conduct disorder" are often placed in programs using forced compliance and coercive control. One type of intervention used to treat conduct disorder is the boot camp. The basic idea is that disruptive behaviors can be corrected by strict behavioral regulation and an emphasis on skills training (Weis & Toolis 2009; Weis,…

Design and material selection for inverter transformer cores

NASA Technical Reports Server (NTRS)

Mclyman, W. T.

1973-01-01

Report is announced which studied magnetic properties of candidate materials for use in spacecraft transformers, static inverters, converters, and transformer-rectifier power supplies. Included are material characteristics for available alloy compositions in tabular form, including: trade names, saturated flux density, dc coercive force, loop squareness, material density, and watts per pound at 3 KHz.

Enhancing the magnetic anisotropy energy by tuning the contact areas of Ag and Ni at the Ag/Ni interface.

PubMed

Chow, Yu-Ting; Jiang, Bin-Han; Chang, Cheng-Hsun-Tony; Tsay, Jyh-Shen

2018-01-17

Modifying the interfacial conditions of magnetic layers by capping with overlayers can efficiently enhance the magnetic functionality of a material. However, the mechanisms responsible for this are closely related to the crystalline structure, compositional combinations, and interfacial quality, and are generally complex. In this contribution, we explored the use of Ag ultrathin overlayers on annealed . A method for preparing magnetic layers with different levels of enhanced magnetic anisotropy energy was developed. The method essentially involves simply modifying the contact area of the metallic/magnetic interface. A rougher interface results in a larger contact area between the Ag and Ni layers, resulting in an increase in magnetic anisotropy energy. Moreover, post-annealing treatments led to the segregation of Ni atoms, thus making the enhancement in the coercive force even more efficient. A model permits an understanding of the contact area and a strategy for enhancing the magnetic anisotropy energy and the coercive force was developed. Our approaches and the developed model promise to be helpful in terms of developing potential applications of ultrathin magnetic layers in the area of spintronics.

In-Situ Preparation and Magnetic Properties of Fe3O4/WOOD Composite

NASA Astrophysics Data System (ADS)

Gao, Honglin; Zhang, Genlin; Wu, Guoyuan; Guan, Hongtao

2011-06-01

Fe3O4/wood composite, a magnetic material, was prepared by In-situ chemosynthesis method at room temperature. The X-ray diffraction (XRD) shows that the average partical size of Fe3O4 was about 14 nm. The magnetic properties of the resulting composites were investigated by vibrating sample magnetometer (VSM). The composites have saturation magnetization (Ms) values from 4.7 to 25.3 emu/g with the increase of weight percent gains (WPG) of the wood for the composites, but coercive forces (Hc) are invariable, which is different from the magnetic materials reported before. It may be due to the fact that the interaction between wood and Fe3O4 becomes stronger when less of Fe3O4 particles are introduced in the composition, and this also changes the surface anisotropy (Ks) of the magnetism. A structural characterization by Fourier transform infrared (FTIR) proved the interaction between Fe3O4 particles and wood matrix, and it also illustrates that this interaction influences the coercive force of the composite.

Exchange spring in A1/L1{sub 0} FePt composite and its application in magnetic force microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guoqing, E-mail: gqli@swu.edu.cn; Zhu, Yanyan, E-mail: zhubai@swu.edu.cn; Zhang, Yong

2015-02-23

This paper reported fabrication of Fe{sub x}Pt{sub 100-x} films with (001) epitaxy on MgO(100) substrates. The atomic percentage of Fe was changed within the range of x = 10–85 in order to search the optimal atomic ratio for achieving both high and isotropic-like coercivity. It was found that the Fe{sub 60}Pt{sub 40} film exhibited large coercivities exceeding 5 kOe along both in-plane and out-of-plane directions due to the formation of A1/L1{sub 0} FePt composite. A penta-domain model for hard/soft/hard exchange spring system was proposed to interpret the anomalous magnetization behaviors observed in Fe{sub 60}Pt{sub 40} sample. By using Fe{sub 60}Pt{sub 40} asmore » the magnetic coating layer on a probe of magnetic force microscope, the flux changes at a linear density of 1000 kfci could be readily observed at a resolution of ∼13 nm.« less

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

PubMed

McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre

2017-01-01

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

ALK immunohistochemistry for ALK gene rearrangement screening in non-small cell lung cancer: a systematic review and meta-analysis.

PubMed

Pyo, Jung-Soo; Kang, Guhyun; Sohn, Jin Hee

2016-12-23

The aim of this study was to investigate the diagnostic accuracy of anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) for ALK gene rearrangement in non-small cell lung cancer (NSCLC) through systematic review, meta-analysis and diagnostic test accuracy review. The current study included 11,806 NSCLC cases in 42 eligible studies. We performed concordance analyses between ALK IHC and fluorescence in situ hybridization (FISH). The diagnostic accuracy of ALK IHC was analyzed based on ALK IHC criteria and antibodies. The overall ALK IHC results were positive in 13.2%. The overall concordance rate between ALK IHC and FISH was 0.950 (95% confidence interval [CI], 0.927-0.966). In the ALK IHC-positive and negative groups, the concordance rates were 0.805 (95% CI 0.733-0.861) and 0.985 (95% CI 0.978-0.990), respectively. The ALK FISH-positive rates were 0.009 (95% CI 0.004-0.023), 0.378 (95% CI 0.217-0.572), 0.628 (95% CI 0.420-0.796) and 0.900 (95% CI 0.840-0.939) in the ALK IHC 0, 1+, 2+ and 3+ groups, respectively. In diagnostic test accuracy review for ALK IHC, the pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.91 (95% CI 0.90-0.91), respectively. The diagnostic odds ratio and the area under the curve on the summary receiver operating characteristic curve were 266.56 (95% CI 110.83-641.14) and 0.983, respectively. Our results suggested that ALK IHC equivocal (score 1+ and 2+) cases should not be considered as IHC-negative in screening for ALK gene rearrangement. Additional detailed criteria for ALK IHC equivocal cases are necessary to determine how to best apply this approach in daily practice.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended.

PubMed

Savic, Spasenija; Diebold, Joachim; Zimmermann, Anne-Katrin; Jochum, Wolfram; Baschiera, Betty; Grieshaber, Susanne; Tornillo, Luigi; Bisig, Bettina; Kerr, Keith; Bubendorf, Lukas

2015-08-01

Immunohistochemistry (IHC) has become a promising method for pre-screening ALK-rearrangements in non-small cell lung carcinomas (NSCLC). Various ALK antibodies, detection systems and automated immunostainers are available. We therefore aimed to compare the performance of the monoclonal 5A4 (Novocastra, Leica) and D5F3 (Cell Signaling, Ventana) antibodies using two different immunostainers. Additionally we analyzed the accuracy of prospective ALK IHC-testing in routine diagnostics. Seventy-two NSCLC with available ALK FISH results and enriched for FISH-positive carcinomas were retrospectively analyzed. IHC was performed on BenchMarkXT (Ventana) using 5A4 and D5F3, respectively, and additionally with 5A4 on Bond-MAX (Leica). Data from our routine diagnostics on prospective ALK-testing with parallel IHC, using 5A4, and FISH were available from 303 NSCLC. All three IHC protocols showed congruent results. Only 1/25 FISH-positive NSCLC (4%) was false negative by IHC. For all three IHC protocols the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) compared to FISH were 96%, 100%, 100% and 97.8%, respectively. In the prospective cohort 3/32 FISH-positive (9.4%) and 2/271 FISH-negative (0.7%) NSCLC were false negative and false positive by IHC, respectively. In routine diagnostics the sensitivity, specificity, PPV and NPV of IHC compared to FISH were 90.6%, 99.3%, 93.5% and 98.9%, respectively. 5A4 and D5F3 are equally well suited for detecting ALK-rearranged NSCLC. BenchMark and BOND-MAX immunostainers can be used for IHC with 5A4. True discrepancies between IHC and FISH results do exist and need to be addressed when implementing IHC in an ALK-testing algorithm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of HER-2/neu status in breast cancer specimens using immunohistochemistry (IHC) & fluorescence in-situ hybridization (FISH) assay.

PubMed

Goud, Kalal Iravathy; Dayakar, Seetha; Vijayalaxmi, Kolanupaka; Babu, Saidam Jangu; Reddy, P Vijay Anand

2012-03-01

Fluorescence in situ hybridization (FISH) is increasingly being recognized as the most accurate and predictive test for HER 2/neu gene amplification and response to therapy in breast cancer. In the present study we investigated HER-2/neu gene amplification by FISH in breast carcinoma tissue specimens and compared the results with that of immunohistochemical (IHC) analysis. A total of 90 breast carcinoma tissue samples were used for immunohistochemical (IHC) and FISH analysis. IHC was performed by using mouse monoclonal antibody to the intracellular domain of HER-2/neu protein. Each slide was scored in a blinded fashion by two pathologists according to the manufacturer's recommended criteria. FISH analysis was performed on paraffin embedded breast tumour tissue sections. The polysomy for centromere 17 (Spec green signal) was read as green signals less than 4 as moderate polysomy, and more than 4 as highly polysomy. Thirty of the 90 patients had negative results by IHC and FISH. Of the 28 patients with the score of 2+ by IHC, 20 were FISH positive for HER-2/neu gene amplification, three were FISH negative and five patients showed equivocal (1.8-2.2) results by FISH. These five cases were retested for IHC and FISH on different paraffin embedded tissue blocks, and all five were found positive for HER-2/neu gene amplification. Twenty five patients with the score of 3+ by IHC were FISH positive for HER-2/neu gene amplification (>2.2). Seven cases with the score of 3+ by IHC were FISH negative for HER-2/neu gene amplification (>2.2), and showed polysomy of chromosome number 17 high polysomy > 4. Our results indicated that HER-2/neu status by FISH should be performed in all cases of breast tumour with a 2+ score by IHC. Cases demonstrating a 3+ score by IHC may be subjected to FISH to rule out polysomy of chromosome 17 which could be falsely interpreted as HER-2/neu overexpression by IHC analysis. There is also a need for establishing a clinically validated cut-off value for HER-2/neu FISH amplification against IHC which may be further compared and calibrated.

New MYC IHC Classifier Integrating Quantitative Architecture Parameters to Predict MYC Gene Translocation in Diffuse Large B-Cell Lymphoma

PubMed Central

Dong, Wei-Feng; Canil, Sarah; Lai, Raymond; Morel, Didier; Swanson, Paul E.; Izevbaye, Iyare

2018-01-01

A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the “percentage of MYC IHC-positive nuclei” methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts “permanent overexpressed MYC protein status,” it might identify nontranslocation-related chromosomal anomalies missed by FISH. PMID:27093450

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

PubMed

Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter

2011-06-01

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

IHC-TM connect-disconnect and efferent control V.

PubMed

Crane, H D

1982-07-01

Four previous papers in this series have explored how the idea of a set of disconnected inner hair cells (IHCs) that can "impact" the tectorial membrane (TM) is consistent with psychophysical data. This paper extends the model and explores the potential for mechanical interaction between the IHCs and outer hair cells (OHCs). In particular, it is speculated that the advantage of IHC-TM disconnect is extended dynamic range, and that movement of the movement of the OHCs and TM, under efferent control, constitutes a mechanical servo system for adjusting IHC-TM spacing along the cochlear partition to achieve this extended range.

Evaluation of HER-2/neu status in breast cancer specimens using immunohistochemistry (IHC) & fluorescence in-situ hybridization (FISH) assay

PubMed Central

Goud, Kalal Iravathy; Dayakar, Seetha; Vijayalaxmi, Kolanupaka; Babu, Saidam Jangu; Vijay, Anand Reddy P.

2012-01-01

Background & objectives: Fluorescence in situ hybridization (FISH) is increasingly being recognized as the most accurate and predictive test for HER2/neu gene amplification and response to therapy in breast cancer. In the present study we investigated HER-2/neu gene amplification by FISH in breast carcinoma tissue specimens and compared the results with that of immunohistochemical (IHC) analysis. Methods: A total of 90 breast carcinoma tissue samples were used for immunohistochemical (IHC) and FISH analysis. IHC was performed by using mouse monoclonal antibody to the intracellular domain of HER-2/neu protein. Each slide was scored in a blinded fashion by two pathologists according to the manufacturer's recommended criteria. FISH analysis was performed on paraffin embedded breast tumour tissue sections. The polysomy for centromere 17 (Spec green signal) was read as green signals less than 4 as moderate polysomy, and more than 4 as highly polysomy. Results: Thirty of the 90 patients had negative results by IHC and FISH. Of the 28 patients with the score of 2+ by IHC, 20 were FISH positive for HER-2/neu gene amplification, three were FISH negative and five patients showed equivocal (1.8-2.2) results by FISH. These five cases were retested for IHC and FISH on different paraffin embedded tissue blocks, and all five were found positive for HER-2/neu gene amplification. Twenty five patients with the score of 3+ by IHC were FISH positive for HER-2/neu gene amplification (>2.2). Seven cases with the score of 3+ by IHC were FISH negative for HER-2/neu gene amplification (>2.2), and showed polysomy of chromosome number 17 high polysomy > 4. Interpretation & conclusions: Our results indicated that HER-2/neu status by FISH should be performed in all cases of breast tumour with a 2+ score by IHC. Cases demonstrating a 3+ score by IHC may be subjected to FISH to rule out polysomy of chromosome 17 which could be falsely interpreted as HER-2/neu overexpression by IHC analysis. There is also a need for establishing a clinically validated cut-off value for HER-2/neu FISH amplification against IHC which may be further compared and calibrated. PMID:22561616

Effect of stress on amorphous bent cores

NASA Astrophysics Data System (ADS)

Saito, Akihiko; Yamamoto, Ken-ichi; Kunimori, Osamu

1992-07-01

The effect of stress on bent amorphous cores with positive magnetostriction has been investigated. Tension has been applied to the ribbon while winding into the toroid to improve the magnetic properties of the core. The properties of the coercive force of the tension winding core due to applied tension have been made clear from the observation of the domain structure.

Comparing four different ALK antibodies with manual immunohistochemistry (IHC) to screen for ALK-rearranged non-small cell lung cancer (NSCLC).

PubMed

Shen, Qin; Wang, Xuan; Yu, Bo; Shi, Shanshan; Liu, Biao; Wang, Yanfen; Xia, Qiuyuan; Rao, Qiu; Zhou, Xiaojun

2015-12-01

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) screening is essential to its treatment such as crizotinib. Different assays have been developed to detect ALK rearrangements, such as fluorescence in situ hybridization (FISH), reverse transcriptase-PCR (RT-PCR), and immunohistochemistry (IHC). However, ALK detection has not been applied widely in all hospitals. Moreover, IHC has been proposed to be a pre-screening tool because of its wide application in clinics. Since the low expression of ALK protein, the sensitivity and specificity of ALK antibody are the keys to the success of IHC screening. Therefore, we compared different antibodies to find the best one for IHC detection. We evaluated ALK expression by four different ALK antibodies: clone D5F3 (Ventana), clone D5F3 (CST), clone 1A4/1H7 (OriGene Tech.), and clone 5A4 (Abcam) based on manual IHC in a cohort of 60 NSCLCs. The results were compared with those from automated IHC (clone D5F3, Ventana). All cases were evaluated independently by ALK FISH. 32 ALK-positive and 28 ALK-negative NSCLCs were identified by automated IHC (D5F3, Ventana) and FISH analysis. Based on conventional manual IHC, the sensitivity of four antibodies-D5F3 (Ventana), D5F3 (CST), 1A4/1H7 (OriGene Tech.), and 5A4 (Abcam)-was 93.8%, 84.4%, 93.8%, and 56.3%, respectively. Their specificities and positive predictive values were 100%. The percentage of strong-moderate staining was 65.6%, 62.5%, 68.8%, and 21.9%, respectively. Compared with automated IHC (D5F3, Ventana), each staining concordance was 96.7%, 91.7%, 96.7%, and 76.7%, respectively, and each presented staining heterogeneity (weak-moderate-strong intensity). These data indicated that manual IHC with a more reliable ALK antibody might provide an effective strategy for screening ALK gene rearrangements in all NSCLC patients, followed by confirmatory FISH analysis in IHC-positive cases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Magnetic Force Microscopy Study of Zr 2 Co 11 -Based Nanocrystalline Materials: Effect of Mo Addition

DOE PAGES

Yue, Lanping; Jin, Yunlong; Zhang, Wenyong; ...

2015-01-01

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample.« less

Magnetic Force Microscopy Study of Zr 2 Co 11 -Based Nanocrystalline Materials: Effect of Mo Addition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue, Lanping; Jin, Yunlong; Zhang, Wenyong

Tmore » he addition of Molybdenum was used to modify the nanostructure and enhance coercivity of rare-earth-free Zr 2Co 11-based nanocrystalline permanent magnets. he effect of Mo addition on magnetic domain structures of melt spun nanocrystalline Zr 16Co 84-xMo x( x = 0 , 0.5, 1, 1.5, and 2.0) ribbons has been investigated. It was found that magnetic properties and local domain structures are strongly influenced by Mo doping. he coercivity of the samples increases with the increase in Mo content ( x ≤ 1.5 ). he maximum energy product ( B H ) max increases with increasing x from 0.5 MGOe for x = 0 to a maximum value of 4.2 MGOe for x = 1.5 . he smallest domain size with a relatively short magnetic correlation length of 128 nm and largest root-mean-square phase shift Φ rms value of 0.66° are observed for the x = 1.5 . he optimal Mo addition promotes magnetic domain structure refinement and thus leads to a significant increase in coercivity and energy product in this sample.« less

BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch Syndrome

PubMed Central

Toon, Christopher W; Walsh, Michael J; Chou, Angela; Capper, David; Clarkson, Adele; Sioson, Loretta; Clarke, Stephen; Mead, Scott; Walters, Rhiannon J.; Clendenning, Mark; Rosty, Christophe; Young, Joanne P.; Win, Aung Ko; Hopper, John L.; Crook, Ashley; von Deimling, Andreas; Jenkins, Mark A.; Buchanan, Daniel B; Gill, Anthony J

2013-01-01

BRAFV600E mutation in microsatellite unstable (MSI) CRCs virtually excludes Lynch Syndrome (LS). In microsatellite stable (MSS) CRC it predicts poor prognosis. We propose a universal CRC LS screening algorithm using concurrent reflex immunohistochemistry (IHC) for BRAFV600E and MMR proteins. We compared BRAFV600E IHC to multiplex polymerase chain reaction (PCR) and MALDI-TOF spectrometry in 216 consecutive CRCs from 2011. Discordant cases were resolved with rt-PCR. BRAFV600E IHC was performed on 51 CRCs from the Australasian Colorectal Cancer Family Registry (ACCFR) which were fully characterised for BRAF mutation by allele-specific PCR, MMR status (MMR IHC and MSI), MLH1 promoter methylation and germline MLH1 mutation. We then assessed MMR and BRAFV600E IHC on 1403 consecutive CRCs. By MALDI-TOF 15 cases did not yield a BRAF result, while 38/201(19%) were positive. By IHC 45/216(20%) were positive. Of the 7 discordant cases, rt-PCR confirmed the IHC result in 6. In the 51 CRCs from the ACCFR, IHC was concordant with allele-specific PCR in 50 cases. BRAFV600E and MSI IHC on 1403 CRCs demonstrated the following phenotypes: BRAF-ve/MSS (1029 cases,73%), BRAF+ve/MSS (98,7%), BRAF+ve/MSI (183,13%), and BRAF-ve/MSI (93,7%). All 11/1403 cancers associated with proven LS were BRAF-ve/MSI. We conclude that BRAF IHC is highly concordant with two commonly used PCR-based BRAFV600E assays, performed well in identifying MLH1 mutation carriers from the ACCFR and identified all cases of proven LS out of 1403 CRCs. Reflex BRAFV600E and MMR IHC are simple cheap tests which facilitate universal LS screening and identify the poor prognosis BRAFV600E mutant MSS CRC phenotype. PMID:23797718

A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma.

PubMed

Kinoshita, Yoshiaki; Hida, Tomoyuki; Hamasaki, Makoto; Matsumoto, Shinji; Sato, Ayuko; Tsujimura, Tohru; Kawahara, Kunimitsu; Hiroshima, Kenzo; Oda, Yoshinao; Nabeshima, Kazuki

2018-01-01

Homozygous deletion of 9p21 detected by fluorescence in situ hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression detected by immunohistochemistry (IHC) are useful for the differentiation between malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The authors previously described that IHC expression of the protein product of the methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21 chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM tissues. In the current study, the authors investigated whether a combination of MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in cell blocks obtained from pleural effusions. The authors examined IHC expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45 cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC expression of MTAP was compared with the deletion status of 9p21 FISH. MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1 IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed between the results of MTAP IHC and 9p21 FISH in cell blocks. A combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to be a reliable and useful method for differentiating MPM cells from RMC and can be used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. © 2017 American Cancer Society. © 2017 American Cancer Society.

Effects of the change in cutoff values for human epidermal growth factor receptor 2 status by immunohistochemistry and fluorescence in situ hybridization: a study comparing conventional brightfield microscopy, image analysis-assisted microscopy, and interobserver variation.

PubMed

Atkinson, Roscoe; Mollerup, Jens; Laenkholm, Anne-Vibeke; Verardo, Mark; Hawes, Debra; Commins, Deborah; Engvad, Birte; Correa, Adrian; Ehlers, Charlotte Cort; Nielsen, Kirsten Vang

2011-08-01

New guidelines for HER2 testing have been introduced. To evaluate the difference in HER2 assessment after introduction of new cutoff levels for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and to compare interobserver agreement and time to score between image analysis and conventional microscopy. Samples from 150 patients with breast cancer were scored by 7 pathologists using conventional microscopy, with a cutoff of both 10% and 30% IHC-stained cells, and using automated microscopy with image analysis. The IHC results were compared individually and to HER2 status as determined by FISH, using both the approved cutoff of 2.0 and the recently introduced cutoff of 2.2. High concordance was found in IHC scoring among the 7 pathologists. The 30% cutoff led to slightly fewer positive IHC observations. Introduction of a FISH equivocal zone affected 4% of the FISH scores. If cutoff for FISH is kept at 2.0, no difference in patient selection is found between the 10% and the 30% IHC cutoff. Among the 150 breast cancer samples, the new 30% IHC and 2.2 FISH cutoff levels resulted in one case without a firm diagnosis because both IHC and FISH were equivocal. Automated microscopy and image analysis-assisted IHC led to significantly better interobserver agreement among the 7 pathologists, with an increase in mean scoring time of only about 30 seconds per slide. The change in cutoff levels led to a higher concordance between IHC and FISH, but fewer samples were classified as HER2 positive.

Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

PubMed Central

Conde, Esther; Suárez-Gauthier, Ana; Benito, Amparo; Garrido, Pilar; García-Campelo, Rosario; Biscuola, Michele; Paz-Ares, Luis; Hardisson, David; de Castro, Javier; Camacho, M. Carmen; Rodriguez-Abreu, Delvys; Abdulkader, Ihab; Ramirez, Josep; Reguart, Noemí; Salido, Marta; Pijuán, Lara; Arriola, Edurne; Sanz, Julián; Folgueras, Victoria; Villanueva, Noemí; Gómez-Román, Javier; Hidalgo, Manuel; López-Ríos, Fernando

2014-01-01

Background Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Methods Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system. Results All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. Conclusions The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations. PMID:25248157

Plasticity and Activation of Spared Intraspinal Respiratory Circuits Following Spinal Cord Injury

DTIC Science & Technology

2016-10-01

fluorescent immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two markers commonly used in the central nervous system (GFAP and...immunohistochemistry (IHC) procedures. Accordingly, we performed IHC with two 365 markers commonly used in the central nervous system (GFAP and NeuN) either...905 mammalian central nervous system . J Neurosci Methods 1: 107-132, 1979. 906 Kirkwood PA, Munson JB, Sears TA, and Westgaard RH. Respiratory

Participatory action inquiry using baccalaureate nursing students: The inclusion of integrative health care modalities in nursing core curriculum.

PubMed

Chan, Roxane Raffin; Schaffrath, Michelle

2017-01-01

Nurses, nursing educators and students support the inclusion of integrative health care (IHC) into nursing core curriculum as a way to create nurses who deliver nursing care to the full extent of their scope of practice and advance evidenced based IHC. Because of the holistic nature of IHC modalities, research to investigate appropriate teaching strategies and potential efficacy of learning IHC in the baccalaureate core curriculum requires a holistic approach. Therefore a phenomenological exploration using participatory action inquiry was conducted at a large Midwestern university. Eighteen first year nursing students were selected as co-researchers. Their experiences in learning and delivering three 15 min IHC interventions (foot reflexology, lavender aromatherapy and mindful breathing) in an acute care setting were captured using reflexive journaling and participation in structured and organic communicative spaces. Of the patients approached, 67% accepted to receive one or more IHC modalities (147/219). Using van Manen's model for holistic data reduction three themes emerged: The experience of presence, competency and unexpected results. Learning IHC modalities is best supported by a self-reflective process that is constructed and modeled by a nurse faculty member with experience in delivering IHC modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

A matrix approach to guide IHC-based tissue biomarker development in oncology drug discovery.

PubMed

Smith, Neil R; Womack, Christopher

2014-01-01

Immunohistochemistry (IHC) is a core platform for the analysis of tissue samples, and there is an increasing demand for reliable and quantitative IHC-based tissue biomarkers in oncology clinical research and development (R&D) environments. Biomarker assay and drug development proceed in parallel. Furthermore, biomarker assay requirements change with each phase of drug development. We have therefore developed a matrix tool to enable researchers to evaluate whether a particular IHC biomarker assay is fit for purpose. Experience gained from the development of 130 IHC biomarkers, supporting a large number of oncology drug projects, was used to formulate a practical approach to IHC assay development. The resultant matrix grid and accompanying work flow incorporates 16 core decision points that link antibody and assay specificity and sensitivity, and assay performance in preclinical and clinical samples, with stages of drug development. The matrix provides a means to ensure that relevant information on an IHC assay in development is recorded and communicated consistently and that minimum assay validation requirements are met. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

PubMed

Mino-Kenudson, Mari

2017-10-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer

PubMed Central

2017-01-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC. PMID:29114473

Proposals for best-quality immunohistochemical staining of paraffin-embedded brain tissue slides in forensics.

PubMed

Trautz, Florian; Dreßler, Jan; Stassart, Ruth; Müller, Wolf; Ondruschka, Benjamin

2018-01-03

Immunohistochemistry (IHC) has become an integral part in forensic histopathology over the last decades. However, the underlying methods for IHC vary greatly depending on the institution, creating a lack of comparability. The aim of this study was to assess the optimal approach for different technical aspects of IHC, in order to improve and standardize this procedure. Therefore, qualitative results from manual and automatic IHC staining of brain samples were compared, as well as potential differences in suitability of common IHC glass slides. Further, possibilities of image digitalization and connected issues were investigated. In our study, automatic staining showed more consistent staining results, compared to manual staining procedures. Digitalization and digital post-processing facilitated direct analysis and analysis for reproducibility considerably. No differences were found for different commercially available microscopic glass slides regarding suitability of IHC brain researches, but a certain rate of tissue loss should be expected during the staining process.

Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine - Part 2: Immunohistochemistry Test Performance Characteristics.

PubMed

Torlakovic, Emina E; Cheung, Carol C; D'Arrigo, Corrado; Dietel, Manfred; Francis, Glenn D; Gilks, C Blake; Hall, Jacqueline A; Hornick, Jason L; Ibrahim, Merdol; Marchetti, Antonio; Miller, Keith; van Krieken, J Han; Nielsen, Soren; Swanson, Paul E; Vyberg, Mogens; Zhou, Xiaoge; Taylor, Clive R

2017-02-01

All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Exploring the link between institutional pressures and environmental management systems effectiveness: An empirical study.

PubMed

Daddi, Tiberio; Testa, Francesco; Frey, Marco; Iraldo, Fabio

2016-12-01

Institutional theory has been widely debated by scholars. A part of literature examines how institutional pressures act on company choices regarding proactive environmental strategies. However, the institutional perspective has still not completely clarified the influence of these pressures on the effectiveness of environmental management systems (EMSs) in achieving goals in terms of eco-innovation, competitiveness and corporate reputation. This paper analyses the role played by coercive, mimetic and normative forces in stimulating innovative and competitive responses by firms with an environmental certification. Using the results of a survey on 242 European EMAS-registered organisations, the paper highlights the more positive influence of mimetic and normative pressures than coercive ones. The paper contributes to the literature debate on EMSs analysed through the lens of institutional theory. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Use of Coercive Interventions in Mental Health Care in Germany and the Netherlands. A Comparison of the Developments in Two Neighboring Countries

PubMed Central

Steinert, Tilman; Noorthoorn, Eric O.; Mulder, Cornelis L.

2014-01-01

In this review, we compare the use of coercion in mental health care in Germany and in the Netherlands. Legal frameworks and published data on involuntary commitment, involuntary medication, seclusion, and restraint are highlighted as well as the role of guidelines, training, and attitudes held by psychiatrists and the public. Legal procedures regulating involuntary admission and commitment are rather similar, and so is the percentage of involuntary admissions and the rate per 100,000 inhabitants. However, opposing trends can be observed in the use of coercive interventions during treatment, which in both countries are considered as a last resort after all other alternative approaches have failed. In the Netherlands, for a long time seclusion has been considered as preferred intervention while the use of medication by force was widely disapproved as being unnecessarily invasive. However, after increasing evidence showed that number and duration of seclusions as well as the number of aggressive incidents per admission were considerably higher than in other European countries, attitudes changed within recent years. A national program with spending of 15 million € was launched to reduce the use of seclusion, while the use of medication was facilitated. A legislation is scheduled, which will allow also outpatient coercive treatment. In Germany, the latter was never legalized. While coercive treatment in Germany was rather common for involuntarily committed patients and mechanical restraint was preferred to seclusion in most hospital as a containment measure, the decisions of the Constitutional Court in 2011 had a high impact on legislation, attitudes, and clinical practice. Though since 2013 coercive medication is approvable again under strict conditions, it is now widely perceived as very invasive and last resort. There is evidence that this change of attitudes lead to a considerable increase of the use of seclusion and restraint for some patients. PMID:25309893

ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH.

PubMed

Minca, Eugen C; Portier, Bryce P; Wang, Zhen; Lanigan, Christopher; Farver, Carol F; Feng, Yan; Ma, Patrick C; Arrossi, Valeria A; Pennell, Nathan A; Tubbs, Raymond R

2013-05-01

ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC's routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Effects of aging time and temperature of Fe-1wt.%Cu on magnetic Barkhausen noise and FORC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saleh, Muad; Cao, Yue; Edwards, Danny J.

Magnetic Barkhausen noise (MBN), hysteresis measurements, first order reversal curves (FORC), Vickers microhardness, and Transmission Electron Microscopy (TEM) analyses were performed on Fe-1wt.%Cu (Fe-Cu) samples isothermally aged at 700°C for 0.5 – 25 hours to obtain samples with different sized Cu precipitates and dislocation structures. Fe-Cu is used to simulate the thermal and irradiation-induced defects in copper-containing nuclear reactor materials such as cooling system pipes and pressure vessel materials. The sample series showed an initial increase followed by a decrease in hardness and coercivity with aging time, which is explained by Cu precipitates formation and growth as observed by TEMmore » measurements. Further, the MBN envelope showed a continuous decrease in its magnitude and the appearance of a second peak with aging. Also, FORC diagrams showed multiple peaks whose intensity and location changed for different aging time. The changes in FORC diagrams are attributed to combined changes of the magnetic behavior due to Cu precipitate characteristics and dislocation structure. A second series of samples aged at 850°C, which is above the solid solution temperature of Fe-Cu, was studied to isolate the effects of dislocations. These samples showed a continuous decrease in MBN amplitude with aging time although the coercivity and hardness did not change significantly. The decrease of MBN amplitude and the appearance of the second MBN envelope peak are attributed to the changes in dislocation density and structure. This study shows that the effect of dislocations on MBN and FORC of Fe-Cu materials can vary significantly and should be considered in interpreting magnetic signatures.« less

Planning for Action: Campaign Concepts and Tools

DTIC Science & Technology

2012-08-01

142 10-15. Stability Mechanisms – Army .................................... 143 10-16. Stability Mechanisms – Joint...defeat mechanisms, which focus 143 the destructive and coercive capabilities of the force to provide security and public order and safety for...Matthew B. Ridgway. GEN Ridgway successfully led the 82d Airborne Division and XVIII Airborne Corps in the ETO during World War II and Eighth (US

Magnetic interactions and reversal mechanisms in Co nanowire and nanotube arrays

NASA Astrophysics Data System (ADS)

Proenca, M. P.; Sousa, C. T.; Escrig, J.; Ventura, J.; Vazquez, M.; Araujo, J. P.

2013-03-01

Ordered hexagonal arrays of Co nanowires (NWs) and nanotubes (NTs), with diameters between 40 and 65 nm, were prepared by potentiostatic electrodeposition into suitably modified nanoporous alumina templates. The geometrical parameters of the NW/NT arrays were tuned by the pore etching process and deposition conditions. The magnetic interactions between NWs/NTs with different diameters were studied using first-order reversal curves (FORCs). From a quantitative analysis of the FORC measurements, we are able to obtain the profiles of the magnetic interactions and the coercive field distributions. In both NW and NT arrays, the magnetic interactions were found to increase with the diameter of the NWs/NTs, exhibiting higher values for NW arrays. A comparative study of the magnetization reversal processes was also performed by analyzing the angular dependence of the coercivity and correlating the experimental data with theoretical calculations based on a simple analytical model. The magnetization in the NW arrays is found to reverse by the nucleation and propagation of a transverse-like domain wall; on the other hand, for the NT arrays a non-monotonic behavior occurs above a diameter of ˜50 nm, revealing a transition between the vortex and transverse reversal modes.

Natronolimnobius baerhuensis gen. nov., sp. nov. and Natronolimnobius innermongolicus sp. nov., novel haloalkaliphilic archaea isolated from soda lakes in Inner Mongolia, China.

PubMed

Itoh, Takashi; Yamaguchi, Takashi; Zhou, Peijin; Takashina, Tomonori

2005-04-01

Three novel isolates of haloalkaliphilic archaea, strains IHC-005T, IHC-010, and N-1311T, from soda lakes in Inner Mongolia, China, were characterized to elucidate their taxonomic positions. The three strains were aerobic, Gram-negative chemoorganotrophs growing optimally at 37-45 degrees C, pH 9.0-9.5, and 15-20% NaCl. Cells of strains IHC-005T/IHC-010 were motile rods, while those of strain N-1311T were non-motile pleomorphic flats or cocci. The three strains contained diphytanyl and phytanyl-sesterterpanyl diether derivatives of phosphatidylglycerol and phosphatidylglycerophosphate methyl ester. No glycolipids were detected. On phylogenetic analysis of 16S rRNA gene sequences, they formed an independent cluster in the Natro group of the family Halobacteriaceae. Comparison of their morphological, physiological, and biochemical properties, DNA G + C content and 16S rRNA gene sequences, and DNA-DNA hybridization study support the view that strains IHC-005T/IHC-010 and strain N-1311T represent separate species. Therefore, we propose Natronolimnobius baerhuensis gen. nov., sp. nov. for strains IHC-005T (=CGMCC 1.3597T =JCM 12253T)/IHC-010 (=CGMCC 1.3598 = JCM 12254) and Natronolimnobius innermongolicus sp. nov. for N-1311T (=CGMCC 1.2124T =JCM 12255T).

Screening for Muir-Torre syndrome using mismatch repair protein immunohistochemistry of sebaceous neoplasms.

PubMed

Roberts, Maegan E; Riegert-Johnson, Douglas L; Thomas, Brittany C; Thomas, Colleen S; Heckman, Michael G; Krishna, Murli; DiCaudo, David J; Bridges, Alina G; Hunt, Katherine S; Rumilla, Kandelaria M; Cappel, Mark A

2013-06-01

Screening for the Muir-Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.

The role of immunohistochemical analysis in the evaluation of EML4-ALK gene rearrangement in lung cancer.

PubMed

Sullivan, Harold C; Fisher, Kevin E; Hoffa, Anne L; Wang, Jason; Saxe, Debra; Siddiqui, Momin T; Cohen, Cynthia

2015-04-01

Among the mutations described in non-small cell lung carcinoma is a rearrangement resulting from an inversion within chromosome 2p leading to the formation of a fusion gene, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK). Fluorescence in situ hybridization (FISH) is the gold standard for the detection of ALK gene rearrangements. However, molecular methods are not readily available in all pathology laboratories. Immunohistochemistry (IHC) using an antibody directed against the EML4-ALK fusion protein provides a widely available alternative method of detection. We assessed whether IHC is a comparable and cost-effective alternative to FISH analysis for the detection of ALK gene rearrangements. A total of 110 non-small cell lung carcinoma cases (63 surgical/biopsy and 47 cytology specimens), previously tested for ALK gene rearrangements by FISH [7 (6.4%) positive for the rearrangement], were probed for the EML4-ALK fusion protein using a monoclonal EML4-ALK antibody, clone 5A4. Cells were considered to stain positive for ALK if >5% of cells showed cytoplasmic staining of at least grade 1 intensity (scale: 0 to 3). A cost analysis was performed using ALK IHC as a screening test. The sensitivity and specificity of the EML4-ALK IHC stain compared with ALK FISH analysis were 100% and 96%, respectively. All 7 FISH-positive cases stained positive by IHC, whereas 4 FISH-negative cases demonstrated positive staining. One of the 4 FISH-negative, IHC-positive cases harbored an EML4-ALK rearrangement by RT-PCR yielding 3 false-positive results overall. The κ agreement between IHC and FISH methods is 0.76 (substantial/excellent). The potential savings of implementing the ALK IHC as a screening method would be $10,418.21. Sensitivity of the EML4-ALK IHC stain is excellent (100%) but due to its suboptimal specificity, IHC cannot reliably supplant FISH analysis for the detection of ALK gene rearrangements. IHC shows promise as a screening tool to prevent unnecessary costly FISH analysis.

Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAF V600E mutations in colorectal carcinoma.

PubMed

Rössle, Matthias; Sigg, Michèle; Rüschoff, Jan H; Wild, Peter J; Moch, Holger; Weber, Achim; Rechsteiner, Markus P

2013-11-01

The activating BRAF (V600) mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAF (V600E) mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAF (V600E) mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAF (V600E) mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7%) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5%) and 15 IHC-positive cases (15/39; 38.5%) showed a BRAF wild-type by SaS. UDS detected a BRAF (V600E) mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100% and 63% and specificities of 95 and 100% for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-BRAF(V600E) (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAF (V600E) mutations in colorectal carcinoma.

Characterization of IDH1 p.R132H Mutant Clones Using Mutation-specific Antibody in Myeloid Neoplasms.

PubMed

Kurt, Habibe; Bueso-Ramos, Carlos E; Khoury, Joseph D; Routbort, Mark J; Kanagal-Shamanna, Rashmi; Patel, Umang V; Jorgensen, Jeffrey L; Wang, Sa A; Ravandi, Farhad; DiNardo, Courtney; Luthra, Rajyalakshmi; Medeiros, L Jeffrey; Patel, Keyur P

2018-05-01

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations occur in a variety of myeloid neoplasms. Immunohistochemistry (IHC)-based direct visualization of mutant clones of hematopoietic cells can be useful for rapid diagnostic screening and for monitoring treatment response. In this study, we first evaluated the sensitivity and specificity of the IDH1 p.R132H mutation-specific antibody by IHC. All IDH1 wild type cases (n=11) and IDH1 mutant cases with a non-p.R132H mutation (n=30) were negative by IHC, demonstrating 100% antibody specificity. All the initial diagnostic specimens with IDH1 p.R132H mutation including acute myeloid leukemia (n=30), myelodysplastic syndromes (MDS) (n=10), MDS/myeloproliferative neoplasms (MPN) (n=4), and MPN (n=5) were positive by IHC, demonstrating 100% antibody sensitivity. Both immature and mature myeloid cells showed immunoreactivity. Erythroid precursors, lymphoid cells, endothelial cells, and osteoblasts were consistently negative by IHC. We then evaluated the follow-up specimens with a known IDH1 mutation status including acute myeloid leukemia (n=23), MDS (n=2), MDS/MPN (n=2), and MPN (n=2). Thirty-three IDH1 p.R132H mutant cases were positive by IHC and 12 IDH1 mutation negative cases were negative by IHC. However, IHC reactivity in up to 25% of bone marrow cells was noted in 8 of 20 polymerase chain reaction-negative cases, all from patients with a known history of IDH1 p.R132H mutation indicating sampling error or a sensitivity issue with molecular tests. These data indicate that IHC is a highly specific and sensitive tool to detect IDH1 p.R132H mutation in bone marrow involved by myeloid neoplasms. In addition, IDH1 p.R132H IHC also allows localization and assessment of the maturation stage of the clones carrying the mutation.

Detection of ALK rearrangements in malignant pleural effusion cell blocks from patients with advanced non-small cell lung cancer: a comparison of Ventana immunohistochemistry and fluorescence in situ hybridization.

PubMed

Wang, Weiya; Tang, Yuan; Li, Jinnan; Jiang, Lili; Jiang, Yong; Su, Xueying

2015-02-01

Surgical resections or tumor biopsies are often not available for patients with late-stage non-small cell lung cancer (NSCLC). Cytological specimens, such as malignant pleural effusion (MPE) cell blocks, are critical for molecular testing. Currently, diagnostic methods to identify anaplastic lymphoma kinase (ALK) rearrangements include fluorescence in situ hybridization (FISH), real-time reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). In the current study, the authors compared Ventana ALK IHC assays and ALK FISH to detect ALK rearrangements in MPE cell blocks from patients with advanced NSCLC. The ALK IHC assay and ALK FISH were performed on 63 MPE cell blocks. RT-PCR analysis was performed as additional validation in cases in which a discrepancy was observed between the IHC assay and FISH results. The Ventana ALK IHC assay was found to be informative for all 63 samples, and 8 cases were positive. Fifty-eight cases were interpretable for FISH detection, and 6 were positive. The concordance between IHC and FISH was 100% among the 58 cases. Of the 5 uninterpretable ALK FISH cases, 2 cases and 3 cases, respectively, were ALK IHC positive and negative. One of the 2 ALK IHC-positive cases also demonstrated a positive result in the RT-PCR assay and the patient benefited from crizotinib treatment. MPE cell blocks can be used successfully for the detection of ALK rearrangement when tumor tissue is not available. The Ventana ALK IHC assay is an effective screening method for ALK rearrangement in MPE cell blocks from patients with advanced NSCLC, demonstrating high agreement with FISH results. © 2014 American Cancer Society.

Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

PubMed Central

Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

2016-01-01

Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

PubMed Central

Wang, Kai; Kim, Sun Young; Jang, Jiryeon; Kim, Seung Tae; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Lee, Jiyun; Lee, Woo Yong; Park, Yoon Ah; Huh, Jung Wook; Yun, Seong Hyeon; Do, In-Gu; Kim, Seok Hyung; Balasubramanian, Sohail; Stephens, Philip J.; Ross, Jeffrey S.; Li, Gang Gary; Hornby, Zachary; Ali, Siraj M.; Miller, Vincent A.; Kim, Kyoung-Mee; Ou, Sai-Hong Ignatius

2015-01-01

Purpose Anaplastic lymphoma kinase (ALK) rearrangement has been detected in colorectal carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence in situ hybridization (FISH), and next generation sequencing (NGS). We investigated if immunohistochemistry (IHC) can be used to detect ALK rearrangement in gastrointestinal malignancies. Experimental designs Tissue microarrays (TMAs) from consecutive gastric carcinoma (GC) and CRC patients who underwent surgical resection at Samsung Medical Center, Seoul, Korea were screened by IHC using ALK monoclonal antibody 5A4. IHC positive cases were confirmed by FISH, nCounter assays, and NGS-based comprehensive genomic profiling (CGP). ALK IHC was further applied to CRC patients enrolled in a pathway-directed therapeutic trial. Results Four hundred thirty-two GC and 172 CRC cases were screened by IHC. No GC sample was ALK IHC positive. One CRC (0.6%) was ALK IHC positive (3+) that was confirmed by ALK FISH and a novel CAD-ALK (C35; A20) fusion variant that resulted from a paracentric inversion event inv(2)(p22–21p23) was identified by CGP. One out of 50 CRC patients enrolled in a pathway-directed therapeutic trial was ALK IHC positive (3+) confirmed by ALK FISH and found to harbor the EML4-ALK (E21, A20) fusion variant by CGP. Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib. Conclusions ALK IHC is a viable screening strategy for identifying ALK rearrangement in CRC. ALK rearrangement is a potential actionable driver mutation in CRC based on survival inhibition of patient tumor-derived cell line by potent ALK inhibitors. PMID:26172300

Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

PubMed Central

Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter

2011-01-01

Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

Mechanical Excitation of IHC Stereocilia: An Attempt to Fit Together Diverse Evidence

NASA Astrophysics Data System (ADS)

Guinan, John J.

2011-11-01

The output of the cochlea is controlled by the bending of inner-hair-cell (IHC) stereocilia, but the mechanisms that produce this bending are poorly understood. Relevant evidence comes from several sources: measurements of cochlear motion from in-vitro and live preparations, as well as inferences about cochlear motions from responses of auditory-nerve fibers. The common conception that IHC excitation is due to shearing between the reticular lamina (RL) and the tectorial membrane (TM) does not explain the data. A hypothesis is presented that fits many of the observations into a coherent picture of how IHCs are excited. The key new concept is that stretching of outer-hair-cell (OHC) stereocilia (defined broadly) changes the RL-TM gap and produces fluid flow within the gap that bends the IHC stereocilia. Changes in the RL-TM gap and the resulting bending of IHC stereocilia provide a mechanism by which OHC active processes can enhance cochlear output without a corresponding enhancement of basilar-membrane motion.

Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis

PubMed Central

Reisinger, Ellen; Bresee, Chris; Neef, Jakob; Nair, Ramya; Reuter, Kirsten; Bulankina, Anna; Nouvian, Régis; Koch, Manuel; Bückers, Johanna; Kastrup, Lars; Roux, Isabelle; Petit, Christine; Hell, Stefan W.; Brose, Nils; Rhee, Jeong-Seop; Kügler, Sebastian; Brigande, John; Moser, Tobias

2011-01-01

Cochlear inner hair cells (IHCs) use Ca2+-dependent exocytosis of glutamate to signal sound information. Otoferlin, a C2-domain protein essential for IHC exocytosis and hearing, may serve as a Ca2+ sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca2+ sensors synaptotagmin 1 (Syt1) and 2. Support for the Ca2+ sensor of fusion hypothesis for otoferlin function comes from biochemical experiments, but additional roles in late exocytosis upstream of fusion have been indicated by physiological studies. Here, we tested the functional equivalence of otoferlin and Syt1 in three neurosecretory model systems: auditory IHCs, adrenal chromaffin cells and hippocampal neurons. Long-term and short-term ectopic expression of Syt1 in IHCs of Otof−/− mice by viral gene transfer in the embryonic inner ear and organotypic culture failed to rescue their Ca2+ influx-triggered exocytosis. On the other hand, virally mediated overexpression of otoferlin did not restore phasic exocytosis in Syt1-deficient chromaffin cells or neurons, but enhanced asynchronous release in the latter. We further tested exocytosis in Otof−/− hippocampal neurons and in Syt1−/− IHCs, but found no deficits in vesicle fusion. Expression analysis of different synaptotagmin isoforms indicated that Syt1 and Syt2 are absent from mature IHCs. Our data argue against a simple functional equivalence of the two C2 domain proteins in exocytosis of IHC ribbon synapses, chromaffin cells and hippocampal synapses. PMID:21451027

Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.

PubMed

Pekar-Zlotin, Marina; Hirsch, Fred R; Soussan-Gutman, Lior; Ilouze, Maya; Dvir, Addie; Boyle, Theresa; Wynes, Murry; Miller, Vincent A; Lipson, Doron; Palmer, Gary A; Ali, Siraj M; Dekel, Shlomi; Brenner, Ronen; Bunn, Paul A; Peled, Nir

2015-03-01

The U.S. Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating. Previous studies that compared FISH and IHC considered FISH the gold standard, but none compared data with the results of next-generation sequencing (NGS) analysis. We studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance. Of 51 patients, 4 were positive with FISH (7.8%), and 8 were positive with IHC (15.7%). Three were positive with both. NGS confirmed that four of the five patients who were positive with IHC and negative with FISH were positive for ALK. Two were treated by crizotinib, with progression-free survival of 18 and 6 months. Considering NGS as the most accurate test, the sensitivity and specificity were 42.9% and 97.7%, respectively, for FISH and 100% and 97.7%, respectively, for IHC. The FISH-based method of detecting EML4-ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. Screening for EML4-ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. Two patients who were negative with FISH and positive with IHC were treated with crizotinib and responded to therapy. ©AlphaMed Press.

Comparison of immunohistochemistry and polymerase chain reaction for detection of West Nile virus in naturally infected dead birds.

PubMed

Sandhu, Tejbir; Sidhu, Dalbinder; Dhillon, Major; Fang, Ying

2010-10-04

Credible vector-borne disease surveillance programs, especially in developing countries with limited resources, must include diagnostic tests that are efficient, inexpensive and simple and safe to administer while maintaining high levels of sensitivity and specificity. Since immunohistochemistry (IHC) includes most of these features, its sensitivity, specificity, predictive positive value (PPV) and predictive negative value (PNV) for West Nile virus (WNv) screening were compared to those of the gold standard, RT-PCR testing of kidney tissue in dead birds. IHC and RT-PCR were performed for WNv antigen on 41 dead birds (belonging to five orders) collected from the northwest region of the Riverside County of California. Fixed tissue sections were screened by IHC using polyclonal antibodies, and frozen kidney tissues were tested with RT-PCR. Kidney screening with IHC showed sensitivity, specificity, PPV and NPV of 95.45%, 73.68%, 80.77% and 93.33%, respectively. Based on WNv screening of kidney tissue, IHC and RT-PCR were in agreement with 95.45% (21/22) for positive dead birds and were in 100% (22/22) agreement when multi-organ screening by IHC was performed. The present study showed that IHC is as equally effective as RT-PCR in screening for WNv in dead birds. Therefore, IHC can effectively serve as a competent screening technique for those disease surveillance agencies that lack expensive RT-PCR technology while promoting safer biohazardous conditions, except at the initial stage of tissue collection.

"He Could Scare Me Without Laying a Hand on Me": Mothers' Experiences of Nonviolent Coercive Control During Marriage and After Separation.

PubMed

Crossman, Kimberly A; Hardesty, Jennifer L; Raffaelli, Marcela

2016-03-01

Studies demonstrate the negative effects of violent coercive control but few examine coercive control without violence. This study describes the characteristics of nonviolent coercive control among 8 divorcing mothers and compares them with 47 mothers who experienced violent coercive control or no violence/no control. Mothers with nonviolent coercive control reported more coping strategies, risk, harassment, and perceived threat than mothers with no violence/no control; similar levels of fear and control during marriage as mothers with violent coercive control; and more postseparation fear than both groups. Findings highlight the need to include nonviolent coercive control in screening methods and research measures. © The Author(s) 2015.

Personality and organizational influences on aerospace human performance

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1989-01-01

Individual and organizational influences on performance in aerospace environments are discussed. A model of personality with demonstrated validity is described along with reasons why personality's effects on performance have been underestimated. Organizational forces including intergroup conflict and coercive pressures are also described. It is suggested that basic and applied research in analog situations is needed to provide necessary guidance for planning future space missions.

Effect of sintering in a hydrogen atmosphere on the density and coercivity of (Sm,Zr)(Co,Cu,Fe)Z permanent magnets

NASA Astrophysics Data System (ADS)

Burkhanov, G. S.; Dormidontov, N. A.; Kolchugina, N. B.; Dormidontov, A. G.

2018-04-01

The effect of heat treatments in manufacturing (Sm,Zr)(Co,Cu,Fe)Z-based permanent magnets sintered in a hydrogen atmosphere on their properties has been studied. It was shown that the dynamics of the magnetic hardening of the studied magnets during heat treatments, in whole, corresponds to available concepts of phase transformations in five-component precipitation-hardened SmCo-based alloys. Peculiarities of the studied compositions consist in the fact that the coercive force magnitude of magnets quenched from the isothermal aging temperature is higher by an order of magnitude than those available in the literature. It was noted that, in using the selected manufacturing procedure, the increase in the density of samples does not finish at the sintering stage but continues in the course of solid-solution heat treatment.

Psychological Coercion in Human Trafficking: An Application of Biderman's Framework.

PubMed

Baldwin, Susie B; Fehrenbacher, Anne E; Eisenman, David P

2015-09-01

This study examined coercive conditions experienced by trafficked persons in the context of Biderman's theory of coercion. We conducted semi-structured interviews with 12 adult women trafficked into Los Angeles County, from 10 countries, for domestic work and/or sex work. Participants described health problems they experienced in relation to their trafficking experience and their perceptions of conditions that caused health problems. Utilizing a framework analysis approach, we analyzed themes using Biderman's framework. Participants reported experiencing the range of nonphysical coercive tactics outlined by Biderman, including isolation, monopolization of perception, induced debility or exhaustion, threats, occasional indulgences, demonstration of omnipotence, degradation, and enforcement of trivial demands. Our analysis demonstrates how these coercion tactics reinforced the submission of trafficked persons to their traffickers even in the absence of physical force or restraints. Such psychological abuse creates extreme stress that can lead to acute and chronic, physical and mental health problems. © The Author(s) 2014.

Standardization of Negative Controls in Diagnostic Immunohistochemistry: Recommendations From the International Ad Hoc Expert Panel

PubMed Central

Torlakovic, Emina E.; Francis, Glenn; Garratt, John; Gilks, Blake; Hyjek, Elizabeth; Ibrahim, Merdol; Miller, Rodney; Nielsen, Søren; Petcu, Eugen B.; Swanson, Paul E.; Taylor, Clive R.; Vyberg, Mogens

2014-01-01

Standardization of controls, both positive and negative controls, is needed for diagnostic immunohistochemistry (dIHC). The use of IHC-negative controls, irrespective of type, although well established, is not standardized. As such, the relevance and applicability of negative controls continues to challenge both pathologists and laboratory budgets. Despite the clear theoretical notion that appropriate controls serve to demonstrate the sensitivity and specificity of the dIHC test, it remains unclear which types of positive and negative controls are applicable and/or useful in day-to-day clinical practice. There is a perceived need to provide “best practice recommendations” for the use of negative controls. This perception is driven not only by logistics and cost issues, but also by increased pressure for accurate IHC testing, especially when IHC is performed for predictive markers, the number of which is rising as personalized medicine continues to develop. Herein, an international ad hoc expert panel reviews classification of negative controls relevant to clinical practice, proposes standard terminology for negative controls, considers the total evidence of IHC specificity that is available to pathologists, and develops a set of recommendations for the use of negative controls in dIHC based on “fit-for-use” principles. PMID:24714041

Crowdsourcing scoring of immunohistochemistry images: Evaluating Performance of the Crowd and an Automated Computational Method

NASA Astrophysics Data System (ADS)

Irshad, Humayun; Oh, Eun-Yeong; Schmolze, Daniel; Quintana, Liza M.; Collins, Laura; Tamimi, Rulla M.; Beck, Andrew H.

2017-02-01

The assessment of protein expression in immunohistochemistry (IHC) images provides important diagnostic, prognostic and predictive information for guiding cancer diagnosis and therapy. Manual scoring of IHC images represents a logistical challenge, as the process is labor intensive and time consuming. Since the last decade, computational methods have been developed to enable the application of quantitative methods for the analysis and interpretation of protein expression in IHC images. These methods have not yet replaced manual scoring for the assessment of IHC in the majority of diagnostic laboratories and in many large-scale research studies. An alternative approach is crowdsourcing the quantification of IHC images to an undefined crowd. The aim of this study is to quantify IHC images for labeling of ER status with two different crowdsourcing approaches, image-labeling and nuclei-labeling, and compare their performance with automated methods. Crowdsourcing- derived scores obtained greater concordance with the pathologist interpretations for both image-labeling and nuclei-labeling tasks (83% and 87%), as compared to the pathologist concordance achieved by the automated method (81%) on 5,338 TMA images from 1,853 breast cancer patients. This analysis shows that crowdsourcing the scoring of protein expression in IHC images is a promising new approach for large scale cancer molecular pathology studies.

Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry.

PubMed

Hida, Tomoyuki; Hamasaki, Makoto; Matsumoto, Shinji; Sato, Ayuko; Tsujimura, Tohru; Kawahara, Kunimitsu; Iwasaki, Akinori; Okamoto, Tatsuro; Oda, Yoshinao; Honda, Hiroshi; Nabeshima, Kazuki

2017-02-01

Differentiating malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH) is still challenging. Detection of homozygous deletion (HD) of 9p21 region including p16 INK4A (p16) by fluorescence in situ hybridization (FISH) and immunohistochemical detection of loss of BRCA1 associated protein 1 (BAP1), are reliable markers for MPM diagnosis. However, not all laboratories are equipped to perform 9p21 FISH; immunohistochemistry (IHC) is a more common and feasible technique. Thus, we sought to develop a IHC-based method that could predict the deletion of p16 in MPM in concordance with 9p21 FISH. We examined the expression of the 9p21.3-related proteins (p14, p15, p16, and methylthioadenosine phosphorylase (MTAP)) and BAP1 using IHC in 51 MPM and 25 RMH cases, and assessed their correlation with HD of p16 detected by FISH. The diagnostic usefulness of IHC of the 9p21.3-related proteins and BAP1 and their combinations was assessed using the cut-off values set by receiver operating characteristic (ROC) analysis. Among the 9p21.3-related proteins, MTAP IHC findings showed best concordance with 9p21 FISH results (kappa coefficient of 0.69) and a specificity of 100%. We also examined the combinations of MTAP IHC with the other products. The loss of p16 and MTAP had better concordance (kappa coefficient of 0.71), although lower specificity (85%). For differentiating MPM from RMH, only MTAP showed 100% specificity among the 9p21.3-related proteins, as did BAP1 IHC and 9p21 FISH. Among BAP1 combinations, only that of BAP1 with MTAP showed 100% specificity. Its sensitivity was 76.5%, which was lower than BAP1 IHC and 9p21 FISH combination (84.3%), but higher than BAP1 IHC alone (60.8%) or 9p21 FISH alone (60.8%). A combination of MTAP or BAP1 loss detected by IHC can likely detect MPM with good sensitivity and 100% specificity, and serve as useful ancillary IHC for discriminating MPM from RMH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Magnetic Force Switches for Magnetic Fluid Micromixing

NASA Astrophysics Data System (ADS)

Wei, Zung-Hang; Lee, Chiun-Peng; Lai, Mei-Feng

2010-01-01

A magnetic fluid micromixer with energy-saving magnetic force switches that can manipulate the magnetic fluid flow is proposed. The micromixer of high mixing efficiency uses single-domain micro magnets that have strong magnetic anisotropy to produce the magnetic force for the mixing. By altering the magnetization directions of the magnets that have different aspect ratios and coercivities, open and closed magnetic fluxes can be produced around each magnet cluster. For open magnetic flux, the mixing efficiency is numerically found to increase with the saturation magnetization of the magnets. On the contrary, the magnet clusters barely affects the mixing efficiency in the case of closed magnetic flux. Due to the different magnetic forces produced in open and closed magnetic fluxes, the magnetic fluid mixing can be switched on and off.

Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

NASA Astrophysics Data System (ADS)

Mosher, Bryan Patrick

The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into life (up to P65). Furthermore, I performed experiments to investigate if IHc-induced plasticity was more robust at a specific developmental period. No such critical period was identified as IHc-pretreatment induced robust respiratory plasticity when administered at all developmental periods tested (P12-16, P21-25 and P36-0). I propose that IHc-induced plasticity may be able to reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.

Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonda, Kohsuke, E-mail: gonda@med.tohoku.ac.jp; Miyashita, Minoru; Watanabe, Mika

2012-09-28

Highlights: Black-Right-Pointing-Pointer Organic fluorescent material-assembled nanoparticles for IHC were prepared. Black-Right-Pointing-Pointer New nanoparticle fluorescent intensity was 10.2-fold greater than Qdot655. Black-Right-Pointing-Pointer Nanoparticle staining analyzed a wide range of ER expression levels in tissue. Black-Right-Pointing-Pointer Nanoparticle staining enhanced the quantitative sensitivity for ER diagnosis. -- Abstract: The detection of estrogen receptors (ERs) by immunohistochemistry (IHC) using 3,3 Prime -diaminobenzidine (DAB) is slightly weak as a prognostic marker, but it is essential to the application of endocrine therapy, such as antiestrogen tamoxifen-based therapy. IHC using DAB is a poor quantitative method because horseradish peroxidase (HRP) activity depends on reaction time, temperature andmore » substrate concentration. However, IHC using fluorescent material provides an effective method to quantitatively use IHC because the signal intensity is proportional to the intensity of the photon excitation energy. However, the high level of autofluorescence has impeded the development of quantitative IHC using fluorescence. We developed organic fluorescent material (tetramethylrhodamine)-assembled nanoparticles for IHC. Tissue autofluorescence is comparable to the fluorescence intensity of quantum dots, which are the most representative fluorescent nanoparticles. The fluorescent intensity of our novel nanoparticles was 10.2-fold greater than quantum dots, and they did not bind non-specifically to breast cancer tissues due to the polyethylene glycol chain that coated their surfaces. Therefore, the fluorescent intensity of our nanoparticles significantly exceeded autofluorescence, which produced a significantly higher signal-to-noise ratio on IHC-imaged cancer tissues than previous methods. Moreover, immunostaining data from our nanoparticle fluorescent IHC and IHC with DAB were compared in the same region of adjacent tissues sections to quantitatively examine the two methods. The results demonstrated that our nanoparticle staining analyzed a wide range of ER expression levels with higher accuracy and quantitative sensitivity than DAB staining. This enhancement in the diagnostic accuracy and sensitivity for ERs using our immunostaining method will improve the prediction of responses to therapies that target ERs and progesterone receptors that are induced by a downstream ER signal.« less

Hematoxylin and Eosin Counterstaining Protocol for Immunohistochemistry Interpretation and Diagnosis.

PubMed

Grosset, Andrée-Anne; Loayza-Vega, Kevin; Adam-Granger, Éloïse; Birlea, Mirela; Gilks, Blake; Nguyen, Bich; Soucy, Geneviève; Tran-Thanh, Danh; Albadine, Roula; Trudel, Dominique

2017-12-21

Hematoxylin and eosin (H&E) staining is a well-established technique in histopathology. However, immunohistochemistry (IHC) interpretation is done exclusively with hematoxylin counterstaining. Our goal was to investigate the potential of H&E as counterstaining (H&E-IHC) to allow for visualization of a marker while confirming the diagnosis on the same slide. The quality of immunostaining and the fast-technical performance were the main criteria to select the final protocol. We stained multiple diagnostic tissues with class I IHC tests with different subcellular localization markers (anti-CK7, CK20, synaptophysin, CD20, HMB45, and Ki-67) and with double-staining on prostate tissues with anti-high molecular weight keratins/p63 (DAB detection) and p504s (alkaline phosphatase detection). To validate the efficacy of the counterstaining, we stained tissue microarrays from the Canadian Immunohistochemistry Quality Control (cIQc) with class II IHC tests (ER, PR, HER2, and p53 markers). Interobserver and intraobserver concordance was assessed by κ statistics. Excellent agreement of H&E-IHC interpretation was observed in comparison with standard IHC from our laboratory (κ, 0.87 to 1.00), and with the cIQc reference values (κ, 0.81 to 1.00). Interobserver and intraobserver agreement was excellent (κ, 0.89 to 1.00 and 0.87 to 1.00, respectively). We therefore show for the first time the potential of using H&E counterstaining for IHC interpretation. We recommend the H&E-IHC protocol to enhance diagnostic precision for the clinical workflow and research studies.

Web-based cancer communication and decision making systems: connecting patients, caregivers, and clinicians for improved health outcomes.

PubMed

DuBenske, Lori L; Gustafson, David H; Shaw, Bret R; Cleary, James F

2010-01-01

Over the cancer disease trajectory, from diagnosis and treatment to remission or end of life, patients and their families face difficult decisions. The provision of information and support when most relevant can optimize cancer decision making and coping. An interactive health communication system (IHCS) offers the potential to bridge the communication gaps that occur among patients, family, and clinicians and to empower each to actively engage in cancer care and shared decision making. This is a report of the authors' experience (with a discussion of relevant literature) in developing and testing a Web-based IHCS-the Comprehensive Health Enhancement Support System (CHESS)-for patients with advanced lung cancer and their family caregivers. CHESS provides information, communication, and coaching resources as well as a symptom tracking system that reports health status to the clinical team. Development of an IHCS includes a needs assessment of the target audience and applied theory informed by continued stakeholder involvement in early testing. Critical issues of IHCS implementation include 1) need for interventions that accommodate a variety of format preferences and technology comfort ranges; 2) IHCS user training, 3) clinician investment in IHCS promotion, and 4) IHCS integration with existing medical systems. In creating such comprehensive systems, development strategies need to be grounded in population needs with appropriate use of technology that serves the target users, including the patient/family, clinical team, and health care organization. Implementation strategies should address timing, personnel, and environmental factors to facilitate continued use and benefit from IHCS.

Rethinking Coercive Control.

PubMed

Stark, Evan

2009-12-01

The critical appraisals of Coercive Control focus largely on what my analysis implies for intervention, a matter to which the book devotes only limited space. In this reply, I reiterate core concepts in the book and acknowledge that much more work is needed to translate the realities of coercive control into practical legal and advocacy strategies. I review how coercive control differs from partner assaults and so why it merits a distinct response; the extent to which coercive control targets gender identity; the wisdom of complementing the focus on violence with an emphasis on male domination, sexual inequality and personal liberty; what this implies for shelters and the law; why sexual inequality differentiates coercive control from female partner abuse of men; how sexual equality can be both cause and antidote for coercive control; why I think an affirmative concept of freedom is essential to grasp the human rights violations inflicted by coercive control; and what it means to "story" coercive control by integrating women into the larger liberty narrative on which our national identity rests.

Study protocol for a cluster randomised controlled trial to assess the effectiveness of user-driven intervention to prevent aggressive events in psychiatric services.

PubMed

Välimäki, Maritta; Yang, Min; Normand, Sharon-Lise; Lorig, Kate R; Anttila, Minna; Lantta, Tella; Pekurinen, Virve; Adams, Clive E

2017-04-04

People admitted to psychiatric hospitals with a diagnosis of schizophrenia may display behavioural problems. These may require management approaches such as use of coercive practices, which impact the well-being of staff members, visiting families and friends, peers, as well as patients themselves. Studies have proposed that not only patients' conditions, but also treatment environment and ward culture may affect patients' behaviour. Seclusion and restraint could possibly be prevented with staff education about user-centred, more humane approaches. Staff education could also increase collaboration between patients, family members and staff, which may further positively affect treatment culture and lower the need for using coercive treatment methods. This is a single-blind, two-arm cluster randomised controlled trial involving 28 psychiatric hospital wards across Finland. Units will be randomised to receive either a staff educational programme delivered by the team of researchers, or standard care. The primary outcome is the incidence of use of patient seclusion rooms, assessed from the local/national health registers. Secondary outcomes include use of other coercive methods (limb restraint, forced injection, and physical restraint), service use, treatment satisfaction, general functioning among patients, and team climate and employee turn-over (nursing staff). The study, designed in close collaboration with staff members, patients and their relatives, will provide evidence for a co-operative and user-centred educational intervention aiming to decrease the prevalence of coercive methods and service use in the units, increase the functional status of patients and improve team climate in the units. We have identified no similar trials. ClinicalTrials.gov NCT02724748 . Registered on 25 th of April 2016.

Immunohistochemical Identification and Pathologic Findings in Natural Cases of Equine Abortion Caused by Leptospiral Infection

PubMed Central

Szeredi, L.; Haake, D. A.

2009-01-01

The aim of this study was to examine the utility of immunohistochemistry (IHC) in the diagnosis of leptospiral equine abortion and to compare IHC to silver staining and serology of the aborted mares. Ninety-six fetuses from 57 farms were examined using all 3 diagnostic techniques, revealing evidence of leptospiral infection in 3 fetuses (3.1%) from 3 (5.3%) different farms. A new finding in 1 of these confirmed cases of leptospiral abortion was the presence of macroscopic pinpoint grayish-white nodules that had a histologic correlate of hepatic necrosis; other histologic findings were consistent with those previously reported. IHC performed using 2 different leptospiral antisera (multivalent whole-cell rabbit antiserum and rabbit antiserum against the major outer membrane protein LipL32) yielded similar results. IHC was more sensitive (19/21 [90.5%] tissue samples) than silver staining (8/21 [38.1%] tissue samples), and more specific than serology performed using the microscopic agglutination test. The primary advantage of IHC over silver staining was the ability of IHC to identify leptospiral antigen not only as morphologically intact spiral forms. PMID:16966455

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.

PubMed

Al-Rohil, Rami N; Milton, Denái R; Nagarajan, Priyadharsini; Curry, Jonathan L; Feldmeyer, Laurence; Torres-Cabala, Carlos A; Ivan, Doina; Prieto, Victor G; Tetzlaff, Michael T; Aung, Phyu P

2018-07-01

Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2-40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated in 2002 to 2015 were assembled and included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40 IHC studies were reviewed. When LVI was present, the location (peritumoral or intratumoral) and the size of the largest invaded vessel were recorded. LVI findings by H&E staining and D2-40 IHC were compared with each other and with histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58 cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in 7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining. Histologically, D2-40-detected LVI was associated with infiltrative growth pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively). There was a statistically significant difference between the frequency of detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both intratumoral and peritumoral LVI is associated with metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study).

PubMed

Takeuchi, K; Togashi, Y; Kamihara, Y; Fukuyama, T; Yoshioka, H; Inoue, A; Katsuki, H; Kiura, K; Nakagawa, K; Seto, T; Maemondo, M; Hida, T; Harada, M; Ohe, Y; Nogami, N; Yamamoto, N; Nishio, M; Tamura, T

2016-01-01

Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

ALK ambiguous-positive non-small cell lung cancers are tumors challenged by diagnostic and therapeutic issues.

PubMed

Uguen, Arnaud; Andrieu-Key, Sophie; Vergne, Florence; Descourt, Renaud; Quéré, Gilles; Quintin-Roué, Isabelle; Key, Stéphane; Guéguen, Paul; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale

2016-09-01

Searching for ALK rearrangements using the approved fluorescent in situ hybridization (FISH) test and complementary immunohistochemistry (IHC) has become the rule to treat patients with advanced non‑small cell lung cancer (NSCLC) with anti‑ALK targeted therapy. The concordance between the two techniques is reported to be strong but imperfect. We report our experience with cases of ALK‑rearranged lung adenocarcinomas pointing out particularly ambiguous cases. FISH and IHC data on ALK but also c‑MET IHC as well as EGFR and KRAS mutation screening are considered, together with response to crizotinib treatment. We classified the 55 FISH ALK‑rearranged tumors into two groups according to the FISH and IHC results: a concordant FISH+IHC+ group (31 tumors) and an ambiguous group (24 tumors). These tumors were considered as 'ambiguous' ALK‑positive due to negative (21 tumors) or non‑contributive (3 tumors) IHC. In addition, the percentage of FISH-positive nuclei was between 15 and 20% in 17 tumors belonging to one or the other group (now called borderline tumors). We discuss the accuracy of the different tests with intent to determine whether ambiguous and borderline tumors are real positive ALK‑rearranged tumors. To conclude, ambiguous ALK‑positive lung cancers are challenging tumors with diagnosis and therapeutic issues that can justify parallel FISH, IHC and molecular screening strategy.

Diagnosis of Inherited Epidermolysis Bullosa in Resource-Limited Settings: Immunohistochemistry Revisited.

PubMed

Yenamandra, Vamsi Krishna; Bhari, Neetu; Ray, Subrata Basu; Sreenivas, Vishnubhatla; Dinda, Amit Kumar; Scaria, Vinod; Sharma, Vinod Kumar; Sethuraman, Gomathy

2017-01-01

Immunofluorescence (IFM) antigen mapping is the most commonly used technique to diagnose and differentiate epidermolysis bullosa (EB). In India, IFM is limited to few research laboratories and is not readily available, making the diagnosis largely clinical and often inaccurate. Ob jective of the Study: To examine the diagnostic usefulness of immunohistochemistry (IHC) as compared to IFM in resource-limited settings. Forty-four consecutive EB patients were included in this study. IHC and IFM were performed on 7-µm frozen tissue sections using standard laboratory protocols with a limited panel of antibodies. The kappa coefficient of agreement was calculated with genetic analysis as the gold standard. IFM and IHC accurately identified the subtype of EB in 80.9% (p < 0.001) of the cases, when a clear blister cavity was evident on biopsy. The sensitivities and specificities of IHC and IFM for diagnosing EB simplex, junctional EB, and dystrophic EB were 100, 100, and 60% and 82.4, 100, and 100%, respectively. IHC was equally effective (p < 0.001) in establishing the type of EB as IFM. IHC staining and its interpretation were simple and comparable to IFM. IHC had an advantage of showing subtle changes in the epidermal architecture that could not be appreciated on IFM and hence can be considered useful in resource-limited settings. © 2017 S. Karger AG, Basel.

Interprofessional collaboration within Canadian integrative healthcare clinics: Key components.

PubMed

Gaboury, Isabelle; Bujold, Mathieu; Boon, Heather; Moher, David

2009-09-01

Research shows that interprofessional collaboration has become an important factor in the implementation of effective healthcare models. To date, the literature has not focused on the collaboration between medical doctors and complementary and alternative medicine (CAM) healthcare practitioners, an example of interdisciplinary collaboration called integrative healthcare (IHC). Drawing on in-depth, semi-standardized interviews conducted with 21 practitioners working in Canadian IHC clinics, this paper explored and interpreted how IHC is experienced by those working in Canadian IHC clinics. The interview questions and analysis were guided by the Input, Process, Output conceptual framework drawn from the organizational management theory (McGrath, J. E. (1964). Social psychology: A brief introduction. New York: Holt, Rinehart and Winston.) to study collaboration within teams. We found that constructs contributing to collaboration included practitioners' attitudes and educational background, as well as external factors such as the healthcare system and financial pressures. Major processes affecting collaboration included communication, patient referral and power relationships. These determinants of collaboration were found to result in learning opportunities for practitioners, modified burden of work and ultimately, higher affective commitment toward the clinic. These constructs serve as a guide for further investigation of interprofessional collaboration within an IHC clinic. This exploration of interprofessional collaboration in IHC identified a broad array of key factors associated with interprofessional collaboration. These factors are critical to better understand the functioning of IHC clinics, and provide guidance for creation or maintenance of successful clinics.

Correlation among genetic variations of c-MET in Chinese patients with non-small cell lung cancer.

PubMed

Duan, Jianchun; Yang, Xiaodan; Zhao, Jun; Zhuo, Minglei; Wang, Zhijie; An, Tongtong; Bai, Hua; Wang, Jie

2018-01-05

The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive. Among patients with IHC 2+ staining, 35.5% was FISH positive, while cases with IHC 3+ staining,64% was FISH positive. Both protein expression and copy number of c-MET did not significantly correlate with clinical prognosis in these patients treated with EGFR-TKIs. IHC could be used as a preliminary screening method for c-MET copy number amplification and should be confirmed by FISH only in IHC positive case which facilitate selection of ALK or MET inhibitor therapy. c-MET gene copy number, protein expression and somatic mutation for exon 14 were detected by fluorescent- In-Situ -Hybridization (FISH), Immunohistochemistry (IHC), and Denaturing-High-Performance-Liquid-Chromatography (DHPLC), respectively, in 196 NSCLC patients. The relationship between c-MET abnormalities and clinical outcome of targeted therapy was analyzed by McNemar's test.

The Paleolimnological Record of the North Atlantic Oscillation: Magnetic Properties and Diatom Counts from Hemlock and Conesus Lakes, Western New York State

NASA Astrophysics Data System (ADS)

Chaisson, W. P.; Arnold, M. R.; Cottrell, R. D.

2002-05-01

Between 1900 and 1930 CE when the NAO index showed large amplitude positive excursions, but the AO index varied at very small amplitudes, drought conditions frequently prevailed in western New York state according the Palmer Drought Index (PDI). Since 1970, when both the NAO and the AO indices show large and progressively increasing positive excursions, the PDI has been generally positive, indicating moisture surpluses in the region. Magnetic properties, including coercivity of remanence, have been measured and the diatoms have been enumerated in sediments from two gravity cores collected from Hemlock and Conesus Lakes. The sediments date from ~1875 CE in the Hemlock core and ~1923 CE in the Conesus core. Variations in magnetic grain-size are interpreted from the coercivity of remanence, with lower coercivity of remanence associated with large grain size. The primary productivity of lakes is interpreted from the Lake Trophic Status Index (LTSI), which is calculated based on known ecologies of several diatom species. In both lakes we find that larger magnetic grain size is associated with greater productivity in the lakes. In the Hemlock core, through the interval corresponding to 1913-1943 coercivity of remanence values declined to 281-259 Oersteds, from late 19th century values that were >350 Oersteds. The bottom of the Conesus core (1923-1938 CE) has the lowest coercivity of remanance values in the record (309-317 Oersteds). LTSI values in the Hemlock samples increase as remanence of coercivity values decline between 1888 and 1920 CE. This reflects an increase in the abundance of the mesoeutrophic Tabellaria fenestrata during this interval. In the Conesus samples the agreement between coercivity of remanence and LTSI is quite close. The range of variation in both LTSI and magnetic grain size is smaller in Conesus than in Hemlock Lake. The diatom assemblage is also quite different in Conesus, dominated by eutrophic Aulacosiera granulata, which are rare or absent at Hemlock Lake. The Hemlock basin is much steeper than than that of Conesus and its water level fluctuates more extremely because it is the reservoir for the city of Rochester. Hemlock Lake is oligotrophic and its drainage basin is heavily forested and lightly populated. Conesus Lake is eutrophic, its shores lined with cottages and the basin is heavily agricultural. In spite of these differences in both natural conditions and anthropogenic factors, the LTSI and magnetic measurements of the two lakes share variance, ostensibly forced by regional climate change. Initial results suggest that the shared component of variance in these proxy indicators can predict variations in regional drought intensity. Regional drought intensity, in turn, seems associated with an uncoupling of AO and NAO variation.

The Ethnic Factor in the Soviet Armed Forces. The Muslim Dimension

DTIC Science & Technology

1991-01-01

Muslim conscripts into effective soldiers. The types of problems that a Muslim conscript presents for the Soviet military can be narrowed to two categories ... categories : ability and reliability. ETHNICITY AND DEMOGRAPHICS The major Soviet Muslim ethnic groups are creations of the Soviet regime, dating back to...avoid such embarrassments in the future. viii SOVIET MILITARY REFORM The predominantly coercive type of compliance previously used by the Soviet military

Getting to No (Nuclear Weapons) with Iran: Will Coercive Diplomacy Work?

DTIC Science & Technology

2013-12-10

elucidates additional options to better address strategic ends, but with greater risk. Unless a grand bargain is attainable, the U.S. must likely accept...strategic ends, but likely with a substantial increase in risk. Unless an unspoken grand bargain is attainable, the U.S. must likely accept...adroit and vigilant application of counter- force at a series of constantly shifting geographical and political points, corresponding to the shifts

Conflict Containment in the Balkans: Testing Extended Deterrence.

DTIC Science & Technology

1995-03-01

STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution is unlimited. 13. ABSTRACT This thesis critically analyzes a prominent theoretical...Containment 15. NUMBER OF in the Balkans; Deterrence; Coercive Diplomacy; Balance of Forces. PAGES: 161 16. PRICE CODE 17. SECURITY CLASSIFI- 18. SECURITY...Department of National Security Affai sAccesion For NTIS CRA&I DTtC TAB Unannounced Justifca ........... By- Distribution Availability Codes Avail and/or Dist

Hollow Threats: Why Coercive Diplomacy Fails

DTIC Science & Technology

2015-06-01

IDE from the Curso del Estado Mayor de las Fuerzas Armadas in Madrid, Spain. Maj Schore has a bachelor’s degree in Economics from the University...this element presupposes that the nature of a liberal democracy not only reduces its credibility to administer a severe level of hurt, but damages...of resistance increased Aidid’s ability to portray his forces as national liberators and augmented his support among the Somali people.40 This

The Requirement for U.S. Army Special Forces to Conduct Interrogation

DTIC Science & Technology

2012-06-01

SCHARFF .............93  APPENDIX D.  “SUGGESTIONS FOR JAPANESE INTERPRETERS BASED ON WORK IN THE FIELD” BY SHERWOOD MORAN ...............107  INITIAL...reluctant to risk their men simply to capture Japanese soldiers—soldiers they were convinced would never disclose valuable intelligence.44 Through a...only the most severe coercive measures of interrogation would convince a captured Japanese soldier to divulge information. Moran believed “strong

Thermal treatment to enhance saturation magnetization of superparamagnetic Ni nanoparticles while maintaining low coercive force

NASA Astrophysics Data System (ADS)

Ishizaki, Toshitaka; Yatsugi, Kenichi; Akedo, Kunio

2018-05-01

Superparamagnetic nanoparticles capped by insulators have the potential to decrease eddy current and hysteresis losses. However, the saturation magnetization ( M s) decreases significantly with decreasing the particle size. In this study, superparamagnetic Ni nanoparticles having the mean size of 11.6 ± 1.8 nm were synthesized from the reduction of Ni(II) acetylacetonate in oleylamine with the addition of trioctylphosphine, indicating the coercive force ( H c) less than 1 Oe. Thermal treatments of the Ni nanoparticles were investigated as a method to enhance the M s. The results indicated that the M s was enhanced by an increase of the Ni mass ratio with increasing thermal treatment temperature. However, the decomposition behavior of the capping layers indicated that their alkyl chains actively decomposed at temperatures above 523 K to form Ni3P via reaction between Ni and P, resulting in particle growth with a significant increase in the H c. Therefore, the optimal temperature was determined to be 473 K, which increased the Ni ratio without formation of Ni3P while maintaining particle sizes with superparamagnetic properties. Further, the M s could be improved by 22% (relative to the as-synthesized Ni nanoparticles) after thermal treatment at 473 K while maintaining the H c to be less than 1 Oe.

Intersectional Discrimination of Romani Women Forcibly Sterilized in the Former Czechoslovakia and Czech Republic

PubMed Central

Albert, Gwendolyn

2017-01-01

Abstract This paper reviews domestic and international activism seeking justice for Romani and other women harmed by coercive, forced, and involuntary sterilization in the former Czechoslovakia and Czech Republic. Framed by Michel Foucault’s theory of biopower, it summarizes the history of these abuses and describes human rights campaigns involving domestic and international litigation, advocacy, and grassroots activism, as well as the responses of the Czech governments. The paper describes how legal and policy work during the past decade has led to recognition of coercive, forced, and involuntary sterilization as a present-day human rights issue worldwide, to the adoption of new guidelines on female sterilization, and to a joint statement on the issue by seven UN agencies. Relying on academic literature, reports by domestic and international human rights groups, state investigations, judgments from Czech courts and the European Court of Human Rights (ECHR), media reports, and the experience of the authors, who have been allies of the Romani women harmed in the Czech Republic since 2005 and 2012, respectively, the paper describes the current state of play with respect to achieving redress for them, including current conceptual, legal, political, and social obstacles and their antecedents in 20th century notions of population control. PMID:29302160

To enhance the efficiency of a power supply circuit by the use of Fe-P-B-Nb-type ultralow loss glassy metal core

NASA Astrophysics Data System (ADS)

Matsumoto, H.; Urata, A.; Yamada, Y.; Makino, A.

2009-04-01

The inductor in a power supply is required to be capable of dealing satisfactorily with the high-current supply and to improve the power loss characteristic. A novel glassy metal powder with a chemical composition Fe77P7B13Nb3 features both a high saturated magnetic flux density of 1.3 T and a low coercive force of 2.0 A/m, which has a stable amorphous structure suitable for glassy metal composite cores. Hence there is no magnetic saturation even under a high-current supply, and it is confirmed to have significantly low magnetic loss resulting from the low coercive force. As a result of using the glassy metal alloy Fe77P7B13Nb3 powder in an inductor core, we have achieved improvement in power supply efficiency by up to roughly 2.0%. Moreover, the reduction in the standby power requirement by the improvement in the power supply efficiency in the low load current case, where the core loss occupies a high ratio in the entire loss, can be expected. Additionally, heat generation in a core is suppressed by using the low loss powder, and it becomes easy to design a temperature rise in the entire power supply circuit.

Intersectional Discrimination of Romani Women Forcibly Sterilized in the Former Czechoslovakia and Czech Republic.

PubMed

Albert, Gwendolyn; Szilvasi, Marek

2017-12-01

This paper reviews domestic and international activism seeking justice for Romani and other women harmed by coercive, forced, and involuntary sterilization in the former Czechoslovakia and Czech Republic. Framed by Michel Foucault's theory of biopower, it summarizes the history of these abuses and describes human rights campaigns involving domestic and international litigation, advocacy, and grassroots activism, as well as the responses of the Czech governments. The paper describes how legal and policy work during the past decade has led to recognition of coercive, forced, and involuntary sterilization as a present-day human rights issue worldwide, to the adoption of new guidelines on female sterilization, and to a joint statement on the issue by seven UN agencies. Relying on academic literature, reports by domestic and international human rights groups, state investigations, judgments from Czech courts and the European Court of Human Rights (ECHR), media reports, and the experience of the authors, who have been allies of the Romani women harmed in the Czech Republic since 2005 and 2012, respectively, the paper describes the current state of play with respect to achieving redress for them, including current conceptual, legal, political, and social obstacles and their antecedents in 20th century notions of population control.

A sensitive and high throughput TaqMan-based reverse transcription quantitative polymerase chain reaction assay efficiently discriminates ALK rearrangement from overexpression for lung cancer FFPE specimens.

PubMed

Lung, Jrhau; Lin, Yu-Ching; Hung, Ming-Szu; Jiang, Yuan Yuan; Lee, Kuan-Der; Lin, Paul Yann; Tsai, Ying Huang

2016-04-01

ALK fusion gene is an oncogenic driver in lung cancer with low prevalence, which can be ameliorated by crizotinib. Currently, ALK fusion gene can be diagnosed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), but inconstistnt results between the two methods are encountered regularly. To make the ALK fusion gene screening more efficient and to provide a simple solution to clarify the discrepancy between FISH and IHC results, a sensitive TaqMan-based reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay was established. The 3-plex TaqMan-based RT-qPCR assay was established and performed on 102 archived formalin-fixed, paraffin-embedded (FFPE) NSCLC samples to detect ALK rearrangement and overexpression. Break-apart FISH and automatic immunohistochemistry based ALK assays were performed side by side using tissue microarray. The RT-qPCR was performed successfully for 80 samples and 10 of them showed positive signals. Three out of the 10 qPCR positive cases were further confirmed by FISH and IHC test. Two others were IHC positive and FISH negative, and expressed full-length ALK transcript. The rest were neither FISH nor IHC positive and their ALK expression level was significantly lower than those FISH or IHC positive cases. Our RT-qPCR assay demonstrates that the capability and reliability of ALK detection is comparable to FISH and IHC, but it is more effective at discriminating ALK rearrangement from overexpression. The RT-qPCR assay easily clarifies the discrepancy between FISH and IHC, and can be incorporated into routine ALK screening for lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).

PubMed

Long, E; Ilie, M; Lassalle, S; Butori, C; Poissonnet, G; Washetine, K; Mouroux, J; Lespinet, V; Lacour, J P; Taly, V; Laurent-Puig, P; Bahadoran, P; Hofman, V; Hofman, P

2015-12-01

Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed. © 2015 European Academy of Dermatology and Venereology.

Preselection of EGFR mutations in non-small-cell lung cancer patients by immunohistochemistry: comparison with DNA-sequencing, EGFR wild-type expression, gene copy number gain and clinicopathological data.

PubMed

Gaber, Rania; Watermann, Iris; Kugler, Christian; Vollmer, Ekkehard; Perner, Sven; Reck, Martin; Goldmann, Torsten

2017-01-01

Targeting epidermal growth factor receptor (EGFR) in patients with non-small-cell lung cancer (NSCLC) having EGFR mutations is associated with an improved overall survival. The aim of this study is to verify, if EGFR mutations detected by immunohistochemistry (IHC) is a convincing way to preselect patients for DNA-sequencing and to figure out, the statistical association between EGFR mutation, wild-type EGFR overexpression, gene copy number gain, which are the main factors inducing EGFR tumorigenic activity and the clinicopathological data. Two hundred sixteen tumor tissue samples of primarily chemotherapeutic naïve NSCLC patients were analyzed for EGFR mutations E746-A750del and L858R and correlated with DNA-sequencing. Two hundred six of which were assessed by IHC, using 6B6 and 43B2 specific antibodies followed by DNA-sequencing of positive cases and 10 already genotyped tumor tissues were also included to investigate debugging accuracy of IHC. In addition, EGFR wild-type overexpression was IHC evaluated and EGFR gene copy number determination was performed by fluorescence in situ hybridization (FISH). Forty-one÷206 (19.9%) cases were positive for mutated EGFR by IHC. Eight of them had EGFR mutations of exons 18-21 by DNA-sequencing. Hit rate of 10 already genotyped NSCLC mutated cases was 90% by IHC. Positive association was found between EGFR mutations determined by IHC and both EGFR overexpression and increased gene copy number (p=0.002 and p<0.001, respectively). Additionally, positive association was detected between EGFR mutations, high tumor grade and clinical stage (p<0.001). IHC staining with mutation specific antibodies was demonstrated as a possible useful screening test to preselect patients for DNA-sequencing.

Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of the BRAFV600E Mutation in Thyroid Neoplasm

PubMed Central

Oh, Hye-Seon; Kwon, Hyemi; Park, Suyeon; Kim, Mijin; Jeon, Min Ji; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae; Choi, Jene

2018-01-01

Background The BRAFV600E mutation is the most common genetic alteration identified in papillary thyroid carcinoma (PTC). Because of its costs effectiveness and sensitivity, direct Sanger sequencing has several limitations. The aim of this study was to evaluate the efficiency of immunohistochemistry (IHC) as an alternative method to detect the BRAFV600E mutation in preoperative and postoperative tissue samples. Methods We evaluated 71 patients who underwent thyroid surgery with the result of direct sequencing of the BRAFV600E mutation. IHC staining of the BRAFV600E mutation was performed in 49 preoperative and 23 postoperative thyroid specimens. Results Sixty-two patients (87.3%) had PTC, and of these, BRAFV600E was confirmed by direct sequencing in 57 patients (91.9%). In 23 postoperative tissue samples, the BRAFV600E mutation was detected in 16 samples (70%) by direct sequencing and 18 samples (78%) by IHC. In 24 fine needle aspiration (FNA) samples, BRAFV600E was detected in 18 samples (75%) by direct sequencing and 16 samples (67%) by IHC. In 25 core needle biopsy (CNB) samples, the BRAFV600E mutation was detected in 15 samples (60%) by direct sequencing and 16 samples (64%) by IHC. The sensitivity and specificity of IHC for detecting the BRAFV600E mutation were 77.8% and 66.7% in FNA samples and 99.3% and 80.0% in CNB samples. Conclusion IHC could be an alternative method to direct Sanger sequencing for BRAFV600E mutation detection both in postoperative and preoperative samples. However, application of IHC to detect the BRAFV600E mutation in FNA samples is of limited value compared with direct sequencing. PMID:29388401

Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program.

PubMed

Fischer, Andrew H; Schwartz, Mary R; Moriarty, Ann T; Wilbur, David C; Souers, Rhona; Fatheree, Lisa; Booth, Christine N; Clayton, Amy C; Kurtyz, Daniel F I; Padmanabhan, Vijayalakshmi; Crothers, Barbara A

2014-09-01

Immunohistochemistry (IHC) is important for cytology but poses special challenges because preanalytic conditions may differ from the conditions of IHC-positive controls. To broadly survey cytology laboratories to quantify preanalytic platforms for cytology IHC and identify problems with particular platforms or antigens. To discover how validation guidelines for HER2 testing have affected cytology. A voluntary survey of cytology IHC practices was sent to 1899 cytology laboratories participating in the College of American Pathologists Nongynecologic Cytopathology Education Program in the fall of 2009. A total of 818 laboratories (43%) responded to the survey by April 2010. Three hundred fourty-five of 791 respondents (44%) performed IHC on cytology specimens. Seventeen different fixation and processing platforms prior to antibody reaction were reported. A total of 59.2% of laboratories reported differences between the platforms for cytology specimens and positive controls, but most (155 of 184; 84%) did not alter antibody dilutions or antigen retrieval for cytology IHC. When asked to name 2 antibodies for which staining conditions differed between cytology and surgical samples, there were 18 responses listing 14 antibodies. A total of 30.6% of laboratories performing IHC offered HER2 testing before publication of the 2007 College of American Pathologists/American Society of Clinical Oncologists guidelines, compared with 33.6% afterward, with increased performance of testing by reference laboratories. Three laboratories validated a nonformalin HER2 platform. The platforms for cytology IHC and positive controls differ for most laboratories, yet conditions are uncommonly adjusted for cytology specimens. Except for the unsuitability of air-dried smears for HER2 testing, the survey did not reveal evidence of systematic problems with any antibody or platform.

Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods.

PubMed

Kao, Hua-Lin; Yeh, Yi-Chen; Lin, Chin-Hsuan; Hsu, Wei-Fang; Hsieh, Wen-Yu; Ho, Hsiang-Ling; Chou, Teh-Ying

2016-11-01

Analysis of the targetable driver mutations is now recommended in all patients with advanced lung adenocarcinoma. Molecular-based methods are usually adopted, however, along with the implementation of highly sensitive and/or mutation-specific antibodies, immunohistochemistry (IHC) has been considered an alternative method for identifying driver mutations in lung adenocarcinomas. A total of 205 lung adenocarcinomas were examined for EGFR mutations and ALK and ROS1 rearrangements using real-time PCR, fluorescence in situ hybridization (FISH) and IHC in parallel. The performance of different commercially available IHC antibody clones toward targetable driver mutations was evaluated. The association between these driver mutations and clinicopathological characteristics was also analyzed. In 205 cases we studied, 58.5% were found to harbor EGFR mutations, 6.3% ALK rearrangements and 1.0% ROS1 rearrangements. Compared to molecular-based methods, IHC of EGFR mutations showed an excellent specificity but the sensitivity is suboptimal, while IHC of ALK and ROS1 rearrangements demonstrated high sensitivity and specificity. No significant difference regarding the performance of different antibody clones toward these driver mutations was observed, except that clone SP125 showed a higher sensitivity than 43B2 in the detection of p.L858R of EGFR. In circumstances such as poor quality of nucleic acids or low content of tumor cells, IHC of EGFR mutation-specific antibodies could be used as an alternative method. Patients negative for EGFR mutations are subjected to further analysis on ALK and ROS1 rearrangements using IHC methods. Herein, we proposed a lung adenocarcinoma testing algorithm for the application of IHC in therapeutic diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

PubMed

Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

2014-04-01

Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors.

Revisiting the scientific method to improve rigor and reproducibility of immunohistochemistry in reproductive science.

PubMed

Manuel, Sharrón L; Johnson, Brian W; Frevert, Charles W; Duncan, Francesca E

2018-04-21

Immunohistochemistry (IHC) is a robust scientific tool whereby cellular components are visualized within a tissue, and this method has been and continues to be a mainstay for many reproductive biologists. IHC is highly informative if performed and interpreted correctly, but studies have shown that the general use and reporting of appropriate controls in IHC experiments is low. This omission of the scientific method can result in data that lacks rigor and reproducibility. In this editorial, we highlight key concepts in IHC controls and describe an opportunity for our field to partner with the Histochemical Society to adopt their IHC guidelines broadly as researchers, authors, ad hoc reviewers, editorial board members, and editors-in-chief. Such cross-professional society interactions will ensure that we produce the highest quality data as new technologies emerge that still rely upon the foundations of classic histological and immunohistochemical principles.

Infant–Mother and Infant–Caregiver Emotional Relationships: Process Analyses of Interactions in Three Contemporary Childcare Arrangements

PubMed Central

Bornstein, Marc H.; Putnick, Diane L.; Suwalsky, Joan T. D.

2018-01-01

Emotional relationships in infant-mother dyads in families where mothers provided full-time (MC) childcare were compared with those of families where mothers used in-home childcare (IHC) providers and family childcare (FCC) providers (N = 245). Infant relationships with childcare providers were also studied. Emotional relationships were adequate in all 3 childcare arrangements, but infant-mother dyads in IHC arrangements displayed healthier emotional relationships than infant-mother dyads in MC arrangements; no differences in the health of emotional relationships with infants emerged among the three types of childcare providers (MC, IHC, FCC). Infant-mother dyads in IHC arrangements also displayed healthier emotional relationships than infant-IHC caregiver dyads, but infant-mother and infant-caregiver dyads were comparable in FCC families. Emotional relationships in infant-mother and infant-caregiver dyads were not correlated, regardless of the type of childcare. PMID:29576750

Inner hair cell stereocilia movements captured in-situ by a high-speed camera with subpixel image processing

NASA Astrophysics Data System (ADS)

Wang, Yanli; Puria, Sunil; Steele, Charles R.; Ricci, Anthony J.

2018-05-01

Mechanical stimulation of the stereocilia hair bundles of the inner and outer hair cells (IHCs and OHCs, respectively) drives IHC synaptic release and OHC electromotility. The modes of hair-bundle motion can have a dramatic influence on the electrophysiological responses of the hair cells. The in vivo modes of motion are, however, unknown for both IHC and OHC bundles. In this work, we are developing technology to investigate the in situ hair-bundle motion in excised mouse cochleae, for which the hair bundles of the OHCs are embedded in the tectorial membrane but those of the IHCs are not. Motion is generated by pushing onto the stapes at 1 kHz with a glass probe coupled to a piezo stack, and recorded using a high-speed camera at 10,000 frames per second. The motions of individual IHC stereocilia and the cell boundary are analyzed using 2D and 1D Gaussian fitting algorithms, respectively. Preliminary results show that the IHC bundle moves mainly in the radial direction and exhibits a small degree of splay, and that the stereocilia in the second row move less than those in the first row, even in the same focal plane.

Projected impacts of climate change on hydropower potential in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xingcai; Tang, Qiuhong; Voisin, Nathalie

Hydropower is an important renewable energy source in China, but it is sensitive to climate change, because the changing climate may alter hydrological conditions (e.g., river flow and reservoir storage). Future changes and associated uncertainties in China's gross hydropower potential (GHP) and developed hydropower potential (DHP) are projected using simulations from eight global hydrological models (GHMs), including a large-scale reservoir regulation model, forced by five general circulation models (GCMs) with climate data under two representative concentration pathways (RCP2.6 and RCP8.5). Results show that the estimation of the present GHP of China is comparable to other studies; overall, the annual GHP is projectedmore » to change by −1.7 to 2 % in the near future (2020–2050) and increase by 3 to 6 % in the late 21st century (2070–2099). The annual DHP is projected to change by −2.2 to −5.4 % (0.7–1.7 % of the total installed hydropower capacity (IHC)) and −1.3 to −4 % (0.4–1.3 % of total IHC) for 2020–2050 and 2070–2099, respectively. Regional variations emerge: GHP will increase in northern China but decrease in southern China – mostly in south central China and eastern China – where numerous reservoirs and large IHCs currently are located. The area with the highest GHP in southwest China will have more GHP, while DHP will reduce in the regions with high IHC (e.g., Sichuan and Hubei) in the future. The largest decrease in DHP (in %) will occur in autumn or winter, when streamflow is relatively low and water use is competitive. Large ranges in hydropower estimates across GHMs and GCMs highlight the necessity of using multimodel assessments under climate change conditions. This study prompts the consideration of climate change in planning for hydropower development and operations in China, to be further combined with a socioeconomic analysis for strategic expansion.« less

FM Dye Photo-Oxidation as a Tool for Monitoring Membrane Recycling in Inner Hair Cells

PubMed Central

Rizzoli, Silvio O.

2014-01-01

Styryl (FM) dyes have been used for more than two decades to investigate exo- and endocytosis in conventional synapses. However, they are difficult to use in the inner hair cells of the auditory pathway (IHCs), as FM dyes appear to penetrate through mechanotransducer channels into the cytosol of IHCs, masking endocytotic uptake. To solve this problem we applied to IHCs the FM dye photo-oxidation technique, which renders the dyes into electron microscopy markers. Photo-oxidation allowed the unambiguous identification of labeled organelles, despite the presence of FM dye in the cytosol. This enabled us to describe the morphologies of several organelles that take up membrane in IHCs, both at rest and during stimulation. At rest, endosome-like organelles were detected in the region of the cuticular plate. Larger tubulo-cisternal organelles dominated the top and nuclear regions. Finally, the basal region, where the IHC active zones are located, contained few labeled organelles. Stimulation increased significantly membrane trafficking in the basal region, inducing the appearance of labeled vesicles and cistern-like organelles. The latter were replaced by small, synaptic-like vesicles during recovery after stimulation. In contrast, no changes in membrane trafficking were induced by stimulation in the cuticular plate region or in the top and nuclear regions. We conclude that synaptic vesicle recycling takes place mostly in the basal region of the IHCs. Other organelles participate in abundant constitutive membrane trafficking throughout the rest of the IHC volume. PMID:24505482

An immunohistochemical and fluorescence in situ hybridization-based comparison between the Oracle HER2 Bond Immunohistochemical System, Dako HercepTest, and Vysis PathVysion HER2 FISH using both commercially validated and modified ASCO/CAP and United Kingdom HER2 IHC scoring guidelines.

PubMed

O'Grady, Anthony; Allen, David; Happerfield, Lisa; Johnson, Nicola; Provenzano, Elena; Pinder, Sarah E; Tee, Lilian; Gu, Mai; Kay, Elaine W

2010-12-01

Immunohistochemistry (IHC) is used as the frontline assay to determine HER2 status in invasive breast cancer patients. The aim of the study was to compare the performance of the Leica Oracle HER2 Bond IHC System (Oracle) with the current most readily accepted Dako HercepTest (HercepTest), using both commercially validated and modified ASCO/CAP and UK HER2 IHC scoring guidelines. A total of 445 breast cancer samples from 3 international clinical HER2 referral centers were stained with the 2 test systems and scored in a blinded fashion by experienced pathologists. The overall agreement between the 2 tests in a 3×3 (negative, equivocal and positive) analysis shows a concordance of 86.7% and 86.3%, respectively when analyzed using commercially validated and modified ASCO/CAP and UK HER2 IHC scoring guidelines. There is a good concordance between the Oracle and the HercepTest. The advantages of a complete fully automated test such as the Oracle include standardization of key analytical factors and improved turn around time. The implementation of the modified ASCO/CAP and UK HER2 IHC scoring guidelines has minimal effect on either assay interpretation, showing that Oracle can be used as a methodology for accurately determining HER2 IHC status in formalin fixed, paraffin-embedded breast cancer tissue.

[Her2 testing in gastric cancer. What is different in comparison to breast cancer?].

PubMed

Rüschoff, J; Nagelmeier, I; Baretton, G; Dietel, M; Höfler, H; Schildhaus, H U; Büttner, R; Schlake, W; Stoss, O; Kreipe, H H

2010-05-01

Based on data from a large multicenter phase III trial (ToGA study) trastuzumab has very recently been approved by the EMEA for metastatic gastric cancer and adenocarcinoma of the gastro-esophageal junction. Only patients with tumors which over express Her2 as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, determined by an accurate and validated assay are eligible for trastuzumab therapy. However, testing of Her2 status by immunohistochemistry (IHC) differs from breast cancer in core aspects: 1. IHC2+/3+ is scored even though membranous staining is incomplete if membrane staining is clearly detectable even at low magnification (2.5x/5x, 3+) or medium magnification (10x/20x, 2+). 2. Additionally, membrane staining at the appropriate intensity found in at least 10% of tumor cells is restricted to resection specimens. Evaluation of Her2 in situ hybridization (ISH) is similar to breast cancer with ratio values of > or =2.0 indicating Her2 gene amplification. Taking these modifications into account and defining the HER2 positive subgroup as IHC 3+ and IHC2+/FISH+, approximately 16% of gastric cancers are considered Her2 positive, affecting mainly tumor regions with intestinal (gland forming) type carcinoma. In contrast to breast cancer, up to one-third of gastric cancers show a heterogeneous Her2 status both at IHC and ISH levels which favors bright field ISH over FISH.

Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

PubMed Central

2010-01-01

Background Immunohistochemistry (IHC) with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC) cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA) deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93%) patients with exon 21 EGFR mutations (all with L858R) but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients. PMID:21167064

Magnetic properties of the surface layer and its magnetic interaction with the interior of Nd-Fe-B sintered magnets

NASA Astrophysics Data System (ADS)

Kobayashi, Kurima; Nakamura, Michi-hide; Urushibata, Kimiko

2015-05-01

The magnetization and demagnetization mechanisms in the mechanically polished surface layers (SL) of the c-plane and a-b plane of Nd-Fe-B sintered magnets were investigated. The magnetic interaction between the SL and the interior of the magnet was clarified by using vibrating sample magnetometer measurements of a whole sample and magneto-force microscopy observations of the domain structure of the SL layer. The polishing eliminated the Nd-rich grain boundary phases, which was only about 2 nm thick, from the SL crystal grains in the sintered magnets. The a-b plane polishing caused the independent magnetic reversal of the a-b plane SL, which was about 5.5 μm thick, as in the platy samples. The coercivities (μ0Hc) of the SL were less than 0.3 T. In contrast, the c-plane polishing did not produce independent magnetic reversal of the SL, although the coercivity of bulk samples was clearly decreased by the formation of the c-plane SL. The grains in the SL should form clusters that alter the demagnetizing factors, depending on the shape of cluster as a magnetic unit. The magnetic interaction among the SL crystal grains is expected to play an important role in the coercivity mechanism of Nd-Fe-B sintered magnets.

Iron-platinum-coated carbon nanocone probes on tipless cantilevers for high resolution magnetic force imaging.

PubMed

Chen, I-Chen; Chen, Li-Han; Gapin, Andrew; Jin, Sungho; Yuan, Lu; Liou, Sy-Hwang

2008-02-20

High coercivity iron-platinum-coated carbon nanocones (CNCs) have been fabricated for magnetic force microscopy (MFM) by direct-current plasma-enhanced chemical vapor deposition growth of nanocones on tipless cantilevers followed by sputtering and annealing of the FePt film. The FePt-coated CNC probe has many localized magnetic stray fields due to the high-aspect-ratio geometry and small radius of the tip. The MFM imaging on magnetic recording media was performed using CNC probes and compared with the imaging by FePt-coated silicon probes. An image with 20 nm lateral resolution has been demonstrated.

Consequences of thermal acclimation for the mating behaviour and swimming performance of female mosquito fish.

PubMed

Wilson, Robbie S; Condon, Catriona H L; Johnston, Ian A

2007-11-29

The mating system of eastern mosquito fish (Gambusia holbrooki) is dominated by male sexual coercion, where all matings are forced and females never appear to cooperate and actively avoid all attempts. Previous research has shown that male G. holbrooki offer a model system for examining the benefits of reversible thermal acclimation for reproductive success, but examining the benefits to female avoidance behaviour has been difficult. In this study, we examined the ability of non-male-deprived female G. holbrooki to avoid forced-coercive matings following acclimation to either 18 or 30 degrees C for six weeks (12h light:12h dark photoperiod). Thermal acclimation of burst and sustained swimming performance was also assessed, as these traits are likely to underlie their ability to avoid forced matings. There was no influence of thermal acclimation on the burst swimming performance of female G. holbrooki over the range 18-30 degrees C; however, sustained swimming performance was significantly lower in the warm- than the cool-acclimation group. For mating behaviour, we tested the hypothesis that acclimation would enhance the ability of female G. holbrooki to avoid forced matings at their host acclimation temperature relative to females acclimated to another environment. However, our hypothesis was not supported. The rate of copulations was almost three times greater for females acclimated to 30 degrees C than 18 degrees C when tested at 30 degrees C, indicating that they possess the ability to alter their avoidance behaviour to 'allow' more copulations in some environments. Coupled with previous studies, female G. holbrooki appear to have greater control on the outcome of coercive mating attempts than previously considered and can alter their propensity to receive forced matings following thermal acclimation. The significance of this change in female mating-avoidance behaviours with thermal acclimation remains to be explored.

Women and men's use of coercive control in intimate partner violence.

PubMed

Robertson, Kirsten; Murachver, Tamar

2011-01-01

This study examined the relationship between coercive control and intimate partner violence (IPV) for men and women and for targets and perpetrators. One hundred and seventy-two participants (85 men, 87 women) recruited from three samples reported on their own and their partner's behavior. IPV was measured using the Revised Conflict Tactics Scale (CTS2). Coercive control was measured using modified items from the Psychological Maltreatment of Women Inventory (PMWI). Coercive control was associated with IPV, and this relationship was similar for men and women across the three samples. In fact, coercive control was predominantly reciprocal in nature, with women and men reporting both receiving and perpetrating controlling behaviors. Overall, coercive controlling behaviors were characteristic of individuals within violent relationships, regardless of their physical abuse status. The experience of violence, rather than gender, was the best predictor of coercive control.

Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent.

PubMed

Conklin, Chris M J; Craddock, Kenneth J; Have, Cherry; Laskin, Janessa; Couture, Christian; Ionescu, Diana N

2013-01-01

Fluorescence in situ hybridization (FISH) is the standard procedure for the detection of anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement in non-small-cell lung carcinoma (NSCLC) but is expensive and time consuming. We tested three antibodies to ALK, using various detection systems, and hypothesized that ALK immunohistochemistry (IHC) may represent a cost-effective and efficient means of screening for ALK rearrangement in NSCLC. We screened 377 stage I or II NSCLC cases in a tissue microarray by FISH and IHC (5A4 [Leica Biosystems Newcastle Ltd, Newcastle upon Tyne, UYnited Kingdom] by Nichirei's N-Histofine ALK detection kit [Nichirei Biosciences inc., Tokyo, Japan], 5A4 by Novocastra with ADVANCE [Dako Canada inc., Burlington, Ontario, Canada], D5F3 by Cell Signaling Technology with ADVANCE [Cell Signalling Technologies inc., Danvers, MA], and DAKO clone ALK1 with FLEX [Dako Canada inc., Burlington, Ontario, Canada] and ADVANCE). IHC was scored as 0, 1+, 2+, or 3+. Possibly positive or positive cases were further analyzed by IHC and FISH on whole section. Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods. Three cases were ALK-positive by FISH on whole section validation. There was no correlation between semiquantitative IHC score (1+, 2+, 3+) and ALK rearrangement by FISH. D5F3 (Cell Signaling by ADVANCE) and 5A4 (Novocastra by ADVANCE) showed the greatest combination of sensitivity (100%) and specificity (87.5% for 5A4 by Novocastra and 75% for D5F3 by Cell Signaling), and produced no false-negative results. IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. D5F3 (Cell Signaling) and 5A4 (Novocastra) can be used with FISH for identification of IHC-positive cases to reduce screening costs.

The Iranian Revolution: A Case Study in Coercive Power Consolidation

DTIC Science & Technology

1994-03-01

all potential competition . This was accomplished by waging a multi-pillared policy aimed at ethnic minorities, political opposition groups and...reported back to United States Secretary of Defense Harold Brown that working with the Iranian military was difficult due to the compartmentation of the...military leader such as General Djam to hold the armed forces together, fearing that such a situation would work against him if he returned to Iran.° He

Magnetic properties of iron oxide photolytically produced from Fe(CO)5 impregnated porous glass

NASA Astrophysics Data System (ADS)

Borelli, N. F.; Morse, D. L.; Schreurs, J. W. H.

1983-06-01

This article discusses the magnetic properties observed in porous glasses impregnated with metal carbonyls after exposure to light. In the photolyzed and consolidated glasses both superparamagnetic and single domain ferrimagnetic particles were found to be present, with the single domain particles having an exceedingly high coercive force. The concentration ratio between superparamagnetic and single domain particles depends strongly on temperature. An analysis of the observed phenomena is given.

The Coercive Sterilization of Aboriginal Women in Canada

ERIC Educational Resources Information Center

Stote, Karen

2012-01-01

This paper considers the coercive sterilization of Aboriginal women in legislated and non-legislated form in Canada. I provide an historical and materialist critique of coercive sterilization. I argue for coercive sterilization to be understood as one of many policies employed to undermine Aboriginal women, to separate Aboriginal peoples from…

The origin of coercivity decrease in fine grained Nd-Fe-B sintered magnets

NASA Astrophysics Data System (ADS)

Li, W. F.; Ohkubo, T.; Hono, K.; Sagawa, M.

2009-04-01

Microstructures of fine grained Nd-Fe-B sintered magnets that were produced by the pressless process were investigated to understand the origin of the sudden coercivity decrease below a certain grain size. The intrinsic coercivity is inversely proportional to ln D2 with the highest coercivity of 17 kOe at D˜4.5 μm, below which the coercivity drops as the grain size decreases. We found that the degradation of the coercivity of the magnet with a grain size of 3 μm was mainly caused by the inhomogeneous distribution of fcc-Nd oxide whose volume fraction increased with respect to the dhcp Nd-rich phase.

Faculty Perceptions of and Experiences with Students' Use of Coercive Power

ERIC Educational Resources Information Center

Kuhn, Kristine L.

2016-01-01

The purpose of this basic qualitative study was to understand how faculty perceive and experience students' use of coercive power in faculty-student relationships. Interviews were used to gather data from faculty members who had experienced students' use of coercive power. Data reveal that students' use of coercive power can negatively impact…

Integrative Health Coach Training: A Model for Shifting the Paradigm Toward Patient-centricity and Meeting New National Prevention Goals.

PubMed

Smith, Linda L; Lake, Noelle H; Simmons, Leigh Ann; Perlman, Adam; Wroth, Shelley; Wolever, Ruth Q

2013-05-01

To describe the evolution, training, and results of an emerging allied health profession skilled in eliciting sustainable health-related behavior change and charged with improving patient engagement. Through techniques sourced from humanistic and positive psychology, solution-focused and mindfulness-based therapies, and leadership coaching, Integrative Health Coaching (IHC) provides a mechanism to empower patients through various stages of learning and change. IHC also provides a method for the creation and implementation of forward-focused personalized health plans. Clinical studies employing Duke University Integrative Medicine's model of IHC have demonstrated improvements in measures of diabetes and diabetes risk, weight management, and risk for cardiovascular disease and stroke. By supporting and enabling individuals in making major lifestyle changes for the improvement of their health, IHC carries the potential to reduce rates and morbidity of chronic disease and impact myriad aspects of healthcare. As a model of educational and clinical innovation aimed at patient empowerment and lifestyle modification, IHC is aligned well with the tenets and goals of recently sanctioned federal healthcare reform, specifically the creation of the first National Prevention and Health Promotion Strategy. IHC may allow greater patient-centricity while targeting the lifestyle-related chronic disease that lies at the heart of the current healthcare crisis.

Simulation of mechano-electrical transduction in the cochlea considering basilar membrane vibration and the ionic current of the inner hair cells

NASA Astrophysics Data System (ADS)

Lee, Sinyoung; Koike, Takuji

2018-05-01

The inner hair cells (IHCs) in the cochlea transduce mechanical vibration of the basilar membrane (BM), caused by sound pressure, to electrical signals that are transported along the acoustic nerve to the brain. The mechanical vibration of the BM and the ionic behaviors of the IHCs have been investigated. However, consideration of the ionic behavior of the IHCs related to mechanical vibration is necessary to investigate the mechano-electrical transduction of the cochlea. In this study, a finite-element model of the BM, which takes into account the non-linear activities of the outer hair cells (OHCs), and an ionic current model of IHC were combined. The amplitudes and phases of the vibration at several points on the BM were obtained from the finite-element model by applying sound pressure. These values were fed into the ionic current model, and changes in membrane potential and calcium ion concentration of the IHCs were calculated. The membrane potential of the IHC at the maximum amplitude point (CF point) was higher than that at the non-CF points. The calcium ion concentration at the CF point was also higher than that at the non-CF points. These results suggest that the cochlea achieves its good frequency discrimination ability through mechano-electrical transduction.

The effects of the activation of the inner-hair-cell basolateral K+ channels on auditory nerve responses.

PubMed

Altoè, Alessandro; Pulkki, Ville; Verhulst, Sarah

2018-07-01

The basolateral membrane of the mammalian inner hair cell (IHC) expresses large voltage and Ca 2+ gated outward K + currents. To quantify how the voltage-dependent activation of the K + channels affects the functionality of the auditory nerve innervating the IHC, this study adopts a model of mechanical-to-neural transduction in which the basolateral K + conductances of the IHC can be made voltage-dependent or not. The model shows that the voltage-dependent activation of the K + channels (i) enhances the phase-locking properties of the auditory fiber (AF) responses; (ii) enables the auditory nerve to encode a large dynamic range of sound levels; (iii) enables the AF responses to synchronize precisely with the envelope of amplitude modulated stimuli; and (iv), is responsible for the steep offset responses of the AFs. These results suggest that the basolateral K + channels play a major role in determining the well-known response properties of the AFs and challenge the classical view that describes the IHC membrane as an electrical low-pass filter. In contrast to previous models of the IHC-AF complex, this study ascribes many of the AF response properties to fairly basic mechanisms in the IHC membrane rather than to complex mechanisms in the synapse. Copyright © 2018 Elsevier B.V. All rights reserved.

Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer.

PubMed

Doshi, Shivang; Ray, David; Stein, Karen; Zhang, Jie; Koduru, Prasad; Fogt, Franz; Wellman, Axel; Wat, Ricky; Mathews, Charles

2016-01-06

Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies-IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies.

Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer

PubMed Central

Doshi, Shivang; Ray, David; Stein, Karen; Zhang, Jie; Koduru, Prasad; Fogt, Franz; Wellman, Axel; Wat, Ricky; Mathews, Charles

2016-01-01

Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies—IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies. PMID:26838801

HER2 status in non-small cell lung cancer: results from patient screening for enrollment to a phase II study of herceptin.

PubMed

Heinmöller, Petra; Gross, Christof; Beyser, Kurt; Schmidtgen, Claudia; Maass, Gerd; Pedrocchi, Michele; Rüschoff, Josef

2003-11-01

For the first time a large number (563) of non-small cell lung cancer (NSCLC) samples was used to compare three different technologies for the assessment of HER2 status. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were used for tumor tissue samples, and ELISA for serum samples. The results were compared with other tumor entities, mainly breast. Samples (563) from patients suffering from primary advanced or metastatic NSCLC were evaluated. HER2 overexpression was demonstrated using IHC in 20% (83 of 410) of the specimens, whereas 2% (7 of 378) were positive by FISH and 6% (31 of 511) showed elevated serum HER2 levels (>15 ng/ml) by ELISA. Sixty-six specimens were positive by IHC only and 13 by ELISA only, whereas none of the specimens was positive only by FISH. Concordance between all of the techniques was seen for only 3 specimens. Of 7 IHC 3+ specimens, 4 showed gene amplification by FISH, and 3 were positive by ELISA (>15 ng/ml), whereas of 76 IHC 2+ cases only 2 were amplified by FISH, and 4 were positive by ELISA. HER2 positivity by at least one of the three techniques was most common in adenocarcinomas, at 29% (42 of 143). Gene amplification and HER2 protein overexpression at the 3+ level appear to be uncommon in NSCLC. The concordance between FISH and IHC 3+ disease was good in this study, in addition, ELISA would have detected several patients without IHC/FISH-positive disease.

Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification.

PubMed

Agersborg, Sally; Mixon, Christopher; Nguyen, Thanh; Aithal, Sramila; Sudarsanam, Sucha; Blocker, Forrest; Weiss, Lawrence; Gasparini, Robert; Jiang, Shiping; Chen, Wayne; Hess, Gregory; Albitar, Maher

2018-03-22

While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases. Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of the patients tested by FISH, 505/3908 (12.9%) also had IHC data. Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. However, 50.5% of equivocal cases were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe: 78% of positive cases by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (p < 0.0001) among the equivocal cases by conventional FISH testing, 44% of IHC negative cases became positive while 36% of the positive IHC cases became negative by alternative FISH testing. Available data showed that 41% of patients were treated with palbociclib and were positive by alternative FISH. The prevalence of double HER2 equivocal cases and the discrepancy between IHC and alternative FISH testing suggest that FISH alternative testing using both RAI1 and TP53 probes is necessary for conclusive classification. Because almost half of FISH equivocal cases converted to HER2 amplified upon alternative testing, clinical studies to determine the benefit of anti-HER2 therapy in these patients are urgently needed.

[Coercion in Psychiatry - a taboo?].

PubMed

Meise, Ullrich; Frajo-Apor, Beatrice; Stippler, Stippler; Wancata, Johannes

2011-01-01

History shows that the discussion concerning coercive measures against mentally ill is as old as psychiatry itself. The dilemma of psychiatry lies in its double role - having both a therapeutic and a regulatory function. Violence against sick and disabled people conflicts with the ethical principles of helping professions. This, however, is where the danger lies: that the violent parts of psychiatric work - which in the opinion of experts cannot be entirely avoided - are repressed or seen as taboo and are therefore more difficult to control. Comparisons between EU countries of the nature, frequency and duration of coercive measures are difficult because of the heterogeneity of regulation and differences in established practice. Scientific examination of this issue seems to be insufficient. There are only a few studies on important issues such as how patients rate these measures. An open and thorough debate about the meaning and meaninglessness of coercion and violence in psychiatric treatment would be necessary to prevent "routine violence" or the excessive use of force against the mentally ill.

Magnetic vortex state and multi-domain pattern in electrodeposited hemispherical nanogranular nickel films

NASA Astrophysics Data System (ADS)

Samardak, Alexander; Sukovatitsina, Ekaterina; Ognev, Alexey; Stebliy, Maksim; Davydenko, Alexander; Chebotkevich, Ludmila; Keun Kim, Young; Nasirpouri, Forough; Janjan, Seyed-Mehdi; Nasirpouri, Farzad

2014-12-01

Magnetic states of nickel nanogranular films were studied in two distinct structures of individual and agglomerated granules electrodeposited on n-type Si(1 1 1) surface from a modified Watts bath at a low pH of 2. Magnetic force microscopy and micromagnetic simulations revealed three-dimensional out-of-plane magnetic vortex states in stand-alone hemispherical granules and their arrays, and multi-domain patterns in large agglomerates and integrated films. Once the granules coalesce into small chains or clusters, the coercivity values increased due to the reduction of inter-granular spacing and strengthening of the magnetostatic interaction. Further growth leads to the formation of a continuous granulated film which strongly affected the coercivity and remanence. This was characterized by the domain wall nucleation and propagation leading to a stripe domain pattern. Magnetoresistance measurements as a function of external magnetic field are indicative of anisotropic magnetoresistance (AMR) for the continuous films electrodeposited on Si substrate.

Decomposing the permeability spectra of nanocrystalline finemet core

NASA Astrophysics Data System (ADS)

Varga, Lajos K.; Kovac, Jozef

2018-04-01

In this paper we present a theoretical and experimental investigation on the magnetization contributions to permeability spectra of normal annealed Finemet core with round type hysteresis curve. Real and imaginary parts of the permeability were determined as a function of exciting magnetic field (HAC) between 40 Hz -110 MHz using an Agilent 4294A type Precision Impedance Analyzer. The amplitude of the exciting field was below and around the coercive field of the sample. The spectra were decomposed using the Levenberg-Marquardt algorithm running under Origin 9 software in four contributions: i) eddy current; ii) Debye relaxation of magnetization rotation, iii) Debye relaxation of damped domain wall motion and iv) resonant type DW motion. For small exciting amplitudes the first two components dominate. The last two contributions connected to the DW appear for relative large HAC only, around the coercive force. All the contributions will be discussed in detail accentuating the role of eddy current that is not negligible even for the smallest applied exciting field.

Power dissipation in the subtectorial space of the mammalian cochlea is modulated by inner hair cell stereocilia.

PubMed

Prodanovic, Srdjan; Gracewski, Sheryl; Nam, Jong-Hoon

2015-02-03

The stereocilia bundle is the mechano-transduction apparatus of the inner ear. In the mammalian cochlea, the stereocilia bundles are situated in the subtectorial space (STS)--a micrometer-thick space between two flat surfaces vibrating relative to each other. Because microstructures vibrating in fluid are subject to high-viscous friction, previous studies considered the STS as the primary place of energy dissipation in the cochlea. Although there have been extensive studies on how metabolic energy is used to compensate the dissipation, much less attention has been paid to the mechanism of energy dissipation. Using a computational model, we investigated the power dissipation in the STS. The model simulates fluid flow around the inner hair cell (IHC) stereocilia bundle. The power dissipation in the STS because of the presence IHC stereocilia increased as the stimulating frequency decreased. Along the axis of the stimulating frequency, there were two asymptotic values of power dissipation. At high frequencies, the power dissipation was determined by the shear friction between the two flat surfaces of the STS. At low frequencies, the power dissipation was dominated by the viscous friction around the IHC stereocilia bundle--the IHC stereocilia increased the STS power dissipation by 50- to 100-fold. There exists a characteristic frequency for STS power dissipation, CFSTS, defined as the frequency where power dissipation drops to one-half of the low frequency value. The IHC stereocilia stiffness and the gap size between the IHC stereocilia and the tectorial membrane determine the characteristic frequency. In addition to the generally assumed shear flow, nonshear STS flow patterns were simulated. Different flow patterns have little effect on the CFSTS. When the mechano-transduction of the IHC was tuned near the vibrating frequency, the active motility of the IHC stereocilia bundle reduced the power dissipation in the STS. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer.

PubMed

Xu, Chen; Liu, Yalan; Ge, Xiaowen; Jiang, Dongxian; Zhang, Ying; Ji, Yuan; Hou, Jun; Huang, Jie; Su, Jieakesu; Zeng, Haiying; Qin, Jing; Hou, Yingyong

2017-05-26

HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited biopsy material. The aim of this study is to explore how tumor-containing fragment number and biopsy specimen number affect HER2 immunohistochemistry (IHC) positive rate. Eight hundred and ninety biopsy specimens and 459 paired resected specimens were collected. IHC staining of HER2 was performed. HER2 IHC positive (scored 3+) rate was compared based on tumor-containing fragment number, biopsy specimen number, average size and tumor tissue proportion of tumor-containing fragments. The positive predictability of biopsy specimens to resected specimens was analyzed based on tumor fragment number. HER2 IHC positive rates were 2.0, 3.5, 7.0, 13.2, 17.1, and 15.9% when tumor fragment numbers were 1, 2, 3, 4, 5 and 6 respectively. The rate rose with the increase of tumor fragment number (P = 0.004). ROC curve analysis showed that biopsy specimens exhibited positive predictability when tumor fragment number reached 3, but showed better performance when the number was ≥4 (P < 0.05). After fragment number reached 4, no statistic differences were reached in either HER2 IHC positive rate or positive predictability with further increase of the number (P > 0.05). HER2 IHC positive rate was not associated with biopsy number (P = 0.127), average size of tumor fragments (P = 0.397), and tumor tissue proportion of tumor fragments (P = 0.825) directly. The number of tumor-containing fragments influences HER2 IHC positive (scored 3+) rate. Greater than or equal to 4 (≥4) tumor fragments give better results in the positive rate as well as positive predictability. We recommend the number of tumor containing fragments be described in the HER2 IHC pathology reports for clinical reference in endoscopic biopsy specimens of GC.

Does immunohistochemical staining have a clinical impact in early gastric cancer conducted endoscopic submucosal dissection?

PubMed Central

Jeon, Seong Ran; Cho, Joo Young; Bok, Gene Hyun; Lee, Tae Hee; Kim, Hyun Gun; Cho, Won Young; Jin, So Young; Kim, Yeon Soo

2012-01-01

AIM: To evaluate clinicopathologic parameters and the clinical significance related lymphovascular invasion (LVI) by immunohistochemical staining (IHCS) in endoscopic submucosal dissection (ESD). METHODS: Between May 2005 and May 2010, a total of 348 lesions from 321 patients (mean age 63 ± 10 years, men 74.6%) with early gastric cancer (EGC) who met indication criteria after ESD were analyzed retrospectively. The 348 lesions were divided into the absolute (n = 100, differentiated mucosal cancer without ulcer ≤ 20 mm) and expanded (n = 248) indication groups after ESD. The 248 lesions were divided into four subgroups according to the expanded ESD indication. The presence of LVI was determined by factor VIII-related antigen and D2-40 assessment. We compared LVI IHCS-negative group with LVI IHCS-positive in each group. RESULTS: LVI by hematoxylin-eosin staining (HES) and IHCS were all negative in the absolute group, while was observed in only the expanded groups. The positive rate of LVI by IHCS was higher than that of LVI by HES (n = 1, 0.4% vs n = 11, 4.4%, P = 0.044). LVI IHCS-positivity was observed when the cancer invaded to the mucosa 3 (M3) or submucosa 1 (SM1) levels, with a predominance of 63.6% in the subgroup that included only SM1 cancer (P < 0.01). In a univariate analysis, M3 or SM1 invasion by the tumor was significantly associated with a higher rate of LVI by IHCS, but no factor was significant in a multivariate analysis. There were no cases of tumor recurrence or metastasis during the median 26 mo follow-up. CONCLUSION: EGCs of the absolute group are immunohistochemically stable. The presence of LVI may be carefully examined by IHCS in an ESD expanded indication group with an invasion depth of M3 or greater. PMID:22969232

Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape Project.

PubMed

Blackhall, Fiona H; Peters, Solange; Bubendorf, Lukas; Dafni, Urania; Kerr, Keith M; Hager, Henrik; Soltermann, Alex; O'Byrne, Kenneth J; Dooms, Christoph; Sejda, Aleksandra; Hernández-Losa, Javier; Marchetti, Antonio; Savic, Spasenija; Tan, Qiang; Thunnissen, Erik; Speel, Ernst-Jan M; Cheney, Richard; Nonaka, Daisuke; de Jong, Jeroen; Martorell, Miguel; Letovanec, Igor; Rosell, Rafael; Stahel, Rolf A

2014-09-01

The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS. © 2014 by American Society of Clinical Oncology.

Implementation of Universal Microsatellite Instability and Immunohistochemistry Screening for Diagnosing Lynch Syndrome in a Large Academic Medical Center

PubMed Central

Heald, Brandie; Plesec, Thomas; Liu, Xiuli; Pai, Rish; Patil, Deepa; Moline, Jessica; Sharp, Richard R.; Burke, Carol A.; Kalady, Matthew F.; Church, James; Eng, Charis

2013-01-01

Purpose In 2009, the Evaluation of Genomic Applications in Practice and Prevention recommended that all colorectal cancers (CRCs) be screened for Lynch syndrome (LS) through microsatellite instability (MSI) or immunohistochemistry (IHC). No studies report how this process is implemented on a health system–wide basis. Methods Since 2004, Cleveland Clinic has screened CRC specimens with MSI/IHC. Between January 2004 and July 2007, MSI/IHC results went only to the colorectal surgeon (approach 1). Between August 2007 and June 2008, colorectal surgeons and a genetic counselor received the MSI/IHC results, and the counselor e-mailed the colorectal surgeon regarding appropriate patients for genetic counseling (GC) referral (approach 2). After July 2008, the colorectal surgeon and counselor received MSI/IHC results, but the counselor contacted the patient to facilitate referral (approach 3). In approaches 2 and 3, patients were presumed to have sporadic CRC if the tumor lacked MLH1 expression and was also BRAF mutated or if the patient was diagnosed at age greater than 72 years and had no cancer family history. Results Abnormal MSI/IHC results occurred in 178 (16%) of 1,108 patients. In approach 1, 21 (55%) of 38 patients with abnormal MSI/IHC were referred for GC, 12 (32%) of 38 underwent GC, and 10 (26%) of 38 underwent genetic testing (GT). In approach 2, nine (82%) of 11 patients were referred for GC, seven (64%) of 11 underwent GC, and five (45%) of 11 underwent GT. In approach 3, 56 (100%) of 56 patients were referred for GC, 40 (71%) of 56 underwent GC, and 37 (66%) of 56 underwent GT. Time from referral to GC was 10-fold quicker in approach 3 than approach 1. Conclusion Implementation of universal MSI/IHC with GC/GT, along with effective multidisciplinary communication and plans of responsibility for patient contact, resulted in increased identification of patients with LS. PMID:23401454

Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

PubMed Central

Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

2013-01-01

Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%. PMID:23233704

Gendering Coercive Control.

PubMed

Anderson, Kristin L

2009-12-01

This article examines the theory of gender presented in Stark's Coercive Control: How Men Entrap Women in Personal Life. Stark suggests that gender is a form of structural inequality that makes women more vulnerable than men to the strategies of coercive control. However, Stark assumes rather than demonstrates that gendered structural inequality increases women's vulnerability. In this article, the author applies the multilevel theory of gender as identity, interaction, and social structure to document the multiple ways coercive control is gendered. The author argues that, to understand the gender dynamics of coercive control, researchers must examine the interactions across levels of gender. The author concludes with an assessment of the prospects and pitfalls of applying the concept of coercive control to renew the feminist social movement to end domestic violence.

Detecting Tie2, an endothelial growth factor receptor, by using immunohistochemistry in mouse lungs.

PubMed

Guha, Prajna P; David, Sascha A; Ghosh, Chandra C

2014-01-01

Immunohistochemical (IHC) staining is an invaluable, sensitive, and effective method to detect the presence and localization of proteins in the cellular compartment in tissues. The basic concept of IHC is detecting the antigen in tissues by means of specific antibody binding, which is then demonstrated with a colored histochemical reaction that can be observed under a light microscope. The most challenging aspect of IHC techniques is optimizing the precise experimental conditions that are required to get a specific and a strong signal. The critical steps of IHC are specimen acquisition, fixation, permeabilization, detection system, and selection of the antigen specific antibody and its optimization. Here, we elaborate the technique using the endothelial growth factor binding receptor Tie2 in mouse lungs.

An Alternative Approach: Examining Arguments Against Coercive Interrogation Techniques from a Biblical-Ethics Perspective

DTIC Science & Technology

2016-06-10

that CIT contradict the ethics of their faith. Considering that Christianity remains the religious tradition for the majority of U.S. military service...that Christianity remains the religious tradition for the majority of U.S. military service members, it is a worthy task to examine if a potentially...force in influencing the method by which a majority of its citizens make ethical judgments. In a 2010 national survey of religious preferences, 47.7

Electrodeposition and magnetic characterization of iron and iron-silicon alloys from the ionic liquid 1-butyl-1-methylpyrrolidinium trifluoromethylsulfonate.

PubMed

Giridhar, Pulletikurthi; Weidenfeller, Bernd; El Abedin, Sherif Zein; Endres, Frank

2014-11-10

The electrodeposition of soft magnetic iron and iron-silicon alloys for magnetic measurements is presented. The preparation of these materials in 1-butyl-1-methylpyrrolidinium trifluoromethylsulfonate, [Py1,4]TfO, at 100 °C with FeCl2 and FeCl2 +SiCl4 was studied by using cyclic voltammetry. Constant-potential electrolysis was carried out to deposit either Fe or FeSi, and deposits of approximately 10 μm thicknesses were obtained. By using scanning electron microscopy and X-ray diffraction, the microstructure and crystallinity of the deposits were investigated. Grain sizes in the nanometer regime (50-80 nm) were found and the presence of iron-silicon alloys was verified. Frequency-dependent magnetic polarizations, coercive forces, and power losses of some deposits were determined by using a digital hysteresis recorder. Corresponding to the small grain sizes, the coercive forces are around 950-1150 A m(-1) and the power losses were at 6000 J m(-3), which is much higher than in commercial Fe(3.2 wt %)Si electrical steel. Below a polarization of 1.8 T, the power losses are mainly caused by domain wall movements and, above 1.8 T, by rotation of magnetic moments as well as domain wall annihilation and recreation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Defining and Predicting Pimps' Coerciveness Toward Sex Workers: Socialization Processes.

PubMed

Stalans, Loretta J; Finn, Mary A

2016-10-01

Prior research has found that pimps use both non-coercive and coercive management styles across and within market segments of the illicit sex trade. The current study is the first to examine the socialization processes underlying variation in the self-reported coerciveness of pimps. This study begins to fill a void in the almost non-existent research on pimps who are actively managing Internet-solicited sex workers, and adds to the sparse research on pimps' coerciveness. We extend Anderson's concepts of "street code" families, where respect is acquired through displaying physical violence and toughness, and "decent" families, where middle class values of avoiding unnecessary aggression and complying with the law prevail, to understand variation in the degree of coerciveness that pimps utilize toward sex workers. A purposive sample of 44 active pimps was obtained through referrals from selected pimps and through placing advertisements on Backpage, a website utilized by the illicit prostitution trade. Qualitative coding revealed a wide range of coercive control tactics such as supplying drugs, surveillance, and physical violence. Pimps who served as sex workers and those raised by parents who supported "the code of the street" reported use of a greater number of more severe coercive tactics. College-educated pimps, pimps operating business that charged fees of at least US$300, and those from "decent" families were more likely to use non-coercive management. These findings suggest that early prevention programs might address the "street code" mentality that contributes to coerciveness, and that "End Demand" policies need to recognize that many male pimps also have served as sex workers.

Monitoring and forecasting the 2009-2010 severe drought in Southwest China

NASA Astrophysics Data System (ADS)

Zhang, X.; Tang, Q.; Liu, X.; Leng, G.; Li, Z.; Cui, H.

2015-12-01

From the fall of 2009 to the spring of 2010, an unprecedented drought swept across southwest China (SW) and led to a severe shortage in drinking water and a huge loss to regional economy. Monitoring and predicting the severe drought with several months in advance is of critical importance for such hydrological disaster assessment, preparation and mitigation. In this study, we attempted to carry out a model-based hydrological monitoring and seasonal forecasting framework, and assessed its skill in capturing the evolution of the SW drought in 2009-2010. Using the satellite-based meteorological forcings and the Variable Infiltration Capacity (VIC) hydrologic model, the drought conditions were assessed in a near-real-time manner based on a 62-year (1952-2013) retrospective simulation, wherein the satellite data was adjusted by a gauge-based forcing to remove systematic biases. Bias-corrected seasonal forecasting outputs from the National Centers for Environmental Prediction (NCEP) Climate Forecast System Version 2 (CFSv2) was tentatively applied for a seasonal hydrologic prediction and its predictive skill was overall evaluated relative to a traditional Ensemble Streamflow Prediction (ESP) method with lead time varying from 1 to 6 months. The results show that the climate model-driven hydrologic predictability is generally limited to 1-month lead time and exhibits negligible skill improvement relative to ESP during this drought event, suggesting the initial hydrologic conditions (IHCs) play a dominant role in forecasting performance. The research highlights the value of the framework in providing accurate IHCs in a real-time manner which will greatly benefit drought early-warning.

Digital immunohistochemistry platform for the staining variation monitoring based on integration of image and statistical analyses with laboratory information system.

PubMed

Laurinaviciene, Aida; Plancoulaine, Benoit; Baltrusaityte, Indra; Meskauskas, Raimundas; Besusparis, Justinas; Lesciute-Krilaviciene, Daiva; Raudeliunas, Darius; Iqbal, Yasir; Herlin, Paulette; Laurinavicius, Arvydas

2014-01-01

Digital immunohistochemistry (IHC) is one of the most promising applications brought by new generation image analysis (IA). While conventional IHC staining quality is monitored by semi-quantitative visual evaluation of tissue controls, IA may require more sensitive measurement. We designed an automated system to digitally monitor IHC multi-tissue controls, based on SQL-level integration of laboratory information system with image and statistical analysis tools. Consecutive sections of TMA containing 10 cores of breast cancer tissue were used as tissue controls in routine Ki67 IHC testing. Ventana slide label barcode ID was sent to the LIS to register the serial section sequence. The slides were stained and scanned (Aperio ScanScope XT), IA was performed by the Aperio/Leica Colocalization and Genie Classifier/Nuclear algorithms. SQL-based integration ensured automated statistical analysis of the IA data by the SAS Enterprise Guide project. Factor analysis and plot visualizations were performed to explore slide-to-slide variation of the Ki67 IHC staining results in the control tissue. Slide-to-slide intra-core IHC staining analysis revealed rather significant variation of the variables reflecting the sample size, while Brown and Blue Intensity were relatively stable. To further investigate this variation, the IA results from the 10 cores were aggregated to minimize tissue-related variance. Factor analysis revealed association between the variables reflecting the sample size detected by IA and Blue Intensity. Since the main feature to be extracted from the tissue controls was staining intensity, we further explored the variation of the intensity variables in the individual cores. MeanBrownBlue Intensity ((Brown+Blue)/2) and DiffBrownBlue Intensity (Brown-Blue) were introduced to better contrast the absolute intensity and the colour balance variation in each core; relevant factor scores were extracted. Finally, tissue-related factors of IHC staining variance were explored in the individual tissue cores. Our solution enabled to monitor staining of IHC multi-tissue controls by the means of IA, followed by automated statistical analysis, integrated into the laboratory workflow. We found that, even in consecutive serial tissue sections, tissue-related factors affected the IHC IA results; meanwhile, less intense blue counterstain was associated with less amount of tissue, detected by the IA tools.

Digital immunohistochemistry platform for the staining variation monitoring based on integration of image and statistical analyses with laboratory information system

PubMed Central

2014-01-01

Background Digital immunohistochemistry (IHC) is one of the most promising applications brought by new generation image analysis (IA). While conventional IHC staining quality is monitored by semi-quantitative visual evaluation of tissue controls, IA may require more sensitive measurement. We designed an automated system to digitally monitor IHC multi-tissue controls, based on SQL-level integration of laboratory information system with image and statistical analysis tools. Methods Consecutive sections of TMA containing 10 cores of breast cancer tissue were used as tissue controls in routine Ki67 IHC testing. Ventana slide label barcode ID was sent to the LIS to register the serial section sequence. The slides were stained and scanned (Aperio ScanScope XT), IA was performed by the Aperio/Leica Colocalization and Genie Classifier/Nuclear algorithms. SQL-based integration ensured automated statistical analysis of the IA data by the SAS Enterprise Guide project. Factor analysis and plot visualizations were performed to explore slide-to-slide variation of the Ki67 IHC staining results in the control tissue. Results Slide-to-slide intra-core IHC staining analysis revealed rather significant variation of the variables reflecting the sample size, while Brown and Blue Intensity were relatively stable. To further investigate this variation, the IA results from the 10 cores were aggregated to minimize tissue-related variance. Factor analysis revealed association between the variables reflecting the sample size detected by IA and Blue Intensity. Since the main feature to be extracted from the tissue controls was staining intensity, we further explored the variation of the intensity variables in the individual cores. MeanBrownBlue Intensity ((Brown+Blue)/2) and DiffBrownBlue Intensity (Brown-Blue) were introduced to better contrast the absolute intensity and the colour balance variation in each core; relevant factor scores were extracted. Finally, tissue-related factors of IHC staining variance were explored in the individual tissue cores. Conclusions Our solution enabled to monitor staining of IHC multi-tissue controls by the means of IA, followed by automated statistical analysis, integrated into the laboratory workflow. We found that, even in consecutive serial tissue sections, tissue-related factors affected the IHC IA results; meanwhile, less intense blue counterstain was associated with less amount of tissue, detected by the IA tools. PMID:25565007

Functional role of NT-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro

PubMed Central

Wang, Qiong; Green, Steven H.

2011-01-01

Spiral ganglion neurons (SGNs) are postsynaptic to hair cells and project to the brainstem. The inner hair cell (IHC) to SGN synapse is susceptible to glutamate excitotoxicity and to acoustic trauma, with potentially adverse consequences to long-term SGN survival. We used a cochlear explant culture from P6 rat pups consisting of a portion of organ of Corti maintained intact with the corresponding portion of spiral ganglion to investigate excitotoxic damage to IHC-SGN synapses in vitro. The normal innervation pattern is preserved in vitro. Brief treatment with NMDA and kainate results in loss of IHC–SGN synapses and degeneration of the distal type 1 SGN peripheral axons, mimicking damage to SGN peripheral axons caused by excitotoxicity or noise in vivo. The number of IHC presynaptic ribbons is not significantly altered. Reinnervation of IHCs occurs and regenerating axons remain restricted to the IHC row. However, the number of postsynaptic densities (PSDs) does not fully recover and not all axons regrow to the IHCs. Addition of either NT-3 or BDNF increases axon growth and synaptogenesis. Selective blockade of endogenous NT-3 signaling with TrkC-IgG reduced regeneration of axons and PSDs, but TrkB-IgG, which blocks BDNF, has no such effect, indicating that endogenous NT-3 is necessary for SGN axon growth and synaptogenesis. Remarkably, TrkC-IgG reduced axon growth and synaptogenesis even in the presence of BDNF, indicating that endogenous NT-3 has a distinctive role, not mimicked by BDNF, in promoting SGN axon growth in the organ of Corti and synaptogenesis on IHCs. PMID:21613508

Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial.

PubMed

Bartlett, John M S; Christiansen, Jason; Gustavson, Mark; Rimm, David L; Piper, Tammy; van de Velde, Cornelis J H; Hasenburg, Annette; Kieback, Dirk G; Putter, Hein; Markopoulos, Christos J; Dirix, Luc Y; Seynaeve, Caroline; Rea, Daniel W

2016-01-01

Hormone receptors HER2/neu and Ki-67 are markers of residual risk in early breast cancer. An algorithm (IHC4) combining these markers may provide additional information on residual risk of recurrence in patients treated with hormone therapy. To independently validate the IHC4 algorithm in the multinational Tamoxifen Versus Exemestane Adjuvant Multicenter Trial (TEAM) cohort, originally developed on the trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination Trial) cohort, by comparing 2 methodologies. The IHC4 biomarker expression was quantified on TEAM cohort samples (n = 2919) by using 2 independent methodologies (conventional 3,3'-diaminobezidine [DAB] immunohistochemistry with image analysis and standardized quantitative immunofluorescence [QIF] by AQUA technology). The IHC4 scores were calculated by using the same previously established coefficients and then compared with recurrence-free and distant recurrence-free survival, using multivariate Cox proportional hazards modeling. The QIF model was highly significant for prediction of residual risk (P < .001), with continuous model scores showing a hazard ratio (HR) of 1.012 (95% confidence interval [95% CI]: 1.010-1.014), which was significantly higher than that for the DAB model (HR: 1.008, 95% CI: 1.006-1.009); P < .001). Each model added significant prognostic value in addition to recognized clinical prognostic factors, including nodal status, in multivariate analyses. Quantitative immunofluorescence, however, showed more accuracy with respect to overall residual risk assessment than the DAB model. The use of the IHC4 algorithm was validated on the TEAM trial for predicting residual risk in patients with breast cancer. These data support the use of the IHC4 algorithm clinically, but quantitative and standardized approaches need to be used.

Evaluating cytochrome p450 in lesser scaup (Aythya affinis) and tree swallow (Tachycineta bicolor) by monooxygenase activity and immunohistochemistry: Possible nonlethal assessment by skin immunohistochemistry

USGS Publications Warehouse

Melancon, M.J.; Kutay, A.L.; Woodin, Bruce R.; Stegeman, John J.

2006-01-01

Six-month-old lesser scaup (Aythya affinis) and nestling tree swallows (Tachycineta bicolor) were injected intraperitoneally with beta-naphthoflavone (BNF) in corn oil or in vehicle alone. Liver samples were taken and stored at -80 degrees C until microsome preparation and monooxygenase assay. Skin samples were placed in buffered formalin for subsequent immunohistochemical (IHC) analysis for cytochrome P4501A (CYP1A). Lesser scaup treated with BNF at 20 or 100 mg/kg body weight showed approximately 6- to 18-fold increases in four monooxygenases (benzyloxyresorufin-O-dealkylase, ethoxyresorufin-O-dealkylase, methoxyresorufin-O-dealkylase, and pentoxyresorufin-O-dealkylase). No IHC response was observed for CYP1A in the skin of vehicle-injected ducks, whereas in the skin from BNF-treated ducks, the positive IHC response was of similar magnitude for both dose levels of BNF. Tree swallows injected with BNF at 100 mg/kg, but not at. 20 mg/kg, showed significant increases (approximately fivefold) in hepatic microsomal O-dealkylase activities. Cytochrome P4501A was undetectable by IHC response in skin from corn oil-treated swallows, but positive IHC responses were observed in the skin of one of five swallows at 20 mg/kg and four of five swallows at 100 mg/kg. Although these data do not allow construction of significant dose-response curves, the IHC responses for CYP1A in skin support the possible use of this nonlethal approach for biomonitoring contaminant exposure of birds. In addition, the CYP1A signal observed at the bases of emerging feathers suggest that these might provide less invasive sampling sites for IHC analysis of CYP1A.

The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

PubMed Central

Conde, Esther; Angulo, Bárbara; Redondo, Pilar; Toldos, Oscar; García-García, Elena; Suárez-Gauthier, Ana; Rubio-Viqueira, Belén; Marrón, Carmen; García-Luján, Ricardo; Sánchez-Céspedes, Montse; López-Encuentra, Angel; Paz-Ares, Luis; López-Ríos, Fernando

2010-01-01

Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs. PMID:20808915

Correlation of immunohistochemical mismatch repair protein status between colorectal carcinoma endoscopic biopsy and resection specimens.

PubMed

O'Brien, Odharnaith; Ryan, Éanna; Creavin, Ben; Kelly, Michael E; Mohan, Helen M; Geraghty, Robert; Winter, Des C; Sheahan, Kieran

2018-02-01

Microsatellite instability is reflective of a deficient mismatch repair system (dMMR), which may be due to either sporadic or germline mutations in the relevant mismatch repair (MMR) gene. MMR status is frequently determined by immunohistochemistry (IHC) for mismatch repair proteins (MMRPs) on colorectal cancer (CRC) resection specimens. However, IHC testing performed on endoscopic biopsy may be as reliable as that performed on surgical resections. We aimed to evaluate the reliability of MMR IHC staining on preoperative CRC endoscopic biopsies compared with matched-surgical resection specimens. A retrospective search of our institution's histopathology electronic database was performed. Patients with CRC who had MMR IHC performed on both their preoperative endoscopic biopsy and subsequent resection from January 2010 to January 2016 were included. Concordance of MMR staining between biopsy and resection specimens was assessed. From 2000 to 2016, 53 patients had MMR IHC performed on both their preoperative colorectal endoscopic biopsy and resection specimens; 10 patients (18.87%) demonstrated loss of ≥1 MMRP on their initial endoscopic tumour biopsy. The remainder (81.13%) showed preservation of staining for all MMRPs. There was complete agreement in MMR IHC status between the preoperative endoscopic biopsies and corresponding resection specimens in all cases (κ=1.000, P<0.000) with a sensitivity of 100% (95% CI 69.15 to 100) and specificity of 100% (95% CI 91.78 to 100) for detection of dMMR. Endoscopic biopsies are a suitable source of tissue for MMR IHC analysis. This may provide a number of advantages to both patients and clinicians in the management of CRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Analytic Validation of Immunohistochemistry Assays: New Benchmark Data From a Survey of 1085 Laboratories.

PubMed

Stuart, Lauren N; Volmar, Keith E; Nowak, Jan A; Fatheree, Lisa A; Souers, Rhona J; Fitzgibbons, Patrick L; Goldsmith, Jeffrey D; Astles, J Rex; Nakhleh, Raouf E

2017-09-01

- A cooperative agreement between the College of American Pathologists (CAP) and the United States Centers for Disease Control and Prevention was undertaken to measure laboratories' awareness and implementation of an evidence-based laboratory practice guideline (LPG) on immunohistochemical (IHC) validation practices published in 2014. - To establish new benchmark data on IHC laboratory practices. - A 2015 survey on IHC assay validation practices was sent to laboratories subscribed to specific CAP proficiency testing programs and to additional nonsubscribing laboratories that perform IHC testing. Specific questions were designed to capture laboratory practices not addressed in a 2010 survey. - The analysis was based on responses from 1085 laboratories that perform IHC staining. Ninety-six percent (809 of 844) always documented validation of IHC assays. Sixty percent (648 of 1078) had separate procedures for predictive and nonpredictive markers, 42.7% (220 of 515) had procedures for laboratory-developed tests, 50% (349 of 697) had procedures for testing cytologic specimens, and 46.2% (363 of 785) had procedures for testing decalcified specimens. Minimum case numbers were specified by 85.9% (720 of 838) of laboratories for nonpredictive markers and 76% (584 of 768) for predictive markers. Median concordance requirements were 95% for both types. For initial validation, 75.4% (538 of 714) of laboratories adopted the 20-case minimum for nonpredictive markers and 45.9% (266 of 579) adopted the 40-case minimum for predictive markers as outlined in the 2014 LPG. The most common method for validation was correlation with morphology and expected results. Laboratories also reported which assay changes necessitated revalidation and their minimum case requirements. - Benchmark data on current IHC validation practices and procedures may help laboratories understand the issues and influence further refinement of LPG recommendations.

Integrative Health Coach Training: A Model for Shifting the Paradigm Toward Patient-centricity and Meeting New National Prevention Goals

PubMed Central

Smith, Linda L.; Lake, Noelle H.; Simmons, Leigh Ann; Perlman, Adam; Wroth, Shelley

2013-01-01

Objective: To describe the evolution, training, and results of an emerging allied health profession skilled in eliciting sustainable health-related behavior change and charged with improving patient engagement. Methods: Through techniques sourced from humanistic and positive psychology, solution-focused and mindfulness-based therapies, and leadership coaching, Integrative Health Coaching (IHC) provides a mechanism to empower patients through various stages of learning and change. IHC also provides a method for the creation and implementation of forward-focused personalized health plans. Results: Clinical studies employing Duke University Integrative Medicine's model of IHC have demonstrated improvements in measures of diabetes and diabetes risk, weight management, and risk for cardiovascular disease and stroke. By supporting and enabling individuals in making major lifestyle changes for the improvement of their health, IHC carries the potential to reduce rates and morbidity of chronic disease and impact myriad aspects of healthcare. Conclusion: As a model of educational and clinical innovation aimed at patient empowerment and lifestyle modification, IHC is aligned well with the tenets and goals of recently sanctioned federal healthcare reform, specifically the creation of the first National Prevention and Health Promotion Strategy. Practice Implications: IHC may allow greater patient-centricity while targeting the lifestyle-related chronic disease that lies at the heart of the current healthcare crisis. PMID:24416674

Nano spin-diodes using FePt-NDs with huge on/off current ratio at room temperature

PubMed Central

Makihara, Katsunori; Kato, Takeshi; Kabeya, Yuuki; Mitsuyuki, Yusuke; Ohta, Akio; Oshima, Daiki; Iwata, Satoshi; Darma, Yudi; Ikeda, Mitsuhisa; Miyazaki, Seiichi

2016-01-01

Spin transistors have attracted tremendous interest as new functional devices. However, few studies have investigated enhancements of the ON/OFF current ratio as a function of the electron spin behavior. Here, we found a significantly high spin-dependent current ratio—more than 102 at 1.5 V—when changing the relative direction of the magnetizations between FePt nanodots (NDs) and the CoPtCr-coated atomic force microscope (AFM) probe at room temperature. This means that ON and OFF states were achieved by switching the magnetization of the FePt NDs, which can be regarded as spin-diodes. The FePt magnetic NDs were fabricated by exposing a bi-layer metal stack to a remote H2 plasma (H2-RP) on ~1.7 nm SiO2/Si(100) substrates. The ultrathin bi-layers with a uniform surface coverage are changed drastically to NDs with an areal density as high as ~5 × 1011 cm−2. The FePt NDs exhibit a large perpendicular anisotropy with an out-of-plane coercivity of ~4.8 kOe, reflecting the magneto-crystalline anisotropy of (001) oriented L10 phase FePt. We also designed and fabricated double-stacked FePt-NDs with low and high coercivities sandwiched between an ultra-thin Si-oxide interlayer, and confirmed a high ON/OFF current ratio when switching the relative magnetization directions of the low and high coercivity FePt NDs. PMID:27615374

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

PubMed Central

2011-01-01

Introduction The human epidermal growth factor receptor 2 (HER2) is an established biomarker for management of patients with breast cancer. While conventional testing of HER2 protein expression is based on semi-quantitative visual scoring of the immunohistochemistry (IHC) result, efforts to reduce inter-observer variation and to produce continuous estimates of the IHC data are potentiated by digital image analysis technologies. Methods HER2 IHC was performed on the tissue microarrays (TMAs) of 195 patients with an early ductal carcinoma of the breast. Digital images of the IHC slides were obtained by Aperio ScanScope GL Slide Scanner. Membrane connectivity algorithm (HER2-CONNECT™, Visiopharm) was used for digital image analysis (DA). A pathologist evaluated the images on the screen twice (visual evaluations: VE1 and VE2). HER2 fluorescence in situ hybridization (FISH) was performed on the corresponding sections of the TMAs. The agreement between the IHC HER2 scores, obtained by VE1, VE2, and DA was tested for individual TMA spots and patient's maximum TMA spot values (VE1max, VE2max, DAmax). The latter were compared with the FISH data. Correlation of the continuous variable of the membrane connectivity estimate with the FISH data was tested. Results The pathologist intra-observer agreement (VE1 and VE2) on HER2 IHC score was almost perfect: kappa 0.91 (by spot) and 0.88 (by patient). The agreement between visual evaluation and digital image analysis was almost perfect at the spot level (kappa 0.86 and 0.87, with VE1 and VE2 respectively) and at the patient level (kappa 0.80 and 0.86, with VE1max and VE2max, respectively). The DA was more accurate than VE in detection of FISH-positive patients by recruiting 3 or 2 additional FISH-positive patients to the IHC score 2+ category from the IHC 0/1+ category by VE1max or VE2max, respectively. The DA continuous variable of the membrane connectivity correlated with the FISH data (HER2 and CEP17 copy numbers, and HER2/CEP17 ratio). Conclusion HER2 IHC digital image analysis based on membrane connectivity estimate was in almost perfect agreement with the visual evaluation of the pathologist and more accurate in detection of HER2 FISH-positive patients. Most immediate benefit of integrating the DA algorithm into the routine pathology HER2 testing may be obtained by alerting/reassuring pathologists of potentially misinterpreted IHC 0/1+ versus 2+ cases. PMID:21943197

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays.

PubMed

Laurinaviciene, Aida; Dasevicius, Darius; Ostapenko, Valerijus; Jarmalaite, Sonata; Lazutka, Juozas; Laurinavicius, Arvydas

2011-09-23

The human epidermal growth factor receptor 2 (HER2) is an established biomarker for management of patients with breast cancer. While conventional testing of HER2 protein expression is based on semi-quantitative visual scoring of the immunohistochemistry (IHC) result, efforts to reduce inter-observer variation and to produce continuous estimates of the IHC data are potentiated by digital image analysis technologies. HER2 IHC was performed on the tissue microarrays (TMAs) of 195 patients with an early ductal carcinoma of the breast. Digital images of the IHC slides were obtained by Aperio ScanScope GL Slide Scanner. Membrane connectivity algorithm (HER2-CONNECT, Visiopharm) was used for digital image analysis (DA). A pathologist evaluated the images on the screen twice (visual evaluations: VE1 and VE2). HER2 fluorescence in situ hybridization (FISH) was performed on the corresponding sections of the TMAs. The agreement between the IHC HER2 scores, obtained by VE1, VE2, and DA was tested for individual TMA spots and patient's maximum TMA spot values (VE1max, VE2max, DAmax). The latter were compared with the FISH data. Correlation of the continuous variable of the membrane connectivity estimate with the FISH data was tested. The pathologist intra-observer agreement (VE1 and VE2) on HER2 IHC score was almost perfect: kappa 0.91 (by spot) and 0.88 (by patient). The agreement between visual evaluation and digital image analysis was almost perfect at the spot level (kappa 0.86 and 0.87, with VE1 and VE2 respectively) and at the patient level (kappa 0.80 and 0.86, with VE1max and VE2max, respectively). The DA was more accurate than VE in detection of FISH-positive patients by recruiting 3 or 2 additional FISH-positive patients to the IHC score 2+ category from the IHC 0/1+ category by VE1max or VE2max, respectively. The DA continuous variable of the membrane connectivity correlated with the FISH data (HER2 and CEP17 copy numbers, and HER2/CEP17 ratio). HER2 IHC digital image analysis based on membrane connectivity estimate was in almost perfect agreement with the visual evaluation of the pathologist and more accurate in detection of HER2 FISH-positive patients. Most immediate benefit of integrating the DA algorithm into the routine pathology HER2 testing may be obtained by alerting/reassuring pathologists of potentially misinterpreted IHC 0/1+ versus 2+ cases.

Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome.

PubMed

Kilgore, Mark R; McIlwain, Carrie A; Schmidt, Rodney A; Norquist, Barbara M; Swisher, Elizabeth M; Garcia, Rochelle L; Rendi, Mara H

2016-01-01

Endometrial carcinoma (EC) is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS). LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR) genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC) expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC). In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ) with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O). Pathologists must answer these questions: is patient ≤60 (yes/no), if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered), if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp) and postimplementation (PostImp) that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism ® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA). There were 147 patients who met criteria (29 PreImp and 118 PostImp). IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8%) cases did not get any IHC, but PostImp, only 4/118 (3.39%) were missed ( P = 0.0448). Of cases with IHC ordered, 60.0% (15/25) were ordered before or at S/O PreImp versus 91.2% (104/114) PostImp ( P = 0.0004). Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227), with the average being before S/O PostImp. This algorithm ensures MMR IHC ordering in women ≤60 with EC and can be applied to similar scenarios. Ancillary tests for management are increasing, especially genetic and molecular-based methods. The burden of managing orders and results remains with the pathologist and relying on human intervention alone is ineffective. Ordering IHC before or at S/O prevents oversight and the additional work of retrospective ordering and reporting.

HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer.

PubMed

Press, Michael F; Finn, Richard S; Cameron, David; Di Leo, Angelo; Geyer, Charles E; Villalobos, Ivonne E; Santiago, Angela; Guzman, Roberta; Gasparyan, Armen; Ma, Yanling; Danenberg, Kathy; Martin, Anne Marie; Williams, Lisa; Oliva, Cristina; Stein, Steven; Gagnon, Robert; Arbushites, Michael; Koehler, Maria T

2008-12-01

Biomarkers from two randomized phase III trials were analyzed to optimize selection of patients for lapatinib therapy. In available breast cancer tissue from EGF30001 (paclitaxel +/- lapatinib in HER-2-negative/unknown metastatic breast cancer, n = 579) and EGF100151 (capecitabine +/- lapatinib in HER-2-positive metastatic breast cancer, n = 399), HER-2 gene amplification by fluorescence in situ hybridization (FISH), HER-2 mRNA by reverse transcription-PCR (RT-PCR), HER-2 protein expression by HercepTest immunohistochemistry (IHC), epidermal growth factor receptor (EGFR) mRNA level by RT-PCR, and EGFR protein by IHC were analyzed and compared with clinical outcome. HER-2 was determined by FISH in an academic reference/research laboratory and in a large, high-volume commercial reference laboratory. The HER-2 gene was amplified in 47% (344 of 733) and IHC was 3+ in 35% (279 of 798), with significant correlation (P < 0.01) between FISH and IHC. Positive EGFR immunostaining (IHC 1+, 2+, or 3+) in 28% (213 of 761) correlated with EGFR mRNA levels by RT-PCR (r = 0.59; P < 0.01). HER-2 gene amplification/overexpression was associated with improved clinical outcomes (progression-free survival; P < 0.001) in both trials. A significant improvement in outcome was seen in FISH-positive and IHC 0, 1+, or 2+ patients. HER-2 mRNA expression correlated with HER-2 FISH (r = 0.83) and IHC status (r = 0.72; n = 138). No correlation was found between EGFR expression (IHC or mRNA) and responsiveness to lapatinib regardless of HER-2 status. Although a significant correlation with lapatinib responsiveness was observed among "HER-2-negative" breast cancer patients in the large, high-volume commercial reference laboratory, this was not confirmed in the academic reference/research laboratory. Women with HER-2-positive metastatic breast cancer benefit from lapatinib, whereas women with HER-2-negative metastatic breast cancer derive no incremental benefit from lapatinib.

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008

PubMed Central

Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-01-01

Background Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Methodology Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Principal findings Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%–1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Conclusion/Significance Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are needed to evaluate the true prevalence of cysticercosis in humans and pigs in different zones of the country in order to better implement and manage prevention and/or control campaigns. PMID:26580210

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008.

PubMed

Ron-Garrido, Lenin; Coral-Almeida, Marco; Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-11-01

Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%-1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are needed to evaluate the true prevalence of cysticercosis in humans and pigs in different zones of the country in order to better implement and manage prevention and/or control campaigns.

Web-Based Cancer Communication and Decision Making Systems: Connecting Patients, Caregivers, and Clinicians for Improved Health Outcomes

PubMed Central

DuBenske, Lori L.; Gustafson, David H.; Shaw, Bret R.; Cleary, James F.

2011-01-01

Over the cancer disease trajectory, from diagnosis and treatment to remission or end of life, patients and their families face difficult decisions. The provision of information and support when most relevant can optimize cancer decision making and coping. An interactive health communication system (IHCS) offers the potential to bridge the communication gaps that occur among patients, family, and clinicians and to empower each to actively engage in cancer care and shared decision making. This is a report of the authors' experience (with a discussion of relevant literature) in developing and testing a Web-based IHCS—the Comprehensive Health Enhancement Support System (CHESS)—for patients with advanced lung cancer and their family caregivers. CHESS provides information, communication, and coaching resources as well as a symptom tracking system that reports health status to the clinical team. Development of an IHCS includes a needs assessment of the target audience and applied theory informed by continued stakeholder involvement in early testing. Critical issues of IHCS implementation include 1) need for interventions that accommodate a variety of format preferences and technology comfort ranges; 2) IHCS user training, 3) clinician investment in IHCS promotion, and 4) IHCS integration with existing medical systems. In creating such comprehensive systems, development strategies need to be grounded in population needs with appropriate use of technology that serves the target users, including the patient/family, clinical team, and health care organization. Implementation strategies should address timing, personnel, and environmental factors to facilitate continued use and benefit from IHCS. An interactive health communication system (IHCS) offers one platform for providing the information, communication, and coaching resources that cancer patients and their families need to understand the disease, find support, and develop decision-making and coping skills. One such IHCS—the Comprehensive Health Enhancement Support System (CHESS)—has evolved over the past 20 years. Based on our recent experience creating and testing a new version of CHESS—“Coping with Lung Cancer: A Network of Support”—this article outlines the issues faced in developing and implementing such a system within the cancer context. PMID:21041539

Influence of the particle size and intrinsic magnetic characteristics on the coercivity of sintered magnets

NASA Astrophysics Data System (ADS)

Turilli, G.; Paoluzi, A.; Lucenti, M.; Pareti, L.

1992-02-01

Using sintered specimens of Ba-hexaferrite powders as a model system, a study was made of the dependence of coercivity on the particle dimensions and on the temperature from RT up to the Curie temperature. The temperature behaviour of the coercive and anisotropy field are the same in single-domain particle specimens while they are rather different in polydomain particle specimens. However, the coercivity behaviour of both systems can be fitted well up to 350°C using a simple relation between Hc, HA, and Ms. Further contributions to the coercivity have to be taken into account at higher temperatures.

Fabrication of Material and Devices for Very High Density Information Storage.

DTIC Science & Technology

1986-11-24

IKawanishi, "Miagnetic anid opticeal propert I e of Co. I It substituted garnet films p~rep~ared by the lPE niethod and its ipplication to hlermtmt"Ile( i...medium. Highly Bi-substituted garnet films on glass and G( substrates were successfully RF sputtered and characterized by the group of M. Goni.1 The filns...writing due to the temperature dependence of the coercive force 11. Preparation of bismuth iron garnet films by ion bean sputtering onto GGG

Coercive Nuclear Campaigns in the 21st Century: Understanding Adversary Incentives and Options for Nuclear Escalation

DTIC Science & Technology

2013-01-01

powers  armed  with  nuclear  weapons   may   employ   those   weapons...balance   of   power   is   reversed.     Now  U.S.  military   forces   are   the   most  formidable,  and  potential...the   balance   of   power   helps   explain   why   the   United   States   now   seeks   to  

The psychohistorical roots of the American "Tea Party" Movement.

PubMed

Tilden, William W

2011-01-01

Extreme resistance to governmental taxation and authority is derived, according to Freud's theory of anal characterology, from premature and harshly coercive toilet training, in which a child is forced unfairly and against its will to surrender the products of his eliminations (which represent money, among other things, in the unconscious) to parental authority. Among these individuals anal eroticism plays a significant role in the psychogenesis of paranoia and conspiracy theorizing, which may represent a defense mechanism erected against repressed fears of passive submission.

Air Defense Options for Taiwan: An Assessment of Relative Costs and Operational Benefits

DTIC Science & Technology

2016-01-01

and analyzes them in comparison to current People’s Liberation Army ( PLA ) capabilities. It begins with a description of the PLA air- power threat and... PLA ) to easily counter. Still, air defense in a major war is only one possible category of demands for Taiwan’s air defenses. A variety of more-limited...high, the PLA could check Taiwan’s fighter aircraft if it chose. However, in coercive scenarios that feature very constrained use of force, Taiwan’s

Local structure of high-coercivity Fe-Ni-Al alloys

NASA Astrophysics Data System (ADS)

Menushenkov, A. P.; Menushenkov, V. P.; Chernikov, R. V.; Sviridova, T. A.; Grishina, O. V.; Sidorov, V. V.

2011-04-01

Results of hard magnetic Fe-Ni-Al alloys after various thermal processing local structure researches by method of EXAFS-spectroscopy with use of synchrotron radiation at temperature 77 K are presented. It is established, that during cooling a firm solution with critical speed reorganization of a local environment of nickel relative to quickly tempered sample owing to stratification of a firm solution is observed. The subsequent aging at 780°C practically restores local structure, characteristic for quickly tempered sample, keeping thus rather high coercitive force.

Challenges of Systematic Reviewing Integrative Health Care

PubMed Central

Coulter, Ian D.; Khorsan, Raheleh; Crawford, Cindy; Hsiao, An-Fu

2013-01-01

This article is based on an extensive review of integrative medicine (IM) and integrative health care (IHC). Since there is no general agreement of what constitutes IM/IHC, several major problems were identified that make the review of work in this field problematic. In applying the systematic review methodology, we found that many of those captured articles that used the term integrative medicine were in actuality referring to adjunctive, complementary, or supplemental medicine. The objective of this study was to apply a sensitivity analysis to demonstrate how the results of a systematic review of IM and IHC will differ according to what inclusion criteria is used based on the definition of IM/IHC. By analyzing 4 different scenarios, the authors show that, due to unclear usage of these terms, results vary dramatically, exposing an inconsistent literature base for this field. PMID:23843689

Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine: Part 4: Tissue Tools for Quality Assurance in Immunohistochemistry.

PubMed

Cheung, Carol C; D'Arrigo, Corrado; Dietel, Manfred; Francis, Glenn D; Fulton, Regan; Gilks, C Blake; Hall, Jacqueline A; Hornick, Jason L; Ibrahim, Merdol; Marchetti, Antonio; Miller, Keith; van Krieken, J Han; Nielsen, Soren; Swanson, Paul E; Taylor, Clive R; Vyberg, Mogens; Zhou, Xiaoge; Torlakovic, Emina E

2017-04-01

The numbers of diagnostic, prognostic, and predictive immunohistochemistry (IHC) tests are increasing; the implementation and validation of new IHC tests, revalidation of existing tests, as well as the on-going need for daily quality assurance monitoring present significant challenges to clinical laboratories. There is a need for proper quality tools, specifically tissue tools that will enable laboratories to successfully carry out these processes. This paper clarifies, through the lens of laboratory tissue tools, how validation, verification, and revalidation of IHC tests can be performed in order to develop and maintain high quality "fit-for-purpose" IHC testing in the era of precision medicine. This is the final part of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Time-instant sampling based encoding of time-varying acoustic spectrum

NASA Astrophysics Data System (ADS)

Sharma, Neeraj Kumar

2015-12-01

The inner ear has been shown to characterize an acoustic stimuli by transducing fluid motion in the inner ear to mechanical bending of stereocilia on the inner hair cells (IHCs). The excitation motion/energy transferred to an IHC is dependent on the frequency spectrum of the acoustic stimuli, and the spatial location of the IHC along the length of the basilar membrane (BM). Subsequently, the afferent auditory nerve fiber (ANF) bundle samples the encoded waveform in the IHCs by synapsing with them. In this work we focus on sampling of information by afferent ANFs from the IHCs, and show computationally that sampling at specific time instants is sufficient for decoding of time-varying acoustic spectrum embedded in the acoustic stimuli. The approach is based on sampling the signal at its zero-crossings and higher-order derivative zero-crossings. We show results of the approach on time-varying acoustic spectrum estimation from cricket call signal recording. The framework gives a time-domain and non-spatial processing perspective to auditory signal processing. The approach works on the full band signal, and is devoid of modeling any bandpass filtering mimicking the BM action. Instead, we motivate the approach from the perspective of event-triggered sampling by afferent ANFs on the stimuli encoded in the IHCs. Though the approach gives acoustic spectrum estimation but it is shallow on its complete understanding for plausible bio-mechanical replication with current mammalian auditory mechanics insights.

Robust vascular invasion concurrent with intense EGFR immunostaining can predict recurrence in patients with stage IB node-negative gastric cancer.

PubMed

Araki, Ippeita; Washio, Marie; Yamashita, Keishi; Hosoda, Kei; Ema, Akira; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Kikuchi, Shiro; Watanabe, Masahiko

2018-05-01

The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence. The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors. Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001). In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.

NanoString nCounter® Approach in Breast Cancer: A Comparative Analysis with Quantitative Real-Time Polymerase Chain Reaction, In Situ Hybridization, and Immunohistochemistry.

PubMed

Hyeon, Jiyeon; Cho, Soo Youn; Hong, Min Eui; Kang, So Young; Do, Ingu; Im, Young Hyuck; Cho, Eun Yoon

2017-09-01

Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2. Data on IHC/FISH results for ER, PR, and HER2 in 240 patients from a single tertiary hospital in Korea were collected and compared with NanoString nCounter® and qRT-PCR results at a single institution. Expression levels for each gene using NanoString nCounter® showed good correlation with the corresponding data for protein expression by IHC ( p <0.001) and gene amplification status for HER2 ( p <0.001). Comparisons between gene expression and IHC data showed good overall agreement with a high area under the curve (AUC) for ESR1 /ER (AUC=0.939), PgR /PR (AUC=0.796), and HER2 /HER2 (AUC=0.989) ( p <0.001). The quantification of ER , PgR , and HER2 mRNA expression with NanoString nCounter® may be a viable alternative to conventional IHC/FISH methods.

From antisocial behavior to violence: a model for the amplifying role of coercive joining in adolescent friendships.

PubMed

Van Ryzin, Mark J; Dishion, Thomas J

2013-06-01

Aggression is one of the more stable characteristics of child and adolescent development, and violent behavior in early adulthood is often foreshadowed by aggressive behavior in childhood and early adolescence. Considerable evidence has linked coercive family interactions to aggressive behavior in childhood, but less research has been conducted on the joint role of family and peer interaction in the escalation of aggression to violence in adulthood. We coded family interactions at age 12-13 and friendship interaction at age 16-17 in a multiethnic sample of youth and families. Violence in young adulthood (age 22-23) was measured using self-report, criminal records, and parent report. We tested the hypothesis that a process of 'coercive joining' in friendship interactions mediated the relationship between coercive family interactions and serious violence. We found that observed coercive joining in friendships at age 16-17 predicted early-adulthood violent behavior over and above an established tendency toward antisocial behavior. We also found that observed coercive family interactions at age 12 predicted early-adulthood violence, and that coercive joining with friends fully mediated this link. These results significantly extend coercion theory by suggesting that coercive joining in the context of peer groups is an additional mechanism by which coercive processes in the family are extended and amplified to violent behavior in early adulthood. Our findings suggest the importance of addressing both individual interpersonal skills and self-organizing peer groups when intervening to prevent violent behavior. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining

NASA Astrophysics Data System (ADS)

van Eycke, Yves-Rémi; Allard, Justine; Salmon, Isabelle; Debeir, Olivier; Decaestecker, Christine

2017-02-01

Immunohistochemistry (IHC) is a widely used technique in pathology to evidence protein expression in tissue samples. However, this staining technique is known for presenting inter-batch variations. Whole slide imaging in digital pathology offers a possibility to overcome this problem by means of image normalisation techniques. In the present paper we propose a methodology to objectively evaluate the need of image normalisation and to identify the best way to perform it. This methodology uses tissue microarray (TMA) materials and statistical analyses to evidence the possible variations occurring at colour and intensity levels as well as to evaluate the efficiency of image normalisation methods in correcting them. We applied our methodology to test different methods of image normalisation based on blind colour deconvolution that we adapted for IHC staining. These tests were carried out for different IHC experiments on different tissue types and targeting different proteins with different subcellular localisations. Our methodology enabled us to establish and to validate inter-batch normalization transforms which correct the non-relevant IHC staining variations. The normalised image series were then processed to extract coherent quantitative features characterising the IHC staining patterns.

Review of Current Applications of Immunohistochemistry in Pediatric Nonneoplastic Gastrointestinal, Hepatobiliary, and Pancreatic Lesions

PubMed Central

de Nanassy, Joseph; El Demellawy, Dina

2017-01-01

Immunohistochemical (IHC) stains are widely used by pathologists for a variety of considerations in the diagnostic workup of pediatric nonneoplastic lesions in gastrointestinal (GI), hepatic, biliary, and pancreatic lesions. The pathologic changes cover a wide range and types of presentations, including inflammatory (bacterial and viral), metaplastic, posttransplant lymphoproliferative, autoimmune, metabolic, degenerative, developmental, and genetic conditions, among others. The everyday practical value of IHC stains covers primary identification, confirmation, differential, and/or exclusionary roles in the hands and eyes and minds of the practitioners. This article is intended to review and discuss the currently available IHC stains for a variety of pediatric GI, hepatobiliary, and pancreatic lesions as encountered in the day-to-day practice of pathologists and clinicians. It reflects the most recent methods and types of IHC stains with the stated aim of helping to provide a quick reference for diagnostic considerations and thereby facilitate the workup of a broad range of GI and related conditions in a pediatric population. The tables provide a handy reference on a wide range of IHC stains for commonly encountered lesions covering a variety of pediatric GI, hepatobiliary, and pancreatic conditions that are amenable to light microscopic diagnostic interpretation. PMID:28469406

Comparison of flow cytometry and immunohistochemistry in non-radioisotopic murine lymph node assay using bromodeoxyuridine.

PubMed

Jung, Kyoung-Mi; Bae, Il-Hong; Kim, Bae-Hwan; Kim, Wang-Ki; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2010-02-01

Non-radioisotopic local lymph node assay (LLNA) employing 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FACS) or immunohistochemistry (IHC) is gaining attention due to a regulatory issue of using radioisotope, (3)H-thymidine, in vivo in traditional LLNA. In this study, to compare the performance of these non-radioisotopic endpoints, 7 chemicals with known sensitizing potencies were examined in LLNA. Mice were topically treated with chemicals or vehicle on both ears for 3 days. After intraperitoneal injection of BrdU, bilateral lymph nodes were isolated separately and undergone respectively, FACS or IHC to determine BrdU incorporated lymph node cells (LNCs). Weight and histology of treated ears were also examined to evaluate chemical-induced edema and irritation. Both FACS and IHC could successively identify the skin sensitizers from non-sensitizers. Comparison of FACS and IHC with traditional LLNA revealed that FACS has a higher sensitivity although both assays produced comparable sensitivity and performance to traditional LLNA. In conclusion, non-radioisotopic LLNA using FACS and IHC can successfully detect sensitizers with a good correlation to traditional LLNA. Notably, FACS showed almost equivalent sensitivity and accuracy to traditional LLNA. 2009 Elsevier Ireland Ltd. All rights reserved.

Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining

PubMed Central

Van Eycke, Yves-Rémi; Allard, Justine; Salmon, Isabelle; Debeir, Olivier; Decaestecker, Christine

2017-01-01

Immunohistochemistry (IHC) is a widely used technique in pathology to evidence protein expression in tissue samples. However, this staining technique is known for presenting inter-batch variations. Whole slide imaging in digital pathology offers a possibility to overcome this problem by means of image normalisation techniques. In the present paper we propose a methodology to objectively evaluate the need of image normalisation and to identify the best way to perform it. This methodology uses tissue microarray (TMA) materials and statistical analyses to evidence the possible variations occurring at colour and intensity levels as well as to evaluate the efficiency of image normalisation methods in correcting them. We applied our methodology to test different methods of image normalisation based on blind colour deconvolution that we adapted for IHC staining. These tests were carried out for different IHC experiments on different tissue types and targeting different proteins with different subcellular localisations. Our methodology enabled us to establish and to validate inter-batch normalization transforms which correct the non-relevant IHC staining variations. The normalised image series were then processed to extract coherent quantitative features characterising the IHC staining patterns. PMID:28220842

The use of immunohistochemistry for biomarker assessment--can it compete with other technologies?

PubMed

Dunstan, Robert W; Wharton, Keith A; Quigley, Catherine; Lowe, Amanda

2011-10-01

A morphology-based assay such as immunohistochemistry (IHC) should be a highly effective means to define the expression of a target molecule of interest, especially if the target is a protein. However, over the past decade, IHC as a platform for biomarkers has been challenged by more quantitative molecular assays with reference standards but that lack morphologic context. For IHC to be considered a "top-tier" biomarker assay, it must provide truly quantitative data on par with non-morphologic assays, which means it needs to be run with reference standards. However, creating such standards for IHC will require optimizing all aspects of tissue collection, fixation, section thickness, morphologic criteria for assessment, staining processes, digitization of images, and image analysis. This will also require anatomic pathology to evolve from a discipline that is descriptive to one that is quantitative. A major step in this transformation will be replacing traditional ocular microscopes with computer monitors and whole slide images, for without digitization, there can be no accurate quantitation; without quantitation, there can be no standardization; and without standardization, the value of morphology-based IHC assays will not be realized.

[Coercive Measures in Child and Adolescent Psychiatry].

PubMed

Rabe, Silke C; Fegert, Jörg M; Krüger, Ulrich; Kölch, Michael

2017-01-01

Coercive Measures in Child and Adolescent Psychiatry To keep the use of coercive measures in child and adolescent psychiatry low or reduce them completely, there needs to be a specific knowledge of the starting point. The study provides an overview of the current situation using a systematic literature review of published studies from the European and the outer European regions between 2005 and 2015. In summary only twelve publications addressed the topic, differentiated in four studies from inner and eight studies from outer European countries. In the studies from Europe, girls in their late adolescence experienced coercive measures more often, whereas the outer European studies identified more boys in early school age. Regarding the diagnoses of the respective patients, no distinct trend could be identified, as coercive measures were applied with a range of different diagnoses. In the European studies, coercive measures were more often used with children and adolescents fitting in the ICD-10-category F9. Results point to a lack of empirical studies concerning coercive measures in the context of child and adolescent psychiatry. Besides, clinical practice between the countries varies tremendously, resulting in difficulties comparing the findings. One possibility to address these issues might be a central register for every kind of coercive measure, as it was introduced in Baden-Württemberg lately and is currently in development for North Rhine-Westphalia.

Review of isothermal haze chamber performance

NASA Technical Reports Server (NTRS)

Fitzgerald, J. W.; Rogers, C. F.; Hudson, J. G.

1981-01-01

The theory of this method of characterizing cloud condensation nuclei (CCN) over the critical supersaturation range of about 0.01% to 0.2% was reviewed, and guidelines for the design and operation of IHC's are given. IHC data are presented and critically analyzed. Two of the four IHC's agree to about 40% over the entire range of critical. a third chamber shows similar agreement with the first two over the lower part of the critical supersaturation range but only a factor of two agreement at higher supersaturation. Some reasons for the discrepancies are given.

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

PubMed Central

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

2015-01-01

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313

A Phase II Trial of Dovitinib in BCG-Unresponsive Urothelial Carcinoma with FGFR3 Mutations or Overexpression: Hoosier Cancer Research Network Trial HCRN 12-157.

PubMed

Hahn, Noah M; Bivalacqua, Trinity J; Ross, Ashley E; Netto, George J; Baras, Alex; Park, Jong Chul; Chapman, Carolyn; Masterson, Timothy A; Koch, Michael O; Bihrle, Richard; Foster, Richard S; Gardner, Thomas A; Cheng, Liang; Jones, David R; McElyea, Kyle; Sandusky, George E; Breen, Timothy; Liu, Ziyue; Albany, Costantine; Moore, Marietta L; Loman, Rhoda L; Reed, Angela; Turner, Scott A; De Abreu, Francine B; Gallagher, Torrey; Tsongalis, Gregory J; Plimack, Elizabeth R; Greenberg, Richard E; Geynisman, Daniel M

2017-06-15

Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non-muscle-invasive urothelial carcinoma of the bladder (NMIUC) population. Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC ( > 2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate. Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut-, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3-4 event. Six-month CR rate was 8% (0% in IHC+ Mut-; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94-5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment. Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003-11. ©2016 AACR . ©2016 American Association for Cancer Research.

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

PubMed

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT- PCR on paraffin-embedded tissues.

PubMed

Zhang, Yun-Gang; Jin, Mu-Lan; Li, Li; Zhao, Hong-Ying; Zeng, Xuan; Jiang, Lei; Wei, Ping; Diao, Xiao-Li; Li, Xue; Cao, Qing; Tian, Xin-Xia

2013-01-01

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation.

Descriptive analysis of neurological in-hospital consultations in a tertiary hospital.

PubMed

Aller-Alvarez, J S; Quintana, M; Santamarina, E; Álvarez-Sabín, J

2017-04-01

In-hospital consultations (IHC) are essential in clinical practice in tertiary hospitals. The aim of this study is to analyse the impact of neurological IHCs. One-year retrospective descriptive study of neurological IHCs conducted from May 2013 to April 2014 at our tertiary hospital. A total of 472 patients were included (mean age, 62.1 years; male patients, 56.8%) and 24.4% had previously been evaluated by a neurologist. Patients were hospitalised a median of 18 days and 19.7% had been referred by another hospital. The departments requesting the most in-hospital consultations were intensive care (20.1%), internal medicine (14.4%), and cardiology (9.1%). Reasons for requesting an IHC were stroke (26.9%), epilepsy (20.6%), and confusional states (7.6%). An on-call neurologist evaluated 41.9% of the patients. The purpose of the IHC was to provide a diagnosis in 56.3% and treatment in 28.2% of the cases; 69.5% of the patients required additional tests. Treatment was adjusted in 18.9% of patients and additional drugs were administered to 27.3%. While 62.1% of cases required no additional IHCs, 11% required further assessment, and 4.9% were transferred to the neurology department. Of the patient total, 16.9% died during hospitalisation (in 37.5%, the purpose of the consultation was to certify brain death); 45.6% were referred to the neurology department at discharge and 6.1% visited the emergency department due to neurological impairment within 6 months of discharge. IHCs facilitate diagnosis and management of patients with neurological diseases, which may help reduce the number of visits to the emergency department. On-call neurologists are essential in tertiary hospitals, and they are frequently asked to diagnose brain death. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

A comparative study of quantitative immunohistochemistry and quantum dot immunohistochemistry for mutation carrier identification in Lynch syndrome.

PubMed

Barrow, Emma; Evans, D Gareth; McMahon, Ray; Hill, James; Byers, Richard

2011-03-01

Lynch Syndrome is caused by mutations in DNA mismatch repair (MMR) genes. Mutation carrier identification is facilitated by immunohistochemical detection of the MMR proteins MHL1 and MSH2 in tumour tissue and is desirable as colonoscopic screening reduces mortality. However, protein detection by conventional immunohistochemistry (IHC) is subjective, and quantitative techniques are required. Quantum dots (QDs) are novel fluorescent labels that enable quantitative multiplex staining. This study compared their use with quantitative 3,3'-diaminobenzidine (DAB) IHC for the diagnosis of Lynch Syndrome. Tumour sections from 36 mutation carriers and six controls were obtained. These were stained with DAB on an automated platform using antibodies against MLH1 and MSH2. Multiplex QD immunofluorescent staining of the sections was performed using antibodies against MLH1, MSH2 and smooth muscle actin (SMA). Multispectral analysis of the slides was performed. The staining intensity of DAB and QDs was measured in multiple colonic crypts, and the mean intensity scores calculated. Receiver operating characteristic (ROC) curves of staining performance for the identification of mutation carriers were evaluated. For quantitative DAB IHC, the area under the MLH1 ROC curve was 0.872 (95% CI 0.763 to 0.981), and the area under the MSH2 ROC curve was 0.832 (95% CI 0.704 to 0.960). For quantitative QD IHC, the area under the MLH1 ROC curve was 0.812 (95% CI 0.681 to 0.943), and the area under the MSH2 ROC curve was 0.598 (95% CI 0.418 to 0.777). Despite the advantage of QD staining to enable several markers to be measured simultaneously, it is of lower utility than DAB IHC for the identification of MMR mutation carriers. Automated DAB IHC staining and quantitative slide analysis may enable high-throughput IHC.

Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in prostate cancer.

PubMed

Suh, Ja Hee; Park, Jeong Hwan; Lee, Cheol; Moon, Kyung Chul

2017-10-01

Prostate cancer is considered to be highly heterogeneous, with various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion is the most frequently observed genetic aberration in prostate cancer. The aim of this study was to elucidate the intrafocal heterogeneity of ERG gene fusion status. ERG immunohistochemistry (IHC) was performed in samples from 168 prostate cancer patients who had undergone radical prostatectomy, and 40 cases showing ERG-positive IHC staining were selected for tissue microarray (TMA) construction. Two to six representative cores were selected from each tumor focus. In the cases with heterogeneous ERG IHC staining intensity, the areas showing different intensities were separately selected. Using the TMA blocks, IHC and fluorescence in situ hybridization (FISH) were conducted to evaluate the heterogeneity of ERG protein expression and ERG fusion gene patterns, respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was defined as the simultaneous presence of negative and positive cores in the same tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with positive and negative FISH signals or cores with break-apart and interstitial deletion FISH signals in the same tumor focus. A total of 202 TMA cores were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores showed ERG break-apart FISH signals, and the remaining 72 cores revealed interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was found in 32.5% (13/40) of cases. In summary, this study showed significantly frequent intrafocal heterogeneity of ERG protein expression, gene fusion status and fusion pattern. This heterogeneity can be caused by the development of subclones during cancer progression or the intermingling of different tumors. © 2017 Wiley Periodicals, Inc.

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing.

PubMed

Agarwal, Shipra; Sharma, Mehar Chand; Jha, Prerana; Pathak, Pankaj; Suri, Vaishali; Sarkar, Chitra; Chosdol, Kunzang; Suri, Ashish; Kale, Shashank Sharad; Mahapatra, Ashok Kumar; Jha, Pankaj

2013-06-01

Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas. Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations. Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells. IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing

PubMed Central

Agarwal, Shipra; Sharma, Mehar Chand; Jha, Prerana; Pathak, Pankaj; Suri, Vaishali; Sarkar, Chitra; Chosdol, Kunzang; Suri, Ashish; Kale, Shashank Sharad; Mahapatra, Ashok Kumar; Jha, Pankaj

2013-01-01

Background Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas. Materials and methods Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations. Results Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells. Conclusions IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas. PMID:23486690

Coercivity Enhancement in Exchange Biased Bilayers

NASA Astrophysics Data System (ADS)

Leighton, C.

2001-03-01

The well-known enhancement in coercivity in ferromagnet / antiferromagnet bilayers has been studied in the model epitaxial system MnF2 / Fe. We have investigated how the coercivity depends on temperature, cooling field, layer thickness and interfacial disorder. In all cases a typical enhancement is observed on cooling below the Neel temperature of the antiferromagnet. However, for the case of positively exchange biased layers we observe an extra coercivity enhancement which occurs when the interface is deliberately driven to a situation of maximum magnetic frustration(C. Leighton, J. Nogues, B.J. Jonsson-Akerman and I.K. Schuller, Phys. Rev. Lett. 84 3466 (2000)). This situation is controlled by the magnitude of the cooling field, giving us an external parameter through which we can vary the coercivity. We propose a model where a frustrated interface provides local energy minima which effectively pin domain walls leading to an increase in coercivity. We further examine the ferromagnet thickness dependence of the effect as a probe of the coercive mechanisms(Z. Li and S. Zhang, Phys. Rev. B61 R14897 (2000) ; S. Zhang et al J. Mag. Mag. Mat. 198-199 468 (1999)). Work supported by the US DoE and the NSF.

Microstructure Evolution During Continuous Cooling in AISI 5140 Steel Processed by Induction Heating Chromizing

NASA Astrophysics Data System (ADS)

Hu, Jianjun; Ma, Chaoping; Yang, Xian; Xu, Hongbin; Guo, Ning; Yu, Hongbing

2017-11-01

In this study, induction heating chromizing (IHC) and box-type furnace heating chromizing (BFHC) were conducted on commercial AISI 5140 steels, respectively. Microstructure, microhardness and wear resistance of the chromized samples were characterized. The results show that the IHC samples have thicker Cr coating layer and stronger interface bond due to pre-compressive stress among the packed powders. Three kinds of microstructures including alloyed cementite (AC-layer), fine pearlite zone (FP-zone) and carbon-poor zone (CP-zone) are formed near the interface in the IHC samples. The main reason given for this is that different contents of Cr and C have different effects on pearlite phase and morphology. The IHC sample shows better wear properties due to its stronger interface bonding strength than that of the BFHC sample. The formation mechanism of CP-zone and its influences on microhardness and wear resistance are also discussed.

Mesoscopic bar magnet based on ε-Fe2O3 hard ferrite.

PubMed

Ohkoshi, Shin-Ichi; Namai, Asuka; Yamaoka, Takehiro; Yoshikiyo, Marie; Imoto, Kenta; Nasu, Tomomichi; Anan, Shizuka; Umeta, Yoshikazu; Nakagawa, Kosuke; Tokoro, Hiroko

2016-06-07

Ferrite magnets have a long history. They are used in motors, magnetic fluids, drug delivery systems, etc. Herein we report a mesoscopic ferrite bar magnet based on rod-shaped ε-Fe2O3 with a large coercive field (>25 kOe). The ε-Fe2O3-based bar magnet is a single crystal with a single magnetic domain along the longitudinal direction. A wide frequency range spectroscopic study shows that the crystallographic a-axis of ε-Fe2O3, which corresponds to the longitudinal direction of the bar magnet, plays an important role in linear and non-linear magneto-optical transitions, phonon modes, and the magnon (Kittel mode). Due to its multiferroic property, a magnetic-responsive non-linear optical sheet is manufactured as an application using an ε-Fe2O3-based bar magnet, resin, and polyethylene terephthalate. Furthermore, from the viewpoint of the large coercive field property, we demonstrate that a mesoscopic ε-Fe2O3 bar magnet can be used as a magnetic force microscopy probe.

Mesoscopic bar magnet based on ɛ-Fe2O3 hard ferrite

NASA Astrophysics Data System (ADS)

Ohkoshi, Shin-Ichi; Namai, Asuka; Yamaoka, Takehiro; Yoshikiyo, Marie; Imoto, Kenta; Nasu, Tomomichi; Anan, Shizuka; Umeta, Yoshikazu; Nakagawa, Kosuke; Tokoro, Hiroko

2016-06-01

Ferrite magnets have a long history. They are used in motors, magnetic fluids, drug delivery systems, etc. Herein we report a mesoscopic ferrite bar magnet based on rod-shaped ɛ-Fe2O3 with a large coercive field (>25 kOe). The ɛ-Fe2O3-based bar magnet is a single crystal with a single magnetic domain along the longitudinal direction. A wide frequency range spectroscopic study shows that the crystallographic a-axis of ɛ-Fe2O3, which corresponds to the longitudinal direction of the bar magnet, plays an important role in linear and non-linear magneto-optical transitions, phonon modes, and the magnon (Kittel mode). Due to its multiferroic property, a magnetic-responsive non-linear optical sheet is manufactured as an application using an ɛ-Fe2O3-based bar magnet, resin, and polyethylene terephthalate. Furthermore, from the viewpoint of the large coercive field property, we demonstrate that a mesoscopic ɛ-Fe2O3 bar magnet can be used as a magnetic force microscopy probe.

Stimulus dependent properties of mammalian cochlear hair cell mechanoelectrical transduction

NASA Astrophysics Data System (ADS)

Scharr, A. L.; Ricci, Anthony

2018-05-01

Cochlear hair cell stereocilia move semi-independently, shaping the force transfer to mechanoelectrical transduction (MET) channels, as indicated by the MET current response. Semi-independent movement of stereocilia was evoked by stimulating inner hair cell (IHC) bundles from acutely dissected rat cochlea with stiff probes ranging in size from 1 to 10 µm. MET current responses were recorded using whole-cell patch-clamp electrophysiology. Small probes directly displaced stereocilia they contacted, and recruited adjacent stereocilia depending on stimulus magnitude. We inferred that the recruitment of stereocilia resulted in less uniform and less synchronous movement. Step displacements using smaller probes resulted in smaller current responses (from 1 nA for large probes to 0.3 nA for small, p <.0001), slower rate of current activation, as measured from the linear portion (from 4 nA/ms to 1 nA/ms, p <.0001), slower time constants of adaptation, as measured from double exponential fits from peak to steady state current (fast component: from 0.6 to 1.2 ms, p =.004; slow component: from 8 ms to 12 ms, p =.001) and less complete adaptation (from 95% to 30%, p <.0001). These results indicate that the mechanical properties of less coherent bundles greatly affect force transfer to MET channels as indicated by the electrical response of the cell. Thus, outer hair cells (OHCs), with their bundles embedded in the tectorial membrane, may exhibit synchronous MET activation and therefore time-dependent adaptation where fast adaptation provides a high pass filter. Hair cells with free standing bundles, like inner hair cells (IHC), may exhibit more asynchronous MET activation and adaptation, in which case adaptation would not provide this additional filter.

Variables Associated With the Subjective Experience of Coercive Measures in Psychiatric Inpatients: A Systematic Review.

PubMed

Aguilera-Serrano, Carlos; Guzman-Parra, Jose; Garcia-Sanchez, Juan A; Moreno-Küstner, Berta; Mayoral-Cleries, Fermin

2018-02-01

This systematic review presents evidence regarding factors that may influence the patient's subjective experience of an episode of mechanical restraint, seclusion, or forced administration of medication. Two authors searched CINAHL, PubMed, SCOPUS, Web of Science, and Psych-Info, considering published studies between 1 January 1992 and 1 February 2016. Based on the inclusion criteria and methodological quality, 34 studies were selected, reporting a total sample of 1,869 participants. The results showed that the provision of information, contact and interaction with staff, and adequate communication with professionals are factors that influence the subjective experience of these measures. Humane treatment, respect, and staff support are also associated with a better experience, and debriefing is an important procedure/technique to reduce the emotional impact of these measures. Likewise, the quality of the working and physical environment and some individual and treatment variables were related to the experience of these measures. There are different results in relation to the most frequently associated experiences and, despite some data that indicate positive experiences, the evidence shows such experiences to be predominantly negative and frequently with adverse consequences. It seems that patients find forced medication and seclusion to be more tolerable than mechanical restraint and combined measures. It appears that the role of the staff and the environmental conditions, which are potentially modifiable, affect the subjective experience of these measures. There was considerable heterogeneity among studies in terms of coercive measures experienced by participants and study designs.

Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

PubMed

Linge, Annett; Schötz, Ulrike; Löck, Steffen; Lohaus, Fabian; von Neubeck, Cläre; Gudziol, Volker; Nowak, Alexander; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Lauber, Kirsten; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Krause, Mechthild; Belka, Claus; Baumann, Michael

2018-04-01

To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

A combination of immunohistochemistry and molecular approaches improves highly sensitive detection of BRAF mutations in papillary thyroid cancer.

PubMed

Martinuzzi, Claudia; Pastorino, Lorenza; Andreotti, Virginia; Garuti, Anna; Minuto, Michele; Fiocca, Roberto; Bianchi-Scarrà, Giovanna; Ghiorzo, Paola; Grillo, Federica; Mastracci, Luca

2016-09-01

The optimal method for BRAF mutation detection remains to be determined despite advances in molecular detection techniques. The aim of this study was to compare, against classical Sanger sequencing, the diagnostic performance of two of the most recently developed, highly sensitive methods: BRAF V600E immunohistochemistry (IHC) and peptide nucleic-acid (PNA)-clamp qPCR. BRAF exon 15 mutations were searched in formalin-fixed paraffin-embedded tissues from 86 papillary thyroid carcinoma using the three methods. The limits of detection of Sanger sequencing in borderline or discordant cases were quantified by next generation sequencing. BRAF mutations were found in 74.4 % of cases by PNA, in 71 % of cases by IHC, and in 64 % of cases by Sanger sequencing. Complete concordance for the three methods was observed in 80 % of samples. Better concordance was observed with the combination of two methods, particularly PNA and IHC (59/64) (92 %), while the combination of PNA and Sanger was concordant in 55 cases (86 %). Sensitivity of the three methods was 99 % for PNA, 94.2 % for IHC, and 89.5 % for Sanger. Our data show that IHC could be used as a cost-effective, first-line method for BRAF V600E detection in daily practice, followed by PNA analysis in negative or uninterpretable cases, as the most efficient method. PNA-clamp quantitative PCR is highly sensitive and complementary to IHC as it also recognizes other mutations besides V600E and it is suitable for diagnostic purposes.

Microstructure evolution and coercivity enhancement in Nd-Fe-B thin films diffusion-processed by R-Al alloys (R=Nd, Pr)

NASA Astrophysics Data System (ADS)

Xie, Yigao; Yang, Yang; Zhang, Tongbo; Fu, Yanqing; Jiang, Qingzheng; Ma, Shengcan; Zhong, Zhenchen; Cui, Weibin; Wang, Qiang

2018-05-01

Diffusion process by Nd-Al and Pr-Al alloys was compared and investigated in Nd-Fe-B thin films. Enhanced coercivity 2.06T and good squareness was obtained by using Pr85Al15 and Nd85Al15 alloys as diffusion sources. But the coercivity of diffusion-processed thin films by Pr70Al30 and Pr55Al45 alloys decreased to 2.04T and 1.82T. High ambient coercivity of 2.26T was achieved in diffusion-processed thin film by Nd70Al30 leading to an improved coercivity thermal stability because Nd2Fe14B grains were enveloped by Nd-rich phase as seen by transmission electron microscopy Nd-loss image. Meanwhile, microstructure-dependent parameters α and Neff were improved. However, high content of Al in diffusion-processed thin film by Nd55Al45 lead to degraded texture and coercivity.

Beneficial Use Of Contaminated Sediment

EPA Science Inventory

The western portion of the Lake George Branch of the Indian Harbor Canal (IHC) is no longer used for commercial purposes, but contains petroleum contaminated sediments. The IHC is considered an important habitat for many animal species. Several future development projects have ...

Sexual experiences in childhood: young adults' recollections.

PubMed

Larsson, IngBeth; Svedin, Carl-Göran

2002-06-01

Childhood sexuality and children's sexual experiences have become increasingly important to study because our knowledge on the impact of sexually abusive experiences on children's developing sexuality has increased. The main aim of this paper was to study aspects of young adults' recollections of their sexual experiences before the age of 13, solitary and shared, mutual as well as coercive. Anonymous questionnaires were answered by 269 final year, senior high-school students, mean age 18.6 years; 82.9% of the students reported solitary sexual experiences and 82.5% had mutual experiences together with another child. Most of the children had their experiences together with a same-age friend. Girls had more same-sex experiences than boys did. Thirteen percent reported coercive experiences where they had been tricked, bribed, threatened, or physically forced into participation. Some children, 8.2%, had coerced another child into participation in sexual activities. The majority thought of their childhood experiences as normal. There were also 6.3% of the respondents who had had inappropriate sexual experiences with someone at least 5 years older, the majority being girls. Gender differences were evident in several respects: girls were more often coerced, they felt more guilt, and they had far less experience of masturbation, whereas boys were somewhat more active in explorative activities on their own as well as with peers. Some kind of coercive sexual experiences appears to be part of growing up for quite a few children, although in general the years before puberty seem to be years of frequent mutual sexual exploration and experimentation.

Annealing induced low coercivity, nanocrystalline Co-Fe-Si thin films exhibiting inverse cosine angular variation

NASA Astrophysics Data System (ADS)

Hysen, T.; Al-Harthi, Salim; Al-Omari, I. A.; Geetha, P.; Lisha, R.; Ramanujan, R. V.; Sakthikumar, D.; Anantharaman, M. R.

2013-09-01

Co-Fe-Si based films exhibit high magnetic moments and are highly sought after for applications like soft under layers in perpendicular recording media to magneto-electro-mechanical sensor applications. In this work the effect of annealing on structural, morphological and magnetic properties of Co-Fe-Si thin films was investigated. Compositional analysis using X-ray photoelectron spectroscopy and secondary ion mass spectroscopy revealed a native oxide surface layer consisting of oxides of Co, Fe and Si on the surface. The morphology of the as deposited films shows mound like structures conforming to the Volmer-Weber growth model. Nanocrystallisation of amorphous films upon annealing was observed by glancing angle X-ray diffraction and transmission electron microscopy. The evolution of magnetic properties with annealing is explained using the Herzer model. Vibrating sample magnetometry measurements carried out at various angles from 0° to 90° to the applied magnetic field were employed to study the angular variation of coercivity. The angular variation fits the modified Kondorsky model. Interestingly, the coercivity evolution with annealing deduced from magneto-optical Kerr effect studies indicates a reverse trend compared to magetisation observed in the bulk. This can be attributed to a domain wall pinning at native oxide layer on the surface of thin films. The evolution of surface magnetic properties is correlated with morphology evolution probed using atomic force microscopy. The morphology as well as the presence of the native oxide layer dictates the surface magnetic properties and this is corroborated by the apparent difference in the bulk and surface magnetic properties.

Magnetic properties and magnetic hardening mechansim of Pt-Co-B alloys

NASA Technical Reports Server (NTRS)

Qiu, Ning; Flanagan, F.; Wittig, James E.

1994-01-01

The intrinsic coercivity is found to be maximized in the Pt42Co45B13 ternary alloy which is undercooled and rapidly solidified (quenched using a 70 m/s wheel speed after undercooling), and then annealed (800 C for 2400 min). The same alloy, processed at slower cooling rates and annealed in the same way, has a much larger scale microstructure and a much lower resulting magnetic coercivity. The microstructure which would optimize the coercitvity of this coercivity of this ternary alloy is a completely ordered L1(sub zero) Pt-Co matrix with a submicron magnetic single-domion Co-boride precipitate. The L1(sub zero) phase is highly anistropic magnetically while the Co-boride precipate is somewhat less so. Annealing treatments designed to produced single-domain Co-boride precipitates enhance the coercivity. This suggests that the refined microstructures is responsible for the high coercivities found in the rapidly solidified and annealed alloy. The magnetic domain wall thickness for a Co-boride precipitate is determined from both experimental observation and theoretical calculation in order to evaluate its influence on the coercivity of the alloy. The effects of the pinning of domain walls and the barrier to the nucleation of reverse domains on the coercivity are discussed. Both microstrucutral analysis and theoretical calculation indicate that the high coercivities in the Pt42Co45B13 alloy are due to the difficult nucleation of reverse magnetic domains.

Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis.

PubMed

Colling, Richard; Church, David N; Carmichael, Juliet; Murphy, Lucinda; East, James; Risby, Peter; Kerr, Rachel; Chetty, Runjan; Wang, Lai Mun

2015-12-01

Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is caused by germline mutations in mismatch repair (MMR) genes. Recently, screening strategies to identify patients with LS have become popular. We audited CRCs screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC performed at a cost of £12 540. 47/209 (21%) cases showed IHC loss of expression in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF V600E testing, at a cost of £5040. MMR IHC reduced the number of potential clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a subset of cases with MLH1 loss, further reduced this to 21. At a cost of £1340 per referral, this model of LS screening for clinical genetics referral had significant potential savings (£234 340) and can be easily implemented in parallel with MMR IHC done for prognostication in CRCs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Correlation between HER2 gene amplification and protein overexpression through fluorescence in situ hybridization and immunohistochemistry in breast carcinoma patients.

PubMed

Makroo, R N; Chowdhry, Mohit; Kumar, Manoj; Srivastava, Priyanka; Tyagi, Richa; Bhadauria, Preeti; Kaul, Sumaid; Sarin, Ramesh; Das, P K; Dua, Harsh

2012-01-01

In India, the incidence of breast cancer has increased in the urban population, with 1 in every 22 women diagnosed with breast cancer. It is important to know the HER2/neu gene status for a better prognostication of these patients. The aim of this study was to compare the efficacy of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for determining HER2/neu alteration in breast carcinoma. A total of 188 histologically proven breast carcinoma cases between the years 2007 and 2011 were retrospectively analyzed on the paraffin tissue sections by both IHC and FISH techniques. FISH for HER2/neu gene amplification was performed on cases where the IHC status was already known and the results were compared. A total of 64 (30%) patients were found to be amplified and the remaining 124 (65.9%) cases were found to be unamplified through FISH. Patients observed with 3+ reading on IHC were later confirmed as unamplified in 29.5% cases through FISH. It has been confirmed with the present study that IHC is a prudent first-step technique to screen tissue samples for HER2/neu gene status, but should be supplemented with the FISH technique especially in equivocal cases.

Diagnostic sensitivity and specificity of in situ hybridization and immunohistochemistry for Eastern equine encephalitis virus and West Nile virus in formalin-fixed, paraffin-embedded brain tissue of horses.

PubMed

Pennick, Kate E; McKnight, Christy A; Patterson, Jon S; Latimer, Kenneth S; Maes, Roger K; Wise, Annabel G; Kiupel, Matti

2012-03-01

Immunohistochemistry (IHC) and in situ hybridization (ISH) can be used either to detect or to differentiate between Eastern equine encephalitis virus (EEEV) and West Nile virus (WNV) within formalin-fixed, paraffin-embedded (FFPE) brain tissue of horses. To compare the diagnostic sensitivity and specificity of ISH and IHC, FFPE brain tissue from 20 EEEV-positive horses and 16 WNV-positive horses were tested with both EEEV and WNV oligoprobes and EEEV- and WNV-specific antibodies. Reverse transcription polymerase chain reaction (RT-PCR) for detection of EEEV and WNV was used as the gold standard to confirm infection. All horses that tested positive for EEEV by RT-PCR also tested positive by IHC and ISH, except for 1 case that was false-negative by ISH. In contrast, all horses that tested positive for WNV by RT-PCR tested negative by IHC and only 2 horses tested positive by ISH. No false-positives were detected with either method for both viruses. Both IHC and ISH are highly specific and sensitive diagnostic methods to detect EEEV in equine FFPE brain tissues, although neither appear effective for the diagnosis of WNV in equine neurologic cases.

Magnetic and structural properties of CoFe 2O 4 thin films synthesized via a sol-gel process

NASA Astrophysics Data System (ADS)

dos S. Duque, J. G.; Macêdo, M. A.; Moreno, N. O.; Lopez, J. L.; Pfanes, H.-D.

2001-05-01

Using a sol-gel process having the coconut water as a precursor of organic chain, we synthesized thin films of cobalt ferrite. The films were characterized by using a SQUID magnetometer, an X-ray diffractometer, an X-ray spectrophotometer, Mössbauer spectroscopy and atomic force microscope. Co ferrite films annealed at 500°C for 2 h show grain sizes between 10 and 20 nm, grown as single-phase spinel structure and exhibit high coercivity and a moderate saturation magnetization (above 30 kOe).

[Associations of short-term evaluation assessments and patient characteristics with the use of coercive measures].

PubMed

Vermeulen, R C; Nijman, H L I; van de Sande, R; Lohuis-Heesink, H A G M

Dutch mental health care institutes are currently making a tremendous effort to reduce the number of coercive measures they impose, such as seclusion. Despite this effort, a group of patients are still being subjected to enforced medication or seclusion. To obtain more knowledge about which patient characteristics are associated with coercive measures and thereby to identify signs that could be acted upon at an earlier stage to prevent deterioration of the patient's condition and reduce the need for coercive measures. We performed a prospective, naturalistic three-month study involving patients in two acute psychiatric admission wards. To collect the data we required, we used two short-term risk-assessment instruments: the Brøset Violence Checklist (BVC) and the Kennedy Axis V (KA-V). By means of statistical analyses we investigated which patient characteristics were associated with the use of coercive measures. Of the 179 patients, 52 patients (29%) were subjected to a coercive measure during the admission procedure. The following patient characteristics were found to be associated with coercive measures: a bipolar disorder, involuntarily admission, display of physical violence just before admission, scores on the BVC and the KA-V items assessing 'social skills' and 'violence'. The two BVC items 'attacks on objects' and 'display of physical violence just before admission' were the ones most strongly associated with seclusion. Although the sensitivity of the regression model was modest, the associated patient characteristics, combined with the two short-term risk assessment scores, may be helpful for identifying at an early stage those patients who run a high risk of being subjected to coercive measures.

Structure and magnetic properties of low-temperature phase Mn-Bi nanosheets with ultra-high coercivity and significant anisotropy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Rongming, E-mail: rmliu@iphy.ac.cn, E-mail: shenbg@iphy.ac.cn; Zhang, Ming; Niu, E

2014-05-07

The microstructure, crystal structure, and magnetic properties of low-temperature phase (LTP) Mn-Bi nanosheets, prepared by surfactant assistant high-energy ball milling (SA-HEBM) with oleylamine and oleic acid as the surfactant, were examined with scanning electron microscopy, X-ray diffraction, and vibrating sample magnetometer, respectively. Effect of ball-milling time on the coercivity of LTP Mn-Bi nanosheets was systematically investigated. Results show that the high energy ball milling time from tens of minutes to several hours results in the coercivity increase of Mn-Bi powders and peak values of 14.3 kOe around 10 h. LTP Mn-Bi nanosheets are characterized by an average thickness of tensmore » of nanometers, an average diameter of ∼1.5 μm, and possess a relatively large aspect ratio, an ultra-high room temperature coercivity of 22.3 kOe, a significant geometrical and magnetic anisotropy, and a strong (00l) crystal texture. Magnetization and demagnetization behaviors reveal that wall pinning is the dominant coercivity mechanism in these LTP Mn-Bi nanosheets. The ultrafine grain refinement introduced by the SA-HEBM process contribute to the ultra-high coercivity of LTP Mn-Bi nanosheets and a large number of defects put a powerful pinning effect on the magnetic domain movement, simultaneously. Further magnetic measurement at 437 K shows that a high coercivity of 17.8 kOe and a strong positive temperature coefficient of coercivity existed in the bonded permanent magnet made by LTP Mn-Bi nanosheets.« less

Quality of Life and its Determinants in a Multi-Center Cohort of Children with Alagille Syndrome

PubMed Central

Kamath, Binita M.; Chen, Zhen; Romero, Rene; Fredericks, Emily M.; Alonso, Estella M.; Arnon, Ronen; Heubi, James; Hertel, Paula M.; Karpen, Saul J.; Loomes, Kathleen M.; Murray, Karen F.; Rosenthal, Philip; Schwarz, Kathleen B.; Subbarao, Girish; Teckman, Jeffrey H.; Turmelle, Yumirle P.; Wang, Kasper S.; Sherker, Averell H.; Sokol, Ronald J.; Magee, John C.

2015-01-01

Objectives To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS. Study design Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory™ (PedsQL) questionnaires were administered to 70 ALGS, 95 alpha-1-antitrypsin deficiency (A1ATD) and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent-proxy PedsQL scores were recorded for children aged 2-18 (98 ALGS, 123 A1ATD, 68 IHC). Results Mean ages and total bilirubin (mg/dL) were: ALGS 9.4y; 4.4, A1ATD 9.5y; 0.7, IHC 10.3y; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs. 83 p=0.001). Children with ALGS and IHC were similar, except in physical scores (73 vs. 79 p=0.05). ALGS parents perceived their children to have worse HRQOL than A1ATD (p<=0.001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated INR and an intra-cardiac defect were predictive of poor parental scores (p<=0.05). In multivariate analysis, only weight z-score remained significant for child and parent-reported scores. Conclusions HRQOL is impaired in ALGS compared with healthy and children with A1ATD, similar to IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL. PMID:26059338

Evaluating the Minimal Specimens From Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Pancreatic Masses

PubMed Central

Park, Joo Kyung; Kang, Ki Joo; Oh, Cho Rong; Lee, Jong Kyun; Lee, Kyu Taek; Jang, Kee Taek; Park, Sang-Mo; Lee, Kwang Hyuck

2016-01-01

Abstract Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become one of the most useful diagnostic modalities for the diagnosis of pancreatic mass. The aim of this study was to investigate the role of analyzing the minimal specimens obtained by EUS-FNA for the diagnosis of solid masses of pancreas. This study consisted of retrospective and prospective analyses. The retrospective study was performed on 116 patients who underwent EUS-FNA of solid masses for cytological smear, histological analysis, and combined analysis including immunohistochemical (IHC) staining. In the prospective study, 79 patients were enrolled to evaluate the quality and accuracy of EUS-FNA histological analysis and feasibility of IHC staining. The final diagnoses of all patients included pancreatic cancer (n = 126), nonpancreatic cancer (n = 21), other neoplasm (n = 27), and benign lesions (n = 21). In our retrospective study, the combined analysis was more sensitive than cytological analysis alone (P < 0.01). The overall sensitivity of cytology, histology, and combined analysis was 69.8%, 67.2%, and 81.8%, respectively. In the prospective analysis, 64.2% of all punctures were helpful for determining the diagnosis and 40.7% provided sufficient tissue for IHC staining. Histological analysis was helpful for diagnosis in 74.7% of patients. IHC staining was necessary for a definite diagnosis in 11.4% of patients, especially in the cases of nonmalignant pancreatic mass. Histological analysis and IHC study of EUS-FNA specimens was useful for the accurate diagnosis of pancreatic and peripancreatic lesions. Combined analysis showed significantly higher sensitivity than cytology alone because IHC staining was helpful for a diagnosis in some patients. PMID:27227937

Molecular analysis of HER2 signaling in human breast cancer by functional protein pathway activation mapping

PubMed Central

Wulfkuhle, Julia D.; Berg, Daniela; Wolff, Claudia; Langer, Rupert; Tran, Kai; Illi, Julie; Espina, Virginia; Pierobon, Mariaelena; Deng, Jianghong; DeMichele, Angela; Walch, Axel; Bronger, Holger; Becker, Ingrid; Waldhör, Christine; Höfler, Heinz; Esserman, Laura; Liotta, Lance A.; Becker, Karl-Friedrich; Petricoin, Emanuel F.

2017-01-01

Purpose Targeting of the HER2 protein in human breast cancer represents a major advance in oncology, but relies on measurements of total HER2 protein and not HER2 signaling network activation. We utilized reverse phase protein microarrays (RPMAs) to measure total and phosphorylated HER2 in the context of HER family signaling to understand correlations between phosphorylated and total levels of HER2 and downstream signaling activity. Experimental Design Three independent study sets, comprising a total of 415 individual patient samples from flash frozen core biopsy samples and FFPE surgical and core samples, were analyzed via RPMA. The phosphorylation and total levels of the HER receptor family proteins and downstream signaling molecules were measured in laser capture microdissected (LCM) enriched tumor epithelium from 127 frozen pre-treatment core biopsy samples and whole tissue lysates from 288 FFPE samples and these results were compared to FISH and IHC. Results RPMA measurements of total HER2 were highly concordant (> 90% all sets) with FISH and/or IHC data, as was phosphorylation of HER2 in the FISH/IHC+ population. Phosphorylation analysis of HER family signaling identified HER2 activation in some FISH/IHC- tumors and, identical to that seen with FISH/IHC+ tumors, the HER2 activation was concordant with EGFR and HER3 phosphorylation and downstream signaling endpoint activation. Conclusions Molecular profiling of HER2 signaling of a large cohort of human breast cancer specimens using a quantitative and sensitive functional pathway activation mapping technique reveals IHC-/FISH-/pHER2+ tumors with HER2 pathway activation independent of total HER2 levels and functional signaling through HER3 and EGFR. PMID:23045247

Immunohistochemical detection of the BRAF V600E mutation in papillary thyroid carcinoma. Evaluation against real-time polymerase chain reaction.

PubMed

Paja Fano, Miguel; Ugalde Olano, Aitziber; Fuertes Thomas, Elena; Oleaga Alday, Amelia

2017-02-01

The BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma and is associated with a poorer clinical course. Usual methods for its study (DNA sequencing or molecular test based on PCR) are expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation has been introduced. To compare the results of IHC and real time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid carcinoma. Analysis of clinical and pathological differences depending on RT-PCR results is included. A prospective study was performed in 82 consecutive samples, 54 of them taken through a core needle biopsy. IHC was performed on tissue fixed for 24hours with 10% neutral formalin using the anti-BRAF V600E (VE-1) mouse monoclonal primary antibody and was rated as positive or negative. DNA was extracted from formalin-fixed, paraffin-embedded tissues by manual microdissection, and BRAF mutation was detected by RT-PCR using the Cobas® 4800 BRAF V600 mutation test (Roche). Both techniques were concordant in 81 cases, and BRAF was positive in 49. Discordance appeared in a follicular variant showing positive IHC and negative RT-PCR, attributed to histological heterogeneity. Cost of materials for IHC was less than half of the cost for RT-PCR. IHC appears to be a reliable, economical and easily available alternative to molecular biology techniques for routine detection of the BRAF V600E mutation in papillary thyroid carcinoma patients, provided optimal fixation conditions are used. It may be a useful technique in hospitals with no access to molecular biology techniques. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized

PubMed Central

Pickett, Justine L.; Chou, Angela; Andrici, Juliana A.; Clarkson, Adele; Sioson, Loretta; Sheen, Amy; Reagh, Jessica; Najdawi, Fedaa; Kim, Yoomee; Riley, Denise; Maidens, Jayne; Nevell, David; McIlroy, Kirsten; Valmadre, Susan; Gard, Greg; Hogg, Russell; Turchini, John; Robertson, Gregory; Friedlander, Michael

2017-01-01

Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) “leiomyomas” and 1 of 44 (2.3%) “leiomyosarcomas” were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT. On review significant areas of all 4 tumors closely mimicked smooth muscle tumors morphologically, but all showed at least subtle/focal features suggesting IMT. Recognizing that the distinction between IMT and leiomyoma/leiomyosarcoma can be subtle, we then reviewed 1 hematoxylin and eosin slide from each patient undergoing surgery for “leiomyoma” from 2014 to 2017 and selected cases for ALK IHC with a low threshold. Of these, 30 of 571 (5.3%) underwent IHC. Two were confirmed to be IHC positive and FISH rearranged. Of the 6 IMTs, only 1 tumor with a previous diagnosis of leiomyosarcoma, an infiltrative margin and equivocal necrosis, metastasized. Of note it demonstrated a less aggressive clinical course compared with most metastatic leiomyosarcomas (alive with disease at 6 y). The patient was subsequently offered crizotinib to which she responded rapidly. In conclusion, IMTs may closely mimic gynecologic smooth muscle tumors. IMTs account for at least 5 of 1747 (0.3%) tumors previously diagnosed as leiomyoma and 1 of 44 (2.3%) as leiomyosarcoma. These tumors may be recognized prospectively with awareness of subtle/focal histologic clues, coupled with a low threshold for ALK IHC. PMID:28731868

Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry.

PubMed

Dufresne, Martin; Guneysu, Daniel; Patterson, Nathan Heath; Marcinkiewicz, Mieczyslaw Martin; Regina, Anthony; Demeule, Michel; Chaurand, Pierre

2017-02-01

Mucopolysaccharidosis type II (Hunter's disease) mouse model (IdS-KO) was investigated by both imaging mass spectrometry (IMS) and immunohistochemistry (IHC) performed on the same tissue sections. For this purpose, IdS-KO mice brain sections were coated with sublimated 1,5-diaminonaphtalene and analyzed by high spatial resolution IMS (5 μm) and anti-GM3 IHC on the same tissue sections to characterize the ganglioside monosialated ganglioside (GM) deposits found in Hunter's disease. IMS analysis have found that two species of GM3 and GM2 that are only different due to the length of their fatty acid residue (stearic or arachidic residue) were overexpressed in the IdS-KO mice compared to a control mouse. GM3 and GM2 were characterized by on-tissue exact mass and MS/MS compared to a GM3 standard. Realignment of both IMS and IHC data sets further confirmed the observed regioselective signal previously detected by providing direct correlation of the IMS image for the two GM3 overly expressed MS signals with the anti-GM3 IHC image. Furthermore, these regioselective GM MS signals were also found to have highly heterogeneous distributions within the GM3-IHC staining. Some deposits showed high content in GM3 and GM2 stearic species (r = 0.74) and others had more abundant GM3 and GM2 arachidic species (r = 0.76). Same-section analysis of Hunter's disease mouse model by both high spatial resolution IMS and IHC provides a more in-depth analysis of the composition of the GM aggregates while providing spatial distribution of the observed molecular species. Graphical Abstract Ganglioside imaging mass spectrometry followed by immunohistochemistry performed on the same tissue section.

Screening for ROS1 gene rearrangements in non-small cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target

PubMed Central

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Yee; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija RJ; O’Toole, Sandra A; Cooper, Wendy A

2016-01-01

Aims To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. Methods A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective NSCLC cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in situ hybridisation (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Results Eighty eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining of which 12 (12%) cases were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wildtype and ALK rearrangement negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. Conclusions ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK positive cases and use of IHC to screen for potentially positive cases can be used to enrich for the likelihood of a identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time consuming FISH testing in all cases. PMID:27599111

Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target.

PubMed

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Y; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija R J; O'Toole, Sandra A; Cooper, Wendy A

2017-02-01

To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective non-small-cell lung cancer (NSCLC) cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in-situ hybridization (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Eighty-eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining, 12 (12%) cases of which were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wild-type and anaplastic lymphoma kinase (ALK) rearrangement-negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK-positive cases and use of IHC to screen for potentially positive cases, can be used to enrich for the likelihood of identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time-consuming FISH testing in all cases. © 2016 John Wiley & Sons Ltd.

ALK rearrangement in a large series of consecutive non-small cell lung cancers: comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment.

PubMed

Alì, Greta; Proietti, Agnese; Pelliccioni, Serena; Niccoli, Cristina; Lupi, Cristiana; Sensi, Elisa; Giannini, Riccardo; Borrelli, Nicla; Menghi, Maura; Chella, Antonio; Ribechini, Alessandro; Cappuzzo, Federico; Melfi, Franca; Lucchi, Marco; Mussi, Alfredo; Fontanini, Gabriella

2014-11-01

Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application. To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC. We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK(+) by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK(+) cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis.

HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: Implication for further clinical research.

PubMed

Pietrantonio, F; Caporale, M; Morano, F; Scartozzi, M; Gloghini, A; De Vita, F; Giommoni, E; Fornaro, L; Aprile, G; Melisi, D; Berenato, R; Mennitto, A; Volpi, C C; Laterza, M M; Pusceddu, V; Antonuzzo, L; Vasile, E; Ongaro, E; Simionato, F; de Braud, F; Torri, V; Di Bartolomeo, M

2016-12-15

Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score <3+ and absence of ISH amplification, and IHC "downscoring" from 2+/3+ to 0/1+, respectively. HER2 IHC was always performed, while ISH was missing in 3 post-progression samples. Patients with initial HER2 IHC score 3+ and 2+ were 14 (64%) and 8 (36%), respectively. Loss of HER2 positivity and HER2 over-expression was observed in 32 and 32% samples, respectively. The chance of HER2 loss was not associated with any of the baseline clinicopathological variables. The only exception was in patients with initial IHC score 2+ versus 3+, for both endpoints of HER2 positivity (80 vs. 14%; p = 0.008) and HER2 over-expression (63 vs. 14%; p = 0.025). As already shown in breast cancer, loss of HER2 may be observed also in gastric cancers patients treated with trastuzumab-based chemotherapy in the clinical practice. This phenomenon may be one of the biological reasons explaining the failure of anti-HER2 second-line strategies in initially HER2-positive disease. © 2016 UICC.

Histopathological and immunohistochemical approaches for the diagnosis of Pasteurellosis in swine population of Punjab.

PubMed

Bhat, Payal; Singh, Nittin Dev; Leishangthem, Geeta Devi; Kaur, Amninder; Mahajan, Vishal; Banga, Harmanjit Singh; Brar, Rajinder Singh

2016-09-01

Infectious porcine bronchopneumonia, caused by Pasteurella multocida , is a widespread disease of major economic significance. Thus, the aim of the present study was to diagnose swine Pasteurellosis using gross, histopathological, and immunopathological approaches in the swine population of Punjab and to compare the efficacy of immunohistochemical (IHC) techniques with conventional diagnostic techniques. A total of 71 adult swine lung samples showing gross pneumonic changes were collected along with the associated lymph nodes to carry out the study. The collected samples were then processed for histopathological and IHC studies. Out of the total 71 lung samples, 26 samples were found to be suspected for Pasteurellosis as per the microscopic changes observed, and out of these 26 samples, 16 cases were confirmed to be positive for Pasteurellosis by IHC. Varied macroscopic changes noted in lungs were pneumonic patches with consolidation of many lobes, congestion, and focal hemorrhages. Main lesions associated with lymph nodes were its enlargement and hemorrhages. Histologically, the lung showed fibrinous and suppurative bronchopneumonia, multifocal suppuration, thickening of septa with fibrin combined with cellular infiltration and edema. The higher IHC expression of P. multocida was seen in the bronchial epithelium besides in alveolar and bronchial exudate. Moreover, on comparing the histopathological and IHC scores which were calculated on the basis of characteristic microscopic lesions and number of antigen positive cells, respectively, a significant positive correlation (r=0.4234) was found. It was concluded that swine population of Punjab is having P. multocida infection. The gross and histopathological lesions can be helpful in the preliminary diagnosis of Pasteurellosis but needs to be supplemented by other immunodiagnostic tests. Moreover, IHC technique proved to be a specific, reliable, precise, and rapid technique to supplement these conventional methods of diagnosis for Pasteurellosis.

Somatostatin receptor immunohistochemistry in neuroendocrine tumors: comparison between manual and automated evaluation

PubMed Central

Daniel, Kaemmerer; Maria, Athelogou; Amelie, Lupp; Isabell, Lenhardt; Stefan, Schulz; Luisa, Peter; Merten, Hommann; Vikas, Prasad; Gerd, Binnig; Paul, Baum Richard

2014-01-01

Background: Manual evaluation of somatostatin receptor (SSTR) immunohistochemistry (IHC) is a time-consuming and cost-intensive procedure. Aim of the study was to compare manual evaluation of SSTR subtype IHC to an automated software-based analysis, and to in-vivo imaging by SSTR-based PET/CT. Methods: We examined 25 gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and correlated their in-vivo SSTR-PET/CT data (determined by the standardized uptake values SUVmax,-mean) with the corresponding ex-vivo IHC data of SSTR subtype (1, 2A, 4, 5) expression. Exactly the same lesions were imaged by PET/CT, resected and analyzed by IHC in each patient. After manual evaluation, the IHC slides were digitized and automatically evaluated for SSTR expression by Definiens XD software. A virtual IHC score “BB1” was created for comparing the manual and automated analysis of SSTR expression. Results: BB1 showed a significant correlation with the corresponding conventionally determined Her2/neu score of the SSTR-subtypes 2A (rs: 0.57), 4 (rs: 0.44) and 5 (rs: 0.43). BB1 of SSTR2A also significantly correlated with the SUVmax (rs: 0.41) and the SUVmean (rs: 0.50). Likewise, a significant correlation was seen between the conventionally evaluated SSTR2A status and the SUVmax (rs: 0.42) and SUVmean (rs: 0.62).Conclusion: Our data demonstrate that the evaluation of the SSTR status by automated analysis (BB1 score), using digitized histopathology slides (“virtual microscopy”), corresponds well with the SSTR2A, 4 and 5 expression as determined by conventional manual histopathology. The BB1 score also exhibited a significant association to the SSTR-PET/CT data in accordance with the high affinity profile of the SSTR analogues used for imaging. PMID:25197368

Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens.

PubMed

Sauter, Jennifer L; Grogg, Karen L; Vrana, Julie A; Law, Mark E; Halvorson, Jennifer L; Henry, Michael R

2016-02-01

The objective of the current study was to establish a process for validating immunohistochemistry (IHC) protocols for use on the Cellient cell block (CCB) system. Thirty antibodies were initially tested on CCBs using IHC protocols previously validated on formalin-fixed, paraffin-embedded tissue (FFPE). Cytology samples were split to generate thrombin cell blocks (TCB) and CCBs. IHC was performed in parallel. Antibody immunoreactivity was scored, and concordance or discordance in immunoreactivity between the TCBs and CCBs for each sample was determined. Criteria for validation of an antibody were defined as concordant staining in expected positive and negative cells, in at least 5 samples each, and concordance in at least 90% of the samples total. Antibodies that failed initial validation were retested after alterations in IHC conditions. Thirteen of the 30 antibodies (43%) did not meet initial validation criteria. Of those, 8 antibodies (calretinin, clusters of differentiation [CD] 3, CD20, CDX2, cytokeratin 20, estrogen receptor, MOC-31, and p16) were optimized for CCBs and subsequently validated. Despite several alterations in conditions, 3 antibodies (Ber-EP4, D2-40, and paired box gene 8 [PAX8]) were not successfully validated. Nearly one-half of the antibodies tested in the current study failed initial validation using IHC conditions that were established in the study laboratory for FFPE material. Although some antibodies subsequently met validation criteria after optimization of conditions, a few continued to demonstrate inadequate immunoreactivity. These findings emphasize the importance of validating IHC protocols for methanol-fixed tissue before clinical use and suggest that optimization for alcohol fixation may be needed to obtain adequate immunoreactivity on CCBs. © 2016 American Cancer Society.

Coercivity enhancement of Dy-coated Nd-Fe-B flakes by crystallization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukunaga, H.; Sugimoto, Y.; Nakano, M.

2011-04-01

The coercivity of isotropic Dy-coated Nd-Fe-B flakes was enhanced by crystallization and simultaneous diffusion of Dy from their surfaces. Amorphous Dy-coated Nd-Fe-B flakes were crystallized by heating them to 923 K 2over a 2 min period followed by rapid cooling. During crystallization, the Dy on the surface diffused into the flakes. This low-temperature rapid annealing produced flakes with fine grains and the Dy diffusion enhanced their coercivity. The coercivity after crystallization increased with increasing Dy layer thickness, although the remanence decreased when the layer thickness exceeded 3 {mu}m. Thick coatings of over 6 {mu}m resulted in the formation of DyFe{submore » 2}, which degraded the magnetic properties of the crystallized flakes. Flakes with a 3-{mu}m-thick coating exhibited excellent magnetic properties after annealing: They had a coercivity of 1880 kA/m and a remanence of 78 emu/g. This coercivity is approximately 500 kA/m higher than that of uncoated flakes, whereas the remanence is comparable to that of uncoated flakes.« less

Effects of microstructures on the performance of rare-earth-free MnBi magnetic materials and magnets

NASA Astrophysics Data System (ADS)

Nguyen, Vuong Van; Nguyen, Truong Xuan

2018-03-01

Since the solidification of MnBi alloys is peritectic, their microstructures always consist of the starting phases of Mn and Bi and the productive phase MnBi. The high performance of MnBi bulk magnets requires appropriate routes of preparing MnBi powders of high spontaneous magnetization Ms and large coercivity iHc as well a route of producing bulk magnets thereof. In these routes, the microstructures of arc-melted alloys, annealed alloys and magnets strongly related to the quality of powders and the performance of magnets. The paper proves that: i) The microstructure of fine Mn-inclusions embedded in the matrix of Bi is preferred for arc-melted alloys to realize the rapid evolution of the ferromagnetic phase inside them during their sequent annealing process; ii) The time-controlled annealing process plays a key role in controlling the microstructure with the main ferromagnetic phase matrix, in which the rest of Mn and the Bi accumulations are embedded; iii) The cold (in-liquid-nitrogen) ball milling annealed alloys is required for preparing a high quality powders with the preferred sub-micrometer microstructure without a Bi-decomposition; iv) The short-time warm compaction is crucial to fabricate dense, highly textured bulk magnets with the micrometer microstructure. The realization and control of these preferred microstructures figured in these routes enhance the chance of preparing MnBi bulk magnets with the energy product (BH)max larger than 8 MGOe.

Relationships Between Shame, Restrictiveness, Authoritativeness, and Coercive Control in Men Mandated to a Domestic Violence Offenders Program.

PubMed

Kaplenko, Hannah; Loveland, Jennifer E; Raghavan, Chitra

2018-04-01

Coercive control, a key element of intimate partner violence (IPV), is defined as an abuse dynamic that intends to strip the target of autonomy and liberty. While coercive control is gaining popularity in the research world, little is known about its correlates and causes. This study sought to examine how shame and men's need for dominance, measured by two trait indexes of dominance, restrictiveness and the need for authority, influence coercive control. The present study used a diverse sample of men (n = 134) who were mandated to attend a domestic violence offenders program. Findings suggest that shame plays a role in the commission of coercively controlling behavior both directly and partially through its influence on authority but not through restrictiveness. Implications for understanding IPV in a domestic violence offenders program are discussed.

Ventana immunohistochemistry ALK (D5F3) detection of ALK expression in pleural effusion samples of lung adenocarcinoma.

PubMed

Wang, Zheng; Wu, Xiaonan; Shi, Yuankai; Han, Xiaohong; Cheng, Gang; Cui, Di; Li, Lin; Zhang, Yuhui; Mu, Xinlin; Zhang, Li; Yang, Li; Di, Jing; Yu, Qi; Liu, Dongge

2015-08-01

To evaluate the Ventana IHC ALK (D5F3) assay for detecting anaplastic lymphoma kinase (ALK) protein expression in pleural effusion samples. Historical, selected (wild-type EGFR, K-RAS) pleural effusion cytologic blocks of lung adenocarcinoma samples (Study 1) and unselected lung adenocarcinoma pleural effusion cytologic blocks (Study 2) were tested by Ventana IHC ALK (D5F3) assay. Quantitative real-time-PCR was used to verify immunohistochemistry results. A total of 17 out of 100 (Study 1) and ten out of 104 (Study 2) pleural effusion samples were ALK expression positive by the Ventana IHC ALK (D5F3) assay. The ALK fusion results with immunohistochemistry and quantitative real-time-PCR had a concordance rate of 87.5% (κ = 0.886; p < 0.001). The Ventana IHC ALK (D5F3) assay is a reliable tool for detecting ALK protein expression in pleural effusion samples.

A Qualitative Study Comparing the Assay Performance Characteristics Between the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists HER2 Scoring Methods in Mucinous Epithelial Ovarian Cancer

PubMed Central

Chen, Chi-Kuan; Lee, Ming-Yung; Lin, Wea-Lung; Wang, Yu-Ting; Han, Chih-Ping; Yu, Cheng-Ping; Chao, Wan-Ru

2014-01-01

Abstract The remarkable success of trastuzumab and other newly developed anti-HER2 (human epidermal growth factor receptor 2) therapies in breast, gastric, or gastroesophageal junction cancer patients has supported us to investigate the HER2 status and its possible therapeutic implication in mucinous epithelial ovarian cancer (EOC). However, there is currently no standardization of HER2 scoring criteria in mucinous EOC. In this study, we aimed to compare both the assay performance characteristics of the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists scoring methods. Forty-nine tissue microarray samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using the 2007 and the 2013 criteria, respectively. The overall concordance between IHC and FISH by the 2007 criteria was 97.92 % (kappa = 0.921), and that by the 2013 criteria was 100% (kappa = 1.000). The percentage of Her2 FISH-amplified cases showed an increasing trend significantly through their corresponding HER2 IHC ordinals by the 2007 and the 2013 criteria, respectively (P < 0.001, P < 0.001). After excluding equivocal cases, the specificity (100%) and positive predictive value (100%) were unchanged under either the 2007 or the 2013 criteria. The sensitivity (100%), negative predictive value (NPV) (100%), and accuracy (100%) of HER2 IHC were higher under the 2013 criteria than those (sensitivity 87.5%, NPV 97.6%, and accuracy 97.9%) under the 2007 criteria. Of the total 49 cases, the number (n = 4) of HER2 IHC equivocal results under the 2013 criteria was 4-fold higher than that (n = 1) under the 2007 criteria (8.16% vs 2.04%). Conclusively, if first tested by IHC, the 2013 criteria caused more equivocal HER2 IHC cases to be referred to Her2 FISH testing than the 2007 criteria. That decreased the false-negative rate of HER2 status and increased the detection rates of HER2 positivity in mucinous EOC. PMID:25501060

Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status

PubMed Central

Li, Qiyuan; Eklund, Aron C.; Juul, Nicolai; Haibe-Kains, Benjamin; Workman, Christopher T.; Richardson, Andrea L.; Szallasi, Zoltan; Swanton, Charles

2010-01-01

Background Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold[1], [2]. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome. Methodology/Principal Findings Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHC-based ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that between 15.1% and 21.8% patients of IHC-based negative ER status would be classified with ER positive breast cancer. Conclusion/Significance Expression-based ER status classification may complement IHC to minimise false negative ER status classification and optimise patient stratification for endocrine therapies. PMID:21152022

Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms.

PubMed

Ilie, Marius; Khambata-Ford, Shirin; Copie-Bergman, Christiane; Huang, Lingkang; Juco, Jonathan; Hofman, Veronique; Hofman, Paul

2017-01-01

For non-small cell lung cancer (NSCLC), treatment with pembrolizumab is limited to patients with tumours expressing PD-L1 assessed by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx (Dako, Inc.) companion diagnostic test, on the Dako Autostainer Link 48 (ASL48) platform. Optimised protocols are urgently needed for use of the 22C3 antibody concentrate to test PD-L1 expression on more widely available IHC autostainers. We evaluated PD-L1 expression using the 22C3 antibody concentrate in the three main commercially available autostainers Dako ASL48, BenchMark ULTRA (Ventana Medical Systems, Inc.), and Bond-III (Leica Biosystems) and compared the staining results with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Several technical conditions for laboratory-developed tests (LDTs) were evaluated in tonsil specimens and a training set of three NSCLC samples. Optimised protocols were then validated in 120 NSCLC specimens. Optimised protocols were obtained on both the VENTANA BenchMark ULTRA and Dako ASL48 platforms. Significant expression of PD-L1 was obtained on tissue controls with the Leica Bond-III autostainer when high concentrations of the 22C3 antibody were used. It therefore was not tested on the 120 NSCLC specimens. An almost 100% concordance rate for dichotomized tumour proportion score (TPS) results was observed between TPS ratings using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Interpathologist agreement was high on both LDTs and the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Availability of standardized protocols for determining PD-L1 expression using the 22C3 antibody concentrate on the widely available Dako ASL48 and VENTANA BenchMark ULTRA IHC platforms will expand the number of laboratories able to determine eligibility of patients with NSCLC for treatment with pembrolizumab in a reliable and concordant manner.

Evaluation of ALK Rearrangement in Chinese Non-Small Cell Lung Cancer Using FISH, Immunohistochemistry, and Real-Time Quantitative RT- PCR on Paraffin-Embedded Tissues

PubMed Central

Zhang, Yun-Gang; Jin, Mu-Lan; Li, Li; Zhao, Hong-Ying; Zeng, Xuan; Jiang, Lei; Wei, Ping; Diao, Xiao-Li; Li, Xue; Cao, Qing; Tian, Xin-Xia

2013-01-01

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation. PMID:23741400

Laboratory compliance with the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 testing guidelines: a 3-year comparison of validation procedures.

PubMed

Dyhdalo, Kathryn S; Fitzgibbons, Patrick L; Goldsmith, Jeffery D; Souers, Rhona J; Nakhleh, Raouf E

2014-07-01

The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) published guidelines in 2007 regarding testing accuracy, interpretation, and reporting of results for HER2 studies. A 2008 survey identified areas needing improved compliance. To reassess laboratory response to those guidelines following a full accreditation cycle for an updated snapshot of laboratory practices regarding ASCO/CAP guidelines. In 2011, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program identical to the 2008 survey. Of the 1150 surveys sent, 977 (85.0%) were returned, comparable to the original survey response in 2008 (757 of 907; 83.5%). New participants submitted 124 of 977 (12.7%) surveys. The median laboratory accession rate was 14,788 cases with 211 HER2 tests performed annually. Testing was validated with fluorescence in situ hybridization in 49.1% (443 of 902) of the laboratories; 26.3% (224 of 853) of the laboratories used another IHC assay. The median number of cases to validate fluorescence in situ hybridization (n = 40) and IHC (n = 27) was similar to those in 2008. Ninety-five percent concordance with fluorescence in situ hybridization was achieved by 76.5% (254 of 332) of laboratories for IHC(-) findings and 70.4% (233 of 331) for IHC(+) cases. Ninety-five percent concordance with another IHC assay was achieved by 71.1% (118 of 168) of the laboratories for negative findings and 69.6% (112 of 161) of the laboratories for positive cases. The proportion of laboratories interpreting HER2 IHC using ASCO/CAP guidelines (86.6% [798 of 921] in 2011; 83.8% [605 of 722] in 2008) remains similar. Although fixation time improvements have been made, assay validation deficiencies still exist. The results of this survey were shared within the CAP, including the Laboratory Accreditation Program and the ASCO/CAP panel revising the HER2 guidelines published in October 2013. The Laboratory Accreditation Program checklist was changed to strengthen HER2 validation practices.

Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma.

PubMed

Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne-Marie; Brenton, James D

2016-10-01

TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged-amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain-of-function (GOF or nonsynonymous), loss-of-function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low-grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%.

Laboratory compliance with the American Society of Clinical Oncology/college of American Pathologists guidelines for human epidermal growth factor receptor 2 testing: a College of American Pathologists survey of 757 laboratories.

PubMed

Nakhleh, Raouf E; Grimm, Erin E; Idowu, Michael O; Souers, Rhona J; Fitzgibbons, Patrick L

2010-05-01

To ensure quality human epidermal growth receptor 2 (HER2) testing in breast cancer, the American Society of Clinical Oncology/College of American Pathologists guidelines were introduced with expected compliance by 2008. To assess the effect these guidelines have had on pathology laboratories and their ability to address key components. In late 2008, a survey was distributed with the HER2 immunohistochemistry (IHC) proficiency testing program. It included questions regarding pathology practice characteristics and assay validation using fluorescence in situ hybridization or another IHC laboratory assay and assessed pathologist HER2 scoring competency. Of the 907 surveys sent, 757 (83.5%) were returned. The median laboratory accessioned 15 000 cases and performed 190 HER2 tests annually. Quantitative computer image analysis was used by 33% of laboratories. In-house fluorescence in situ hybridization was performed in 23% of laboratories, and 60% of laboratories addressed the 6- to 48-hour tissue fixation requirement by embedding tissue on the weekend. HER2 testing was performed on the initial biopsy in 40%, on the resection specimen in 6%, and on either in 56% of laboratories. Testing was validated with only fluorescence in situ hybridization in 47% of laboratories, whereas 10% of laboratories used another IHC assay only; 13% used both assays, and 12% and 15% of laboratories had not validated their assays or chose "not applicable" on the survey question, respectively. The 90% concordance rate with fluorescence in situ hybridization results was achieved by 88% of laboratories for IHC-negative findings and by 81% of laboratories for IHC-positive cases. The 90% concordance rate for laboratories using another IHC assay was achieved by 80% for negative findings and 75% for positive cases. About 91% of laboratories had a pathologist competency assessment program. This survey demonstrates the extent and characteristics of HER2 testing. Although some American Society of Clinical Oncology/College of American Pathologists guidelines have been implemented, gaps remain in validation of HER2 IHC testing.

Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma

PubMed Central

Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne‐Marie

2016-01-01

Abstract TP53 mutations are ubiquitous in high‐grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low‐grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged‐amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain‐of‐function (GOF or nonsynonymous), loss‐of‐function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low‐grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%. PMID:27840695

Ultrasensitive detection of oncogenic human papillomavirus in oropharyngeal tissue swabs.

PubMed

Isaac, Andre; Kostiuk, Morris; Zhang, Han; Lindsay, Cameron; Makki, Fawaz; O'Connell, Daniel A; Harris, Jeffrey R; Cote, David W J; Seikaly, Hadi; Biron, Vincent L

2017-01-14

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR. Secondary objectives were to compare the accuracy of ddPCR swabs to fresh tissue p16 IHC and RT-qPCR, and to compare the cost of ddPCR with p16 IHC. We prospectively included patients with p16 + oral cavity/oropharyngeal cancer (OC/OPSCC), and two control groups: p16 - OC/OPSCC patients, and healthy controls undergoing tonsillectomy. All underwent an oropharyngeal swab with ddPCR for quantitative detection of E6 and E7 mRNA. Surgical specimens had p16 IHC performed. Agreement between ddPCR and p16 IHC was determined for patients with p16 positive and negative OC/OPSCC as well as for healthy control patients. The sensitivity and specificity of ddPCR of oropharyngeal swabs were calculated against p16 IHC for OPSCC. 122 patients were included: 36 patients with p16 + OPSCC, 16 patients with p16 - OPSCC, 4 patients with p16 + OCSCC, 41 patients with p16 - OCSCC, and 25 healthy controls. The sensitivity and specificity of ddPCR of oropharyngeal swabs against p16 IHC were 92 and 98% respectively, using 20-50 times less RNA than that required for conventional RT-qPCR. Overall agreement between ddPCR of tissue swabs and p16 of tumor tissue was high at ĸ = 0.826 [0.662-0.989]. Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

[Coercive procedures in forensic psychiatry : Current treatment practice in forensic psychiatric hospitals from a medical ethics perspective].

PubMed

Jakovljević, A-K; Wiesemann, C

2016-07-01

In 2011 the legal foundations of coercive treatment in German forensic psychiatric clinics were declared to be unconstitutional. In the present study we analyzed the frequency of coercive procedures in forensic psychiatric hospitals before and after 2011, the consequences for medical care as well as the ethical assessments by attending chief physicians. By a questionnaire-based survey of views of attending chief physicians in forensic psychiatric clinics in 2013, data on the current state of patient care were collected and analyzed from an ethical perspective. These were compared with treatment data from a large forensic psychiatric clinic collected over the period 2007-2013. Even after 2011 coercive forms of treatment were applied in forensic psychiatric hospitals. In practice, there is a high degree of legal uncertainty regarding the limits of coercive treatment. Of all patients treated in forensic psychiatric clinics in 2012, on average 13 % had been in isolation at least once, approximately 3 % had been treated under fixation at least once and 2.2 % had been subjected to coercive medical treatment at least once. From an ethical perspective an open debate about the practice of coercive treatment is urgently required. Legal regulations, ethical guidelines and treatment standards have to be developed for the special situation of patient care in forensic psychiatric hospitals.

Parental Perceptions of the Use of Coercive Measures on Children with Developmental Disabilities

ERIC Educational Resources Information Center

Saloviita, Timo; Pirttimaa, Raija; Kontu, Elina

2016-01-01

Background: Children with developmental disabilities who exhibit challenging behaviour are potentially subject to the use of coercive interventions. The aim of the study was to investigate the prevalence of the use of coercive measures by authorities, according to parents' reports. Materials and Methods: A postal survey was distributed, as a total…

Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes

PubMed Central

Ohn, Tzu-Lun; Rutherford, Mark A.; Jing, Zhizi; Jung, Sangyong; Duque-Afonso, Carlos J.; Hoch, Gerhard; Picher, Maria Magdalena; Scharinger, Anja; Strenzke, Nicola; Moser, Tobias

2016-01-01

For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs. PMID:27462107

HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer.

PubMed

Styczen, Hanna; Nagelmeier, Iris; Beissbarth, Tim; Nietert, Manuel; Homayounfar, Kia; Sprenger, Thilo; Boczek, Ute; Stanek, Kathrin; Kitz, Julia; Wolff, Hendrik A; Ghadimi, B Michael; Middel, Peter; Liersch, Torsten; Rüschoff, Josef; Conradi, Lena-Christin

2015-06-20

In this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value. Overall 208 patients with CRLM were enrolled. HER-2 and HER-3 expression were determined in metastatic tissue of diagnostic punch biopsies (n = 29) or resection specimens (n = 179). The results of immunohistochemistry (IHC) scoring and In-situ-hybridization (ISH)-amplification were correlated with clinical parameters and for the 179 resected patients with cancer-specific (CSS) and overall survival (OS). The mean follow-up time was 56.7 months. Positivity of HER-2 status (IHC score 2+/ISH+ and IHC 3+) was found in 8.2% of CRLM. High expression of HER-3 (IHC score 2+ and IHC 3+) was detected in 75.0% of liver metastases. CSS after liver surgery was determined and was independent from the HER-2 status (p = 0.963); however HER-3 was prognostic with a favorable course for patients showing an overexpression of HER-3 (p = 0.037). HER-2 overexpression occurs in only 8% of patients with CRLM but with 75% of cases HER-3 is frequently overexpressed in CRLM. Therefore, HER-2 and particularly HER-3 could serve as novel targets to be addressed within multimodal treatment approaches.

Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer.

PubMed

Han, Xiao-Hong; Zhang, Ning-Ning; Ma, Li; Lin, Dong-Mei; Hao, Xue-Zhi; Liu, Yu-Tao; Wang, Lin; Liu, Peng; Yuan, Zheng; Li, Dan; Lin, Hua; Sun, Yan; Shi, Yuan-Kai

2013-10-01

Accurate determination of anaplastic lymphoma kinase (ALK) rearrangements is critical in identifying ALK-positive patients for targeted therapy in non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the current standard method to detect ALK rearrangements but is technically challenging and costly. We compared optimised immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization techniques in this study of 139 samples of advanced NSCLC with non-squamous histology. ALK alteration was found in 32.6 % (43/132) of patients by FISH, 32.9 % (45/137) of patients by IHC and 27.9 % (34/122) of samples by qRT-PCR (concordance rate of 96.9 % between FISH and IHC, 95.7 % between FISH and qRT-PCR, P < 0.001). IHC sensitivity and specificity were 97.7 % and 96.6 %, respectively, while the sensitivity and specificity of qRT-PCR were 89.2 % and 98.7 %, respectively. ALK rearrangements were more common in young patients (P = 0.007), non-smokers or light smokers (P = 0.008) and adenocarcinoma histology, especially with signet ring cell features (P < 0.001). Optimised IHC could be a useful method in screening ALK rearrangements in clinical practice with qRT-PCR as an alternative diagnostic tool to clarify specific ALK variants.

Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses

PubMed Central

Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T.; Wangsawihardja, Felix; Ricci, Anthony J.; Mustapha, Mirna

2016-01-01

Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. PMID:26386265

Variability in Platelet-Derived Growth Factor Receptor Alpha Antibody Specificity May Impact Clinical Utility of Immunohistochemistry Assays

PubMed Central

Holzer, Timothy R.; O’Neill Reising, Leslie; Credille, Kelly M.; Schade, Andrew E.; Oakley, Gerard J.

2016-01-01

Aberrant regulation of the receptor tyrosine kinase platelet-derived growth factor alpha (PDGFRα) is implicated in several types of cancer. Inhibition of the PDGFRα pathway may be a beneficial therapy, and detection of PDGFRα in tumor biopsies may lead to insights about which patients respond to therapy. Exploratory or clinical biomarker use of PDGFRα IHC has been frequently reported, often with polyclonal antibody sc-338. An sc-338-based assay was systematically compared with anti-PDGFRα rabbit monoclonal antibody D13C6 using immunoblot profiling and IHC in formalin-fixed and paraffin-embedded human tumor cell lines. Application of sc-338 to blots of whole cell lysates showed multiple bands including some of unknown origin, whereas application of D13C6 resulted in a prominent band at the expected molecular mass of PDGFRα. The IHC assay using D13C6 showed appropriate staining in cell lines, whereas the assay using sc-338 suggested nonspecific detection of proteins. An optimized IHC assay using D13C6 showed a range of staining in the tumor stromal compartment in lung and ovarian carcinomas. These observations suggest that use of clone sc-338 produced unreliable results and should not be used for an IHC research grade assay. In addition, this precludes its use as a potential antibody for a clinical diagnostic tool. PMID:27837159

Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative.

PubMed

Ma, Di; Wang, Zheng; Yang, Lin; Mu, Xinlin; Wang, Yan; Zhao, Xinming; Li, Junling; Lin, Dongmei

2016-09-27

Although the Ventana immunohistochemistry (IHC) platform for detecting anaplastic lymphoma kinase gene (ALK) (D5F3) expression was recently approved by the US Food and Drugs Administration (FDA), fluorescence in situ hybridization (FISH) is still the "gold-standard" method recommended by the US National Comprehensive Cancer Network (NCCN) guideline for NSCLC. We evaluated 6 ALK-positive lung adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Histologic and cytologic specimens from the 6 patients were stained with Ventana anti-ALK(D5F3) rabbit monoclonal primary antibody using the OptiView™ DAB IHC detection kit and OptiView™ amplification kit on a Ventana BenchMark XT processor. In addition, they were also tested by FISH, qRT-PCR, next-generation sequencing (NGS), and RNAscope ISH analysis. All patients received crizotinib treatment and their follow-up clinical data were recorded. The objective response rate achieved with crizotinib therapy was 66.7% (4/6 partial responses and 2/6 stable disease). One patient in whom a new fusion type (EML4->EXOC6B->ALK fusion) was identified obtained a partial response. These findings indicate that patients with ALK-positive lung adenocarcinoma who test Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.

The Process of Creating Integrated Home Care in Lithuania: from Idea to Reality

PubMed Central

Jurkuvienė, Ramunė; Butkevičienė, Rūta; Gajdosikienė, Indrė

2016-01-01

Background: The article presents an analysis of the formulation and implementation of a social innovation: integrated home care (IHC) in post-soviet Lithuania. From 1998 a series of top-down orders to implement IHC were issued, however, home nursing did not start. In 2011 the Ministry of Social Security and Labour began a process to develop integrated home care using new, collaborative processes. The result was 21 pilot projects with well-conceptualized IHC services. Method: Using data from focus groups, interviews, and recorded observations, the research team systematically documented the innovation process, including themes and deviations, employing Smale’s Innovation Trinity framework to organize the larger picture. Results: In the Lithuanian post-totalitarian context, top-down communication was found to be prevalent. Not only IHC, but also openness to change and dialogue at high levels were innovations. Patient-centered practice at local levels could only occur when a new attitude of mind was reached through dialogue with officials at higher levels and between peers. Conclusions: The enactment, rather than the mask of dialogue, participatory program development were critical in the success of IHC innovation. This is difficult to achieve in the light of antiquated public bureaucracies, but in this case, the Ministry team, rather than avoiding the expectation of top-down communication, made it into an asset through promotion of collaboration. PMID:28435419

Secondary syphilis in HIV positive individuals: correlation with histopathologic findings, CD4 counts, and quantity of treponemes in microscopic sections.

PubMed

Rosa, Gabriela; Procop, Gary W; Schold, Jesse D; Piliang, Melissa P

2016-10-01

Although syphilis is uncommon, infection rates are much higher in HIV-infected individuals than the general population. A proposed explanation is impaired cellular immunity with HIV infection. A search of one institution yielded 10 patients with a diagnosis of secondary syphilis on skin biopsy, positive syphilis serology and available CD4 counts. We evaluated 11 biopsies from the 10 patients. We correlated the patients' CD4 counts with the histologic findings and with the number of treponemes on skin biopsies, highlighted by immunohistochemistry (IHC). We also compared the detection of spirochetes in silver stained sections (e.g. Warthin-Starry) with T. pallidum IHC. All biopsies were assessed for various histologic features. The sensitivity of IHC to detect treponemes was 64% and of silver stain was 9% (p-value 0.04). The number of treponemes on the biopsies was determined by IHC. High numbers of spirochetes (i.e. >100 per 10 hpf) were only seen in patients with CD4 counts less than 250 cells/ml. The most consistent histologic finding was a moderate to severe lymphoplasmacytic infiltrate. Although the study is small, it appears that a higher number of spirochetes is associated with CD4 counts less than 250 cell/ml. The T. pallidum IHC stain was vastly superior to the Warthin-Starry stain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An evidence-based approach to interactive health communication: a challenge to medicine in the information age. Science Panel on Interactive Communication and Health.

PubMed

Robinson, T N; Patrick, K; Eng, T R; Gustafson, D

1998-10-14

To examine the current status of interactive health communication (IHC) and propose evidence-based approaches to improve the quality of such applications. The Science Panel on Interactive Communication and Health, a 14-member, nonfederal panel with expertise in clinical medicine and nursing, public health, media and instructional design, health systems engineering, decision sciences, computer and communication technologies, and health communication, convened by the Office of Disease Prevention and Health Promotion, US Department of Health and Human Services. Published studies, online resources, expert panel opinions, and opinions from outside experts in fields related to IHC. The panel met 9 times during more than 2 years. Government agencies and private-sector experts provided review and feedback on the panel's work. Interactive health communication applications have great potential to improve health, but they may also cause harm. To date, few applications have been adequately evaluated. Physicians and other health professionals should promote and participate in an evidence-based approach to the development and diffusion of IHC applications and endorse efforts to rigorously evaluate the safety, quality, and utility of these resources. A standardized reporting template is proposed to help developers and evaluators of IHC applications conduct evaluations and disclose their results and to help clinicians, purchasers, and consumers judge the quality of IHC applications.

Computational alloy design of (Co1-xNix)88Zr7B4Cu1 nanocomposite soft magnets

NASA Astrophysics Data System (ADS)

Dong, B.; Healy, J.; Lan, S.; Daniil, M.; Willard, M. A.

2018-05-01

The dependence of coercivity on composition is an important factor for establishing optimized soft magnetic properties. In this study, we have used the random anisotropy and coherent rotation models to estimate the variation of coercivity with composition in (Co1-xNix)88Zr7B4Cu1 nanocomposite alloys. Our calculations that the magnetoelastic anisotropy contribution to coercivity dominates for Ni rich compositions (x > 0.5). A small range of compositions (0.65 < x < 0.75) is predicted to result in low values of coercivity (<10 A/m). To validate this prediction, (Co1-xNix)88Zr7B4Cu1 nanocomposites in this range were prepared by melt spinning followed by 3600 s isothermal annealing at the primary crystallization peak temperature (˜673 K). Hysteresis loops were measured using vibrating sample magnetometry at room temperature and saturation magnetostriction was measured using a strain gage based magnetostrictometer. Moderately small coercivities (30-40 A/m) and magnetostrictions (3-4 ppm) were measured at for samples with 0.685 < x < 0.725. Our measured coercivity had a minimum value of 32 A/m at x = 0.725, a shift in composition of about 5 at% in the direction of higher Ni content and without the anticipated low value of coercivity. Several reasons for the inaccuracy of this approach are described, including: ignored contributions from amorphous phase (especially in magnetoealstic anisotropy), composition segregation during crystallization leading to unpredictable compositional shifts in prediction, and the general observation that the predictability of minimum coercivity from minimal combined anisotropies has unexplained deviation even in far less complicated materials.

Random-anisotropy model: Monotonic dependence of the coercive field on D/J

NASA Astrophysics Data System (ADS)

Saslow, W. M.; Koon, N. C.

1994-02-01

We present the results of a numerical study of the zero-temperature remanence and coercivity for the random anisotropy model (RAM), showing that, contrary to early calculations for this model, the coercive field increases monotonically with increases in the strength D of the random anisotropy relative to the strength J at the exchange field. Local-field adjustments with and without spin flips are considered. Convergence is difficult to obtain for small values of the anisotropy, suggesting that this is the likely source of the nonmonotonic behavior found in earlier studies. For both large and small anisotropy, each spin undergoes about one flip per hysteresis cycle, and about half of the spin flips occur in the vicinity of the coercive field. When only non-spin-flip adjustments are considered, at large anisotropy the coercivity is proportional to the anisotropy. At small anisotropy, the rate of convergence is comparable to that when spin flips are included.

Perceptions of sexual coercion: learning from young people in Ibadan, Nigeria.

PubMed

Ajuwon, A J; Akin-Jimoh, I; Olley, B O; Akintola, O

2001-05-01

This study explored the problem of sexual coercion from the perspectives of 77 young people aged 14-21 in Ibadan, Nigeria, the behaviours they perceive to be sexually coercive and the contexts in which these occur through four narrative workshops. Participants were drawn from two secondary schools and 15 apprentice workshops. All four groups identified similar coercive behaviours and developed narratives of the events that typically lead up to them. Behaviours included rape, unwanted touching, incest, assault, verbal abuse, threats, unwanted kissing; forced exposure to pornographic films, use of drugs for sedation and traditional charms for seduction, and insistence on abortion if unwanted pregnancy occurs. Men were typically the perpetrators and young women the victims. Perpetrators included acquaintances, boyfriends, neighbours, parents and relatives. All the narratives revealed the inability of young people to communicate effectively with each other and resolve differences. The results suggest the need for life-skills training that facilitates communication, seeks to redress gender power imbalances, teaches alternatives to coercion as a means of resolving conflict over sexual relations and respect for sexual and reproductive rights, and provides victims with information on appropriate services, support and referral.

Thermal treatment induced modification of structural, surface and bulk magnetic properties of Fe61.5Co5Ni8Si13.5B9Nb3 metallic glass

NASA Astrophysics Data System (ADS)

Shah, M.; Satalkar, M.; Kane, S. N.; Ghodke, N. L.; Sinha, A. K.; Varga, L. K.; Teixeira, J. M.; Araujo, J. P.

2018-05-01

Effect of thermal annealing induced modification of structural, surface and bulk magnetic properties of Fe61.5Co5Ni8Si13.5B9Nb3 alloy is presented. The changes in properties were observed using synchrotron x-ray diffraction technique (SXRD), atomic force microscopy (AFM), magneto-optical kerr effect (MOKE) and bulk magnetic measurements. Significant variations on the both side of surface occur for the annealing temperature upto 500 °C promotes the surface crystallization. Surface roughness appears due to presence of nanocrystallization plays an important role in determining magnetic properties. Observed lower value of bulk coercivity Hc of 6.2 A/m annealed temperature at 450 °C/1 h ascribed to reduction of disorder as compared to the surface (both shiny and wheel side observed by MOKE measurement) whereas improvement of bulk saturation magnetization with annealing temperature indicates first near neighbor shell of Fe atoms are surrounded by Fe atoms. Evolution of coercivity of surface and bulk with annealing temperature has been presented in conjunction with the structural observations.

Environmental Impact Of The Use Of Contaminated Sediments As Partial Replacement Of The Aggregate Used In Road Construction

EPA Science Inventory

The Indiana Harbor Canal (IHC) is a waterway extensively polluted with heavy metals and petroleum. Since there are limited disposal options for the petroleum-contaminated sediments (PCSs) of the canal, the environmental impact of IHC dewatered sediment when used as partial repla...

Trace elements, organochlorines, polycyclic aromatic hydrocarbons, dioxins, and furans in lesser scaup wintering on the Indiana Harbor Canal

USGS Publications Warehouse

Custer, T.W.; Custer, Christine M.; Hines, R.K.; Sparks, D.W.

2000-01-01

During the winter of 1993a??94, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal (IHC), East Chicago, IN, USA, and examined for tissue contaminant levels. Lesser scaup collected on the IHC had higher concentrations of cadmium (Cd), mercury (Hg), selenium (Se), polychlorinated biphenyls (PCBs), selected organchlorine pesticides, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polycyclic aromatic hydrocarbons, and aliphatic hydrocarbons than reference birds. Of the scaup collected on the IHC, 44% had Cd concentrations in the liver considered above background for freshwater waterfowl (>3 I?g/g dry wt.), 50% had Se concentrations in the liver above a level possibly harmful to the health of young and adult birds (>33 I?g/g dry wt.), and 88% of the scaup carcasses exceeded the PCB human consumption guidelines for edible poultry in the USA (>3.0 I?g/g lipid wt.). The ratio of pristane:n-heptadecane concentrations in 47% of lesser scaup collected on IHC was elevated above 1.0, which is indicative of chronic exposure to petroleum hydrocarbons. Copyright A? 2009 Elsevier B.V.

Trace elements, organochlorines, polycyclic aromatic hydrocarbons, dioxins, and furans in lesser scaup wintering on the Indiana Harbor Canal.

PubMed

Custer, T W; Custer, C M; Hines, R K; Sparks, D W

2000-12-01

During the winter of 1993-94, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal (IHC), East Chicago, IN, USA, and examined for tissue contaminant levels. Lesser scaup collected on the IHC had higher concentrations of cadmium (Cd), mercury (Hg), selenium (Se), polychlorinated biphenyls (PCBs), selected organchlorine pesticides, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polycyclic aromatic hydrocarbons, and aliphatic hydrocarbons than reference birds. Of the scaup collected on the IHC, 44% had Cd concentrations in the liver considered above background for freshwater waterfowl (>3 microg/g dry wt.), 50% had Se concentrations in the liver above a level possibly harmful to the health of young and adult birds (>33 microg/g dry wt.), and 88% of the scaup carcasses exceeded the PCB human consumption guidelines for edible poultry in the USA (>3.0 microg/g lipid wt.). The ratio of pristane:n-heptadecane concentrations in 47% of lesser scaup collected on IHC was elevated above 1.0, which is indicative of chronic exposure to petroleum hydrocarbons.

Next-generation sequencing facilitates detection of the classic E13-A20 EML4-ALK fusion in an ALK-FISH/IHC inconclusive biopsy of a stage IV lung cancer patient: a case report.

PubMed

Volckmar, Anna-Lena; Endris, Volker; Bozorgmehr, Farastuk; Lier, Clemens; Porcel, Carlota; Kirchner, Martina; Leichsenring, Jonas; Penzel, Roland; Thomas, Michael; Schirmacher, Peter; Warth, Arne; Stenzinger, Albrecht

2016-11-18

Inhibition of the oncogenic fusion-gene EML4-ALK is a current first-line approach for patients with stage IV non-small cell lung cancer. While FISH was established as the gold standard for identifying these patients, there is accumulating evidence that other methods of detection, i.e., immunohistochemistry and next-generation sequencing (NGS), exist that may be equally successful. However, the concordance of these methods is under investigation. Adding to the current literature, we here report a 56 year old female never-smoker with stage IV lung adenocarcinoma whose biopsy was IHC and FISH inconclusive but positive in NGS. Retroactive profiling of the resection specimen corroborated fusion reads obtained by NGS, FISH-positivity and showed weak ALK-positivity by IHC. Consequently, we diagnosed the case as ALK-positive rendering the patient eligible to crizotinib treatment. With IHC on biopsy material only, this case would have been overlooked withholding effective therapy.

Best practices recommendations in the application of immunohistochemistry in testicular tumors: report from the International Society of Urological Pathology consensus conference.

PubMed

Ulbright, Thomas M; Tickoo, Satish K; Berney, Daniel M; Srigley, John R

2014-08-01

The judicious use of immunostains can be of significant diagnostic assistance in the interpretation of testicular neoplasms when the light microscopic features are ambiguous. A limited differential diagnosis by traditional morphology is required for the effective use of immunohistochemistry (IHC); otherwise, the inevitable occurrence of exceptions to anticipated patterns will lead to "immunoconfusion." The diagnosis of tumors in the germ cell lineage, the great majority of primary tumors of the testis, has been considerably facilitated over the past decade by IHC directed at developmentally important nuclear transcription factors, including OCT4, SALL4, SOX2, and SOX17, that are mostly restricted to certain tumor histotypes. In conjunction with other markers, a specific diagnosis can be achieved in most instances through a panel of 3 or 4 immunostains and often fewer. IHC among tumors in the sex cord-stromal group may produce a significant proportion of false-negative cases until more sensitive and equally specific markers are validated. The negativity of these tumors for the IHC stains used for germ cell tumors is key in the important distinction of neoplasms in these 2 general categories. In this review, the International Society of Urological Pathologists (ISUP) provides diagnostic guidelines in the form of algorithms to assist practicing pathologists confronting a differential diagnostic question concerning a testicular neoplasm. The goal of ISUP is to anticipate commonly encountered differential diagnoses and recommend an efficient and limited pattern of IHC stains to resolve the question.

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations.

PubMed

Wang, Tao; Stadler, Zsofia K; Zhang, Liying; Weiser, Martin R; Basturk, Olca; Hechtman, Jaclyn F; Vakiani, Efsevia; Saltz, Lenard B; Klimstra, David S; Shia, Jinru

2018-04-01

Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient's age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.

Immunohistochemistry as a surrogate for molecular testing: a review.

PubMed

Swanson, Paul E

2015-02-01

Despite the myriad of genetic and epigenetic alterations in human neoplasms that seem to demand specific molecular probes for their identification and practical application to diagnostic pathology, immunohistochemistry (IHC) remains a vital component of laboratory testing in the emerging molecular era. The development and proper application of sensitive and specific antibodies raised against cryptic proteins only expressed in quantity after gene translocation, translocation-specific chimeric fusion peptides, and gene products overexpressed because of gene amplification demonstrate that IHC is a legitimate surrogate for traditional cytogenetic and in situ hybridization-based identification of chromosomal abnormalities, if not a viable molecular technique in its own right. Similarly, the detection of mutational events, through the reliable demonstration of protein loss, the identification of proteins overexpressed because of activating mutations, the specific visualization of mutant gene products, and the localization of splice variant gene products emphasizes the potential value of IHC as a surrogate for mutational analyses of genes important to both diagnosis and prediction of therapeutic response. In the latter setting IHC also provides a means of approximating gene expression profiles in the molecular classification and risk stratification of human neoplasms. For time being, the application of appropriately targeted sensitive and specific antibodies provides a cost-effective screening modality, if not replacement, for selected molecular techniques, but IHC will lose its value if the development of companion tests for emerging novel biomarkers does not keep pace with molecular techniques, particularly as the costs and time constraints of genomic sequencing diminish over time.

Effect of sexual coercion proclivity, insult and fantasy on emotional reactivity and appeal of sexual aggression.

PubMed

Thomas, Lindsey A; Gorzalka, Boris B

2012-08-01

Fifty-nine heterosexual university males were assessed for Sexual Coercion Proclivity (SCP) and randomly assigned to one of three conditions: Insult/nonsexually coercive fantasy material; no insult/sexually coercive fantasy material; or, insult/sexually coercive fantasy material. Although not differing in terms of anger or anxiety, the high SCP became more frustrated than the low group, particularly when exposed to both insult and sexually coercive (SC) fantasy material. Changes in negative affect predicted anticipated likelihood of engaging in SC among the low SCP group and anticipated enjoyment of SC in the high SCP group. Acculturation accounted for differences observed between Caucasian and Chinese men.

Anomalous behaviour of magnetic coercivity in graphene oxide and reduced graphene oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bagani, K.; Bhattacharya, A.; Kaur, J.

In this report, we present the temperature dependence of the magnetic coercivity of graphene oxide (GO) and reduced graphene oxide (RGO). We observe an anomalous decrease in coercivity of GO and RGO with decreasing temperature. The observation could be understood by invoking the inherent presence of wrinkles on graphene oxide due to presence of oxygen containing groups. Scanning electron microscopic image reveals high wrinkles in GO than RGO. We observe higher coercivity in RGO than in GO. At room temperature, we observe antiferromagnetic and ferromagnetic behaviours in GO and RGO, respectively. Whereas, at low temperatures (below T = 60–70 K), both materials showmore » paramagnetic behaviour.« less

High temperature coercive field behavior of Fe-Zr powder

NASA Astrophysics Data System (ADS)

Mishra, Debabrata; Perumal, A.; Srinivasan, A.

2009-04-01

We report the investigation of high temperature coercive field behavior of Fe80Zr20 nanocrystalline alloy powder having two-phase microstructure prepared by mechanical alloying process. Thermomagnetization measurement shows the presence of two different magnetic phase transitions corresponding to the amorphous matrix and nonequilibrium Fe(Zr) solid solution. Temperature dependent coercivity exhibits a sharp increase in its value close to the Curie temperature of the amorphous matrix. This feature is attributed to the loss of intergranular ferromagnetic exchange coupling between the nanocrystallites due to the paramagnetic nature of the amorphous matrix. The temperature dependent coercive field behavior is ascribed to the variations in both the effective anisotropy and the exchange stiffness constant with temperature.

Structure, coercive control, and autonomy promotion: A comparison of fathers' and mothers' food parenting strategies.

PubMed

Pratt, Mercedes; Hoffmann, Debra; Taylor, Maija; Musher-Eizenman, Dara

2017-05-01

This study explored differences in mothers' and fathers' food parenting strategies, specifically coercive control, structure, and autonomy promotion, and whether parenting style and parental responsibility for food parenting related to the use of these strategies. Parents of children aged 2.5-7.5 years ( N = 497) reported about their parenting practices and food parenting strategies. Parenting style accounted for the majority of the variance in food parenting. Fathers were more authoritarian than mothers. Authoritarian and permissive parenting practices were related to more coercive strategies. Mothers reported more food parenting responsibility. Responsibility was related to less coercive practices and more autonomy promotion and structure.

Differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma: utility of p16 in combination with MDM2 and CDK4 immunohistochemistry.

PubMed

Kammerer-Jacquet, Solène-Florence; Thierry, Sixte; Cabillic, Florian; Lannes, Morgane; Burtin, Florence; Henno, Sébastien; Dugay, Frédéric; Bouzillé, Guillaume; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine; Stock, Nathalie

2017-01-01

The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization for MDM2 and CDK4 amplification. We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20). In the differential diagnosis of ALT-WDLPS, p16 had a sensitivity of 89.5% but a specificity of 68.2%, which was impaired by false-positive lipomas with secondary changes, especially in biopsies. Likewise, in the differential diagnosis of DDLPS, p16 had a sensitivity of 94.4% and a specificity of 70%, which hampered its use as a single marker. However, adding p16 to MDM2 and/or CDK4 increased diagnostic specificity. Indeed, MDM2+/p16+ tumors were all ALT-WDLPS, and MDM2-/p16- tumors were all benign adipocytic tumors. Moreover, all MDM2+/CDK4+/p16+ tumors were DDLPS, and the MDM2-/CDK4-/p16- tumor was an undifferentiated sarcoma. Although the use of p16 as a single immunohistochemical marker is limited by its specificity, its combination with MDM2 and CDK4 IHC may help discriminate ALT-WDLPS/DDLPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Analytical validation of quantitative immunohistochemical assays of tumor infiltrating lymphocyte biomarkers.

PubMed

Singh, U; Cui, Y; Dimaano, N; Mehta, S; Pruitt, S K; Yearley, J; Laterza, O F; Juco, J W; Dogdas, B

2018-06-04

Tumor infiltrating lymphocytes (TIL), especially T-cells, have both prognostic and therapeutic applications. The presence of CD8+ effector T-cells and the ratio of CD8+ cells to FOXP3+ regulatory T-cells have been used as biomarkers of disease prognosis to predict response to various immunotherapies. Blocking the interaction between inhibitory receptors on T-cells and their ligands with therapeutic antibodies including atezolizumab, nivolumab, pembrolizumab and tremelimumab increases the immune response against cancer cells and has shown significant improvement in clinical benefits and survival in several different tumor types. The improved clinical outcome is presumed to be associated with a higher tumor infiltration; therefore, it is thought that more accurate methods for measuring the amount of TIL could assist prognosis and predict treatment response. We have developed and validated quantitative immunohistochemistry (IHC) assays for CD3, CD8 and FOXP3 for immunophenotyping T-lymphocytes in tumor tissue. Various types of formalin fixed, paraffin embedded (FFPE) tumor tissues were immunolabeled with anti-CD3, anti-CD8 and anti-FOXP3 antibodies using an IHC autostainer. The tumor area of stained tissues, including the invasive margin of the tumor, was scored by a pathologist (visual scoring) and by computer-based quantitative image analysis. Two image analysis scores were obtained for the staining of each biomarker: the percent positive cells in the tumor area and positive cells/mm 2 tumor area. Comparison of visual vs. image analysis scoring methods using regression analysis showed high correlation and indicated that quantitative image analysis can be used to score the number of positive cells in IHC stained slides. To demonstrate that the IHC assays produce consistent results in normal daily testing, we evaluated the specificity, sensitivity and reproducibility of the IHC assays using both visual and image analysis scoring methods. We found that CD3, CD8 and FOXP3 IHC assays met the fit-for-purpose analytical acceptance validation criteria and that they can be used to support clinical studies.

The Impact of 2013 Updated ASCO/CAP HER2 Guidelines on the Diagnosis and Management of Invasive Breast Cancer: A Single-Center Study of 1739 Cases.

PubMed

Zhang, Xiaofei; Bleiweiss, Ira; Jaffer, Shabnam; Nayak, Anupma

2017-10-01

The purpose of this study was to determine the impact of revised ASCO/CAP 2013 HER2 guidelines on the clinical practice of pathologists and oncologists. Retrospective analysis of 1739 patients with invasive breast carcinoma who underwent reflex HER2 (fluorescence in situ hybridization [FISH]) testing, using both 2007 and 2013 guidelines (2007-2014). Using 2013 guidelines, 255 (15%; 95% confidence interval [CI], 13%-16%) cases were classified as HER2 + as opposed to 186 (11%; 95% CI, 9%-12%) by 2007 guidelines (odds ratio [OR] 1.4; 95% CI, 1.2-1.8; P = .0005). Sixty-nine cases equivocal by 2007 guidelines (12% of all equivocal cases) were converted to HER2 + by 2013 guidelines. Sixty-two of these 69 cases shifted from HER2 equivocal to positive due to change in FISH ratio cutoff from 2.2 to 2.0. Six cases had FISH ratio < 2.0 but immunohistochemistry (IHC) score 3+ in 10% to 30% of tumor cells. One case had FISH ratio of 2.0 and IHC score 3+ in 10% to 30% of tumor cells. FISH and IHC test results were discordant in 5% (95% CI, 4%-6%) of cases using 2013 guidelines. No increase in HER2 FISH equivocal cases was observed. Reflex FISH testing of all IHC 1+ cases at our institution additionally detected 58 patients (5%; 95% CI, 4%-6%) with HER2 amplification. The 2013 guidelines increase the detection of HER2 + cases, without introducing significant difference in discordance rate of the IHC and FISH assays. Inclusion of HER2 copy number criterion does not increase the number of FISH equivocal cases in our cohort. We recommend IHC 1+ cases should be offered reflex FISH testing because failure to test them will miss a small number (5%) of potentially treatable cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Substitution of Formal and Informal Home Care Service Use and Nursing Home Service Use: Health Outcomes, Decision-Making Preferences, and Implications for a Public Health Policy.

PubMed

Chen, Chia-Ching; Yamada, Tetsuji; Nakashima, Taeko; Chiu, I-Ming

2017-01-01

The purposes of this study are: (1) to empirically identify decision-making preferences of long-term health-care use, especially informal and formal home care (FHC) service use; (2) to evaluate outcomes vs. costs based on substitutability of informal and FHC service use; and (3) to investigate health outcome disparity based on substitutability. The methods of ordinary least squares, a logit model, and a bivariate probit model are used by controlling for socioeconomic, demographic, and physical/mental health factors to investigate outcomes and costs based substitutability of informal and formal health-care use. The data come from the 2013 Japanese Study of Aging and Retirement (JSTAR), which is designed by Keizai-Sangyo Kenkyu-jo, Hitotsubashi University, and the University of Tokyo. The JSTAR is a globally comparable data survey of the elderly. There exists a complement relationship between the informal home care (IHC) and community-based FHC services, and the elasticity's ranges from 0.18 to 0.22. These are reasonable results, which show that unobservable factors are positively related to IHC and community-based FHC, but negatively related to nursing home (NH) services based on our bivariate probit model. Regarding health-care outcome efficiency issue, the IHC is the best one among three types of elderly care: IHC, community-based FHC, and NH services. Health improvement/outcome of elderly with the IHC is heavier concentrated on IHC services than the elderly care services by community-based FHC and NH care services. Policy makers need to address a diversity of health outcomes and efficiency of services based on providing services to elderly through resource allocation to the different types of long-term care. A provision of partial or full compensation for elderly care at home is recommendable and a viable option to improve their quality of lives.

Interlaboratory comparison of immunohistochemical testing for HER2: results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey.

PubMed

Fitzgibbons, Patrick L; Murphy, Douglas A; Dorfman, David M; Roche, Patrick C; Tubbs, Raymond R

2006-10-01

Correct assessment of human epidermal growth factor receptor 2 (HER2) status is essential in managing patients with invasive breast carcinoma, but few data are available on the accuracy of laboratories performing HER2 testing by immunohistochemistry (IHC). To review the results of the 2004 and 2005 College of American Pathologists HER2 Immunohistochemistry Tissue Microarray Survey. The HER2 survey is designed for laboratories performing immunohistochemical staining and interpretation for HER2. The survey uses tissue microarrays, each consisting of ten 3-mm tissue cores obtained from different invasive breast carcinomas. All cases are also analyzed by fluorescence in situ hybridization. Participants receive 8 tissue microarrays (80 cases) with instructions to perform immunostaining for HER2 using the laboratory's standard procedures. The laboratory interprets the stained slides and returns results to the College of American Pathologists for analysis. In 2004 and 2005, a core was considered "graded" when at least 90% of laboratories agreed on the result--negative (0, 1+) versus positive (2+, 3+). This interlaboratory comparison survey included 102 laboratories in 2004 and 141 laboratories in 2005. Of the 160 cases in both surveys, 111 (69%) achieved 90% consensus (graded). All 43 graded cores scored as IHC-positive were fluorescence in situ hybridization-positive, whereas all but 3 of the 68 IHC-negative graded cores were fluorescence in situ hybridization-negative. Ninety-seven (95%) of 102 laboratories in 2004 and 129 (91%) of 141 laboratories in 2005 correctly scored at least 90% of the graded cores. Performance among laboratories performing HER2 IHC in this tissue microarray-based survey was excellent. Cores found to be IHC-positive or IHC-negative by participant consensus can be used as validated benchmarks for interlaboratory comparison, allowing laboratories to assess their performance and determine if improvements are needed.

Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry.

PubMed

Chemaly, Roy F; Yen-Lieberman, Belinda; Castilla, Elias A; Reilly, Amy; Arrigain, Susana; Farver, Carol; Avery, Robin K; Gordon, Steven M; Procop, Gary W

2004-05-01

Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.

Digital PCR assessment of MGMT promoter methylation coupled with reduced protein expression optimises prediction of response to alkylating agents in metastatic colorectal cancer patients.

PubMed

Sartore-Bianchi, Andrea; Pietrantonio, Filippo; Amatu, Alessio; Milione, Massimo; Cassingena, Andrea; Ghezzi, Silvia; Caporale, Marta; Berenato, Rosa; Falcomatà, Chiara; Pellegrinelli, Alessio; Bardelli, Alberto; Nichelatti, Michele; Tosi, Federica; De Braud, Filippo; Di Nicolantonio, Federica; Barault, Ludovic; Siena, Salvatore

2017-01-01

O(6)-methylguanine-DNA-methyltransferase (MGMT) is a repair protein, and its deficiency makes tumours more susceptible to the cytotoxic effect of alkylating agents. Five clinical trials with temozolomide or dacarbazine have been performed in metastatic colorectal cancer (mCRC) with selection based on methyl-specific PCR (MSP) testing with modest results. We hypothesised that mitigated results are consequences of unspecific patient selection and that alternative methodologies for MGMT testing such as immunohistochemistry (IHC) and digital polymerase chain reaction (PCR) could enhance patient enrolment. Formalin-fixed paraffin embedded archival tumour tissue samples from four phase II studies of temozolomide or dacarbazine in MGMT MSP-positive mCRCs were analysed by IHC for MGMT protein expression and by methyl-BEAMing (MB) for percentage of promoter methylation. Pooled data were then retrospectively analysed according to objective response rate, progression-free survival (PFS) and overall survival (OS). One hundred and five patients were included in the study. Twelve had achieved partial response (PR) (11.4%), 24 stable disease (SD; 22.9%) and 69 progressive disease (PD; 65.7%). Patients with PR/SD had lower IHC scores and higher MB levels than those with PD. MGMT expression by IHC was negatively and MB levels positively associated with PFS (p < 0.001 and 0.004, respectively), but not with OS. By combining both assays, IHC low/MB high patients displayed an 87% reduction in the hazard of progression (p < 0.001) and a 77% in the hazard for death (p = 0.001). In mCRC selected for MGMT deficiency by MSP, IHC and MB testing improve clinical outcome to alkylating agents. Their combination could enhance patient selection in this setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours

PubMed Central

Lamarca, Angela; Nonaka, Daisuke; Breitwieser, Wolfgang; Ashton, Garry; Barriuso, Jorge; McNamara, Mairéad G.; Moghadam, Sharzad; Rogan, Jane; Mansoor, Wasat; Hubner, Richard A.; Clark, Christopher; Chakrabarty, Bipasha; Valle, Juan W.

2018-01-01

Background The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results. Results Of 109 patients screened, 62 were eligible: 54.8% were male; median age was 63.7 years (95%-CI 59.7-67.2); disease stage II: 4.8%, III: 40.3% and IV: 54.8%; 41.9% were functional. Analysed samples (67.1% from primary tumours, 32.9% from metastases) were of grade 1 (67.1%) or 2 (32.86%) with a median Ki-67 of 2%. From the total of 62 eligible patients, 70 and 63 samples were suitable for IHC and RT-qPCR analysis, respectively. PD-L1 expression within tumour cells and TILs were identified in 12.8% and 24.3% of samples respectively; 30% of samples showed PD-L1 expression within tumour cells and/or TILs. PD-1 was present in TILs in 22.8% of samples. Majority of samples showed significant presence of CD4+ (focal 42.86%; moderate 2.86%) and CD8+ (focal 92.86%; moderate 4.29%) TILs. IHC findings were confirmed with RT-qPCR; which showed higher expression levels of PD-L1 (p-value 0.007) and PD-1 (p-value 0.001) in samples positive for IHC compared to negative-IHC. Conclusions Thirty-percent of patients express PD-L1 within tumour cells and/or TILs. Identification of presence of TILs was also significant and warrant the investigation of immunotherapy in this setting. PMID:29599916

Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer

PubMed Central

Xue, Xiaonan; Lin, Hung-Mo; D’Alfonso, Timothy M.; Ginter, Paula S.; Oktay, Maja H.; Robinson, Brian D.; Ginsberg, Mindy; Gertler, Frank B.; Glass, Andrew G.; Sparano, Joseph A.; Condeelis, John S.; Jones, Joan G.

2014-01-01

Background Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4. Methods We conducted a case–control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1:1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided. Results TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)+/human epidermal growth factor receptor (HER2)− tumors (multivariable OR high vs low tertile = 2.70; 95% CI = 1.39 to 5.26; P trend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2+ subgroups. Conclusions TMEM score predicted risk of distant metastasis in ER+/HER2− breast cancer independently of IHC4 score and classical clinicopathologic features. PMID:24895374

Tumor microenvironment of metastasis and risk of distant metastasis of breast cancer.

PubMed

Rohan, Thomas E; Xue, Xiaonan; Lin, Hung-Mo; D'Alfonso, Timothy M; Ginter, Paula S; Oktay, Maja H; Robinson, Brian D; Ginsberg, Mindy; Gertler, Frank B; Glass, Andrew G; Sparano, Joseph A; Condeelis, John S; Jones, Joan G

2014-08-01

Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer. We prospectively examined the association between TMEM score and risk of distant metastasis and compared risk associated with TMEM score with that associated with IHC4. We conducted a case-control study nested within a cohort of 3760 patients with invasive ductal breast carcinoma diagnosed between 1980 and 2000 and followed through 2010. Case patients were women who developed a subsequent distant metastasis; control subjects were matched (1:1) on age at and calendar year of primary diagnosis. TMEM was assessed by triple immunostain and IHC4 by standard methods; slides were read by pathologists blinded to outcome. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusted for clinical variables. A Receiver Operating Characteristic analysis was performed, and the area under the curve was estimated. All statistical tests were two-sided. TMEM score was associated with increased risk of distant metastasis in estrogen receptor (ER)(+)/human epidermal growth factor receptor (HER2)(-) tumors (multivariable OR high vs low tertile = 2.70; 95% CI = 1.39 to 5.26; P trend = .004), whereas IHC4 score had a borderline positive association (OR10 unit increase = 1.06; 95% CI = 1.00 to 1.13); the association for TMEM score persisted after adjustment for IHC4 score. The area under the curve for TMEM, adjusted for clinical variables, was 0.78. Neither TMEM score nor IHC4 score was independently associated with metastatic risk overall or in the triple negative or HER2(+) subgroups. TMEM score predicted risk of distant metastasis in ER(+)/HER2(-) breast cancer independently of IHC4 score and classical clinicopathologic features. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Validation of a fully automated HER2 staining kit in breast cancer.

PubMed

Moelans, Cathy B; Kibbelaar, Robby E; van den Heuvel, Marius C; Castigliego, Domenico; de Weger, Roel A; van Diest, Paul J

2010-01-01

Testing for HER2 amplification and/or overexpression is currently routine practice to guide Herceptin therapy in invasive breast cancer. At present, HER2 status is most commonly assessed by immunohistochemistry (IHC). Standardization of HER2 IHC assays is of utmost clinical and economical importance. At present, HER2 IHC is most commonly performed with the HercepTest which contains a polyclonal antibody and applies a manual staining procedure. Analytical variability in HER2 IHC testing could be diminished by a fully automatic staining system with a monoclonal antibody. 219 invasive breast cancers were fully automatically stained with the monoclonal antibody-based Oracle HER2 Bond IHC kit and manually with the HercepTest. All cases were tested for amplification with chromogenic in situ hybridization (CISH). HercepTest yielded an overall sharper membrane staining, with less cytoplasmic and stromal background than Oracle in 17% of cases. Overall concordance between both IHC techniques was 89% (195/219) with a kappa value of 0.776 (95% CI 0.698-0.854), indicating a substantial agreement. Most (22/24) discrepancies between HercepTest and Oracle showed a weaker staining for Oracle. Thirteen of the 24 discrepant cases were high-level HER2 amplified by CISH, and in 12 of these HercepTest IHC better reflected gene amplification status. All the 13 HER2 amplified discrepant cases were at least 2+ by HercepTest, while 10/13 of these were at least 2+ for Oracle. Considering CISH as gold standard, sensitivity of HercepTest and Oracle was 91% and 83%, and specificity was 94% and 98%, respectively. Positive and negative predictive values for HercepTest and Oracle were 90% and 95% for HercepTest and 96% and 91% for Oracle, respectively. Fully-automated HER2 staining with the monoclonal antibody in the Oracle kit shows a high level of agreement with manual staining by the polyclonal antibody in the HercepTest. Although Oracle shows in general some more cytoplasmic staining and may be slightly less sensitive in picking up HER2 amplified cases, it shows a higher specificity and may be considered as an alternative method to evaluate the HER2 expression in breast cancer with potentially less analytical variability.

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC): results of a multi-centre ALK-testing.

PubMed

V Laffert, Maximilian; Warth, Arne; Penzel, Roland; Schirmacher, Peter; Jonigk, Danny; Kreipe, Hans; Schildhaus, Hans-Ulrich; Merkelbach-Bruse, Sabine; Büttner, Reinhard; Reu, Simone; Kerler, Rosi; Jung, Andreas; Kirchner, Thomas; Wölfel, Cornelius; Petersen, Iver; Rodriguez, Regulo; Jochum, Wolfram; Bartsch, Holger; Fisseler-Eckhoff, Annette; Berg, Erika; Lenze, Dido; Dietel, Manfred; Hummel, Michael

2013-08-01

The reliable identification of non-small cell lung cancers (NSCLC) with chromosomal breaks in the gene of the anaplastic lymphoma kinase (ALK) is crucial for the induction of therapy with ALK-inhibitors. In order to ensure a reliable detection of ALK-breaks by means of fluorescence in situ hybridization (FISH) testing, round robin tests are essential. In preparation of a nation (German)-wide round robin test we initiated a pre-testing phase involving 8 experts in FISH-diagnostics to identify NSCLC cases (n = 10) with a pre-tested ALK-status. In addition, ALK immunohistochemistry (IHC) was performed to assess ALK protein expression. Sections derived from a tissue microarray, each consisting of 3 cores from 10 NSCLC cases, were independently tested for ALK protein expression by IHC and genomic ALK-breaks by FISH involving 8 institutes of pathology. Based on a pre-screening, 5 cases were identified to be clearly ALK-break negative, whereas the remaining 5 cases were ALK-break positive including one case with low percentage (20%) of positive cells. The latter had been additionally tested by RT-PCR. The 5 unequivocal ALK-break negative NSCLC were almost consistently scored negative by means of FISH and IHC by all 8 experts. Interestingly, 4 of the 5 cases with pre-defined ALK-breaks revealed homogenous FISH results whereas IHC for the detection of ALK protein expression showed heterogeneous results. The remaining case (low number of ALK-break positive cells) was scored negative by 3 experts and positive by the other 5. RT-PCR revealed the expression of an EML4-ALK fusion gene variant 1. ALK-break negative NSCLC cases revealed concordant homogeneous results by means of FISH and IHC (score 0-1) by all 8 experts. Discordant FISH results were raised in one ALK-break positive case with a low number of affected tumor cells. The remaining 4 ALK-break positive cases revealed concordant FISH data whereas the ALK-IHC revealed very diverse results. The cases with concordant FISH results provide an excellent basis for round robin ALK-FISH testing. As long as standardized ALK-IHC protocols are missing, ALK protein expression cannot by regarded as the method of choice for identification of patients eligible for treatment with ALK inhibitors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A preliminary report on the magnetic measurements of samples 72275 and 72255. [direction and magnitude of remanent magnetization

NASA Technical Reports Server (NTRS)

Banerjee, S. K.

1974-01-01

The direction and magnitude of natural remanent magnetization of five approximately 3-g subsamples of 72275 and 72255 and the high field saturation magnetization, coercive force, and isothermal remanent magnetization of 100-mg chip from each of these samples, were studied. Given an understanding of the magnetization processes, group 1 experiments provide information about the absolute direction of the ancient magnetizing field and a qualitative estimate of its size (paleointensity). The group 2 experiments yield a quantitative estimate of the iron content and a qualitative ideal of the grain sizes.

Coercivity enhancement of sintered Nd-Fe-B magnets by chemical bath deposition

NASA Astrophysics Data System (ADS)

Zhang, Qiushuang; Guo, Shuai; Yang, Xiao; Zeng, Jiling; Cao, Xuejing; Chen, Renjie; Yan, Aru

2018-05-01

The chemical bath deposition (CBD) method is used to diffuse the heavy rare earth element in order to obtain the high coercivity magnets with low heavy rare earth element. The jet mill powders are soaked in the alcohol suspension of Dy(CH3CHOHCH3)3 (Dy-ipa) so that Nd2Fe14B powder particles are surrounded by Dy-ipa homogeneously. By adding 1.0 wt. % Dy, the coercivity of magnet is increased from 14.47 kOe to 17.55 kOe with slight reduction of remanence after grain boundary diffusion (GBD) in the sintering and annealing processes. The temperature coefficient of coercivity optimizes from -0.629 %/°C to -0.605 %/°C as well as that of remanence improves from -0.108 %/°C to -0.100 %/°C. The CBD method is helpful for thermal stability and alignment either. The relation between the microstructure and the coercivity has been studied systematically.

Investigation of coercivity for electroplated Fe-Ni thick films

NASA Astrophysics Data System (ADS)

Yanai, T.; Eguchi, K.; Koda, K.; Kaji, J.; Aramaki, H.; Takashima, K.; Nakano, M.; Fukunaga, H.

2018-05-01

We have already reported Fe-Ni firms with good soft magnetic properties prepared by using an electroplating method. In our previous studies, we prepared the Fe-Ni films from citric-acid-based baths (CA-baths) and ammonium-chloride-based ones (AC-baths), and confirmed that the coercivity for the AC-baths was lower than that for the CA-baths. In the present study, we investigated reasons for the lower coercivity for the AC-baths to further improve the soft magnetic properties. From an observation of magnetic domains of the Fe22Ni78 films, we found that Fe22Ni78 film for AC-bath had a magnetic anisotropy in the width direction, and also found that the coercivity in the width direction was lower than the longitudinal one for the AC-bath. As an annealing for a stress relaxation in the films reduced the difference in the coercivity, we considered that the anisotropy is attributed to the magneto-elastic effect.

Operations Odyssey Dawn and Unified Protector: A Coercive Failure?

DTIC Science & Technology

2012-12-06

Coercive Air Power: A Primer for Military Strategists,” Air Power Journal 2, no. 1 (Spring 2007 ): 160. Mueller also argues that compellence and...faced defeat. Coalition Narrative/Strategic Goals As the resistance against the Libyan government stammered , the United States sought to increase...Mueller, Karl. “The Essence of Coercive Air Power: A Primer for Military Strategists,” Air Power Journal 2, no. 1 (Spring 2007 ): 159-174. NATO. Fact

Coercivity enhancement of anisotropic Dy-free Nd-Fe-B powders by conventional HDDR process

NASA Astrophysics Data System (ADS)

Morimoto, K.; Katayama, N.; Akamine, H.; Itakura, M.

2012-11-01

Coercivity enhancement of Dy-free Nd-Fe-Co-B-Ga-Zr powders was studied using the conventional hydrogenation-decomposition-desorption-recombination (HDDR) process. It was found that the addition of Al together with the proper Nd content and the slow hydrogen desorption of the HDDR treatment can induce high coercivity in the powder. For example, the 14.0 at% Nd-2.0 at% Al powder exhibits HcJ of 1560 kA/m, Br of 1.22 T, and (BH)max of 257 kJ/m3. The high coercivity inducement of the powder is thought to be attributed to the formation of Nd-rich phase, which continuously surrounds fine Nd2Fe14B grains.

Protease activity, localization and inhibition in the human hair follicle.

PubMed

Bhogal, R K; Mouser, P E; Higgins, C A; Turner, G A

2014-02-01

In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A framework for improving a seasonal hydrological forecasting system using sensitivity analysis

NASA Astrophysics Data System (ADS)

Arnal, Louise; Pappenberger, Florian; Smith, Paul; Cloke, Hannah

2017-04-01

Seasonal streamflow forecasts are of great value for the socio-economic sector, for applications such as navigation, flood and drought mitigation and reservoir management for hydropower generation and water allocation to agriculture and drinking water. However, as we speak, the performance of dynamical seasonal hydrological forecasting systems (systems based on running seasonal meteorological forecasts through a hydrological model to produce seasonal hydrological forecasts) is still limited in space and time. In this context, the ESP (Ensemble Streamflow Prediction) remains an attractive forecasting method for seasonal streamflow forecasting as it relies on forcing a hydrological model (starting from the latest observed or simulated initial hydrological conditions) with historical meteorological observations. This makes it cheaper to run than a standard dynamical seasonal hydrological forecasting system, for which the seasonal meteorological forecasts will first have to be produced, while still producing skilful forecasts. There is thus the need to focus resources and time towards improvements in dynamical seasonal hydrological forecasting systems which will eventually lead to significant improvements in the skill of the streamflow forecasts generated. Sensitivity analyses are a powerful tool that can be used to disentangle the relative contributions of the two main sources of errors in seasonal streamflow forecasts, namely the initial hydrological conditions (IHC; e.g., soil moisture, snow cover, initial streamflow, among others) and the meteorological forcing (MF; i.e., seasonal meteorological forecasts of precipitation and temperature, input to the hydrological model). Sensitivity analyses are however most useful if they inform and change current operational practices. To this end, we propose a method to improve the design of a seasonal hydrological forecasting system. This method is based on sensitivity analyses, informing the forecasters as to which element of the forecasting chain (i.e., IHC or MF) could potentially lead to the highest increase in seasonal hydrological forecasting performance, after each forecast update.

Distribution of eastern equine encephalomyelitis viral protein and nucleic acid within central nervous tissue lesions in white-tailed deer (Odocoileus virginianus).

PubMed

Kiupel, M; Fitzgerald, S D; Pennick, K E; Cooley, T M; O'Brien, D J; Bolin, S R; Maes, R K; Del Piero, F

2013-11-01

An outbreak of eastern equine encephalomyelitis (EEE) occurred in Michigan free-ranging white-tailed deer (Odocoileus virginianus) during late summer and fall of 2005. Brain tissue from 7 deer with EEE, as confirmed by reverse transcriptase polymerase chain reaction, was studied. Detailed microscopic examination, indirect immunohistochemistry (IHC), and in situ hybridization (ISH) were used to characterize the lesions and distribution of the EEE virus within the brain. The main lesion in all 7 deer was a polioencephalomyelitis with leptomeningitis, which was more prominent within the cerebral cortex, thalamus, hypothalamus, and brainstem. In 3 deer, multifocal microhemorrhages surrounded smaller vessels with or without perivascular cuffing, although vasculitis was not observed. Neuronal necrosis, associated with perineuronal satellitosis and neutrophilic neuronophagia, was most prominent in the thalamus and the brainstem. Positive IHC labeling was mainly observed in the perikaryon, axons, and dendrites of necrotic and intact neurons and, to a much lesser degree, in glial cells, a few neutrophils in the thalamus and the brainstem, and occasionally the cerebral cortex of the 7 deer. There was minimal IHC-based labeling in the cerebellum and hippocampus. ISH labeling was exclusively observed in the cytoplasm of neurons, with a distribution similar to IHC-positive neurons. Neurons positive by IHC and ISH were most prominent in the thalamus and brainstem. The neuropathology of EEE in deer is compared with other species. Based on our findings, EEE has to be considered a differential diagnosis for neurologic disease and meningoencephalitis in white-tailed deer.

Gene expression information improves reliability of receptor status in breast cancer patients

PubMed Central

Kenn, Michael; Schlangen, Karin; Castillo-Tong, Dan Cacsire; Singer, Christian F.; Cibena, Michael; Koelbl, Heinz; Schreiner, Wolfgang

2017-01-01

Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements. Crisp therapeutic decisions are based on IHC estimates, even if they are borderline reliable. We further improve decision quality by a responsibility function, defining a critical domain for gene expression. Refined normalization is devised to file any newly diagnosed patient into existing data bases. Our approach renders receptor estimates more reliable by identifying patients with questionable receptor status. The approach is also more efficient since the rate of conclusive samples is increased. We have curated and evaluated gene expression data, together with clinical information, from 2880 breast cancer patients. Combining IHC with gene expression information yields a method more reliable and also more efficient as compared to common practice up to now. Several types of possibly suboptimal treatment allocations, based on IHC receptor status alone, are enumerated. A ‘therapy allocation check’ identifies patients possibly miss-classified. Estrogen: false negative 8%, false positive 6%. Progesterone: false negative 14%, false positive 11%. HER2: false negative 2%, false positive 50%. Possible implications are discussed. We propose an ‘expression look-up-plot’, allowing for a significant potential to improve the quality of precision medicine. Methods are developed and exemplified here for breast cancer patients, but they may readily be transferred to diagnostic data relevant for therapeutic decisions in other fields of oncology. PMID:29100391

Combination of three-gene immunohistochemical panel and magnetic resonance imaging-detected extramural vascular invasion to assess prognosis in non-advanced rectal cancer patients

PubMed Central

Li, Xiao-Fu; Jiang, Zheng; Gao, Ying; Li, Chun-Xiang; Shen, Bao-Zhong

2016-01-01

AIM To identify a small, clinically applicable immunohistochemistry (IHC) panel that could be combined with magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) for assessment of prognosis concerning the non-advanced rectal cancer patients prior to operation. METHODS About 329 patients with pathologically confirmed rectal carcinoma (RC) were screened in this research, all of whom had been examined via an MRI and were treatment-naïve from July 2011 to July 2014. The candidate proteins that were reported to be altered by RC were examined in tissues by IHC. All chosen samples were adopted from the fundamental cores of histopathologically confirmed carcinomas during the initial surgeries. RESULTS Of the three proteins that were tested, c-MYC, PCNA and TIMP1 were detected with relatively significant expression in tumors, 35.9%, 23.7% and 58.7% respectively. The expression of the three proteins were closely connected with prognosis (P = 0.032, 0.003, 0.021). The patients could be classified into different outcome groups according to an IHC panel (P < 0.01) via these three proteins. Taking into consideration known survival covariates, especially EMVI, the IHC panel served as an independent prognostic factor. The EMVI combined with the IHC panel could categorize patients into different prognostic groups with distinction (P < 0.01). CONCLUSION These studies argue that this three-protein panel of c-MYC, PCNA, coupled with TIMP1 combined with MRI-detected EMVI could offer extra prognostic details for preoperative treatment of RC. PMID:27784970

Histology and immunohistochemistry of severe inflammatory bowel disease versus lymphoma in the ferret (Mustela putorius furo).

PubMed

Watson, Megan K; Cazzini, Paola; Mayer, Joerg; Gottdenker, Nicole; Reavill, Drury; Parry, Nicola; Fox, James G; Sakamoto, Kaori

2016-05-01

Inflammatory bowel disease (IBD) is a common disorder of ferrets (Mustela putorius furo) that may progress to lymphoma. Although routine histology is used to distinguish between these diseases, misclassifications may occur. Immunohistochemistry (IHC) is commonly used to distinguish between IBD and lymphoma in small animals. The objective of our study was to determine the agreement in the diagnosis reached solely using hematoxylin and eosin (HE)-stained, full-thickness sections versus using a combination of HE and IHC. Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal lymphoma and 3 control ferrets were analyzed by pathologists with expertise in ferrets. A pathologist blinded to the original diagnosis assessed the same HE-stained sections. Analysis was then repeated using HE sections in parallel with sections stained using antibodies against CD3 and CD79a. No significant difference was found between the original HE diagnosis and the HE diagnosis reached by the blinded pathologist (p = 0.91) or between the blinded pathologist's HE versus HE with IHC diagnosis (p = 0.16). In the 2 cases where disagreement was present, IHC was pivotal in reaching a final diagnosis. There was no significant age (p = 0.29) difference between diagnoses; however, significantly more male ferrets were affected with IBD than females (p = 0.004). Immunophenotype of the lymphoma was not correlated with predilection for location in the intestinal wall (p = 0.44). Results suggest that although IHC is not necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be useful a definitive diagnosis in cases of severe IBD. © 2016 The Author(s).

Ovarian Brenner tumour: a morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium.

PubMed

Kuhn, Elisabetta; Ayhan, Ayse; Shih, Ie-Ming; Seidman, Jeffrey D; Kurman, Robert J

2013-12-01

Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium. We hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal junction which, when embedded in the ovary as Walthard cell nests, may progress to BTs. The aim of this study was to validate this hypothesis by a morphologic and immunohistochemical (IHC) analysis. The IHC analysis revealed that fallopian tube secretory cells, transitional metaplasia, Walthard cell nests and the epithelial component of BTs shared a similar IHC profile, consistently expressing AKR1C3 (an enzyme involved in androgen biosynthesis) and androgen receptor, but not calretinin. The tumour stromal cells that immediately surrounded the epithelial nests showed strong expression of calretinin, inhibin and steroidogenic factor 1 (markers of steroidogenic cells) in the majority of BTs. Using a highly sensitive immunofluorescent staining method, we detected small groups of cilia in transitional metaplasia and Walthard cell nests, multifocal stretches of cilia and/or ciliated vacuoles in benign BTs and well-developed cilia in atypical proliferative BTs. Our findings suggest a tubal origin of BTs through transitional metaplasia and Walthard cell nests, based on their anatomic proximity, similar IHC profile and the presence of cilia. In addition, we hypothesise a role of androgenic stimulation in the pathogenesis of BT, based on the IHC staining pattern of calretinin, inhibin and steroidogenic factor 1 expressed in the luteinised stromal cells surrounding the epithelial nests of the tumours, and AKR1C3 and androgen receptor expressed in both the epithelial and stromal components. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fully Automated Fluorescent in situ Hybridization (FISH) Staining and Digital Analysis of HER2 in Breast Cancer: A Validation Study

PubMed Central

van der Logt, Elise M. J.; Kuperus, Deborah A. J.; van Setten, Jan W.; van den Heuvel, Marius C.; Boers, James. E.; Schuuring, Ed; Kibbelaar, Robby E.

2015-01-01

HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH) procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with supervised automated analysis with the Visia imaging D-Sight digital imaging platform. HER2 assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50 random IHC scores) full-sized slides of resections/biopsies obtained for diagnostic purposes previously. For digital analysis slides were pre-screened at 20x and 100x magnification for all fluorescent signals and supervised-automated scoring was performed on at least two pictures (in total at least 20 nuclei were counted) with the D-Sight HER2 FISH analysis module by two observers independently. Results were compared to data obtained previously with the manual Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples and 50 selected IHC 2+ cases was 98.8% (κ = 0.94) and 93.8% (κ = 0.88), respectively. The results of 50 additionally tested unselected IHC cases were concordant with previously obtained IHC and/or FISH data. The combination of the Leica FISH system with the D-Sight digital imaging platform is a feasible method for HER2 assessment in routine clinical practice for patients with invasive breast cancer. PMID:25844540

Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis.

PubMed

Marques, Fernanda A; Soares, Rodrigo P; Almeida, Gregório G; Souza, Carolina C; Melo, Maria N; Pinto, Sebastião A; Quixabeira, Valeria B; Pereira, Ledice I; Dorta, Miriam L; Ribeiro-Dias, Fatima; Silveira, Fernando T; Silva, Sydnei M; Gontijo, Celia M; Tafuri, Wagner L

2017-02-01

American tegumentary leishmaniasis (ATL) is a neglected disease widely distributed in Latin America. In Brazil, it is caused by different Leishmania species belonging to the Subgenera Viannia and Leishmania. ATL diagnosis is routinely based on clinical, epidemiological, parasitological and immunological (delayed-type hypersensitivity skin test-DTH) evidences. The main objective of this work was to determine the efficacy of a previous immunohistochemical (IHC) method developed by our group. Seventy eight skin biopsies from patients with different ATL clinical forms and origins were evaluated. The method was previously standardized in ATL patients from the municipality of Caratinga, Minas Gerais, Brazil, all infected with Leishmania (V.) braziliensis. Here, it is evaluated in patients from the North, Southeast and Midwest regions of Brazil. Clinical, parasitological (biopsy PCR) and immunological (Montenegro skin test-MST) diagnosis were performed prior to IHC procedure. The IHC procedure detected 70.5% of the cases having a high agreement with MST diagnosis (kappa=0.84). A distinguished contribution of this work is that IHC succeed in diagnosing some negative DTH patients. Those were infected with Leishmania (L.) amazonensis, commonly causing the anergic form of the disease. In conclusion, IHC succeed in detecting ATL caused by different Leishmania species from various geographic regions and clinical status. Although it was not able to detect ATL in all patients, it was better than MST providing an additional tool for the diagnosis of ATL patients. There was no significant correlation between clinical forms and histological features including the presence of necrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

PubMed Central

Carbone, Michele; Shimizu, David; Napolitano, Andrea; Tanji, Mika; Pass, Harvey I.; Yang, Haining; Pastorino, Sandra

2016-01-01

The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10–20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy. We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 × 10−11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies. PMID:27447750

Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants.

PubMed

Patel, Nimesh R; Salim, Alaa A; Sayeed, Hadi; Sarabia, Stephen F; Hollingsworth, Faith; Warren, Mikako; Jakacky, Jared; Tanas, Munir; Oliveira, Andre M; Rubin, Brian P; Lazar, Alexander J; López-Terrada, Dolores; Wang, Wei-Lien

2015-11-01

Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE. Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC. This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity. © 2015 John Wiley & Sons Ltd.

Utility of p57 immunohistochemistry in differentiating between complete mole, partial mole & non-molar or hydropic abortus.

PubMed

Samadder, Abhimanyu; Kar, Rakhee

2017-01-01

There is considerable inter-observer variability in the diagnosis of molar pregnancies by histomorphological examination of products of conception (POC). The p57KIP2 gene is paternally imprinted and expressed from the maternal allele. On immunohistochemistry (IHC) with p57, complete mole (CM) shows absent staining whereas hydropic abortus (HA) and partial mole (PM) show positive staining. This study was undertaken to evaluate the role of p57 IHC along with histomorphology in differentiating between CM, PM and non-molar or HA. This was a cross-sectional study over a period of three and a half years on archival material. Detailed histomorphological review along with p57 IHC was carried out in 28 diagnosed cases (23 CM, 4 PM and 1 molar pregnancy not categorized) and 25 controls of four normal placentas and 21 POC (8 non-hydropic and 13 HA). In 14.8 per cent (4/27) cases, there was discordance in accurate subtyping of molar pregnancy. One case of CM showed inconsistent IHC pattern. In 15.4 per cent (2/13) HA, molar pregnancy was final diagnosis. After final review, there were 25 CM, five PM, 22 non-molar controls including 10 HA and one not assigned (PM/HA). IHC with p57 was negative in 96 per cent CM and positive in 100 and 95 per cent PM and non-molar controls, respectively. This study showed that negative p57KIP2 immunostaining reliably identified CM and could be used in association with the histological findings to distinguish CM from its mimics.

The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors.

PubMed

Felkai, Luca; Bánusz, Rita; Kovalszky, Ilona; Sápi, Zoltán; Garami, Miklós; Papp, Gergő; Karászi, Katalin; Varga, Edit; Csóka, Monika

2017-10-28

Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study.

PubMed

Nagaraja, V; Shaw, N; Morey, A L; Cox, M R; Eslick, G D

2016-01-01

Several studies have evaluated the prognostic value of HER2 in oesophageal cancer, but the prognostic influence of HER2 overexpression in oesophageal cancer remains uncertain. The aim of this study was to assess the incidence of HER2 positivity and relationship with clinicopathological features in patients with oesophageal cancer. The study cohort consisted of 269 patients diagnosed with oesophageal carcinoma in a single institution. HER2 expression was analysed by immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival analysis was assessed using Hazard models. HER2 expression was IHC3+ in 14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases. SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among 27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of 125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95% CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71-20.00). There was no significant difference in survival between the (HER2 +ve, 14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence rate of 9.9% was found among patients with oesophageal cancer and no correlation with survival was detected overall. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Development of immunohistochemistry services for cancer care in western Kenya: Implications for low- and middle-income countries

PubMed Central

Strother, R. Matthew; Ndiangui, Francis; Chumba, David; Jacobson, William; Dodson, Cecelia; Resnic, Murray B.; Strate, Randall W.; Smith, James W.

2016-01-01

Background Cancer is becoming a major cause of mortality in low- and middle-income countries. Unlike infectious disease, malignancy and other chronic conditions require significant supportive infrastructure for diagnostics, staging and treatment. In addition to morphologic diagnosis, diagnostic pathways in oncology frequently require immunohistochemistry (IHC) for confirmation. We present the experience of a tertiary-care hospital serving rural western Kenya, which developed and validated an IHC laboratory in support of a growing cancer care service. Objectives, methods and outcomes Over the past decade, in an academic North-South collaboration, cancer services were developed for the catchment area of Moi Teaching and Referral Hospital in western Kenya. A major hurdle to treatment of cancer in a resource-limited setting has been the lack of adequate diagnostic services. Building upon the foundations of a histology laboratory, strategic investment and training were used to develop IHC services. Key elements of success in this endeavour included: translation of resource-rich practices to a resource-limited setting, such as using manual, small-batch IHC instead of disposable- and maintenance-intensive automated machinery, engagement of outside expertise to develop reagent-efficient protocols and supporting all levels of staff to meet the requirements of an external quality assurance programme. Conclusion Development of low- and middle-income country models of services, such as the IHC laboratory presented in this paper, is critical for the infrastructure in resource-limited settings to address the growing cancer burden. We provide a low-cost model that effectively develops these necessary services in a challenging laboratory environment. PMID:28879100

Validation of Immunohistochemical Assays for Integral Biomarkers in the NCI-MATCH EAY131 Clinical Trial.

PubMed

Khoury, Joseph D; Wang, Wei-Lien; Prieto, Victor G; Medeiros, L Jeffrey; Kalhor, Neda; Hameed, Meera; Broaddus, Russell; Hamilton, Stanley R

2018-02-01

Biomarkers that guide therapy selection are gaining unprecedented importance as targeted therapy options increase in scope and complexity. In conjunction with high-throughput molecular techniques, therapy-guiding biomarker assays based upon immunohistochemistry (IHC) have a critical role in cancer care in that they inform about the expression status of a protein target. Here, we describe the validation procedures for four clinical IHC biomarker assays-PTEN, RB, MLH1, and MSH2-for use as integral biomarkers in the nationwide NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) EAY131 clinical trial. Validation procedures were developed through an iterative process based on collective experience and adaptation of broad guidelines from the FDA. The steps included primary antibody selection; assay optimization; development of assay interpretation criteria incorporating biological considerations; and expected staining patterns, including indeterminate results, orthogonal validation, and tissue validation. Following assay lockdown, patient samples and cell lines were used for analytic and clinical validation. The assays were then approved as laboratory-developed tests and used for clinical trial decisions for treatment selection. Calculations of sensitivity and specificity were undertaken using various definitions of gold-standard references, and external validation was required for the PTEN IHC assay. In conclusion, validation of IHC biomarker assays critical for guiding therapy in clinical trials is feasible using comprehensive preanalytic, analytic, and postanalytic steps. Implementation of standardized guidelines provides a useful framework for validating IHC biomarker assays that allow for reproducibility across institutions for routine clinical use. Clin Cancer Res; 24(3); 521-31. ©2017 AACR . ©2017 American Association for Cancer Research.

A Healthy Mix: A Case Study of the University of North Carolina at Chapel Hill's Interdisciplinary Health Communication Certificate Program

ERIC Educational Resources Information Center

El-Toukhy, Sherine; Holman, Lynette

2012-01-01

This study evaluated attitudes toward interdisciplinary education by appraising the Interdisciplinary Health Communication (IHC) Certificate program at the University of North Carolina at Chapel Hill as a case study. Sixteen affiliated faculty and thirteen students enrolled in the IHC program as of 2008-2009 were surveyed. Although the attitude…

PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype

PubMed Central

Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

2017-01-01

Background: Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. Methods: 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. Results: ER/PR− tumours demonstrated higher Kepmean and SUVmax than ER or PR+ tumours. HER2− tumours displayed higher ADCmean, Kepmean, and SUVmax than HER2+tumours. Only ADCmean discriminated Ki67⩽14% tumours (lower ADCmean) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62% P=0.001). Conclusions: Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options. PMID:28208155

PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

PubMed

Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

2017-03-28

Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. ER/PR- tumours demonstrated higher Kep mean and SUV max than ER or PR+ tumours. HER2- tumours displayed higher ADC mean , Kep mean , and SUV max than HER2+tumours. Only ADC mean discriminated Ki67⩽14% tumours (lower ADC mean ) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

Application of MCD spectroscopy and TD-DFT to endohedral metallofullerenes for characterization of their electronic transitions.

PubMed

Yamada, Michio; Slanina, Zdenek; Mizorogi, Naomi; Muranaka, Atsuya; Maeda, Yutaka; Nagase, Shigeru; Akasaka, Takeshi; Kobayashi, Nagao

2013-03-14

We describe, for the first time, the application of magnetic circular dichroism (MCD) spectroscopy and time-dependent density functional theory (TD-DFT) calculations using B3LYP and M06-2X functionals to characterize the electronic transitions of endohedral metallofullerenes (EMFs). Results revealed that the electronic transitions of La@C(2v)-C(82), La(2)@I(h)-C(80), and Sc(3)N@I(h)-C(80) can be assigned using these techniques. Particularly, a difference in the electronic transitions between La(2)@I(h)-C(80) and Sc(3)N@I(h)-C(80), which is invisible in absorption spectra, was observed clearly in MCD spectra. The observed MCD bands agree well with the oscillator strengths calculated using the B3LYP functional. In addition, the MCD bands of La(2)@I(h)-C(80) were altered upon [5,6]-addition, demonstrating that the MCD spectroscopy is sensitive to chemical functionalization of EMFs, and that it is therefore powerful to distinguish [5,6]-adducts from pristine La(2)@I(h)-C(80), although no marked difference exists in their absorption spectra.

The Influence of Planetary Waves on Polar Mesospheric Clouds

NASA Astrophysics Data System (ADS)

France, J. A.; Randall, C. E.; Harvey, L.; Siskind, D. E.; Lumpe, J. D.; Bailey, S. M.; Carstens, J. N.; Russell, J. M., III

2016-12-01

Polar mesospheric clouds (PMCs) form as a result of low temperatures and enhanced water vapor near the polar summer mesospause. These conditions occur as a result of upwelling associated with the upper branch of the gravity wave-driven global residual circulation, and are sensitive to changes in planetary wave breaking in the winter hemisphere through interhemispheric coupling (IHC). Observations by the Cloud Imaging and Particle Size (CIPS) instrument on the Aeronomy of Ice in the Mesosphere (AIM) satellite show an anomalous decline in northern hemisphere PMCs in August 2014. The decline is attributed to IHC triggered by planetary wave activity in the Antarctic stratosphere. The results indicate that the IHC in 2014 occurred via a pathway that previous studies have not emphasized. Based on Aura Microwave Limb Sounder data, we suggest that shifts in zonal winds in the summer stratosphere triggered a circulation change that led to the observed PMC decline. We also show that the 5-day planetary wave modulates the response to IHC, in that PMCs persist in the trough when zonal mean temperatures are too high to support PMCs, and are absent in the ridge when mean temperatures are low enough to support PMCs.

Use of routine histopathology and factor VIII-related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs.

PubMed

Giuffrida, M A; Bacon, N J; Kamstock, D A

2017-12-01

Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII-RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA. © 2016 John Wiley & Sons Ltd.

Switching of magnetic easy-axis using crystal orientation for large perpendicular coercivity in CoFe2O4 thin film

PubMed Central

Shirsath, Sagar E.; Liu, Xiaoxi; Yasukawa, Yukiko; Li, Sean; Morisako, Akimitsu

2016-01-01

Perpendicular magnetization and precise control over the magnetic easy axis in magnetic thin film is necessary for a variety of applications, particularly in magnetic recording media. A strong (111) orientation is successfully achieved in the CoFe2O4 (CFO) thin film at relatively low substrate temperature of 100 °C, whereas the (311)-preferred randomly oriented CFO is prepared at room temperature by the DC magnetron sputtering technique. The oxygen-deficient porous CFO film after post-annealing gives rise to compressive strain perpendicular to the film surface, which induces large perpendicular coercivity. We observe the coercivity of 11.3 kOe in the 40-nm CFO thin film, which is the highest perpendicular coercivity ever achieved on an amorphous SiO2/Si substrate. The present approach can guide the systematic tuning of the magnetic easy axis and coercivity in the desired direction with respect to crystal orientation in the nanoscale regime. Importantly, this can be achieved on virtually any type of substrate. PMID:27435010

Angular dependence of coercivity in isotropically aligned Nd-Fe-B sintered magnets

NASA Astrophysics Data System (ADS)

Matsuura, Yutaka; Nakamura, Tetsuya; Sumitani, Kazushi; Kajiwara, Kentaro; Tamura, Ryuji; Osamura, Kozo

2018-05-01

In order to understand the coercivity mechanism in Nd-Fe-B sintered magnets, the angular dependence of the coercivity of an isotropically aligned Nd15Co1.0B6Febal. sintered magnet was investigated through magnetization measurements using a vibrating sample magnetometer. These results are compared with the angular dependence calculated under the assumption that the magnetization reversal of each grain follows the Kondorskii law or, in other words, the 1/cos θ law for isotropic alignment distributions. The calculated angular dependence of the coercivity agrees very well with the experiment for magnetic fields applied between angles of 0 and 60°, and it is expected that the magnetization reversal occurs in each grain individually followed the 1/cos θ law. In contrast, this agreement between calculation and experiment is not found for anisotropic Nd-Fe-B samples. This implies that the coercivity of the aligned magnets depends upon the de-pinning of the domain walls from pinning sites. When the de-pinning occurs, it is expected that the domain walls are displaced through several grains at once.

Substrate bias effects on composition and coercivity of CoCrTa/Cr thin films on canasite and glass

NASA Astrophysics Data System (ADS)

Deng, Y.; Lambeth, D. N.; Sui, X.; Lee, L.-L.; Laughlin, D. E.

1993-05-01

CoCrTa/Cr thin films were prepared by rf diode sputtering onto canasite and glass substrates at various bias voltages from two targets of different compositions (Co82.8Cr14.6Ta2.6 and Co86Cr12Ta2). While Auger depth profile analysis indicates that there is some broadening at the CoCrTa-Cr interface, x-ray fluorescence spectroscopy reveals that changes in alloy composition due to the resputtering processes are even more prominent. For both targets, as the substrate bias increases the Co content in the films declines, and the magnetization decreases. The maximum film coercivity appears to correlate to the final film composition. By investigating the results from both targets, it is concluded that the coercivity reaches a maximum when the film composition is in the neighborhood of Co84Cr13Ta3. Thus, to optimize the coercivity different bias voltages are required for each target. Excessive substrate bias, however, leads to films with low magnetization and coercivity.

Authorities' Coercive and Legitimate Power: The Impact on Cognitions Underlying Cooperation

PubMed Central

Hofmann, Eva; Hartl, Barbara; Gangl, Katharina; Hartner-Tiefenthaler, Martina; Kirchler, Erich

2017-01-01

The execution of coercive and legitimate power by an authority assures cooperation and prohibits free-riding. While coercive power can be comprised of severe punishment and strict monitoring, legitimate power covers expert, and informative procedures. The perception of these powers wielded by authorities stimulates specific cognitions: trust, relational climates, and motives. With four experiments, the single and combined impact of coercive and legitimate power on these processes and on intended cooperation of n1 = 120, n2 = 130, n3 = 368, and n4 = 102 student participants is investigated within two exemplary contexts (tax contributions, insurance claims). Findings reveal that coercive power increases an antagonistic climate and enforced compliance, whereas legitimate power increases reason-based trust, a service climate, and voluntary cooperation. Unexpectedly, legitimate power is additionally having a negative effect on an antagonistic climate and a positive effect on enforced compliance; these findings lead to a modification of theoretical assumptions. However, solely reason-based trust, but not climate perceptions and motives, mediates the relationship between power and intended cooperation. Implications for theory and practice are discussed. PMID:28149286

Predicting sexual coercion in early adulthood: The transaction among maltreatment, gang affiliation, and adolescent socialization of coercive relationship norms.

PubMed

Ha, Thao; Kim, Hanjoe; Christopher, Caroline; Caruthers, Allison; Dishion, Thomas J

2016-08-01

This study tested a transactional hypothesis predicting early adult sexual coercion from family maltreatment, early adolescent gang affiliation, and socialization of adolescent friendships that support coercive relationship norms. The longitudinal study of a community sample of 998 11-year-olds was intensively assessed in early and middle adolescence and followed to 23-24 years of age. At age 16-17 youth were videotaped with a friend, and their interactions were coded for coercive relationship talk. Structural equation modeling revealed that maltreatment predicted gang affiliation during early adolescence. Both maltreatment and gang affiliation strongly predicted adolescent sexual promiscuity and coercive relationship norms with friends at age 16-17 years. Adolescent sexual promiscuity, however, did not predict sexual coercion in early adulthood. In contrast, higher levels of observed coercive relationship talk with a friend predicted sexual coercion in early adulthood for both males and females. These findings suggest that peers have a socialization function in the development of norms prognostic of sexual coercion, and the need to consider peers in the promotion of healthy relationships.

Material deprivation and unemployment affect coercive sex among young people in the urban slums of Blantyre, Malawi: A multi-level approach.

PubMed

Kamndaya, Mphatso; Kazembe, Lawrence N; Vearey, Jo; Kabiru, Caroline W; Thomas, Liz

2015-05-01

We explore relations among material deprivation (measured by insufficient housing, food insecurity and poor healthcare access), socio-economic status (employment, income and education) and coercive sex. A binary logistic multi-level model is used in the estimation of data from a survey of 1071 young people aged 18-23 years, undertaken between June and July 2013, in the urban slums of Blantyre, Malawi. For young men, unemployment was associated with coercive sex (odds ratio [OR]=1.77, 95% confidence interval [CI]: 1.09-3.21) while material deprivation (OR=1.34, 95% CI: 0.75-2.39) was not. Young women in materially deprived households were more likely to report coercive sex (OR=1.37, 95% CI: 1.07-2.22) than in non-materially deprived households. Analysis of local indicators of deprivation is critical to inform the development of effective strategies to reduce coercive sex in urban slums in Malawi. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of Antibodies to Identify Cellular Expression of Dopamine Receptor 4.

PubMed

Deming, Janise D; Van Craenenbroeck, Kathleen; Eom, Yun Sung; Lee, Eun-Jin; Craft, Cheryl Mae

2016-01-01

The dopamine receptor D4 (DRD4) plays an important role in vision. In order to study the DRD4 expression in vivo, it is important to have antibodies that are specific for DRD4 for both immunoblot and immunohistochemical (IHC) applications. In this study, six antibodies raised against DRD4 peptides were tested in vitro, using transfected mammalian cells, and in vivo, using mouse retinas. Three Santa Cruz (SC) antibodies, D-16, N-20, and R-20, were successful in IHC of transfected DRD4; however, N-20 was the only one effective on immunoblot analysis in DRD4 transfected cells and IHC of mouse retinal sections, while R-20, 2B9, and Antibody Verify AAS63631C were non-specific or below detection.

Effect of an annealing on magnetic properties of Fe-Ni films electroplated in citric-acid-based plating baths

NASA Astrophysics Data System (ADS)

Yanai, T.; Koda, K.; Eguchi, K.; Morimura, T.; Takashima, K.; Nakano, M.; Fukunaga, H.

2018-04-01

We have already reported Fe-Ni films with good soft magnetic properties prepared by using an electroplating method. In the present study, we employed an annealing for further improvement in soft magnetic properties of the electroplated Fe-Ni films. The annealing reduces the coercivity of the films, and the reduction rate of the coercivity depended on the Cl- ion concentration in the bath. The Fe22Ni78 films prepared in the plating bath with high Cl- ion concentration showed large reduction rate of the coercivity, and we found that the annealing is more effective for high Cl- ion concentration bath since much lower coercivity value can be obtained compared with that for low Cl- ion concentration one.

5 CFR 950.108 - Preventing coercive activity.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS General Provisions § 950.108 Preventing coercive activity. True voluntary... Section 950.108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... the supervisor's unit or organization. ...

5 CFR 950.108 - Preventing coercive activity.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS General Provisions § 950.108 Preventing coercive activity. True voluntary... Section 950.108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... the supervisor's unit or organization. ...

5 CFR 950.108 - Preventing coercive activity.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS General Provisions § 950.108 Preventing coercive activity. True voluntary... Section 950.108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... the supervisor's unit or organization. ...

5 CFR 950.108 - Preventing coercive activity.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS General Provisions § 950.108 Preventing coercive activity. True voluntary... Section 950.108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... the supervisor's unit or organization. ...

Immunohistochemical findings of the granulomatous reaction associated with tuberculosis.

PubMed

Karimi, Shirin; Shamaei, Masoud; Pourabdollah, Mihan; Sadr, Makan; Karbasi, Mehrdad; Kiani, Arda; Bahadori, Moslem

2016-12-01

The histological diagnosis of Mycobacterium tuberculosis (MTB) has long been a diagnostic challenge in the anatomical pathology field despite availability of different laboratory methods. Immunohistochemistry (IHC) could not only confirm granulomatous tissue involvement but also demonstrate MTB antigen immunolocalization. This study tries to clarify the details of IHC staining for MTB with pAbBCG. A total of 50 patients undergoing simultaneous biopsy and tissue culture with positive tissue culture for MTB during 2005-2009 were selected from the MRC Department at Masih Daneshvari Hospital, Tehran, Iran. Using the archives of the Pathology Department of this hospital, which is a referral center for pathological lung lesions, hematoxylin and eosin slides of the selected patients were evaluated. Twenty-three confirmed TB granulomatous tissue samples with adequate tissue and number of granulomas were chosen and studied by Ziehl-Neelsen and IHC staining with pAbBCG. A total of 23 cases were evaluated, of which 17 (73.9%) were males. The types of tissue obtained from study cases were as follows: pleura (9 cases, 39.1%), lymph node (cervical, axillary, and thoracic [9 cases, 39.1%]), and lung tissues (5 cases, 21.7%). IHC staining was positive in all samples, whereas Ziehl-Neelsen staining was positive in nine cases of 23 (39.1%). IHC showed positive coarse granular cytoplasmic and round, fragmented bacillary staining. In this study, epithelioid cells clearly showed more positive staining at the periphery rather than at the center of granuloma. There is also positive staining in endothelial cells, fibroblasts, plasma cells, macrophages, and lymphocytes outside the granuloma. Detection of TB in tissue slides is still based on the histological pattern of the granuloma, which has several differential diagnoses with different treatments. Presence of mycobacterial antigens and tissue morphology can be evaluated using the IHC technique. Considering the criteria of positive IHC staining of TB granulomatous reactions, this stain not only highlights the presence of mycobacterial antigens for tissue diagnosis, but also could morphologically localize their distribution in different cells. Pathologists must be familiar with adequate staining pattern, elimination of background staining, and type of selected antibody. This method is especially important for application in countries with high prevalence of TB as a technique with early diagnostic value in tissue specimens. Early diagnosis using this technique can reduce related morbidity and mortality and decrease the rate of complications due to misdiagnosis and mistreatment of TB. Copyright © 2016.

PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

PubMed Central

2012-01-01

Background Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. Conclusions The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic. PMID:23035882

Surface analysis of Fe-Co-Mo electrolytic coatings

NASA Astrophysics Data System (ADS)

Yar-Mukhamedova, G. Sh; Sakhnenko, N. D.; Ved', M. V.; Yermolenko, I. Yu; Zyubanova, S. I.

2017-06-01

Coatings Fe-Co-Mo with a composition of 47 at.% iron, 28 at.% Cobalt and 25 at.% Molybdenum were deposited from citrate electrolyte using pulse electrolysis mode. Scanning electron and atomic force microscopy have established the surface morphology and topography. It was identified the parts with a globular structure which have an average size of 0.2-0.5μm and singly located sharp grains. Within the same scan area sites with developed surface were detected the topography of which is identical to the crystal structure of cobalt with the crystallites size of 0.2-1.75μm. The parameters Ra and Rq for parts with different morphology as well as average characteristics of coatings demonstrated the low roughness of the surface. It is found that the coercive force of Fe-Co-Mo films is 7-10 Oe, which allow us to classify the Fe-Co-Mo coatings as soft magnetic materials.

Pathobiological investigation of naturally infected canine rabies cases from Sri Lanka.

PubMed

Beck, S; Gunawardena, P; Horton, D L; Hicks, D J; Marston, D A; Ortiz-Pelaez, A; Fooks, A R; Núñez, A

2017-04-12

The recommended screening of rabies in 'suspect' animal cases involves testing fresh brain tissue. The preservation of fresh tissue however can be difficult under field conditions and formalin fixation provides a simple alternative that may allow a confirmatory diagnosis. The occurrence and location of histopathological changes and immunohistochemical (IHC) labelling for rabies in formalin fixed paraffin embedded (FFPE) canine brain is described in samples from 57 rabies suspect cases from Sri-Lanka. The presence of Negri bodies and immunohistochemical detection of rabies virus antigen were evaluated in the cortex, hippocampus, cerebellum and brainstem. The effect of autolysis and artefactual degeneration of the tissue was also assessed. Rabies was confirmed in 53 of 57 (93%) cases by IHC. IHC labelling was statistically more abundant in the brainstem. Negri bodies were observed in 32 of 53 (60.4%) of the positive cases. Although tissue degradation had no effect on IHC diagnosis, it was associated with an inability to detect Negri bodies. In 13 cases, a confirmatory Polymerase chain reaction (PCR) testing for rabies virus RNA was undertaken by extracting RNA from fresh frozen tissue, and also attempted using FFPE samples. PCR detection using fresh frozen samples was in agreement with the IHC results. The PCR method from FFPE tissues was suitable for control material but unsuccessful in our field cases. Histopathological examination of the brain is essential to define the differential diagnoses of behaviour modifying conditions in rabies virus negative cases, but it is unreliable as the sole method for rabies diagnosis, particularly where artefactual change has occurred. Formalin fixation and paraffin embedding does not prevent detection of rabies virus via IHC labelling even where artefactual degeneration has occurred. This could represent a pragmatic secondary assay for rabies diagnosis in the field because formalin fixation can prevent sample degeneration. The brain stem was shown to be the site with most viral immunoreactivity; supporting recommended sampling protocols in favour of improved necropsy safety in the field. PCR testing of formalin fixed tissue may be successful in certain circumstances as an alternative test.

A nCounter CNV Assay to Detect HER2 Amplification: A Correlation Study with Immunohistochemistry and In Situ Hybridization in Advanced Gastric Cancer.

PubMed

Ahn, Soomin; Hong, Mineui; Van Vrancken, Michael; Lyou, You Jeong; Kim, Seung Tae; Park, Se Hoon; Kang, Won Ki; Park, Young Suk; Jung, Sin-Ho; Woo, Minah; Lee, Jeeyun; Kim, Kyoung-Mee

2016-08-01

Screening amplified genes for targeted therapy with high-throughput technology is very important. The NanoString nCounter system allows multiplexed digital quantification of target molecules through the use of color-coded barcodes with the great advantage that formalin-fixed, paraffin-embedded (FFPE) tissue can be utilized. We tested nCounter custom copy number variation (CNV) panels in 220 gastric cancer samples and evaluated the utility of this method as a screening tool for the detection of CNV using HER2. For the validation of results, we compared the nCounter results with immunohistochemistry (IHC), and we further performed in situ hybridization (ISH) in discrepant cases. The average HER2 gene copy numbers (CNs) by nCounter were 17.25, 2.0 and 2.61 for the HER2 IHC positive (3+), equivocal (2+), and negative cases, respectively. Out of the 16 IHC 3+ cases, 13 (81.3 %) were reported as HER2 CN gain (≥4). Gastric cancers with homogeneous HER2 overexpression or high tumor purity showed HER2 CN ≥10. Among the 192 cases with HER2 IHC negative and without HER2 gene amplification, 29 showed a HER2 CN ≥4 with the nCounter assay. The nCounter assay had a concordance rate of 83.4 % (kappa value, 0.35), a sensitivity of 66.7 %, a specificity of 85.2 %, a negative predictive value of 96 %, and a positive predictive value of 32.6 % compared with HER2 IHC/ISH results. Fresh frozen (FF) samples revealed a higher concordance rate (91.5 %, kappa value, 0.59) than FFPE samples (78.5 %, kappa value 0.27) and showed a high specificity (97.2 %). The nCounter CNV assay is a reliable and practical method to detect high CN variations. Given the intra-tumoral HER2 heterogeneity and normal cell contamination, additional IHC and/or FISH is necessary and needs caution in interpretation, especially in FFPE tissue samples.

Antidot patterned single and bilayer thin films based on ferrimagnetic Tb-Co alloy with perpendicular magnetic anisotropy

NASA Astrophysics Data System (ADS)

Kulesh, N. A.; Vázquez, M.; Lepalovskij, V. N.; Vas'kovskiy, V. O.

2018-02-01

Hysteresis properties and magnetization reversal in TbCo(30 nm) and FeNi(10 nm)/TbCo(30 nm) films with nanoscale antidot lattices are investigated to test the effect of nanoholes on the perpendicular anisotropy in the TbCo layer and the induced exchange bias in the FeNi layer. The antidots are introduced by depositing the films on top of hexagonally ordered porous anodic alumina substrates with pore diameter and interpore distance fixed to 75 nm and 105 nm, respectively. The analysis of combined vibrating sample magnetometry, Kerr microscopy and magnetic force microscopy imaging measurements has allowed us to link macroscopic and local magnetization reversal processes. For magnetically hard TbCo films, we demonstrate the tunability of magnetic anisotropy and coercive field (i.e., it increases from 0.2 T for the continuous film to 0.5 T for the antidot film). For the antidot FeNi/TbCo film, magnetization of FeNi is confirmed to be in plane. Although an exchange bias has been locally detected in the FeNi layer, the integrated hysteresis loop has increased coercivity and zero shift along the field axis due to the significantly decreased magnetic anisotropy of TbCo layer.

Characterization facility for magneto-optic media and systems

NASA Technical Reports Server (NTRS)

Mansuripur, M.; Fu, H.; Gadetsky, S.; Sugaya, S.; Wu, T. H.; Zambuto, J.; Gerber, R.; Goodman, T.; Erwin, J. K.

1993-01-01

Objectives of this research are: (1) to measure the hysteresis loop, Kerr rotation angle, anisotropy energy profile, Hall voltage, and magnetoresistance of thin-film magneto-optic media using our loop-tracer; (2) measure the wavelength-dependence of the Kerr rotation angle, Theta(sub k), and ellipticity, epsilon(sub k), for thin-film media using our magneto-optic Kerr spectrometer (MOKS); (3) measure the dielectric tensor of thin-film and multilayer samples using our variable-angle magneto-optic ellipsometer (VAMOE); (4) measure the hysteresis loop, coercivity, remanent magnetization, saturation magnetization, and anisotropy energy constant for thin film magnetic media using vibrating sample magnetometry; (5) observe small magnetic domains and investigate their interaction with defects using magnetic force microscopy; (6) perform static read/write/erase experiments on thin-film magneto-optic media using our static test station; (7) integrate the existing models of magnetization, magneto-optic effects, coercivity, and anisotropy in an interactive and user-friendly environment, and analyze the characterization data obtained in the various experiments, using this modeling package; (8) measure focusing- and tracking-error signals on a static testbed, determine the 'feedthrough' for various focusing schemes, investigate the effects of polarization and birefringence, and compare the results with diffraction-based calculations; and (9) measure the birefringence of optical disk substrates using two variable angle ellipsometers.

Female reproductive strategies in orangutans, evidence for female choice and counterstrategies to infanticide in a species with frequent sexual coercion

PubMed Central

Knott, Cheryl Denise; Emery Thompson, Melissa; Stumpf, Rebecca M.; McIntyre, Matthew H.

2010-01-01

Intersexual conflicts over mating can engender antagonistic coevolution of strategies, such as coercion by males and selective resistance by females. Orangutans are exceptional among mammals for their high levels of forced copulation. This has typically been viewed as an alternative mating tactic used by the competitively disadvantaged unflanged male morph, with little understanding of how female strategies may have shaped and responded to this behaviour. Here, we show that male morph is not by itself a good predictor of mating dynamics in wild Bornean orangutans but that female conception risk mediated the occurrence and quality of male–female interactions. Near ovulation, females mated cooperatively only with prime flanged males who they encountered at higher rates. When conception risk was low, willingness to associate and mate with non-prime males increased. Our results support the hypothesis that, together with concealed ovulation, facultative association is a mechanism of female choice in a species in which females can rarely avoid coercive mating attempts. Female resistance, which reduced copulation time, may provide an additional mechanism for mate selection. However, coercive factors were also important as prime males were frequently aggressive to females and females used mating strategies consistent with infanticide avoidance. PMID:19812079

Influence of magnet eddy current on magnetization characteristics of variable flux memory machine

NASA Astrophysics Data System (ADS)

Yang, Hui; Lin, Heyun; Zhu, Z. Q.; Lyu, Shukang

2018-05-01

In this paper, the magnet eddy current characteristics of a newly developed variable flux memory machine (VFMM) is investigated. Firstly, the machine structure, non-linear hysteresis characteristics and eddy current modeling of low coercive force magnet are described, respectively. Besides, the PM eddy current behaviors when applying the demagnetizing current pulses are unveiled and investigated. The mismatch of the required demagnetization currents between the cases with or without considering the magnet eddy current is identified. In addition, the influences of the magnet eddy current on the demagnetization effect of VFMM are analyzed. Finally, a prototype is manufactured and tested to verify the theoretical analyses.

Nano-embossing technology on ferroelectric thin film Pb(Zr0.3,Ti0.7)O3 for multi-bit storage application

PubMed Central

2011-01-01

In this work, we apply nano-embossing technique to form a stagger structure in ferroelectric lead zirconate titanate [Pb(Zr0.3, Ti0.7)O3 (PZT)] films and investigate the ferroelectric and electrical characterizations of the embossed and un-embossed regions, respectively, of the same films by using piezoresponse force microscopy (PFM) and Radiant Technologies Precision Material Analyzer. Attributed to the different layer thickness of the patterned ferroelectric thin film, two distinctive coercive voltages have been obtained, thereby, allowing for a single ferroelectric memory cell to contain more than one bit of data. PMID:21794156

Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in comparison with immunohistochemistry and fluorescent in situ hybridization and strongly depends on inflammatory activity.

PubMed

Kocsmár, Éva; Szirtes, Ildikó; Kramer, Zsófia; Szijártó, Attila; Bene, László; Buzás, György Miklós; Kenessey, István; Bronsert, Peter; Csanadi, Agnes; Lutz, Lisa; Werner, Martin; Wellner, Ulrich Friedrich; Kiss, András; Schaff, Zsuzsa; Lotz, Gábor

2017-08-01

Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP. © 2017 John Wiley & Sons Ltd.

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

PubMed

Buchanan, Daniel D; Tan, Yen Y; Walsh, Michael D; Clendenning, Mark; Metcalf, Alexander M; Ferguson, Kaltin; Arnold, Sven T; Thompson, Bryony A; Lose, Felicity A; Parsons, Michael T; Walters, Rhiannon J; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K; Blomfield, Penelope B; Quinn, Michael A; Kirk, Judy A; Stewart, Colin J; Obermair, Andreas; Young, Joanne P; Webb, Penelope M; Spurdle, Amanda B

2014-01-10

Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

Free digital image analysis software helps to resolve equivocal scores in HER2 immunohistochemistry.

PubMed

Helin, Henrik O; Tuominen, Vilppu J; Ylinen, Onni; Helin, Heikki J; Isola, Jorma

2016-02-01

Evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) is subject to interobserver variation and lack of reproducibility. Digital image analysis (DIA) has been shown to improve the consistency and accuracy of the evaluation and its use is encouraged in current testing guidelines. We studied whether digital image analysis using a free software application (ImmunoMembrane) can assist in interpreting HER2 IHC in equivocal 2+ cases. We also compared digital photomicrographs with whole-slide images (WSI) as material for ImmunoMembrane DIA. We stained 750 surgical resection specimens of invasive breast cancers immunohistochemically for HER2 and analysed staining with ImmunoMembrane. The ImmunoMembrane DIA scores were compared with the originally responsible pathologists' visual scores, a researcher's visual scores and in situ hybridisation (ISH) results. The originally responsible pathologists reported 9.1 % positive 3+ IHC scores, for the researcher this was 8.4 % and for ImmunoMembrane 9.5 %. Equivocal 2+ scores were 34 % for the pathologists, 43.7 % for the researcher and 10.1 % for ImmunoMembrane. Negative 0/1+ scores were 57.6 % for the pathologists, 46.8 % for the researcher and 80.8 % for ImmunoMembrane. There were six false positive cases, which were classified as 3+ by ImmunoMembrane and negative by ISH. Six cases were false negative defined as 0/1+ by IHC and positive by ISH. ImmunoMembrane DIA using digital photomicrographs and WSI showed almost perfect agreement. In conclusion, digital image analysis by ImmunoMembrane can help to resolve a majority of equivocal 2+ cases in HER2 IHC, which reduces the need for ISH testing.

Sensitivity and specificity of real-time reverse transcription polymerase chain reaction, histopathology, and immunohistochemical labeling for the detection of Rift Valley fever virus in naturally infected cattle and sheep.

PubMed

Odendaal, Lieza; Fosgate, Geoffrey T; Romito, Marco; Coetzer, Jacobus A W; Clift, Sarah J

2014-01-01

Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), histopathology, and immunohistochemical labeling (IHC) were performed on liver specimens from 380 naturally infected cattle and sheep necropsied during the 2010 Rift Valley fever (RVF) epidemic in South Africa. Sensitivity (Se) and specificity (Sp) of real-time RT-PCR, histopathology, and IHC were estimated in a latent-class model using a Bayesian framework. The Se and Sp of real-time RT-PCR were estimated as 97.4% (95% confidence interval [CI] = 95.2-98.8%) and 71.7% (95% CI = 65-77.9%) respectively. The Se and Sp of histopathology were estimated as 94.6% (95% CI = 91-97.2%) and 92.3% (95% CI = 87.6-95.8%), respectively. The Se and Sp of IHC were estimated as 97.6% (95% CI = 93.9-99.8%) and 99.4% (95% CI = 96.9-100%), respectively. Decreased Sp of real-time RT-PCR was ascribed to cross-contamination of samples. Stratified analysis of the data suggested variations in test accuracy with fetuses and severely autolyzed specimens. The Sp of histopathology in fetuses (83%) was 9.3% lower than the sample population (92.3%). The Se of IHC decreased from 97.6% to 81.5% in the presence of severe autolysis. The diagnostic Se and Sp of histopathology was higher than expected, confirming the value of routine postmortem examinations and histopathology of liver specimens. Aborted fetuses, however, should be screened using a variety of tests in areas endemic for RVF, and results from severely autolyzed specimens should be interpreted with caution. The most feasible testing option for countries lacking suitably equipped laboratories seems to be routine histology in combination with IHC.

Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing

PubMed Central

Kurt, Simone; Sausbier, Matthias; Rüttiger, Lukas; Brandt, Niels; Moeller, Christoph K.; Kindler, Jennifer; Sausbier, Ulrike; Zimmermann, Ulrike; van Straaten, Harald; Neuhuber, Winfried; Engel, Jutta; Knipper, Marlies; Ruth, Peter; Schulze, Holger

2012-01-01

Large conductance, voltage- and Ca2+-activated K+ (BK) channels in inner hair cells (IHCs) of the cochlea are essential for hearing. However, germline deletion of BKα, the pore-forming subunit KCNMA1 of the BK channel, surprisingly did not affect hearing thresholds in the first postnatal weeks, even though altered IHC membrane time constants, decreased IHC receptor potential alternating current/direct current ratio, and impaired spike timing of auditory fibers were reported in these mice. To investigate the role of IHC BK channels for central auditory processing, we generated a conditional mouse model with hair cell-specific deletion of BKα from postnatal day 10 onward. This had an unexpected effect on temporal coding in the central auditory system: neuronal single and multiunit responses in the inferior colliculus showed higher excitability and greater precision of temporal coding that may be linked to the improved discrimination of temporally modulated sounds observed in behavioral training. The higher precision of temporal coding, however, was restricted to slower modulations of sound and reduced stimulus-driven activity. This suggests a diminished dynamic range of stimulus coding that is expected to impair signal detection in noise. Thus, BK channels in IHCs are crucial for central coding of the temporal fine structure of sound and for detection of signals in a noisy environment.—Kurt, S., Sausbier, M., Rüttiger, L., Brandt, N., Moeller, C. K., Kindler, J., Sausbier, U., Zimmermann, U., van Straaten, H., Neuhuber, W., Engel, J., Knipper, M., Ruth, P., Schulze, H. Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing. PMID:22691916

Quantification of protein expression in cells and cellular subcompartments on immunohistochemical sections using a computer supported image analysis system.

PubMed

Braun, Martin; Kirsten, Robert; Rupp, Niels J; Moch, Holger; Fend, Falko; Wernert, Nicolas; Kristiansen, Glen; Perner, Sven

2013-05-01

Quantification of protein expression based on immunohistochemistry (IHC) is an important step for translational research and clinical routine. Several manual ('eyeballing') scoring systems are used in order to semi-quantify protein expression based on chromogenic intensities and distribution patterns. However, manual scoring systems are time-consuming and subject to significant intra- and interobserver variability. The aim of our study was to explore, whether new image analysis software proves to be sufficient as an alternative tool to quantify protein expression. For IHC experiments, one nucleus specific marker (i.e., ERG antibody), one cytoplasmic specific marker (i.e., SLC45A3 antibody), and one marker expressed in both compartments (i.e., TMPRSS2 antibody) were chosen. Stainings were applied on TMAs, containing tumor material of 630 prostate cancer patients. A pathologist visually quantified all IHC stainings in a blinded manner, applying a four-step scoring system. For digital quantification, image analysis software (Tissue Studio v.2.1, Definiens AG, Munich, Germany) was applied to obtain a continuous spectrum of average staining intensity. For each of the three antibodies we found a strong correlation of the manual protein expression score and the score of the image analysis software. Spearman's rank correlation coefficient was 0.94, 0.92, and 0.90 for ERG, SLC45A3, and TMPRSS2, respectively (p⟨0.01). Our data suggest that the image analysis software Tissue Studio is a powerful tool for quantification of protein expression in IHC stainings. Further, since the digital analysis is precise and reproducible, computer supported protein quantification might help to overcome intra- and interobserver variability and increase objectivity of IHC based protein assessment.

Diagnosis of EML4-ALK Translocation With FISH, Immunohistochemistry, and Real-time Polymerase Chain Reaction in Patients With Non-Small Cell Lung Cancer.

PubMed

Cruz-Rico, Graciela; Avilés-Salas, Alejandro; Segura-González, Manuel; Espinosa-García, Ana María; Ramírez-Tirado, Laura Alejandra; Morales-Oyarvide, Vicente; Rojas-Marín, Carlos; Cardona, Andrés-Felipe; Arrieta, Oscar

2017-12-01

To assess anaplastic lymphoma kinase (ALK) rearrangement detection with immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-qPCR) in comparison with fluorescence in situ hybridization (FISH). Tumor tissue samples from 230 patients with advanced non-small cell lung cancer (NSCLC) were analyzed by FISH to detect ALK rearrangements. Additional IHC tests using 5A4 clone and RT-qPCR (variants 1 to 5) were performed in 63 and 48 patients, respectively. Thirteen percent of FISH tests were not evaluable. From the remaining tests (n=200), 18 (9.0%) were ALK positive (ALK). ALK patients were significantly younger at the time of diagnosis (below 55 y, 14.3% vs. 5.5%, P=0.035), were light smokers (tobacco index <10, 12.6% vs. 4.1%, P=0.049), and presented adenocarcinoma with a mucinous component (30.8 vs. 8.0%, P=0.007). When comparing FISH with IHC using a cutoff of 1+ or 2+, and only 2+ staining intensity, the sensitivity, specificity, negative predictive value, and positive predictive value were as follows: 83.3%, 100.0%, 93.75%, and 100.0%; and 55.6%, 100.0%, 84.9%, and 100.0%, respectively. For RT-qPCR, these results were 55.6, 100, 90.7, and 100.0%, respectively. Our results suggest that RT-qPCR is an inadequate initial test for detecting ALK-positive lung cancer. IHC is highly useful as an initial screening test for ALK rearrangement detection in NSCLC. These results contribute to the medical literature on the establishment of IHC as a standard diagnostic test for ALK rearrangements in NSCLC.

Seeded amplification of chronic wasting disease prions in nasal brushings and recto-anal mucosal associated lymphoid tissues from elk by real time quaking-induced conversion

USGS Publications Warehouse

Haley, Nicholas J.; Siepker, Chris; Hoon-Hanks , Laura L.; Mitchell, Gordon; Walter, W. David; Manca, Matteo; Monello, Ryan J.; Powers, Jenny G.; Wild, Margaret A.; Hoover, Edward A.; Caughey, Byron; Richt, Jürgen a.; Fenwick, B.W.

2016-01-01

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.

AutoIHC-scoring: a machine learning framework for automated Allred scoring of molecular expression in ER- and PR-stained breast cancer tissue.

PubMed

Tewary, S; Arun, I; Ahmed, R; Chatterjee, S; Chakraborty, C

2017-11-01

In prognostic evaluation of breast cancer Immunohistochemical (IHC) markers namely, oestrogen receptor (ER) and progesterone receptor (PR) are widely used. The expert pathologist investigates qualitatively the stained tissue slide under microscope to provide the Allred score; which is clinically used for therapeutic decision making. Such qualitative judgment is time-consuming, tedious and more often suffers from interobserver variability. As a result, it leads to imprecise IHC score for ER and PR. To overcome this, there is an urgent need of developing a reliable and efficient IHC quantifier for high throughput decision making. In view of this, our study aims at developing an automated IHC profiler for quantitative assessment of ER and PR molecular expression from stained tissue images. We propose here to use CMYK colour space for positively and negatively stained cell extraction for proportion score. Also colour features are used for quantitative assessment of intensity scoring among the positively stained cells. Five different machine learning models namely artificial neural network, Naïve Bayes, K-nearest neighbours, decision tree and random forest are considered for learning the colour features using average red, green and blue pixel values of positively stained cell patches. Fifty cases of ER- and PR-stained tissues have been evaluated for validation with the expert pathologist's score. All five models perform adequately where random forest shows the best correlation with the expert's score (Pearson's correlation coefficient = 0.9192). In the proposed approach the average variation of diaminobenzidine (DAB) to nuclear area from the expert's score is found to be 7.58%, as compared to 27.83% for state-of-the-art ImmunoRatio software. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Statistical colour models: an automated digital image analysis method for quantification of histological biomarkers.

PubMed

Shu, Jie; Dolman, G E; Duan, Jiang; Qiu, Guoping; Ilyas, Mohammad

2016-04-27

Colour is the most important feature used in quantitative immunohistochemistry (IHC) image analysis; IHC is used to provide information relating to aetiology and to confirm malignancy. Statistical modelling is a technique widely used for colour detection in computer vision. We have developed a statistical model of colour detection applicable to detection of stain colour in digital IHC images. Model was first trained by massive colour pixels collected semi-automatically. To speed up the training and detection processes, we removed luminance channel, Y channel of YCbCr colour space and chose 128 histogram bins which is the optimal number. A maximum likelihood classifier is used to classify pixels in digital slides into positively or negatively stained pixels automatically. The model-based tool was developed within ImageJ to quantify targets identified using IHC and histochemistry. The purpose of evaluation was to compare the computer model with human evaluation. Several large datasets were prepared and obtained from human oesophageal cancer, colon cancer and liver cirrhosis with different colour stains. Experimental results have demonstrated the model-based tool achieves more accurate results than colour deconvolution and CMYK model in the detection of brown colour, and is comparable to colour deconvolution in the detection of pink colour. We have also demostrated the proposed model has little inter-dataset variations. A robust and effective statistical model is introduced in this paper. The model-based interactive tool in ImageJ, which can create a visual representation of the statistical model and detect a specified colour automatically, is easy to use and available freely at http://rsb.info.nih.gov/ij/plugins/ihc-toolbox/index.html . Testing to the tool by different users showed only minor inter-observer variations in results.

Standardization and optimization of fluorescence in situ hybridization (FISH) for HER-2 assessment in breast cancer: A single center experience.

PubMed

Bogdanovska-Todorovska, Magdalena; Petrushevska, Gordana; Janevska, Vesna; Spasevska, Liljana; Kostadinova-Kunovska, Slavica

2018-05-20

Accurate assessment of human epidermal growth factor receptor 2 (HER-2) is crucial in selecting patients for targeted therapy. Commonly used methods for HER-2 testing are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Here we presented the implementation, optimization and standardization of two FISH protocols using breast cancer samples and assessed the impact of pre-analytical and analytical factors on HER-2 testing. Formalin fixed paraffin embedded (FFPE) tissue samples from 70 breast cancer patients were tested for HER-2 using PathVysion™ HER-2 DNA Probe Kit and two different paraffin pretreatment kits, Vysis/Abbott Paraffin Pretreatment Reagent Kit (40 samples) and DAKO Histology FISH Accessory Kit (30 samples). The concordance between FISH and IHC results was determined. Pre-analytical and analytical factors (i.e., fixation, baking, digestion, and post-hybridization washing) affected the efficiency and quality of hybridization. The overall hybridization success in our study was 98.6% (69/70); the failure rate was 1.4%. The DAKO pretreatment kit was more time-efficient and resulted in more uniform signals that were easier to interpret, compared to the Vysis/Abbott kit. The overall concordance between IHC and FISH was 84.06%, kappa coefficient 0.5976 (p < 0.0001). The greatest discordance (82%) between IHC and FISH was observed in IHC 2+ group. A standardized FISH protocol for HER-2 assessment, with high hybridization efficiency, is necessary due to variability in tissue processing and individual tissue characteristics. Differences in the pre-analytical and analytical steps can affect the hybridization quality and efficiency. The use of DAKO pretreatment kit is time-saving and cost-effective.

Fluorescence In Situ Hybridization and Immunohistochemistry as Diagnostic Methods for ALK Positive Non-Small Cell Lung Cancer Patients

PubMed Central

Martinez, Pablo; Hernández-Losa, Javier; Cedrés, Susana; Castellví, Josep; Martinez-Marti, Alex; Tallada, Natalia; Murtra-Garrell, Nuria; Navarro-Mendivill, Alejandro; Rodriguez-Freixinos, Victor; Canela, Mercedes; Ramon y Cajal, Santiago; Felip, Enriqueta

2013-01-01

Background Anaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients. Methods NSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored. Results ninety-nine patients were identified. Median age was 61.5 years (range 35–83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative. Conclusions ALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients. PMID:23359795

Pathology reporting of malignant pleural mesothelioma first diagnosis: A population-based approach.

PubMed

Ascoli, Valeria; Minelli, Giada; Cozzi, Ilaria; Romeo, Elisa; Carnovale Scalzo, Caterina; Ancona, Laura; Forastiere, Francesco

2016-10-01

Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis test). Our findings show that although guidelines are designed to improve actual reporting practices, there is ample room for improvement in their application to standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to be implemented to better utilize pathology information. Copyright © 2016 Elsevier GmbH. All rights reserved.

Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

PubMed Central

Ong, Chin-Ann J.; Shapiro, Joel; Nason, Katie S.; Davison, Jon M.; Liu, Xinxue; Ross-Innes, Caryn; O'Donovan, Maria; Dinjens, Winand N.M.; Biermann, Katharina; Shannon, Nicholas; Worster, Susannah; Schulz, Laura K.E.; Luketich, James D.; Wijnhoven, Bas P.L.; Hardwick, Richard H.; Fitzgerald, Rebecca C.

2013-01-01

Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. Patients and Methods We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). Results Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). Conclusion We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage. PMID:23509313

Detection of feline herpes virus 1 via polymerase chain reaction and immunohistochemistry in cats with ulcerative facial dermatitis, eosinophilic granuloma complex reaction patterns and mosquito bite hypersensitivity.

PubMed

Persico, Paola; Roccabianca, Paola; Corona, Antonio; Vercelli, Antonella; Cornegliani, Luisa

2011-12-01

Ulcerative dermatitis caused by feline herpes virus 1 (FHV-1) is an uncommon disease characterized by cutaneous ulcers secondary to epidermal, adnexal and dermal necrosis. Differential diagnoses for FHV-1 lesions include, but are not limited to, mosquito bite hypersensitivity and eosinophilic granuloma complex. Histopathological diagnosis of FHV-1 dermatitis is based on the detection of the intranuclear inclusion bodies. In cases where intranuclear inclusions are missing but clinical and histological findings are compatible with FHV-1 dermatitis, immunohistochemistry (IHC) and PCRs have been used. In this retrospective study, we evaluated the presence of FHV-1 by IHC and PCR in skin biopsies and compared the results of the two tests. Sixty-four skin biopsy specimens from cats with compatible lesions were reviewed and tested via PCR and IHC for evidence of FHV-1. Polymerase chain reaction was positive in 12 of 64 biopsies; PCR and IHC were positive only in two of 64 biopsies, and these cases were considered true positive cases. The higher number of PCR-positive cases was possibly attributed to amplification of viral DNA from a live attenuated vaccination, but a previous FHV-1 infection with subsequent amplification of latently inserted FHV-1 could not be excluded. If clinical signs and histopathology suggest FHV-1 infection in the absence of typical inclusion bodies, IHC is the preferred diagnostic test; PCR may be useful for initial screening, but due to false positives is not sufficient for a definitive diagnosis. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction.

PubMed

Brell, Marta; Ibáñez, Javier; Tortosa, Avelina

2011-01-26

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Cell block samples from malignant pleural effusion might be valid alternative samples for anaplastic lymphoma kinase detection in patients with advanced non-small-cell lung cancer.

PubMed

Zhou, Jianya; Yao, Hongtian; Zhao, Jing; Zhang, Shumeng; You, Qihan; Sun, Ke; Zou, Yinying; Zhou, Caicun; Zhou, Jianying

2015-06-01

To evaluate the clinical value of cell block samples from malignant pleural effusion (MPE) as alternative samples to tumour tissue for anaplastic lymphoma kinase (ALK) detection in patients with advanced non-small-cell lung cancer (NSCLC). Fifty-two matched samples were eligible for analysis. ALK status was detected by Ventana immunohistochemistry (IHC) (with the D5F3 clone), reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) in MPE cell block samples, and by FISH in tumour tissue block samples. In total, ALK FISH results were obtained for 52 tumour tissue samples and 41 MPE cell block samples. Eight cases (15.4%) were ALK-positive in tumour tissue samples by FISH, and among matched MPE cell block samples, five were ALK-positive by FISH, seven were ALK-positive by RT-PCR, and eight were ALK-positive by Ventana IHC. The ALK status concordance rates between tumour tissue and MPE cell block samples were 78.9% by FISH, 98.1% by RT-PCR, and 100% by Ventana IHC. In MPE cell block samples, the sensitivity and specificity of Ventana IHC (100% and 100%) and RT-PCR (87.5% and 100%) were higher than those of FISH (62.5% and 100%). Malignant pleural effusion cell block samples had a diagnostic performance for ALK detection in advanced NSCLC that was comparable to that of tumour tissue samples. MPE cell block samples might be valid alternative samples for ALK detection when tissue is not available. Ventana IHC could be the most suitable method for ALK detection in MPE cell block samples. © 2014 John Wiley & Sons Ltd.

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

PubMed

Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

2016-04-01

Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity.

A re-appraisal of the proposed rapid Matuyama-Brunhes geomagnetic reversal in the Sulmona Basin, Italy

NASA Astrophysics Data System (ADS)

Evans, M. E.; Muxworthy, A. R.

2018-06-01

An extremely sharp magnetic reversal observed in lacustrine sediments in central Italy has been interpreted as a record of the Matuyama-Brunhes geomagnetic polarity reversal that may represent less than a decade. Here, we report new results from the same Sulmona Basin outcrops that question this interpretation. In particular, we find evidence of reversed (Matuyama) directions well above the proposed Matuyama-Brunhes Boundary (MBB). Coercivity spectra of anhysteretic remanent magnetization imply a three-component magnetic mineralogy: low-, intermediate- and high-coercivity. The low-coercivity component is found in all but one of the samples and carries a strong modern overprint seen throughout the section. The high-coercivity component is dominated by volcanic material which is prone to remagnetization. Since it is much more magnetic than the surrounding lacustrine sediments, it may influence the remanence signal even when present at very low concentrations. The intermediate-coercivity component is the main carrier of any true primary remanence, but whether or not this can be isolated depends on the blocking temperature and coercivity spectra of individual samples and on the demagnetization method used. The complexity of the magnetization, the reversed zones above the proposed MBB and the normal zones that Sagnotti and colleagues found below it lead to the conclusion that this section does not carry a reliable high-resolution record of the geomagnetic field. Thus, we feel that inferences about the stratigraphic position and duration of the MBB are premature.

First order reversal curve study of the dipolar interaction in Ni three-dimensional antidot arrays

NASA Astrophysics Data System (ADS)

Li, Bingqing; Chai, Xuzhao; Moeendarbari, Sina; Hao, Yaowu; Gilbert, Dustin A.; Liu, Kai; Zhang, Di; Feng, Gang; Han, Ping; Cheng, X. M.

2014-03-01

Three-dimensional antidot arrays (3DAAs) have attracted considerable attention due to potential applications in sensors, energy storage and transducers. Magnetic 3DAAs also provide an ideal system for studying the effect of dimensionality and morphology on magnetic properties. We report study of dipolar interactions in Ni 3DAAs using the first-order reversal curve (FORC) method. Ordered Ni 3DAAs were fabricated by electrochemical deposition into colloidal crystal templates of self-assembled polystyrene spheres. The samples have the same pore size of about 500 nm but different thicknesses, ranging from 0.3 μm to 1.2 μm, confirmed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). FORCs of the samples with thicknesses of 0.3 μm, 0.8 μm, and 1.2 μm were measured by a vibrating sample magnetometer. The FORC diagram analysis reveals a demagnetizing magnetic dipolar interaction, and a decrease in the interaction strength with the increasing sample thickness, evidenced by a decrease in the spread of the irreversible peak in the bias distribution, as well as a decrease in the tilting of the FORC distribution from the local coercivity axis. Work at BMC and UCD is supported by NSF DMR-1207085 and DMR-1008791, respectively.

Standards for detailed clinical models as the basis for medical data exchange and decision support.

PubMed

Coyle, Joseph F; Mori, Angelo Rossi; Huff, Stanley M

2003-03-01

Detailed clinical models are necessary to exchange medical data between heterogeneous computer systems and to maintain consistency in a longitudinal electronic medical record system. At Intermountain Health Care (IHC), we have a history of designing detailed clinical models. The purpose of this paper is to share our experience and the lessons we have learned over the last 5 years. IHC's newest model is implemented using eXtensible Markup Language (XML) Schema as the formalism, and conforms to the Health Level Seven (HL7) version 3 data types. The centerpiece of the new strategy is the Clinical Event Model, which is a flexible name-value pair data structure that is tightly linked to a coded terminology. We describe IHC's third-generation strategy for representing and implementing detailed clinical models, and discuss the reasons for this design.

Coercivity Recovery Effect of Sm-Fe-Cu-Al Alloy on Sm2Fe17N3 Magnet

NASA Astrophysics Data System (ADS)

Otogawa, Kohei; Asahi, Toru; Jinno, Miho; Yamaguchi, Wataru; Takagi, Kenta; Kwon, Hansang

2018-03-01

The potential of a Sm-Fe-Cu-Al binder for improvement of the magnetic properties of Sm2Fe17N3 was examined. Transmission electron microscope (TEM) observation of a Sm-Fe-Cu-Al alloy-bonded Sm2Fe17N3 magnet which showed high coercivity revealed that the Sm-Fe-Cu-Al alloy had an effect of removing the surface oxide layer of the Sm2 Fe17N3 grains. However, the Sm-Fe-Cu-Al binder was contaminated by carbon and nitrogen, which originated from the organic solvent used as the milling medium during pulverization. To prevent carbon and nitrogen contamination, the Sm-Fe- Cu-Al alloy was added directly on the surface of the Sm2Fe17N3 grains by sputtering. Comparing the recovered coercivity per unit amount of the added binder the uncontaminated binder-coated sample had a higher coercivity recovery effect than the milled binder-added sample. These results suggested that sufficient addition of the contamination-free Sm-Fe-Cu-Al binder has the possibility to reduce the amount of binder necessary to produce a high coercive Sm2Fe17N3 magnet.

Coercive and legitimate authority impact tax honesty: evidence from behavioral and ERP experiments

PubMed Central

Pfabigan, Daniela M.; Lamm, Claus; Kirchler, Erich; Hofmann, Eva

2017-01-01

Abstract Cooperation in social systems such as tax honesty is of central importance in our modern societies. However, we know little about cognitive and neural processes driving decisions to evade or pay taxes. This study focuses on the impact of perceived tax authority and examines the mental chronometry mirrored in ERP data allowing a deeper understanding about why humans cooperate in tax systems. We experimentally manipulated coercive and legitimate authority and studied its impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal (experiment 2) processes. Experiment 1 showed that in a condition of coercive authority, tax payments are lower, decisions are faster and participants report more rational reasoning and enforced compliance, however, less voluntary cooperation than in a condition of legitimate authority. Experiment 2 confirmed most results, but did not find a difference in payments or self-reported rational reasoning. Moreover, legitimate authority led to heightened cognitive control (expressed by increased MFN amplitudes) and disrupted attention processing (expressed by decreased P300 amplitudes) compared to coercive authority. To conclude, the neuronal data surprisingly revealed that legitimate authority may led to higher decision conflict and thus to higher cognitive demands in tax decisions than coercive authority. PMID:28402477

Coercive treatment and autonomy in psychiatry.

PubMed

Sjöstrand, Manne; Helgesson, Gert

2008-02-01

There are three lines of argument in defence of coercive treatment of patients with mental disorders: arguments regarding (1) societal interests to protect others, (2) the patients' own health interests, and (3) patient autonomy. In this paper, we analyse these arguments in relation to an idealized case, where a person with a mental disorder claims not to want medical treatment for religious reasons. We also discuss who should decide what in situations where patients with mental disorders deny treatment on seemingly rational grounds. We conclude that, in principle, coercive treatment cannot be defended for the sake of protecting others. While coercive actions can be acceptable in order to protect close family and others, medical treatment is not justified for such reasons but should be given only in the interest of patients. Coercive treatment may be required in order to promote the patient's health interests, but health interests have to waive if they go against the autonomous interests of the patient. We argue that non-autonomous patients can have reasons, rooted in their deeply-set values, to renounce compulsory institutional treatment, and that such reasons should be respected unless it can be assumed that their new predicaments have caused them to change their views.

Temperature stability of coercivity in mischmetal-Fe-Co-B melt-spun ribbons

NASA Astrophysics Data System (ADS)

Li, Rui; Zhang, Hong-Rui; Liu, Yao; Zuo, Shu-Lan; Xiong, Jie-Fu; Zuo, Wen-Liang; Zhao, Tong-Yun; Hu, Feng-Xia; Sun, Ji-Rong; Shen, Bao-Gen

2018-05-01

Coercivity temperature coefficient (β) of the permanent magnet depends on its intrinsic magnetic properties and microstructure. In this paper, the relationship between β and the temperature stabilities of magnetocrystalline anisotropy field (H a ) and saturation magnetization (M s ) as well as the microstructure is discussed. Regarding two concerned microstructural factors: grain size and grain boundary, coercivity thermal-stabilities of MM13.5Fe79.5B7 (MM-mischmetal: unseparated La-Ce-Pr-Nd alloy) and MMxFe94‑xB6 (x = 12, 13, 14, 15, 16, 19) melt-spun ribbons, respectively, are investigated. High β values near the theoretical limit are obtained either by decreasing grain size or by reducing MM percentage. In addition, coercivities above room temperature of MM13.5Fe79.5‑yCoyB7 (y = 0, 3, 6, 9, 12, 15) melt-spun ribbons are measured. The detailed influences of Co substitutions on β are analyzed, and the weak temperature dependence of M s is proved to the reason for the observed decrease of β. These findings suggest that proper strategy to minimize local stray fields is the key to enhance coercivity thermal-stability of 2:14:1 structure magnet.

Analysis of metaplastic breast carcinoma: FNAC; histopathology and immunohistochemistry are complementary for diagnosis.

PubMed

Abd El Hafez, Amal; Shawky, Abd El-Aty

2013-01-01

Metaplastic breast carcinoma (MBC) is a rare malignancy comprised of ductal, squamous and/or mesenchymal elements with problematic diagnosis. This study analyses MBC identifying its cytologic and histologic features and emphasizing the combined role of FNAC, histopathology and immunohistochemistry (IHC) in its diagnosis. Cytology and histopathology files search yielded 21 cases identified as MBC from January 2005 to December 2010. FNAC and the histopathology slides were re-examined for the presence and frequency of various elements. Cytological and histopathological diagnoses were made and the cases subtyped according to WHO classification. Cytokeratin and vimenten IHC were used to confirm diagnosis when required. On FNAC, 52.4% were diagnosed as malignant, 9.5% as suspicious for malignancy and 38.1% as benign lesions. Most frequent cytologic findings were squamous and spindle cell elements (52.4% each). Histopathology revealed 76.2% pure epithelial tumors and 23.8% mixed epithelial-mesenchymal tumors. Squamous cell carcinoma was the most frequent histological subtype (33.3%). Carcinosarcomas were dimorphic on IHC& spindle cell carcinomas were positive for both cytokeratin and vimentin. Presence of dual components, squamous, spindle elements, mesenchymal fragments and necrosis in moderate to high cellularity breast FNAC provides clues for the diagnosis of MBC. FNAC; histopathology and IHC complement for diagnosis.

MET expression and amplification in patients with localized gastric cancer

PubMed Central

Janjigian, Yelena Y.; Tang, Laura H.; Coit, Daniel G.; Kelsen, David P.; Francone, Todd D.; Weiser, Martin R.; Jhanwar, Suresh C.; Shah, Manish A.

2013-01-01

Background MET, the receptor for hepatocyte growth factor has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer. Methods Tumor specimens from patients enrolled on a preoperative chemotherapy study (NCI 5700) were examined for presence of MET gene amplification by fluorescence in situ hybridization (FISH), MET mRNA expression by quantitative polymerase chain reaction, MET overexpression by immunohistochemistry (IHC), and for evidence of MET pathway activation by p-MET IHC. Results Although high-level of MET protein and mRNA were commonly encountered (in 63% and 50% of resected tumor specimens, respectively), none of these tumors had MET gene amplification by FISH, and only 6.6% had evidence of MET tyrosine kinase activity by p-MET IHC. Conclusions In this cohort of patients with localized gastric cancer, the presence of high MET protein and RNA expression does not correlate with MET gene amplification or pathway activation as evidenced by the absence of amplification by FISH and negative p-MET IHC analysis. Impact This paper demonstrates a lack of MET amplification and pathway activation in a cohort of 38 patients with localized gastric cancer, suggesting that MET-driven gastric cancers are relatively rare in Western patients. PMID:21393565

Drive mechanisms to the inner and outer hair cell stereocilia

NASA Astrophysics Data System (ADS)

Maftoon, Nima; Motallebzadeh, Hamid; Guinan, John J.; Puria, Sunil

2018-05-01

It has been long believed that inner hair cell (IHC) stimulation can be gleaned from the classic ter-Kuile shear motion between the reticular lamina (RL) and tectorial membrane (TM). The present study explores this and other IHC stimulation mechanisms using a finite-element-model representation of an organ of Corti (OoC) cross section with fluid-structure interaction. A 3-D model of a cross section of the OoC including soft tissue and the fluid in the sub-tectorial space, tunnel of Corti and above the TM was formulated based on anatomical measurements from the gerbil apical turn. The outer hair cells (OHCs), Deiter's cells and their phalangeal processes are represented as Y-shaped building-block elements. Each of the IHC and OHC bundles is represented by a single sterocilium. Linearized Navier-Stokes equations coupled with linear-elastic equations discretized with tetrahedral elements are solved in the frequency domain. We evaluated the dynamic changes in the OoC motion including sub-tectorial gap dimensions for 0.1 to 10 kHz input frequencies. Calculations show the classic ter-Kuile motion but more importantly they show that the gap-height changes which produce oscillatory radial flow in the subtectorial space. Phase changes in the stereocilia across OHC rows and the IHC are also observed.

[Gastroduodenal mucosa sensitivity to estrogen in ulcers complicated by hemorrhage].

PubMed

Duzhiy, I D; Romanyuk, A M; Kharchenko, S V; Moskalenko, R A; Pyatykop, G I; Lyndin, M S

2015-02-01

Expression of alpha-receptors of estrogen (RE) in accordance to immunohistochemical (IHC) labeling in gastroduodenal mucosa cells was studied up in patients, suffering the ulcer disease and without it. In 4 patients (group I) a gastroduodenal mucosa affection was revealed, they were operated on for hemorrhage from gastroduodenal ulcers; in 3 patients (group II) gastroduodenal mucosa affection was not observed; in 4 patients (group III, control), a mammary gland cancer was diagnosed, a positive reaction on alpha-RE was noted. In groups I and II the biopsies were studied, obtained from pylorus and gastric fundus, as well as from duodenal ampula, and in a group III--obtained from the tumor. In a control group a positive labeling of nuclei was revealed in biopsies. In patients of groups I and II the alpha-RE expression by cellular nuclei was not revealed, but, the lots of positive IHC labeling of cytoplasm in glandular and stromal mucosal cells of the investigated gut were noted. Positive IHC labeling of cytoplasm for alpha-RE witnesses about sensitivity to them in norma and pathological processes. But, a trustworthy difference of alpha-RE expression by cellular nuclei was not noted. For confirmation or denial of this hypothesis further clinical and IHC investigations are needed.

"Atypical" chronic wasting disease in PRNP genotype 225FF mule deer.

PubMed

Wolfe, Lisa L; Fox, Karen A; Miller, Michael W

2014-07-01

We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes (225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face of environmental exposure to infectivity. All three 225SS deer had immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure (dpe), developed classic clinical signs by 723-1,200 dpe, and showed gross and microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and IHC staining typical of prion disease in mule deer. In contrast, although all three 225FF deer also became infected, the two individuals surviving >720 dpe had consistently negative biopsies, developed more-subtle clinical signs of CWD, and died 924 or 1,783 dpe. The 225FF deer were "suspect" by ELISA postmortem but showed negative or equivocal IHC staining of lymphoid tissues; both clinically affected 225FF deer had spongiform encephalopathy in the absence of IHC staining in the brain tissue. The experimental cases resembled three cases encountered among five additional captive 225FF deer that were not part of our experiment but also died from CWD. Aside from differences in clinical disease presentation and detection, 225FF mule deer also showed other, more-subtle, atypical traits that may help to explain the rarity of this genotype in natural populations, even in the presence of enzootic CWD.

Histopathological findings in immunohistological staining of the granulomatous tissue reaction associated with tuberculosis.

PubMed

Karimi, Shirin; Shamaei, Masoud; Pourabdollah, Mihan; Sadr, Makan; Karbasi, Mehrdad; Kiani, Arda; Bahadori, Moslem

2014-01-01

Purpose. The histological diagnosis of Mycobacterium tuberculosis (MTB) remains a diagnostic challenge despite different methods. Immunohistochemistry (IHC) not only could confirm granulomatous tissue involvement but also can demonstrate MTB antigen immunolocalization. This study tries to clarify the details of immunohistochemical staining for MTB with pAbBCG. Materials/Methods. Twenty-three confirmed TB granulomatous tissue samples were studied by Ziehl-Neelsen and immunohistochemistry (IHC) staining with pAbBCG. Samples were selected from the archive of the Department of Pathology, National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran. Results. IHC staining was positive in all samples, whereas Ziehl-Neelsen was positive in 9 cases out of 23 (39.1%). Tissue types used were pleural tissue, lymph nodes, and lung tissue. IHC showed positive coarse granular cytoplasmic and round, fragmented bacillary staining. In this study, epithelioid cells clearly showed more positive staining at the periphery of the granuloma rather than the center of granuloma. There is also positive staining in endothelial cells, fibroblasts, plasma cells, lymphocytes, and macrophages outside the granuloma. Conclusion. Considering the criteria of positive immunohistochemical staining of TB granulomatous reactions, this stain not only highlights the presence of mycobacterial antigens for tissue diagnosis, but also could morphologically localize its distribution in different cells.

Histopathological Findings in Immunohistological Staining of the Granulomatous Tissue Reaction Associated with Tuberculosis

PubMed Central

Karimi, Shirin; Pourabdollah, Mihan; Sadr, Makan; Karbasi, Mehrdad; Bahadori, Moslem

2014-01-01

Purpose. The histological diagnosis of Mycobacterium tuberculosis (MTB) remains a diagnostic challenge despite different methods. Immunohistochemistry (IHC) not only could confirm granulomatous tissue involvement but also can demonstrate MTB antigen immunolocalization. This study tries to clarify the details of immunohistochemical staining for MTB with pAbBCG. Materials/Methods. Twenty-three confirmed TB granulomatous tissue samples were studied by Ziehl-Neelsen and immunohistochemistry (IHC) staining with pAbBCG. Samples were selected from the archive of the Department of Pathology, National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran. Results. IHC staining was positive in all samples, whereas Ziehl-Neelsen was positive in 9 cases out of 23 (39.1%). Tissue types used were pleural tissue, lymph nodes, and lung tissue. IHC showed positive coarse granular cytoplasmic and round, fragmented bacillary staining. In this study, epithelioid cells clearly showed more positive staining at the periphery of the granuloma rather than the center of granuloma. There is also positive staining in endothelial cells, fibroblasts, plasma cells, lymphocytes, and macrophages outside the granuloma. Conclusion. Considering the criteria of positive immunohistochemical staining of TB granulomatous reactions, this stain not only highlights the presence of mycobacterial antigens for tissue diagnosis, but also could morphologically localize its distribution in different cells. PMID:24511393

Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition.

PubMed

Lesnikova, Iana; Schreckenbach, Marc Niclas; Kristensen, Maria Pihlmann; Papanikolaou, Liv Lindegaard; Hamilton-Dutoit, Stephen

2018-05-24

Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition.

Chemical Synthesis of Next Generation High Energy Product Hybrid SmCo Permanent Magnets for High Temperature Applications

DTIC Science & Technology

2010-08-01

among CoxC, AINiCo and Ba / Sr ferrite magnets. AINiCo is shown to exhibit high (BH)max, 35 kJmŗ, but a low intrinsic coercivity, mostly ə kOe...whereas Ba / Sr ferrite features high intrinsic coercivity, 3-4.5 kOe, but typical values of (BH)max below 25 kJm-3. However, the multiple...coercivity of cobalt carbide nanoparticles is compared with free powders of AINiCo and ceramic magnets of the Ba / Sr hexaferrite type. Curie temperatures near

Psychometric properties and reliability of the Assessment Screen to Identify Survivors Toolkit for Gender Based Violence (ASIST-GBV): results from humanitarian settings in Ethiopia and Colombia.

PubMed

Vu, Alexander; Wirtz, Andrea; Pham, Kiemanh; Singh, Sonal; Rubenstein, Leonard; Glass, Nancy; Perrin, Nancy

2016-01-01

Refugees and internally displaced persons who are affected by armed-conflict are at increased vulnerability to some forms of sexual violence or other types of gender-based violence. A validated, brief and easy-to-administer screening tool will help service providers identify GBV survivors and refer them to appropriate GBV services. To date, no such GBV screening tool exists. We developed the 7-item ASIST-GBV screening tool from qualitative research that included individual interviews and focus groups with GBV refugee and IDP survivors. This study presents the psychometric properties of the ASIST-GBV with female refugees living in Ethiopia and IDPs in Colombia. Several strategies were used to validate ASIST-GBV, including a 3 month implementation to validate the brief screening tool with women/girls seeking health services, aged ≥15 years in Ethiopia (N = 487) and female IDPs aged ≥ 18 years in Colombia (N = 511). High proportions of women screened positive for past-year GBV according to the ASIST-GBV: 50.6 % in Ethiopia and 63.4 % in Colombia. The factor analysis identified a single dimension, meaning that all items loaded on the single factor. Cronbach's α = 0.77. A 2-parameter logistic IRT model was used for estimating the precision and discriminating power of each item. Item difficulty varied across the continuum of GBV experiences in the following order (lowest to highest): threats of violence (0.690), physical violence (1.28), forced sex (2.49), coercive sex for survival (2.25), forced marriage (3.51), and forced pregnancy (6.33). Discrimination results showed that forced pregnancy was the item with the strongest ability to discriminate between different levels of GBV. Physical violence and forced sex also have higher levels of discrimination with threats of violence discriminating among women at the low end of the GBV continuum and coercive sex for survival among women at the mid-range of the continuum. The findings demonstrate that the ASIST-GBV has strong psychometric properties and good reliability. The tool can be used to screen and identify female GBV survivors confidentially and efficiently among IDPs in Colombia and refugees in Ethiopia. Early identification of GBV survivors can enable safety planning, early referral for treatment, and psychosocial support to prevent long-term harmful consequence of GBV.

The paradox of progress: translating Evan Stark's Coercive Control into legal doctrine for abused women.

PubMed

Hanna, Cheryl

2009-12-01

This article examines Evan Stark's model of coercive control and what this paradigm shift might mean for the law. Coercive control can help redefine both criminal offenses involving domestic violence and defenses available to women who kill their abusers. This redefinition would shift the law away from incident-based violence and toward a more comprehensive and accurate paradigm that accounts for the deprivation of a woman's autonomy within the context of an abusive relationship. Such a change would likely provide more effective state intervention into what were once considered private relationships. Yet, this approach may also have some unintended consequences, including refocusing the law on a victim's mental state and complicity in her own abuse rather than on the harm caused by abusive men. Thus, although the law should more fully account for coercive control, lawyers must be cautiously optimistic in implementing Stark's proposed reforms.

Ultimate intrinsic-coercivity samarium-cobalt magnet: An Earth-based feasibility study for space-shuttle missions. [containerless melts

NASA Technical Reports Server (NTRS)

Das, D. K.; Kumar, K.; Frost, R. T.; Chang, C. W.

1980-01-01

Techniques for containerless melting and solidification of the samarium-cobalt alloy without excessive oxidation were developed. The rationale for extending these experiments in a weightless environment is also discussed. The effect of oxygen content from 0.15 to 0.63 weight percent and grain size in the range of 2 to 10 micrometers has been examined on arc-plasma-sprayed SmCo5 magnets. Contrary to expectations, the larger grain sizes tended to improve the coercivities. This was attributed to an increase in homogeneity resulting from higher temperature treatments used to produce larger grain size. No significant differences in coercivity were observed on the basis of oxygen content in the range examined. It is expected that more meaningful data on the relationship between oxygen content and coercivity will be seen when the oxygen content can be lowered to less than 0.1 weight percent.

Sm5(Fe,Ti)17 melt-spun ribbons with high coercivity

NASA Astrophysics Data System (ADS)

Saito, Tetsuji; Horita, Toru

2018-05-01

It has previously been reported that annealing of amorphous Sm5Fe17 melt-spun ribbon resulted in the formation of the Sm5Fe17 phase and the resultant Sm5Fe17 melt-spun ribbon exhibited a high coercivity. However, the annealing condition of the amorphous Sm5Fe17 melt-spun ribbon was somewhat critical and it was not easy to obtain Sm5Fe17 grains with high coercivity. In the present study, it was found that the small substitution of Ti for Fe in the Sm5Fe17 melt-spun ribbon stabilized the Sm5Fe17 phase. Annealed Sm5Fe16.7Ti0.3 melt-spun ribbon consisted of small and homogeneous Sm5(Fe,Ti)17 grains and exhibited a higher coercivity than the annealed Sm5Fe17 melt-spun ribbon.

Grain boundary diffusion of Dy films prepared by magnetron sputtering for sintered Nd–Fe–B magnets

NASA Astrophysics Data System (ADS)

Chen, W.; Luo, J. M.; Guan, Y. W.; Huang, Y. L.; Chen, M.; Hou, Y. H.

2018-05-01

Dy films, deposited on the surface of sintered Nd–Fe–B magnets by magnetron sputtering, were employed for grain boundary diffusion source. High coercivity sintered Nd–Fe–B magnets were successfully prepared. Effects of sputtering power and grain boundary diffusion processes (GBDP) on the microstructure and magnetic properties were investigated in detail. The dense and uniform Dy films were beneficial to prepare high coercivity magnets by GBDP. The maximum coercivity value of 1189 kA m‑1 could be shown, which was an amplification of 22.3%, compared with that of as-prepared Nd–Fe–B magnet. Furthermore, the improved remanence and maximum energy product were also achieved through tuning grain boundary diffusion processes. Our results demonstrated that the formation of (Nd, Dy)2Fe14B shell surrounding Nd2Fe14B grains and fine, uniform and continuous intergranular RE-rich phases jointly contribute to the improved coercivity.

Coercivity enhancement in hot deformed Nd2Fe14B-type magnets by doping low-melting RCu alloys (R = Nd, Dy, Nd + Dy)

NASA Astrophysics Data System (ADS)

Lee, Y. I.; Huang, G. Y.; Shih, C. W.; Chang, W. C.; Chang, H. W.; You, J. S.

2017-10-01

Magnetic properties of the anisotropic NdFeB magnets prepared by hot pressing followed by die-upsetting NdFeB MQU-F powders doped with low-melting RCu alloy powders were explored, where RCu stands for Nd70Cu30, Dy70Cu30 and (Nd0.5Dy0.5)70Cu30, respectively. In addition, the post-annealing at 600 °C was employed to modify the microstructures and the magnetic properties of the hot deformed magnets. It is found that doping RCu alloy powders is effective in enhancing the coercivity of the hot deformed NdFeB magnets from 15.1 kOe to 16.3-19.5 kOe. For Nd70Cu30-doped magnets, the increment of coercivity is only 1.2 kOe. Meanwhile, Dy70Cu30-doped and (Nd0.5Dy0.5)70Cu30-doped magnets show an almost identical enhancement of coercivity of about 4.4 kOe. Importantly, the latter magnet shows a beneficial effect of reducing the usage of Dy from 1.6 wt% to 0.8 wt%. TEM analysis shows that nonmagnetic Nd, Dy and Cu appear at grain boundary and isolate the magnetic grains, leading to an enhancement of coercivity. Doping lower melting point Dy-lean (Nd0.5Dy0.5)70Cu30 powders into commercial MQU-F powders for making high coercivity hot deformed NdFeB magnets might be a potential and economic way for mass production.

Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements.

PubMed

Teixidó, Cristina; Karachaliou, Niki; Peg, Vicente; Gimenez-Capitan, Ana; Rosell, Rafael

2014-04-01

The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4-6% of lung adenocarcinomas. Crizotinib, along with a diagnostic test-the Vysis ALK Break Apart fluorescence in situ hybridization (FISH) Probe Kit-is approved for the treatment of ALK positive advanced non-small cell lung cancer (NSCLC). However, the success of a targeted drug is critically dependent on a sensitive and specific screening assay to detect the molecular drug target. In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). Although ALK FISH is clinically validated, the assay can be technically challenging and other diagnostic modalities, including IHC and RT-PCR should be further explored.

Coupling the Subtectorial Fluid with the Tectorial Membrane and Hair Bundles of the Cochlea

NASA Astrophysics Data System (ADS)

Li, Yizeng; Meaud, Julien; Grosh, Karl

2011-11-01

Two different kinds of flow—(i) shearing of fluid between the reticular lamina (RL) and tectorial membrane (TM) and (ii) so-called pulsating flow in the RL-TM gap—have been implicated as the dominant source of fluidic stimulation of the inner hair cell (IHC) hair bundle (HB). However, the frequency and spatial dependence of these flows for IHC stimulation is unresolved in vivo and estimates of the effect of the cochlear amplifier on these flows has not been quantified. Indeed, the relative importance these flow modalities and active processes likely varies with tonotopic location. In this paper, a microfluidic model is developed which features the interaction of the subtectorial fluid with the TM, IHC HBs, and the outer hair cell HBs. The framework of the model allows for incorporation into active macroscopic models as well as for comparison of experiments performed on excised sections of the cochlea.

Automated Bone Screw Tightening to Adaptive Levels of Stripping Torque.

PubMed

Reynolds, Karen J; Mohtar, Aaron A; Cleek, Tammy M; Ryan, Melissa K; Hearn, Trevor C

2017-06-01

To use relationships between tightening parameters, related to bone quality, to develop an automated system that determines and controls the level of screw tightening. An algorithm relating current at head contact (IHC) to current at construct failure (Imax) was developed. The algorithm was used to trigger cessation of screw insertion at a predefined tightening level, in real time, between head contact and maximum current. The ability of the device to stop at the predefined level was assessed. The mean (±SD) current at which screw insertion ceased was calculated to be [51.47 ± 9.75% × (Imax - IHC)] + IHC, with no premature bone failures. A smart screwdriver was developed that uses the current from the motor driving the screw to predict the current at which the screw will strip the bone threads. The device was implemented and was able to achieve motor shut-off and cease tightening at a predefined threshold, with no premature bone failures.

The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse

PubMed Central

Becker, Lars; Schnee, Michael E; Niwa, Mamiko; Sun, Willy; Maxeiner, Stephan; Talaei, Sara; Kachar, Bechara; Rutherford, Mark A

2018-01-01

The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon’s contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles. PMID:29328021

Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis.

PubMed

Ward, S; Scope, A; Rafia, R; Pandor, A; Harnan, S; Evans, P; Wyld, L

2013-10-01

Gene expression profiling (GEP) and expanded immunohistochemistry (IHC) tests aim to improve decision-making relating to adjuvant chemotherapy for women with early breast cancer. The aim of this report is to assess the clinical effectiveness and cost-effectiveness of nine GEP and expanded IHC tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer in England and Wales. The nine tests are BluePrint, Breast Cancer Index (BCI), IHC4, MammaPrint, Mammostrat, NPI plus (NPI+), OncotypeDX, PAM50 and Randox Breast Cancer Array. Databases searched included MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. Databases were searched from January 2009 to May 2011 for the OncotypeDX and MammaPrint tests and from January 2002 to May 2011 for the other tests. A systematic review of the evidence on clinical effectiveness (analytical validity, clinical validity and clinical utility) and cost-effectiveness was conducted. An economic model was developed to evaluate the cost-effectiveness of adjuvant chemotherapy treatment guided by four of the nine test (OncotypeDX, IHC4, MammaPrint and Mammostrat) compared with current clinical practice in England and Wales, using clinicopathological parameters, in women with oestrogen receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early breast cancer. The literature searches for clinical effectiveness identified 5993 citations, of which 32 full-text papers or abstracts (30 studies) satisfied the criteria for the effectiveness review. A narrative synthesis was performed. Evidence for OncotypeDX supported the prognostic capability of the test. There was some evidence on the impact of the test on decision-making and to support the case that OncotypeDX predicts chemotherapy benefit; however, few studies were UK based and limitations in relation to study design were identified. Evidence for MammaPrint demonstrated that the test score was a strong independent prognostic factor, but the evidence is non-UK based and is based on small sample sizes. Evidence on the Mammostrat test showed that the test was an independent prognostic tool for women with ER+, tamoxifen-treated breast cancer. The three studies appeared to be of reasonable quality and provided data from a UK setting (one study). One large study reported on clinical validity of the IHC4 test, with IHC4 score a highly significant predictor of distant recurrence. This study included data from a UK setting and appeared to be of reasonable quality. Evidence for the remaining five tests (PAM50, NPI+, BCI, BluePrint and Randox) was limited. The economic analysis suggests that treatment guided using IHC4 has the greatest potential to be cost-effective at a £20,000 threshold, given the low cost of the test; however, further research is needed on the analytical validity and clinical utility of IHC4, and the exact cost of the test needs to be confirmed. Current limitations in the evidence base produce significant uncertainty in the results. OncotypeDX has a more robust evidence base, but further evidence on its impact on decision-making in the UK and the predictive ability of the test in an ER+, LN-, HER- population receiving current drug regimens is needed. For MammaPrint and Mammostrat there were significant gaps in the available evidence and the estimates of cost-effectiveness produced were not considered to be robust by the External Assessment Group. Methodological weaknesses in the clinical evidence base relate to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence. Further evidence is required on the clinical utility of all of the tests and on UK-based populations. A key area of uncertainty relates to whether the tests provide prognostic or predictive ability. The clinical evidence base for OncotypeDX is considered to be the most robust. The economic analysis suggested that treatment guided using IHC4 has the most potential to be cost-effective at a threshold of £20,000; however, the evidence base to support IHC4 needs significant further research. PROSPERO 2011:CRD42011001361, available from www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001361.

Coercivity scaling in antidot lattices in Fe, Ni, and NiFe thin films

NASA Astrophysics Data System (ADS)

Gräfe, Joachim; Schütz, Gisela; Goering, Eberhard J.

2016-12-01

Antidot lattices can be used to artificially engineer magnetic properties in thin films, however, a conclusive model that describes the coercivity enhancement in this class of magnetic nano-structures has so far not been found. We prepared Fe, Ni, and NiFe thin films and patterned each with 21 square antidot lattices with different geometric parameters and measured their hysteretic behavior. On the basis of this extensive dataset we are able to provide a model that can describe both the coercivity scaling over a wide range of geometric lattice parameters and the influence of different materials.

Coercive and legitimate authority impact tax honesty: evidence from behavioral and ERP experiments.

PubMed

Gangl, Katharina; Pfabigan, Daniela M; Lamm, Claus; Kirchler, Erich; Hofmann, Eva

2017-07-01

Cooperation in social systems such as tax honesty is of central importance in our modern societies. However, we know little about cognitive and neural processes driving decisions to evade or pay taxes. This study focuses on the impact of perceived tax authority and examines the mental chronometry mirrored in ERP data allowing a deeper understanding about why humans cooperate in tax systems. We experimentally manipulated coercive and legitimate authority and studied its impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal (experiment 2) processes. Experiment 1 showed that in a condition of coercive authority, tax payments are lower, decisions are faster and participants report more rational reasoning and enforced compliance, however, less voluntary cooperation than in a condition of legitimate authority. Experiment 2 confirmed most results, but did not find a difference in payments or self-reported rational reasoning. Moreover, legitimate authority led to heightened cognitive control (expressed by increased MFN amplitudes) and disrupted attention processing (expressed by decreased P300 amplitudes) compared to coercive authority. To conclude, the neuronal data surprisingly revealed that legitimate authority may led to higher decision conflict and thus to higher cognitive demands in tax decisions than coercive authority. © The Author (2017). Published by Oxford University Press.

Magnetization reversal mechanism and coercivity enhancement in three-dimensional granular Nd-Fe-B magnets studied by micromagnetic simulations

NASA Astrophysics Data System (ADS)

Lee, Jae-Hyeok; Choe, Jinhyeok; Hwang, Shinwon; Kim, Sang-Koog

2017-08-01

We studied the mechanism of magnetization reversals and coercivity enhancements in three-dimensional (3D) granular Nd-Fe-B permanent magnets using finite-element micromagnetic simulations. The magnetization reversals in the hard magnets consisting of hard-phase grains separated by relatively soft-phase grain boundaries were analyzed with reference to the simulation results for the magnetic field-dependent distributions of the local magnetizations. The saturation magnetization of the grain-boundary phase plays a crucial role in the transition between nucleation- and domain-wall-propagation-controlled reversal processes. The smaller the saturation magnetization of the grain-boundary phase is, the more preferable is the nucleation-controlled process, which results in a larger coercivity. The exchange stiffness of the grain-boundary phase determines the preferred paths of domain-wall propagations, whether inward into grains or along the grain boundaries for relatively small and large exchange stiffness, respectively. However, the exchange stiffness of the grain-boundary phase alone does not significantly contribute to coercivity enhancement in cases where the size of hard-phase grains is much greater than the exchange length. This work paves the way for the design of high-performance hard magnets of large coercivity and maximum-energy-product values.

[Coercive Measures in Child and Adolescent Psychiatry in Post-war Germany, Using the Example of the "Pflege- und Beobachtungsstation" in the State Psychiatric Hospital Weissenau (1951-1966)].

PubMed

Afschar-Hamdi, Sima; Schepker, Klaus

2017-09-01

Coercive Measures in Child and Adolescent Psychiatry in Post-war Germany, Using the Example of the "Pflege- und Beobachtungsstation" in the State Psychiatric Hospital Weissenau (1951-1966) The patient admissions at the children's ward of the State Psychiatric Hospital Weissenau in the years 1951, 1956, 1961 and 1966 were analyzed regarding documented coercive measures. Shortage of staff, mainly inadequately skilled personnel, a mixing of age groups in the patient cohort, neurological and psychiatric disorders and of patients who were in need of nursing and of those who needed treatment constituted the general work environment. Coercive measures against patients, mostly disproportionate isolations, were a constant part of daily life on the ward. This affected in particular patients who had to stay longer at the hospital and whose stay was financed by public authority. The uselessness of such measures was known, which can be seen e. g. in the Caretaker's Handbook of that time and the comments in the patient files. The situation still escalated in some cases (for example by transfer to an adult ward). For a long time, coercive measures against patients were part of everyday life at the children's ward of the Weissenau; the actual figures are suspected to be much higher.

Comparison of PD-L1 mRNA Expression Measured with the CheckPoint Typer® Assay with PD-L1 Protein Expression Assessed with Immunohistochemistry in Non-small Cell Lung Cancer.

PubMed

Erber, Ramona; Stöhr, Robert; Herlein, Stefanie; Giedl, Claudia; Rieker, Ralf Joachim; Fuchs, Florian; Ficker, Joachim H; Hartmann, Arndt; Veltrup, Elke; Wirtz, Ralph M; Brueckl, Wolfgang M

2017-12-01

Immunohistochemical (IHC) assessment of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) has become important since the development of anti-PD-1/-PD-L1 directed drugs. Various PD-L1 antibodies and cut-offs have been used in different trials to predict response to these drugs, thus comparison of those studies is difficult. We compared PD-L1 mRNA expression measured by RT-qPCR with PD-L1 protein expression evaluated by IHC. Moreover, we investigated the impact of different tumour tissue acquisition methods on the reliability of PD-L1 measurement techniques. NSCLC cases (N=22), including n=9 mediastinal lymph node biopsies acquired by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and n=5 metastases, were evaluated prospectively for PD-L1 protein on tumor cells (TC) and immune cells (IC) using E1L3N and 28-8 antibodies and PD-L1 mRNA using the CheckPoint TYPER® assay. In primary NSCLC tissues, agreement between PD-L1 mRNA and TC staining using the 28-8 antibody was excellent (ĸ=0.85, p=0.0002). Comparing both PD-L1 antibodies against each other showed a kappa value of 0.58 (p=0.0106). In EBUS-TBNA, PD-L1 mRNA correlated perfectly with the 28-8 antibody (ĸ=1.0, p=0.0023). PD-L1 mRNA levels significantly differed when comparing 28-8 TC staining of tumours >49% with 1-49% and 0% (p=0.0040; p=0.0081, respectively). In metastatic lesions, differences between PD-L1 mRNA and IHC became apparent (ĸ=0.2, p=0.2525). Testing of PD-L1 mRNA and 28-8 IHC showed an excellent agreement in NSCLC samples including mediastinal lymph node biopsies. Since PD-L1 expression in >50% TC detected by 28-8 IHC can be reliably detected by RT-qPCR, quantitative PD-L1 mRNA determination should be considered as an alternative to IHC as there is no interobserver variability in RNA results. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A Strategy for Helicobacter Immunohistochemistry Utilization in Pediatric Practice:  Insights From Morphologic and Cost-Benefit Analyses.

PubMed

Conces, Miriam R; Arnold, Christina A; Baker, Peter B; Carter, Christopher M; Fung, Bonita; Prasad, Vinay; Arnold, Michael A

2016-11-01

Recent studies in adults have examined the utility of immunohistochemistry (IHC) in detecting Helicobacter in gastric biopsy specimens and reached differing conclusions. Dedicated cost-benefit analysis of Helicobacter IHC in pediatric gastric biopsy specimens has not been performed. From 1,955 pediatric gastric biopsies in a 1-year period, we identified 63 Helicobacter -positive and 120 Helicobacter -negative biopsy specimens. All cases were scored according to the Updated Sydney System for the severity of inflammation. We observed that pediatric Helicobacter infection was significantly associated with germinal center formation, active inflammation, oxyntic mucosa with moderate to severe chronic inflammation, and antral mucosa with any chronic inflammation, exclusive of mild and superficial chronic inflammation. At least one associated pattern was seen in each Helicobacter -positive biopsy specimen. In comparison with adults, pediatric Helicobacter -positive biopsy specimens are more likely to lack acute inflammation and more likely to show moderate to marked chronic inflammation. We recommend performing Helicobacter IHC on pediatric gastric biopsy specimens with any of the above inflammatory patterns. This approach can sensitively identify pediatric patients with Helicobacter gastritis, limit IHC staining to approximately 30% of all gastric biopsy specimens, and reduce costs by up to $55,306.90 per 1,000 biopsy specimens. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Parasite detection in patients with post kala-azar dermal leishmaniasis in India: a comparison between molecular and immunological methods

PubMed Central

Salotra, P; Sreenivas, G; Beena, K R; Mukherjee, A; Ramesh, V

2003-01-01

Aims: To evaluate the sensitivity and specificity of serological, immunohistochemical, and molecular methods in the diagnosis of post kala-azar dermal leishmaniasis (PKDL). Methods: Twenty five patients with confirmed PKDL and 25 controls were included in the study. G2D10, a monoclonal antibody against Leishmania, was used for the immunohistochemical (IHC) staining of lesion sections to visualise anti-Leishmania donovani antibodies. The diagnostic usefulness of IHC was compared with enzyme linked immunosorbent assay (ELISA) with a recombinant (rk39) antigen, and a species specific polymerase chain reaction (PCR) assay, amplifying a kinetoplast minicircle DNA sequence. Results: IHC detected 22 of 25 PKDL cases, giving a sensitivity of 88%. The diagnostic sensitivity of both the ELISA and PCR tests was higher (96%). All of the 25 controls examined were negative in PCR, indicating 100% specificity of the test, whereas ELISA showed 96% specificity. Conclusions: IHC with G2D10 significantly enhances the sensitivity of detection of PKDL over routine haematoxylin and eosin staining. ELISA with a recombinant antigen is an economical and practical assay. PCR is the most sensitive and specific diagnostic method for PKDL. The tests described would facilitate the recognition of patients with PKDL, enabling timely treatment, which would contribute greatly to the control of kala-azar. PMID:14600129

Effect of motion artifacts and their correction on near-infrared spectroscopy oscillation data: a study in healthy subjects and stroke patients.

PubMed

Selb, Juliette; Yücel, Meryem A; Phillip, Dorte; Schytz, Henrik W; Iversen, Helle K; Vangel, Mark; Ashina, Messoud; Boas, David A

2015-05-01

Functional near-infrared spectroscopy is prone to contamination by motion artifacts (MAs). Motion correction algorithms have previously been proposed and their respective performance compared for evoked rain activation studies. We study instead the effect of MAs on "oscillation" data which is at the basis of functional connectivity and autoregulation studies. We use as our metric of interest the interhemispheric correlation (IHC), the correlation coefficient between symmetrical time series of oxyhemoglobin oscillations. We show that increased motion content results in a decreased IHC. Using a set of motion-free data on which we add real MAs, we find that the best motion correction approach consists of discarding the segments of MAs following a careful approach to minimize the contamination due to band-pass filtering of data from "bad" segments spreading into adjacent "good" segments. Finally, we compare the IHC in a stroke group and in a healthy group that we artificially contaminated with the MA content of the stroke group, in order to avoid the confounding effect of increased motion incidence in the stroke patients. After motion correction, the IHC remains lower in the stroke group in the frequency band around 0.1 and 0.04 Hz, suggesting a physiological origin for the difference. We emphasize the importance of considering MAs as a confounding factor in oscillation-based functional near-infrared spectroscopy studies.

Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes.

PubMed

Vaughn, Cecily P; Robles, Jorge; Swensen, Jeffrey J; Miller, Christine E; Lyon, Elaine; Mao, Rong; Bayrak-Toydemir, Pinar; Samowitz, Wade S

2010-05-01

Germline mutation detection in PMS2, one of four mismatch repair genes associated with Lynch syndrome, is greatly complicated by the presence of numerous pseudogenes. We used a modification of a long-range PCR method to evaluate PMS2 in 145 clinical samples. This modification avoids potential interference from the pseudogene PMS2CL by utilizing a long-range product spanning exons 11-15, with the forward primer anchored in exon 10, an exon not shared by PMS2CL. Large deletions were identified by MLPA. Pathogenic PMS2 mutations were identified in 22 of 59 patients whose tumors showed isolated loss of PMS2 by immunohistochemistry (IHC), the IHC profile most commonly associated with a germline PMS2 mutation. Three additional patients with pathogenic mutations were identified from 53 samples without IHC data. Thirty-seven percent of the identified mutations were large deletions encompassing one or more exons. In 27 patients whose tumors showed absence of either another protein or combination of proteins, no pathogenic mutations were identified. We conclude that modified long-range PCR can be used to preferentially amplify the PMS2 gene and avoid pseudogene interference, thus providing a clinically useful germline analysis of PMS2. Our data also support the use of IHC screening to direct germline testing of PMS2. (c) 2010 Wiley-Liss, Inc.

Evaluation of ALK gene rearrangement in central nervous system metastases of non-small-cell lung cancer using two-step RT-PCR technique.

PubMed

Nicoś, M; Krawczyk, P; Wojas-Krawczyk, K; Bożyk, A; Jarosz, B; Sawicki, M; Trojanowski, T; Milanowski, J

2017-12-01

RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status. 21% of CNS metastases of NSCLC (30/145) showed presence of mRNA containing abnormal ALK sequences. FISH and IHC tests confirmed the presence of ALK gene rearrangement and expression of ALK abnormal protein in seven patients with positive result of RT-PCR analysis (4.8% of all patients, 20% of RT-PCR positive patients). RT-PCR method compared to FISH analysis achieved 100% of sensitivity and only 82.7% of specificity. IHC method compared to FISH method indicated 100% of sensitivity and 97.8% of specificity. In comparison to IHC, RT-PCR showed identical sensitivity with high number of false positive results. Utility of RT-PCR technique in screening of ALK abnormalities and in qualification patients for molecularly targeted therapies needs further validation.

Plagioclase-Hosted Magnetite Inclusions From the Bushveld Complex

NASA Astrophysics Data System (ADS)

Feinberg, J. M.; Scott, G. R.; Renne, P. R.; Wenk, H.

2004-12-01

Gabbros from the Main Zone of the 2.064 Ga Bushveld Complex have long been known to possess unusually stable magnetizations due to the presence of high coercivity, exsolved magnetite inclusions in plagioclase and clinopyroxene. The paleomagnetic pole for these rocks has been used to anchor apparent polar wander paths for the Kaapval craton during the Early-Mid Proterozoic. To better understand the rock magnetic properties of silicate-hosted magnetite inclusions, oriented paleomagnetic samples of gabbro were collected from quarries near Belfast and Rustenberg, South Africa, sampling the eastern and western limbs of the Complex, respectively. Plagioclase composition at both sites ranges from An55 (rims) to An65 (cores) based on optical and electron microprobe data. Four kinds of inclusions are present within the plagioclase: elongate magnetite needles, nanometer-scale magnetite particles (responsible for the "cloudy" appearance of some crystals), translucent brown hematite/ilmenite platelets, and colorless euhedral inclusions of pyroxene and/or feldspar. Magnetite inclusions are most abundant at the cores of the plagioclase crystals. Orientations of the needles and the platelets are crystallographically controlled by the silicate host. Although the elongation direction of the magnetite inclusions can occur in any of five possible orientations, only two or three of these directions dominates each plagioclase crystal. Alternating field demagnetization of bulk samples (NRM = 1.5 x 101 A m-1) shows univectorial remanence with average median destructive fields (MDF) of 115 mT (Belfast) and 90 mT (Rustenberg). AF demagnetization of single plagioclase crystals (NRM = 100 A m-1) also shows single component remanence with average MDFs >150 mT. The NRM coercivity spectra of single plagioclase crystals are indistinguishable from that of the bulk samples. When normalized to their abundance in bulk samples the magnetite-bearing plagioclase fully accounts for the NRM of Bushveld gabbros at both sites. Close examination of the inclusions' interiors using magnetic force microscopy shows no ulvöspinel exsolution as observed in other silicate exsolved titanomagnetites with comparably high coercivities. Consequently, we interpret the high coercivities of the inclusions to be a product of their small size and extreme shape anisotropy. Single crystals of plagioclase demonstrate a strong anisotropy of IRM acquisition (see Scott, et al. this conference). Additionally, electron backscatter diffraction (EBSD) orientation indexing shows a strongly preferred orientation for plagioclase and pyroxene (with (010)plag and (100)pyr parallel to subhorizontal layering) consistent with gravitational settling within a magma chamber. Thus, there are two anisotropies (silicate preferred orientation and magnetite inclusion remanence) to consider when describing the ancient magnetic field present during the emplacement of the Bushveld.

Longitudinal recording on FePt and FePtX (X = B, Ni) intermetallic compounds

NASA Astrophysics Data System (ADS)

Li, Ning

1999-11-01

Near field recording on high coercivity FePt intermetallic compound media using a high Bsat write element was investigated. Untextured FePt media were prepared by magnetron sputtering on ZrO2 disks at a substrate temperature of 450°C, with post annealing at 450°C for 8 hrs. Both multilayer and cosputtered precursors produced the ordered tetragonal L10 phase with high coercivity between 5kOe and 12kOe. To improve readback noise decrease magnetic domain size, FePtB media were subsequently prepared by cosputtering. Over-write, roll-off, signal to noise ratio and non-linear transition shift (NLTS) ere measured by both metal in gap (MIG) and merged MR heads. FePtB media showed similar NLTS to commercial CoCrPtTa longitudinal media, but 5dB lower signal to noise ratio. By operating recording transducers in near contact, reasonable values of (>30dB) could be obtained. VSM Rotational Transverse Magnetization has been used for measuring the anisotropy field of magnetic thin films. Magnetization reversal during rotation of a 2D isotropic an applied field is discussed. The relationship between the transverse magnetization My and the applied field H was numerically solved. An excellent approximation for the transverse magnetization is found to be: My/Ms=A(1- H/Hk) 2.5, where A = 1.1434, and Hk is the anisotropy field. For curve fitting to experimental data, both A and Hk were used as fitting parameters. Comparison between a constructed torque hysteresis method and this VSM RTM method have been made theoretically and experimentally. Both results showed that VSM RTM will give better extrapolation of the anisotropy field. The torque measurement will slightly overestimate the anisotropy field. The anisotropy fields of FePt and FePtX (X = B, Ni) films were characterized using this VSM RTM technique with comparison to a CoCrTaPt disk. Anisotropy energy was derived. Hc/Hk was used as an indicator for coherent rotation of a single domain. Interactions between magnetic domains were characterized by Kelly-Henkel plot and interactive field factor (IFF). Correlation between coercive force and magnetic anisotropy of grains and the degree of magnetic isolation among grains were discussed. B and Ni were used as diluting agents to the FePt system to decrease saturation magnetization, coercivity, anisotropy field and anisotropy energy. They also decrease the magnetic coupling between neighboring domains, and promote coherent rotation inside each domain.

5 CFR 950.108 - Preventing coercive activity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Preventing coercive activity. 950.108 Section 950.108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... giving is fundamental to Federal fundraising activities. Actions that do not allow free choices or create...

Comparative magnetic measurements on social insects

NASA Astrophysics Data System (ADS)

Ferreira, Jandira; Cernicchiaro, Geraldo; Winklhofer, Michael; Dutra, Humberto; de Oliveira, Paulo S.; S. Esquivel, Darci M.; Wajnberg, Eliane

2005-03-01

Biogenic magnetite has been detected in several species of social insects and may well form the basis of a magnetic sensory system in these animals, although other physiological functions are possible, too. We report here on hysteresis measurements on honeybees ( Apis mellifera) and the termite Neocapritermes opacus. The ratio of saturation remanence to saturation magnetization, Jrs/ Js, was determined as 0.11 (0.15) in bees (termite), the coercive force Hc as 90 (50 Oe). The magnetic remanence is generally low (of the order of 10 -6 emu per individual). The values obtained are similar to the ones reported previously on a migratory ant species, which suggests that biomineralization of magnetic material in social insects may underlie a generic process.

Magnetic Properties and Phase Composition of Metamaterials Based on an Opal Matrix with 3 d-Transition Metal Particles

NASA Astrophysics Data System (ADS)

Rinkevich, A. B.; Korolev, A. V.; Samoilovich, M. I.; Perov, D. V.; Nemytova, O. V.

2018-02-01

The magnetic properties of metamaterials based on an opal matrix with transition-metal (iron, nickel, cobalt) particles have been studied. Magnetization curves and magnetic hysteresis loops have been measured and the dependences of real and imaginary parts of magnetization have been determined using the dynamic ac susceptibility measuring procedure. Structural studies of metamaterials have been performed. The saturation magnetization and coercive force of the studied metamaterials have been found to depend weakly on the temperature. The temperature dependence of magnetic susceptibility at a temperature above 30 K can be described adequately by Curie-Weiss law and, at lower temperature, deviates from the law.

MAGNETIC MEASUREMENT OF THE PLASTIC STRESS-STRAIN CURVE OF MULTICRYSTALLINE NICKEL (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwink, Ch.; Zankl, G.

1962-01-01

Ballistic measurements of the coercive force H/sub c/ and the initial permeability mu /sub alpha / were made on nlckel wires, and their dependence on plastic tensile deformation was followed. The results are shown graphically. H/ sub c/ and 1/ mu /sub alpha / start to increase at a given tensile stress with the introduction of plastic expansion and increases almost linearly with the tensile stress applied. At a tensile stress of 7.2 plus or minus 0.5 kp/mm/sup 2/ both curves have noticable bends. The bend point is related by a special process to the plastic deformation of the multicrystallinemore » material. (J.S.R.)« less

Effect of neutron irradiation on magnetic properties in the low alloy Ni-Mo steel SA508-3

NASA Astrophysics Data System (ADS)

Park, D. G.; Kim, C. G.; Kim, H. C.; Hong, J. H.; Kim, I. S.

1997-04-01

The B-H hysteresis loop and Barkhausen noise have been measured in the neutron irradiated SA508 steel of 45 μm thickness. The coercive force of B-H loop showed a slow change up to a neutron dose of 1014 n/cm2 and increased by 15.4% for a 1016 n/cm2 dose sample compared with that of the unirradiated one, related to the domain wall motion hindered by the increased defects. However, the amplitude of Barkhausen noise reflecting the wall motion decreased slowly up to 1014 n/cm2 irradiation, followed by a rapid decrease of 37.5% at 1016 n/cm2.

Structure and magnetic properties of Co-Ni-Mn alloy coatings (part 2)

NASA Astrophysics Data System (ADS)

Schmidt, V. V.; Zhikhareva, I. G.; Smirnova, N. V.; Shchipanov, V. P.

2018-03-01

Using the method of high-frequency alternating current (HFAC), based on the preliminary model forecasting of the ratio of metal ions in the electrolyte and the phase composition of the coating, Co-Ni-Mn alloy precipitates with the specified magnetic properties are obtained. It is shown that precipitation with a hexagonal close-packed α-Co phase has the highest coercive force. The presence of a free phase in a small amount (2.1 - 2.6% of weight) of Mn increases the ferromagnetic properties of films due to the domain structures with a poorly defecting α-Mn crystal lattice. The adjustable amount of the amorphous Co(OH)2 phase provides the nanostructure dimensions of the crystals.

A harsh parenting team? Maternal reports of coparenting and coercive parenting interact in association with children's disruptive behaviour.

PubMed

Latham, Rachel M; Mark, Katharine M; Oliver, Bonamy R

2017-05-01

Parenting and coparenting are both important for children's adjustment, but their interaction has been little explored. Using a longitudinal design and considering two children per family, we investigated mothers' and fathers' perceptions of coparenting as moderators of associations between their coercive parenting and children's disruptive behaviour. Mothers and fathers from 106 'intact' families were included from the Twins, Family and Behaviour study. At Time 1 (M child age  = 3 years 11 months, SD child age  = 4.44 months) parents reported on their coercive parenting and children's disruptive behaviour via questionnaire; at Time 2 (M child age  = 4 years 8 months, SD child age  = 4.44 months) perceptions of coparenting and the marital relationship were collected by telephone interview. Questionnaire-based reports of children's disruptive behaviour were collected at follow-up (M child age  = 5 years 11 months, SD child age  = 5.52 months). Multilevel modelling was used to examine child-specific and family-wide effects. Conservative multilevel models including both maternal and paternal perceptions demonstrated that maternal perceptions of coparenting and overall coercive parenting interacted in their prediction of parent-reported child disruptive behaviour. Specifically, accounting for perceived marital quality, behavioural stability, and fathers' perceptions, only in the context of perceived higher quality coparenting was there a positive association between mother-reported overall coercive parenting and children's disruptive behaviour at follow-up. When combined with highly coercive parenting, maternal perceptions of high quality coparenting may be detrimental for children's adjustment. © 2016 Association for Child and Adolescent Mental Health.

Cross-sectional study on nurses' attitudes regarding coercive measures: the importance of socio-demographic characteristics, job satisfaction, and strategies for coping with stress.

PubMed

Bregar, Branko; Skela-Savič, Brigita; Kores Plesničar, Blanka

2018-06-04

Coercive measures are containment methods used in psychiatry to curb patients' disruptive and aggressive behaviours towards themselves, others or objects. The prevalence of the practice of coercive measures in psychiatry is directly related to the attitudes of the staff. When discussing these attitudes, nurses are often particularly singled out. The purpose of the study is to research the impact of individual factors on nurses' attitudes in the decision-making process for the use of coercive measures. A cross-sectional study among all psychiatric nursing staff in Slovenia (n = 367, 79%) was conducted over the years 2013/2014. Standardized questionnaires were used, including a survey of nurses' attitudes to the use of seclusion, the Job Descriptive Index, and the Folkman-Lazarus test. Nurses' attitudes towards special coercive measures are predominantly negative ([Formula: see text] = 11.312, SD = 2.641). The factors that explain a positive attitude are as follows: female gender (β = - 0.236, p <  0.001), fewer years of service (β = - 0.149, p = 0.023), emotion-focused strategies of coping with stress (β = 0.139, p = 0.020), and less-threatening patient behaviour (β = 0.157, p = 0.012). The effects of some known factors did not prove important in the model. Newly recognized factors are "less-threatening patient behaviour" and "emotion-focused strategies of coping with stress". Therefore, attitudes towards special coercive measures in psychiatry must be regarded as contextualized, interactive, and multidimensional phenomena that cannot be explained merely through a defined set of factors.

Across-frequency behavioral estimates of the contribution of inner and outer hair cell dysfunction to individualized audiometric loss

PubMed Central

Johannesen, Peter T.; Pérez-González, Patricia; Lopez-Poveda, Enrique A.

2014-01-01

Identifying the multiple contributors to the audiometric loss of a hearing impaired (HI) listener at a particular frequency is becoming gradually more useful as new treatments are developed. Here, we infer the contribution of inner (IHC) and outer hair cell (OHC) dysfunction to the total audiometric loss in a sample of 68 hearing aid candidates with mild-to-severe sensorineural hearing loss, and for test frequencies of 0.5, 1, 2, 4, and 6 kHz. It was assumed that the audiometric loss (HLTOTAL) at each test frequency was due to a combination of cochlear gain loss, or OHC dysfunction (HLOHC), and inefficient IHC processes (HLIHC), all of them in decibels. HLOHC and HLIHC were estimated from cochlear I/O curves inferred psychoacoustically using the temporal masking curve (TMC) method. 325 I/O curves were measured and 59% of them showed a compression threshold (CT). The analysis of these I/O curves suggests that (1) HLOHC and HLIHC account on average for 60–70 and 30–40% of HLTOTAL, respectively; (2) these percentages are roughly constant across frequencies; (3) across-listener variability is large; (4) residual cochlear gain is negatively correlated with hearing loss while residual compression is not correlated with hearing loss. Altogether, the present results support the conclusions from earlier studies and extend them to a wider range of test frequencies and hearing-loss ranges. Twenty-four percent of I/O curves were linear and suggested total cochlear gain loss. The number of linear I/O curves increased gradually with increasing frequency. The remaining 17% I/O curves suggested audiometric losses due mostly to IHC dysfunction and were more frequent at low (≤1 kHz) than at high frequencies. It is argued that in a majority of listeners, hearing loss is due to a common mechanism that concomitantly alters IHC and OHC function and that IHC processes may be more labile in the apex than in the base. PMID:25100940

Cytology specimens offer an effective alternative to formalin-fixed tissue as demonstrated by novel automated detection for ALK break-apart FISH testing and immunohistochemistry in lung adenocarcinoma.

PubMed

Rosenblum, Frida; Hutchinson, Lloyd M; Garver, Joann; Woda, Bruce; Cosar, Ediz; Kurian, Elizabeth M

2014-11-01

Minimally invasive sampling by cytology or core needle biopsy often provides an initial diagnosis for treatment in patients with lung nodules. From these limited specimens, multiple molecular studies are frequently requested. Current guidelines from the US Food and Drug Administration recommend using formalin-fixed paraffin-embedded tissue sections for the detection of anaplastic lymphoma kinase (ALK) gene rearrangement by fluorescence in situ hybridization (FISH). The authors compared alcohol-fixed and formalin-fixed cytology specimens using a novel automated detection for ALK rearrangements by FISH and immunohistochemistry (IHC). ALK FISH testing was performed on 129 lung adenocarcinomas from 71 cytology cases and 58 biopsy/resection specimens using Papanicolaou staining with integrated cytomorphology. IHC with the ALK D5F3 antibody was performed on cases with residual material (88 of 129 cases). The mean age of the patients was 66 years; there were 62 women and 67 men. ALK gene rearrangement was present in 4% of cytology specimens (3 of 71 specimens) and 7% of surgical specimens (4 of 58 specimens). FISH in 13 cases was technically unsuccessful. Of the 7 FISH-positive cases, only 2 cytology cases (4%) and 2 surgical cases (6%) were found to be positive with the ALK antibody, demonstrating 80% concordance. The one case found to be negative for ALK by IHC demonstrated a variant rearrangement of the ALK 2p23 gene locus by FISH. The results of the current study validate the usefulness of alcohol-fixed and/or formalin-fixed cytology specimens for ALK rearrangement by a novel automated FISH method. IHC using the D5F3 antibody for ALK is specific in this limited cohort. The authors also demonstrated that alcohol-fixed cytology specimens can be used for ALK rearrangement by automated FISH, alone or in conjunction with IHC. © 2014 American Cancer Society.

Gene protein detection platform--a comparison of a new human epidermal growth factor receptor 2 assay with conventional immunohistochemistry and fluorescence in situ hybridization platforms.

PubMed

Stålhammar, Gustav; Farrajota, Pedro; Olsson, Ann; Silva, Cristina; Hartman, Johan; Elmberger, Göran

2015-08-01

Human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are widely used semiquantitative assays for selecting breast cancer patients for HER2 antibody therapy. However, both techniques have been shown to have disadvantages. Our aim was to test a recent automated technique of combined IHC and brightfield dual in situ hybridization-gene protein detection platform (GPDP)-in breast cancer HER2 protein, gene, and chromosome 17 centromere status evaluations, comparing the results in accordance to the American Society of Clinical Oncology/College of American Pathologists recommendations for HER2 testing in breast cancer from both 2007 and 2013. The GPDP technique performance was evaluated on 52 consecutive whole slide invasive breast cancer cases with HER2 IHC 2/3+ scoring results. Applying in turns the American Society of Clinical Oncology/College of American Pathologists recommendations for HER2 testing in breast cancer from 2007 and 2013 to both FISH and GPDP DISH assays, the HER2 gene amplification results showed 100% concordance among amplified/nonamplified cases, but there was a shift in 4 cases toward positive from equivocal results and toward equivocal from negative results. This might be related to the emphasis on the average HER2 copy number in the 2013 criteria. HER2 expression by IVD market IHC kit (Pathway®) has a strong correlation with GPDP HER2 protein, including a full concordance for all cases scored as 3+ and a reduction from 2+ to 1+ in 7 cases corresponding to nonamplified cases. Gene protein detection platform HER2 protein "solo" could have spared the need for 7 FISH studies. In addition, the platform offered advantages on interpretation reassurance including selecting areas for counting gene signals paralleled with protein IHC expression, on heterogeneity detection, interpretation time, technical time, and tissue expense. Copyright © 2015 Elsevier Inc. All rights reserved.

Mass spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: Comparison to IHC and FISH

PubMed Central

Catenacci, Daniel V.T.; Liao, Wei-Li; Zhao, Lei; Whitcomb, Emma; Henderson, Les; O’Day, Emily; Xu, Peng; Thyparambil, Sheeno; Krizman, David; Bengali, Kathleen; Uzzell, Jamar; Darfler, Marlene; Cecchi, Fabiola; Blackler, Adele; Bang, Yung-Jue; Hart, John; Xiao, Shu-Yuan; Lee, Sang Mee; Burrows, Jon; Hembrough, Todd

2015-01-01

Background Trastuzumab showed survival benefit for Her2-positive gastroesophageal cancers (GEC). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) currently determine eligibility for trastuzumab-based therapy. However, these low-throughput assays often produce discordant or equivocal results. Methods We developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/ug) of Her2-SRM protein in cell lines (n=27) and GEC tissues (n=139). We compared Her2-SRM protein expression with IHC/FISH, seeking to determine optimal SRM protein expression cut-offs to identify HER2 gene amplification. Results After demonstrating assay development, precision, and stability, Her2-SRM protein measurement was observed to be highly concordant with HER2/CEP17 ratio, particularly in a multivariate regression model adjusted for SRM-expression of Met, Egfr, Her3, and HER2-heterogeneity covariates, and their interactions (cell lines r2=0.9842; FFPE r2=0.7643). In GEC tissues, Her2-SRM protein was detected in 71.2% of cases. ROC curves demonstrated Her2-SRM protein levels to have high specificity (100%) at an upper-level cut-off of >750 amol/μg and sensitivity (75%) at lower-level cut-off of <450 amol/ug to identify HER2 FISH amplified tumors. An ‘equivocal-zone’ of 450-750 amol/ug of Her2-SRM protein was analogous to ’IHC2+#x2019;, but represented fewer cases (9-16% of cases versus 36-41%). Conclusions Compared to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal cases. Along with the multiplex capability for other relevant oncoproteins, these results demonstrated a refined HER2 protein expression assay for clinical application. PMID:26581548

Quantitative image analysis of immunohistochemical stains using a CMYK color model

PubMed Central

Pham, Nhu-An; Morrison, Andrew; Schwock, Joerg; Aviel-Ronen, Sarit; Iakovlev, Vladimir; Tsao, Ming-Sound; Ho, James; Hedley, David W

2007-01-01

Background Computer image analysis techniques have decreased effects of observer biases, and increased the sensitivity and the throughput of immunohistochemistry (IHC) as a tissue-based procedure for the evaluation of diseases. Methods We adapted a Cyan/Magenta/Yellow/Key (CMYK) model for automated computer image analysis to quantify IHC stains in hematoxylin counterstained histological sections. Results The spectral characteristics of the chromogens AEC, DAB and NovaRed as well as the counterstain hematoxylin were first determined using CMYK, Red/Green/Blue (RGB), normalized RGB and Hue/Saturation/Lightness (HSL) color models. The contrast of chromogen intensities on a 0–255 scale (24-bit image file) as well as compared to the hematoxylin counterstain was greatest using the Yellow channel of a CMYK color model, suggesting an improved sensitivity for IHC evaluation compared to other color models. An increase in activated STAT3 levels due to growth factor stimulation, quantified using the Yellow channel image analysis was associated with an increase detected by Western blotting. Two clinical image data sets were used to compare the Yellow channel automated method with observer-dependent methods. First, a quantification of DAB-labeled carbonic anhydrase IX hypoxia marker in 414 sections obtained from 138 biopsies of cervical carcinoma showed strong association between Yellow channel and positive color selection results. Second, a linear relationship was also demonstrated between Yellow intensity and visual scoring for NovaRed-labeled epidermal growth factor receptor in 256 non-small cell lung cancer biopsies. Conclusion The Yellow channel image analysis method based on a CMYK color model is independent of observer biases for threshold and positive color selection, applicable to different chromogens, tolerant of hematoxylin, sensitive to small changes in IHC intensity and is applicable to simple automation procedures. These characteristics are advantageous for both basic as well as clinical research in an unbiased, reproducible and high throughput evaluation of IHC intensity. PMID:17326824

Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer.

PubMed

Mok, Tony; Ladrera, Guia; Srimuninnimit, Vichien; Sriuranpong, Virote; Yu, Chong-Jen; Thongprasert, Sumitra; Sandoval-Tan, Jennifer; Lee, Jin Soo; Fuerte, Fatima; Shames, David S; Klughammer, Barbara; Truman, Matt; Perez-Moreno, Pablo; Wu, Yi-Long

2016-08-01

The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight. This multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas(®) test, KRAS mutation by cobas(®)KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate. Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p<0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR=0.32, 95% confidence intervals [CI]: 0.14-0.69, p=0.0024). Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Immunostaining with EGFR mutation-specific antibodies: a reliable screening method for lung adenocarcinomas harboring EGFR mutation in biopsy and resection samples.

PubMed

Fan, Xiangshan; Liu, Biao; Xu, Haodong; Yu, Bo; Shi, Shanshan; Zhang, Jin; Wang, Xuan; Wang, Jiandong; Lu, Zhenfeng; Ma, Henghui; Zhou, Xiaojun

2013-08-01

Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation-specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation-specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

Correlation of EGFR expression, gene copy number and clinicopathological status in NSCLC.

PubMed

Gaber, Rania; Watermann, Iris; Kugler, Christian; Reinmuth, Nils; Huber, Rudolf M; Schnabel, Philipp A; Vollmer, Ekkehard; Reck, Martin; Goldmann, Torsten

2014-09-17

Epidermal Growth Factor Receptor (EGFR) targeting therapies are currently of great relevance for the treatment of lung cancer. For this reason, in addition to mutational analysis immunohistochemistry (IHC) of EGFR in lung cancer has been discussed for the decision making of according therapeutic strategies. The aim of this study was to obtain standardization of EGFR-expression methods for the selection of patients who might benefit of EGFR targeting therapies. As a starting point of a broad investigation, aimed at elucidating the expression of EGFR on different biological levels, four EGFR specific antibodies were analyzed concerning potential differences in expression levels by Immunohistochemistry (IHC) and correlated with fluorescence in situ hybridization (FISH) analysis and clinicopathological data. 206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was compared to FISH utilizing two different probes. EGFR protein expression determined by IHC with Dako PharmDx kit, clone 31G7 and clone 2.1E1 (p ≤ 0.05) correlated significantly with both FISH probes independently of the three scoring methods; best correlation is shown for 31G7 using the scoring method that defined EGFR positivity when ≥ 10% of the tumor cells show membranous staining of moderate and severe intensity (p=0.001). Overall, our data show differences in EGFR expression determined by IHC, due to the applied antibody. Highest concordance with FISH is shown for antibody clone 31G7, evaluated with score B (p=0.001). On this account, this antibody clone might by utilized for standard evaluation of EGFR expression by IHC. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_165.

Tissue tropism of highly pathogenic avian influenza virus subtype H5N1 in naturally infected mute swans (Cygnus Olor ), domestic geese (Aser Anser var. domestica), pekin ducks (Anas platyrhynchos) and mulard ducks ( Cairina moschata x anas platyrhynchos).

PubMed

Szeredi, Levente; Dán, Adám; Pálmai, Nimród; Ursu, Krisztina; Bálint, Adám; Szeleczky, Zsófia; Ivanics, Eva; Erdélyi, Károly; Rigó, Dóra; Tekes, Lajos; Glávits, Róbert

2010-03-01

The 2006 epidemic due to highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in Hungary caused the most severe losses in waterfowl which were, according to the literature at the time, supposed to be the most resistant to this pathogen. The presence of pathological lesions and the amount of viral antigen were quantified by gross pathology, histopathology and immunohistochemistry (IHC) in the organs of four waterfowl species [mute swans (n = 10), domestic geese (n = 6), mulard ducks (n = 6) and Pekin ducks (n = 5)] collected during the epidemic. H5N1 subtype HPAIV was isolated from all birds examined. Quantitative real-time reverse transcriptase-polymerase chain reaction (qRRT-PCR) was also applied on a subset of samples [domestic geese (n = 3), mulard (n = 4) and Pekin duck (n = 4)] in order to compare its sensitivity with IHC. Viral antigen was detected by IHC in all cases. However, the overall presence of viral antigen in tissue samples was quite variable: virus antigen was present in 56/81 (69%) swan, 22/38 (58%) goose, 28/46 (61%) mulard duck and 5/43 (12%) Pekin duck tissue samples. HPAIV subtype H5N1 was detected by qRRT-PCR in all birds examined, in 19/19 (100%) goose, 7/28 (25%) mulard duck and 12/28 (43%) Pekin duck tissue samples. As compared to qRRTPCR, the IHC was less sensitive in geese and Pekin ducks but more sensitive in mulard ducks. The IHC was consistently positive above 4.31 log10 copies/reaction but it gave very variable results below that level. Neurotropism of the isolated virus strains was demonstrated by finding the largest amount of viral antigen and the highest average RNA load in the brain in all four waterfowl species examined.

Magnetic nanostructuring and overcoming Brown's paradox to realize extraordinary high-temperature energy products

NASA Astrophysics Data System (ADS)

Balasubramanian, Balamurugan; Mukherjee, Pinaki; Skomski, Ralph; Manchanda, Priyanka; Das, Bhaskar; Sellmyer, David J.

2014-09-01

Nanoscience has been one of the outstanding driving forces in technology recently, arguably more so in magnetism than in any other branch of science and technology. Due to nanoscale bit size, a single computer hard disk is now able to store the text of 3,000,000 average-size books, and today's high-performance permanent magnets--found in hybrid cars, wind turbines, and disk drives--are nanostructured to a large degree. The nanostructures ideally are designed from Co- and Fe-rich building blocks without critical rare-earth elements, and often are required to exhibit high coercivity and magnetization at elevated temperatures of typically up to 180 °C for many important permanent-magnet applications. Here we achieve this goal in exchange-coupled hard-soft composite films by effective nanostructuring of high-anisotropy HfCo7 nanoparticles with a high-magnetization Fe65Co35 phase. An analysis based on a model structure shows that the soft-phase addition improves the performance of the hard-magnetic material by mitigating Brown's paradox in magnetism, a substantial reduction of coercivity from the anisotropy field. The nanostructures exhibit a high room-temperature energy product of about 20.3 MGOe (161.5 kJ/m3), which is a record for a rare earth- or Pt-free magnetic material and retain values as high as 17.1 MGOe (136.1 kJ/m3) at 180°C.

"He forced me to love him": putting violence on adolescent sexual health agendas.

PubMed

Wood, K; Maforah, F; Jewkes, R

1998-07-01

Violence against women within sexual relationships is a neglected area in public health despite the fact that, in partially defining women's capacity to protect themselves against STDs, pregnancy and unwanted sexual intercourse, it directly affects female reproductive health. This paper presents the findings of a qualitative study conducted among Xhosa-speaking adolescent women in South Africa which revealed male violent and coercive practices to dominate their sexual relationships. Conditions and timing of sex were defined by their male partners through the use of violence and through the circulation of certain constructions of love, intercourse and entitlement to which the teenage girls were expected to submit. The legitimacy of these coercive sexual experiences was reinforced by female peers who indicated that silence and submission was the appropriate response. Being beaten was such a common experience that some peers were said to perceive it to be an expression of love. Informants indicated that they did not terminate the relationships for several reasons: beyond peer pressure and the probability of being subjected to added abuse for trying to end a relationship, teenagers said that they perceived that their partners loved them because they gave them gifts of clothing and money. The authors argue that violence has been particularly neglected in adolescent sexuality arenas, and propose new avenues for sexuality research which could inform the development of much-needed adolescent sexual health interventions.

A strong pinning model for the coercivity of die-upset Pr-Fe-B magnets

NASA Astrophysics Data System (ADS)

Pinkerton, F. E.; fürst, C. D.

1991-04-01

We have measured the temperature dependence of the intrinsic coercivity Hci(T) between 5 and 565 K in a die-upset Pr-Fe-B magnet. Over a very wide temperature range up to 477 K, Hci(T) is in excellent agreement with a model for strong domain-wall pinning by a random array of pinning sites proposed by Gaunt [P. Gaunt, Philos. Mag. B 48, 261 (1983)]. The model includes both the temperature dependence of the intrinsic magnetic properties of the Pr2Fe14B phase and the effects of thermal activation of domain walls over the pinning barrier. The pinning sites are modeled as nonmagnetic planar inhomogeneities at the boundaries between platelet-shaped Pr2Fe14B grains. We develop an expression for the maximum pinning force per site, f, and derive the model prediction that (Hci/γHA)1/2 varies linearly with (T/γ)2/3, where HA and γ are the magnetocrystalline anisotropy field and the domain-wall energy per unit area of the Pr2Fe14B phase, respectively. Significant deviations from the model are observed only at high temperature, suggesting that the strong pinning model is no longer valid very close to the Curie temperature (565 K). The present result agrees with the model fit obtained for a die-upset Nd-Fe-B magnet.

Study of microstress state of P91 steel using complementary mechanical Barkhausen, magnetoacoustic emission, and X-ray diffraction techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Augustyniak, Bolesław, E-mail: bolek@mif.pg.gda.pl; Piotrowski, Leszek; Maciakowski, Paweł

2014-05-07

The paper deals with assessment of microstress state of martensite P91 steel using three complementary techniques: mechanical Barkhausen emission, magnetoacoustic emission (MAE), and X-ray diffraction (XRD) profile analysis. Magnetic coercivity Hc and microstructure were investigated with inductive magnetometry and magnetic force microscopy (MFM), respectively. Internal stress level of P91 steel was modified by heat treatment. Steel samples were austenitized, quenched, and then tempered at three temperatures (720 °C, 750 °C, and 780 °C) during increasing time (from 15 min up to 240 min). The microstrain level ε{sub i} was evaluated using Williamson–Hall method. It was revealed that during tempering microstrain systematically decreases from ε{sub i} = 2.5more » × 10{sup −3} for as quenched state down to ε{sub i} = 0.3 × 10{sup −3} for well tempered samples. Both mechanical hardness (Vicker's HV) and magnetic hardness (coercivity) decrease almost linearly with decreasing microstrain while the MAE and MBE intensities strongly increase. Tempering leads to evident shift of the MeBN intensity maximum recorded for the first load towards lower applied strain values and to increase of MAE intensity. This indicates that the microstress state deduced by magnetic techniques is correlated with microstrains evaluated with XRD technique.« less

Tailoring magnetic properties in arrays of pulse-electrodeposited Co nanowires: The role of Cu additive

NASA Astrophysics Data System (ADS)

Esmaeili, A.; Almasi Kashi, M.; Ramazani, A.; Montazer, A. H.

2016-01-01

In this study, we aim to report the role of Cu additive in arrays of pulse-electrodeposited Co nanowires (NWs) with diameters from 30 to 75 nm, embedded in porous aluminum oxide templates. This features the role of Cu additive in composition and crystalline characteristics as well as in the magnetic properties of Co NWs. Increasing the duration of off-time between pulses during the electrodeposition of Co NWs made it possible to increase the amount of Cu content, so that Co-rich CoCu NWs were obtained. The parallel coercivity and squareness values increased up to 1500 Oe and 0.8 for 30 nm diameter Co94Cu6 NWs, starting from 500 Oe and 0.3 for pure Co NWs. On the other hand, although there was a substantial difference between the crystalline characteristics of 75 nm diameter pure Co and CoCu NWs, no considerable change in their magnetic properties was observed using hysteresis loop measurements. In this respect, the first-order reversal curve (FORC) analysis revealed strong inter-wire magnetostatic interactions for the CoCu NWs. Moreover, we studied the effect of thermal annealing, which resulted in an increase in the coercivity of CoCu NWs with different diameters up to 15%. As a result, the addition of small amount of Cu provides an alternative approach to tailoring the magnetic properties of Co NWs.

Empowerment, Coercive Persuasion and Organizational Learning: Do They Connect?

ERIC Educational Resources Information Center

Schein, Edgar H.

1999-01-01

Individual learning in organizations can be de facto coercive persuasion when organizational learning and culture change require that learners develop appropriate attitudes and thinking. If the goal of organizational learning--innovative organizations--is accepted, moral choices that restrict individual freedom must be made. (SK)

Mechanical stress modified ferroelectric aging behavior

NASA Astrophysics Data System (ADS)

Xu, Tingting; Kan, Yi; Jin, Yaming; Sun, Hui; Du, Yingchao; Wu, Xiumei; Bo, Huifeng; Cai, Wei; Huang, Fengzhen; Lu, Xiaomei; Zhu, Jinsong

2013-05-01

Mechanical stress effect on aging behavior of Bi3.25La0.75Ti3O12 (BLT) and PbZr0.53Ti0.47O3 (PZT) films was investigated. It is found that the remnant polarization decreases with time while the coercive field increases in stress-free BLT films. For unconfined PZT films, both the remnant polarization and the coercive field decrease as time elapses. The applied tensile stress weakens the aging of remnant polarization of BLT films but strengthens the aging of coercive field, while the applied tensile stress possesses opposite effect. In contrary, the applied compressive stress simultaneously improves the aging behavior of both remnant polarization and coercive field of PZT films. Mechanical-stress-induced variation of domain wall mobility in different materials was suggested as the possible origin of these observations. This work indicates that the aging behavior modification using stress could be realized, and it is helpful for promoting the reliability of ferroelectric films for industrial applications.

Domain wall pinning on strain relaxation defects (stacking faults) in nanoscale FePd (001)/MgO thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsiao, C. H.; Ouyang, Chuenhou, E-mail: wei0208@gmail.com, E-mail: houyang@mx.nthu.edu.tw; Yao, Y. D.

FePd (001) films, prepared by an electron beam deposition system on MgO(100), exhibit a perpendicular magnetic anisotropy (1.7 × 10{sup 7 }erg/cc) with a high order parameter (0.92). The relation between stacking faults induced by the strain relaxation, which act as strong domain wall pinning sites, and the perpendicular coercivity of (001) oriented L1{sub 0} FePd films prepared at different temperatures have been investigated. Perpendicular coercivity can be apparently enhanced by raising the stacking fault densities, which can be elevated by climbing dissociation of total dislocation. The increased stacking fault densities (1.22 nm{sup −2}) with large perpendicular coercivity (6000 Oe) are obtained for samples preparedmore » at 650 °C. This present work shows through controlling stacking fault density in FePd film, the coercivity can be manipulated, which can be applied in future magnetic devices.« less

Coercivity enhancement of sintered Nd-Fe-B magnets by chemical bath deposition of TbCl{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Shuai, E-mail: gshuai@nimte.ac.cn; Zhang, Xiaofeng; Ding, Guangfei

2014-05-07

The chemical bath deposition (CBD) and the grain boundary diffusion method were combined to diffuse the heavy rare earth for obtain the thick magnets with high coercivity and low heavy rare earth. The jet mill powders were soaked into the alcohol solution of 0.2 wt. % TbCl{sub 3}. A thin layer of TbCl{sub 3} was wrapped to the surface of (PrNd){sub 2}Fe{sub 14}B powder particles. The coercivity of magnet is increased from 11.89 kOe to 14.72 kOe without significant reduction of remanence after grain boundary diffusion in the sintering and the annealing processes. The temperature coefficients of the remanence and themore » coercivity are improved by the substitution of PrNd by Tb in the surface of grains. The highly accelerated temperature/humidity stress test (HAST) results indicate that the CBD magnet has poor corrosion resistance, attributing to the present of Cl atoms in the grain boundaries.« less

Proven practices for reducing aggressive and noncompliant behaviors exhibited by young children at home and at school.

PubMed

Vanderheyden, A; Witt, J C

2000-10-01

One of the single most powerful predictors of aggressive and noncompliant behaviors exhibited in early childhood is coercive parent-child interaction. Coercive parent-child interaction has been linked to multiple negative outcomes in the lives of children. When children learn to relate to their parents and the world in the context of coercive interaction, they are likely to experience significant deficits in the prosocial skills critical to school success. These children are much more likely to experience school failure and teacher and peer rejection. Further, when noncompliant and aggressive children enter school, they are most frequently exposed to a series of ineffective and increasingly restrictive treatments. Proven strategies exist to teach parents and children prosocial ways of interacting and to address these problems in the classroom, but in many cases these types of services are not easily accessible or routinely available. This paper makes recommendations for identifying effective, proven treatment strategies when practitioners observe coercive parent-child interaction or child noncompliance and aggression.

Phase of neural excitation relative to basilar membrane motion in the organ of Corti: Theoretical considerations

NASA Astrophysics Data System (ADS)

Andoh, Masayoshi; Nakajima, Chihiro; Wada, Hiroshi

2005-09-01

Although the auditory transduction process is dependent on neural excitation of the auditory nerve in relation to motion of the basilar membrane (BM) in the organ of Corti (OC), specifics of this process are unclear. In this study, therefore, an attempt was made to estimate the phase of the neural excitation relative to the BM motion using a finite-element model of the OC at the basal turn of the gerbil, including the fluid-structure interaction with the lymph fluid. It was found that neural excitation occurs when the BM exhibits a maximum velocity toward the scala vestibuli at 10 Hz and shows a phase delay relative to the BM motion with increasing frequency up to 800 Hz. It then shows a phase advance until the frequency reaches 2 kHz. From 2 kHz, neural excitation again shows a phase delay with increasing frequency. From 800 Hz up to 2 kHz, the phase advances because the dominant force exerted on the hair bundle shifts from a velocity-dependent Couette flow-induced force to a displacement-dependent force induced by the pressure difference. The phase delay that occurs from 2 kHz is caused by the resonance process of the hair bundle of the IHC.

Valproic Acid Increases Expression of Neuronal Stem/Progenitor Cell in Spinal Cord Injury

PubMed Central

Bang, Woo-Seok; Cho, Dae-Chul; Kim, Hye-Jeong; Sung, Joo-Kyung

2013-01-01

Objective This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model. Methods Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively. Results Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group. Conclusion Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI. PMID:24044073

The Inflammatory Milieu Permits Metastasis in Pregnancy-Associated Breast Cancer

DTIC Science & Technology

2008-07-01

by the CT ask 5f) Characterization of tumor desmoplasia by IHC. The same panel of markers for taken in ask 5g ) Animal and human PABC IHC data...pregnancy. 12 Borges V, Albrektsen G, and Schedin P 13 We have also evaluated this model for differences in tumor latency with pregnancy. In...model, differences in latency are not observed between groups. Early time points in both of these models are confounded by the density of mammary tissue

Should Quality School Education Be a Kaizen (Improvement) or an Innovation?

ERIC Educational Resources Information Center

Sun-Keung Pang, Nicholas

1998-01-01

Reviews Hong Kong's School Management Initiative implementation strategies (rational-empirical, power-coercive, and normative-reeducative), compares them with New South Wales, Australia's strategies, and suggests an appropriate strategy for future reforms. In Australia, changes were radical and thorough (using power-coercive strategies), whereas…

Paraphilic Sexual Interests and Sexually Coercive Behavior: A Population-Based Twin Study.

PubMed

Baur, Elena; Forsman, Mats; Santtila, Pekka; Johansson, Ada; Sandnabba, Kenneth; Långström, Niklas

2016-07-01

Prior research with selected clinical and forensic samples suggests associations between paraphilic sexual interests (e.g., exhibitionism and sexual sadism) and sexually coercive behavior. However, no study to date used a large, representative and genetically informative population sample to address the potential causal nature of this association. We used self-report data on paraphilic and sexually coercive behavior from 5990 18- to 32-year-old male and female twins from a contemporary Finnish population cohort. Logistic regression and co-twin control models were employed to examine if paraphilic behaviors were causally related to coercive behavior or if suggested links were confounded by familial (genetic or common family environment) risk factors. Results indicated that associations between four out of five tested paraphilic behaviors (exhibitionism, masochism, sadism, and voyeurism, respectively) and sexually coercive behavior were moderate to strong. Transvestic fetishism was not independently associated with sexual coercion. Comparisons of twins reporting paraphilic behavior with their paraphilic behavior-discordant twin further suggested that associations were largely independent of shared genetic and environmental confounds, consistent with a causal association. In conclusion, similar to previously reported predictive effects of paraphilias on sexual crime recidivism, paraphilic behavior among young adults in the general population increases sexual offending risk. Further, early identification of paraphilic interest and preventive interventions with at-risk individuals might also reduce perpetration of first-time sexual violence.

Improved magnetic properties and thermal stabilities of Pr-Nd-Fe-B sintered magnets by Hf addition

NASA Astrophysics Data System (ADS)

Jiang, Qingzheng; Lei, Weikai; Zeng, Qingwen; Quan, Qichen; Zhang, Lili; Liu, Renhui; Hu, Xianjun; He, Lunke; Qi, Zhiqi; Ju, Zhihua; Zhong, Minglong; Ma, Shengcan; Zhong, Zhenchen

2018-05-01

Nd2Fe14B-type permanent magnets have been widely applied in various fields such as wind power, voice coil motors, and medical instruments. The large temperature dependence of coercivity, however, limits their further applications. We have systematically investigated the magnetic properties, thermal stabilities and coercivity mechanisms of the (Pr0.2Nd0.8)13Fe81-xB6Hfx (x=0, 0.5) nanocrystalline magnets fabricated by a spark plasma sintering (SPS) technique. The results indicate that the influence of Hf addition is significant on magnetic properties and thermal stabilities of the (PrNd)2Fe14B-type sintered magnets. It is shown that the sample with x = 0.5 at 300 K has much higher coercivity and remanent magnetization than those counterparts without Hf. The temperature coefficients of remanence (α) and coercivity (β) of the (Pr0.2Nd0.8)13Fe81-xB6Hfx magnets are improved significantly from -0.23 %/K, -0.57 %/K for the sample at x = 0 to -0.17 %/K, -0.49 %/K for the sample at x = 0.5 in the temperature range of 300-400 K. Furthermore, it is found out that the domain wall pinning mechanism is more likely responsible for enhancing the coercivity of the (Pr0.2Nd0.8)13Fe81-xB6Hfx magnets.

Determination of the effective anisotropy constant of CoFe2O4 nanoparticles through the T-dependence of the coercive field

NASA Astrophysics Data System (ADS)

Carvalho, M. H.; Lima, R. J. S.; Meneses, C. T.; Folly, W. S. D.; Sarmento, V. H. V.; Coelho, A. A.; Duque, J. G. S.

2016-03-01

We present a systematic study of the coercive field of CoFe2O4-SiO2 nanocomposites. The samples were prepared via the sol-gel method by using the Tetraethyl Orthosilicate as starting reagent. Results of X-ray diffraction, transmission electron microscopy, and X-ray fluorescence confirm the dispersion of the magnetic nanoparticles inside the silica matrix. In addition, the shift in the maximum of Zero-Field-Cooled curves observed by varying the weight ratio of CoFe2O4 nanoparticles to the precursor of silica is consistent with the increasing of average interparticle distances. Because our samples present a particle size distribution, we have used a generalized model which takes account such parameter to fit the experimental data of coercive field extracted from the magnetization curves as a function of applied field. Unlike most of the coercive field results reported in the literature for this material, the use of this model provided a successful description of the temperature dependence of the coercive field of CoFe2O4 nanoparticles in a wide temperature range. Surprisingly, we have observed the decreasing of the nanoparticles anisotropy constant in comparison to the bulk value expected for the material. We believe that this can be interpreted as due to both the migration of the Co2+ from octahedral to tetrahedral sites.

Structural, magnetic, and transport properties of Permalloy for spintronic experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nahrwold, Gesche; Scholtyssek, Jan M.; Motl-Ziegler, Sandra

2010-07-15

Permalloy (Ni{sub 80}Fe{sub 20}) is broadly used to prepare magnetic nanostructures for high-frequency experiments where the magnetization is either excited by electrical currents or magnetic fields. Detailed knowledge of the material properties is mandatory for thorough understanding its magnetization dynamics. In this work, thin Permalloy films are grown by dc-magnetron sputtering on heated substrates and by thermal evaporation with subsequent annealing. The specific resistance is determined by van der Pauw methods. Point-contact Andreev reflection is employed to determine the spin polarization of the films. The topography is imaged by atomic-force microscopy, and the magnetic microstructure by magnetic-force microscopy. Transmission-electron microscopymore » and transmission-electron diffraction are performed to determine atomic composition, crystal structure, and morphology. From ferromagnetic resonance absorption spectra the saturation magnetization, the anisotropy, and the Gilbert damping parameter are determined. Coercive fields and anisotropy are measured by magneto-optical Kerr magnetometry. The sum of the findings enables optimization of Permalloy for spintronic experiments.« less

Detection of BRAF mutation in Chinese tumor patients using a highly sensitive antibody immunohistochemistry assay

NASA Astrophysics Data System (ADS)

Qiu, Tian; Lu, Haizhen; Guo, Lei; Huang, Wenting; Ling, Yun; Shan, Ling; Li, Wenbin; Ying, Jianming; Lv, Ning

2015-03-01

BRAF mutations can be found in various solid tumors. But accurate and reliable screening for BRAF mutation that is compatible for clinical application is not yet available. In this study, we used an automated immunohistochemistry (IHC) staining coupled with mouse monoclonal anti-BRAF V600E (VE1) primary antibody to screen the BRAF V600E mutation in 779 tumor cases, including 611 colorectal carcinomas (CRC), 127 papillary thyroid carcinomas (PTC) and 41 malignant melanomas. Among the 779 cases, 150 cases were positive for BRAF (V600E) staining, including 38 (of 611, 6%) CRCs, 102 (of 127, 80%) PTCs and 10 (of 41, 24%) malignant melanomas. Sanger sequencing and real-time PCR confirmed the sensitivity and specificity of IHC staining for the V600E mutation are 100% and 99%, respectively. Therefore, our study demonstrates that the fully automated IHC is a reliable tool to determine BRAF mutation status in CRC, PTC and melanoma and can be used for routine clinical screen.

Awaiting a Spark: How Three Chinese Territorial Disputes Could Jeopardize Peace in Asia

DTIC Science & Technology

2013-12-01

annexation.120 Therefore, 117 Koji Sonoda and Takashi Oshima, “U.S. Warns Against ‘Coercive Action...of Law, 1999. Sonoda, Koji , and Takashi Oshima. “U.S. Warns against ‘Coercive Action’ over Senkaku Issue.” The Asahi Shinbum, April 30, 2013. http

Initiation, Desistance, and Persistence of Men's Sexual Coercion

ERIC Educational Resources Information Center

Hall, Gordon C. Nagayama; Degarmo, David S.; Eap, Sopagna; Teten, Andra L.; Sue, Stanley

2006-01-01

Patterns of sexually coercive behavior were examined among 266 Asian American and 299 European American men over 1 year. Noncoercer (n = 358), desister (n = 120), initiator (n = 39), and persistent (n = 48) sexually coercive groups were identified. The strongest predictor of sexual coercion was past sexual coercion. Persistent sexual coercers were…

Modified rapid immunohistochemical staining for intraoperative diagnosis of malignant brain tumors.

PubMed

Suzuki, Akane; Maruyama, Takashi; Nitta, Masayuki; Komori, Takashi; Ikuta, Soko; Kawamata, Takakazu; Muragaki, Yoshihiro

2017-10-01

Rapid immunohistochemistry (R-IHC) has been developing mainly as a support technique in the rapid diagnosis of central nervous system tumors; however, there have been problems regarding instability in specimen preparation and immunostaining. To overcome the weakness of this technology, the instability of immunostaining, we developed a modified R-IHC. This was achieved by switching to 4% paraformaldehyde as the fixative solution and utilizing a commercially available Polymer Refine Detection Kit, as a high-sensitivity kit, in place of the secondary antibodies. In this study, we tested the modified R-IHC by evaluating rapid immunostaining on new staining items in 94 brain tumor removal cases, which took place at Tokyo Women's Medical University from 2014 to 2015. The results showed that, based on GFAP and p53 markers, the modified method obtained a higher stability in specimens than the standard rapid immunostaining method. It also achieved stainability on the same level as that of a permanent specimen. The modified method tested 86.6% (46/53) and 82.8% (24/29) in pHH3 and ATRX, respectively, in the percentage of correct classification (PCC) against the permanent specimens, and 100% (7/7) in the PCC against malignant lymphomas and gliomas that used CD20/CD3 for discrimination. We concluded that the modified R-IHC method indicated a higher stainability and PCC against the permanent specimens in comparison to the standard method in GFAP, p53, CD20/CD3, pHH3, and ATRX.

Piglet colibacillosis diagnosis based on multiplex polymerase chain reaction and immunohistochemistry of paraffin-embedded tissues

PubMed Central

de Andrade, Caroline P.; Machado, Verônica S. L.; Bianchi, Matheus V.; Rolim, Veronica M.; Cruz, Raquel A. S.; Driemeier, David

2018-01-01

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs, referred to as colibacillosis. The aim of this study was to optimize multiplex polymerase chain reaction (PCR) and immunohistochemistry (IHC) analyses of paraffin-embedded material to detect pathogenic E. coli strains causing colibacillosis in pigs. Multiplex PCR was optimized for fimbriae (F18, F4, F6, F5, and F41) and toxins (types A and B heat-stable toxins [STaP and STb], heat-labile toxin [LT], and type 2 Shiga toxin [STx2e]), and IHC was optimized for an anti-E. coli polyclonal antibody. Samples (132) from pigs received between 2006 and 2014 with clinical and histopathological diagnoses of colibacillosis were analyzed. E. coli was detected by IHC in 78.7%, and at least one virulence factor gene was detected in 71.2%. Pathogenic strains of ETEC with at least one fimbria and one toxin were detected in 40% of the samples in multiplex PCR. The most frequent virulence types were F18-STaP (7.5%), F18-STaP-STb (5.7%), and F4-STaP (3.8%). A statistically significant association was noted between virulence factors F4, F18, STaP, and STb and positive immunostaining results. Colibacillosis diagnosis through multiplex PCR and IHC of paraffin-embedded tissues is a practical approach, as samples can be fixed and stored for long periods before analysis. PMID:28693311

Detection of EML4-ALK in Lung Adenocarcinoma Using Pleural Effusion with FISH, IHC, and RT-PCR Methods

PubMed Central

Zhou, Xiaodie; Song, Yong; Zhou, Xiaojun; Yu, Like; Wang, Jiandong

2015-01-01

Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib. Malignant pleural effusion occurs in most patients with advanced lung cancer, especially adenocarcinoma, and tissue samples are not always available from these patients. We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. We obtained 66 samples of pleural effusion from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were formalin fixed and paraffin embedded. The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH), reverse transcription—polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). EML4-ALK was detected in three of 66 patient samples (4.5%) with RT-PCR. When the RT-PCR data were used as the standard, one false positive and one false negative samples were identified with IHC; and one false negative sample was identified with FISH. These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. IHC had good sensitivity, but low specificity. FISH had low sensitivity, but high specificity. RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients. PMID:25785456

Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods.

PubMed

Liu, Leilei; Zhan, Ping; Zhou, Xiaodie; Song, Yong; Zhou, Xiaojun; Yu, Like; Wang, Jiandong

2015-01-01

Anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC), leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib. Malignant pleural effusion occurs in most patients with advanced lung cancer, especially adenocarcinoma, and tissue samples are not always available from these patients. We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. We obtained 66 samples of pleural effusion from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were formalin fixed and paraffin embedded. The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). EML4-ALK was detected in three of 66 patient samples (4.5%) with RT-PCR. When the RT-PCR data were used as the standard, one false positive and one false negative samples were identified with IHC; and one false negative sample was identified with FISH. These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. IHC had good sensitivity, but low specificity. FISH had low sensitivity, but high specificity. RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients.

The strategic use of outcome information.

PubMed

Thompson, D I; Sirio, C; Holt, P

2000-10-01

Most health care executives see outcome measurement as a technical or tactical matter rather than as a strategic tool. Accordingly, provider investment in outcome measurement and management is relatively small. Nevertheless, outcome information can be key to achieving an organization's strategic objectives. Advances in risk adjustment and improvements in technology for data collection and analysis have made outcome measurement a practical tool for individual hospital use. Strategically integrated outcome measurement efforts can give providers a competitive advantage over organizations that only use outcomes tactically. One of the best examples of an acute care provider that has used outcome information for strategic advantage is Intermountain Health Care (IHC; Salt Lake City). In 1997 IHC made clinical quality and outcomes the primary focus of its five-year strategic plan. To support the new strategy IHC's board of trustees approved the development of an outcome information system that generated data along clinical processes of care and the creation of a new management structure to use these data to hold professionals accountable and to set and achieve clinical improvement goals. From 1996 to 1999, IHC's share of the commercial health care market in Utah increased from roughly 50% to about 62% of the market, with the result that it has stopped actively marketing its services. Health care executives will not willingly invest in outcomes until they believe that they have business value. Therefore, making the business case for outcomes can help improve the quality of health care and the lives of individuals.

A multicolour flow cytometric assay for c-MYC protein in B-cell lymphoma.

PubMed

Alayed, Khaled; Schweitzer, Karen; Awadallah, Amad; Shetty, Shashirekha; Turakhia, Samir; Meyerson, Howard

2018-05-16

Develop an objective assay to detect c-MYC protein expression using multiparametric flow cytometry (FCM) as an alternative to immunohistochemistry (IHC). 57 patient samples and 11 cell line samples were evaluated. Cell suspensions were obtained and c-MYC staining was performed in combination with CD45 and CD19 and, in some samples, CD10. The percentage of c-MYC+ cells by FCM was correlated with the percentage determined by IHC. The relationship between c-MYC protein expression and the presence of a c-MYC gene rearrangement in aggressive and high-grade lymphomas was also assessed. c-MYC expression by FCM and IHC demonstrated a high degree of correlation in a training set of 33 patient cases, r=0.92, 11 cell line samples, r=0.81 and in a validation set of 24 aggressive and high-grade B-cell lymphomas, r=0.85. c-MYC gene was rearranged by fluorescence in situ hybridisation in 6/9 samples with high c-MYC expression (>40%) by FCM and 6/14 by IHC. We have developed a reliable multicolour FCM assay to detect c-MYC expression suitable for clinical laboratories that should be helpful to accurately quantify c-MYC expression in B-cell lymphomas. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lessons learnt from implementation of a Lynch syndrome screening program for patients with gynaecological malignancy.

PubMed

Najdawi, Fedaa; Crook, Ashley; Maidens, Jayne; McEvoy, Christopher; Fellowes, Andrew; Pickett, Justine; Ho, Musei; Nevell, David; McIlroy, Kirsten; Sheen, Amy; Sioson, Loretta; Ahadi, Mahsa; Turchini, John; Clarkson, Adele; Hogg, Russell; Valmadre, Sue; Gard, Greg; Dooley, Susan J; Scott, Rodney J; Fox, Stephen B; Field, Michael; Gill, Anthony J

2017-08-01

Despite a trend towards universal testing, best practice to screen patients presenting with gynaecological malignancy for Lynch syndrome (LS) is uncertain. We report our institutional experience of a co-ordinated gynaecological LS screening program. All patients with endometrial carcinoma or carcinosarcoma, or gynaecological endometrioid or clear cell carcinomas undergo reflex four panel immunohistochemistry (IHC) for MLH1, PMS2, MSH2 and MSH6 followed by cascade somatic hypermethylation analysis of the MLH1 promoter locus for dual MLH1/PMS2 negative tumours. On the basis of these results, genetic counselling and targeted germline mutation testing is then offered to patients considered at high risk of LS. From 1 August 2013 to 31 December 2015, 124 patients were screened (mean age 64.6 years). Thirty-six (29.0%) demonstrated abnormal MMR IHC: 26 (72.2%) showed dual loss of MLH1/PMS2, five (13.9%) dual loss of MSH2/MSH6, three (8.3%) isolated loss of MSH6, and two (5.6%) isolated loss of PMS2. Twenty-five of 26 (96.1%) patients with dual MLH1/PMS2 loss demonstrated MLH1 promoter methylation. Therefore, 11 (8.9%) patients screened were classified as high risk for LS, of whom nine (81.8%) accepted germline mutation testing. Three (2.4% of total screened) were confirmed to have LS, two with germline PMS2 and one with germline MSH2 mutation. Massive parallel sequencing of tumour tissue demonstrated somatic mutations which were concordant with the IHC results in the remainder. Interestingly, the one MLH1/PMS2 IHC negative but not hypermethylated tumour harboured only somatic MLH1 mutations, indicating that universal cascade methylation testing in MLH1/PMS2 IHC negative tumours is very low yield and could be reconsidered in a resource-poor setting. In conclusion, universal screening for LS in patients presenting with gynaecological malignancy using the algorithm described above identified LS in three of 124 (2.4%) of our population. Only three of nine (33.3%) patients considered at high risk for LS by combined IHC and hypermethylation analysis were proven to have LS. Only one of the LS patients was less than 50 years of age and none of these patients would have been identified had more restrictive Amsterdam or Bethesda criteria been applied. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Clinicopathologic Comparison of Lynch Syndrome-associated and "Lynch-like" Endometrial Carcinomas Identified on Universal Screening Using Mismatch Repair Protein Immunohistochemistry.

PubMed

Mills, Anne M; Sloan, Emily A; Thomas, Martha; Modesitt, Susan C; Stoler, Mark H; Atkins, Kristen A; Moskaluk, Christopher A

2016-02-01

Expanded testing for Lynch syndrome (LS) is increasingly recommended for patients with endometrial carcinomas, and immunohistochemistry (IHC) for tumor loss of mismatch-repair (MMR) protein expression is the most common primary screen. This has led to the recognition of MMR-IHC-deficient cases without identifiable mutations on directed germline sequencing. The clinical implications of such "Lynch-like" (LL) cancers are unclear. We here report the clinicopathologic features of putative familial endometrial carcinoma identified on universal MMR-IHC screening with attention to cases with discordant IHC and germline results. The files of the University of Virginia Pathology Department were retrospectively searched for all MMR-deficient endometrial carcinomas identified on screening. Cases were categorized as likely sporadic (MLH1/PMS2 loss, evidence of MLH1 promoter hypermethylation) or putative LS (PLS) (loss of MSH2/MSH6, MSH6, or PMS2). PLS cases were further subdivided into LS and LL groups on the basis of the presence or absence of a confirmatory mutation by germline testing, and the clinicopathologic features of these cases were compared. A deficiency of ≥1 MMR protein was observed in 31.4% (66/210) of endometrial carcinomas, including 26 PLS cases, 15 of which had germline testing. Directed germline sequencing confirmed LS in 46.7% (7/15); the remaining cases were classified as LL. High-grade and/or biphasic morphology was seen in 42.9% (3/7) of LS and 62.5% (5/8) of LL cases; the remaining cases showed low-grade, conventional endometrioid morphology. High level microsatellite instability was observed in 71.4% (5/7) of LL cases. The majority of cases from both groups (LS: 85.7% [6/7]; LL: 87.5% [7/8]) were low-stage (T1a/T1b). Endometrial carcinoma was the presenting malignancy in 85.7% (6/7) of LS patients and 87.5% (7/8) of LL patients. Family history was suggestive of LS in 28.5% (2/7) of LS patients and 12.5% (1/8) of LL patients. Screening algorithms based on age and cancer history would have failed to identify LS patients in 57.1% (4/7) of cases. Although universal MMR-IHC identifies endometrial carcinoma patients with LS who would have been missed using targeted screening algorithms, it also identifies cancers with discordant IHC and germline results for which the somatic versus germline origin of the MMR defect is unclear. Further study of this LL group is required before drawing definitive conclusions about their familial cancer risk.

Quantitative measurement of HER2 expression in breast cancers: comparison with 'real-world' routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival.

PubMed

Yardley, Denise A; Kaufman, Peter A; Huang, Weidong; Krekow, Lea; Savin, Michael; Lawler, William E; Zrada, Stephen; Starr, Alexander; Einhorn, Harvey; Schwartzberg, Lee S; Adams, John W; Lie, Yolanda; Paquet, Agnes C; Sperinde, Jeff; Haddad, Mojgan; Anderson, Steve; Brigino, Marlon; Pesano, Rick; Bates, Michael P; Weidler, Jodi; Bosserman, Linda

2015-03-18

Accurate assessment of HER2 status is critical in determining appropriate therapy for breast cancer patients but the best HER2 testing methodology has yet to be defined. In this study, we compared quantitative HER2 expression by the HERmark™ Breast Cancer Assay (HERmark) with routine HER2 testing by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and correlated HER2 results with overall survival (OS) of breast cancer patients in a multicenter Collaborative Biomarker Study (CBS). Two hundred and thirty-two formalin-fixed, paraffin-embedded breast cancer tissues and local laboratory HER2 testing results were provided by 11 CBS sites. HERmark assay and central laboratory HER2 IHC retesting were retrospectively performed in a blinded fashion. HER2 results by all testing methods were obtained in 192 cases. HERmark yielded a continuum of total HER2 expression (H2T) ranging from 0.3 to 403 RF/mm2 (approximately 3 logs). The distribution of H2T levels correlated significantly (P<0.0001) with all routine HER2 testing results. The concordance of positive and negative values (equivocal cases excluded) between HERmark and routine HER2 testing was 84% for local IHC, 96% for central IHC, 85% for local FISH, and 84% for local HER2 status. OS analysis revealed a significant correlation of shorter OS with HER2 positivity by local IHC (HR=2.6, P=0.016), central IHC (HR=3.2, P=0.015), and HERmark (HR=5.1, P<0.0001) in this cohort of patients most of whom received no HER2-targeted therapy. The OS curve of discordant low (HER2 positive but H2T low, 10% of all cases) was aligned with concordant negative (HER2 negative and H2T low, HR=1.9, P=0.444), but showed a significantly longer OS than concordant positive (HER2 positive and H2T high, HR=0.31, P=0.024). Conversely, the OS curve of discordant high (HER2 negative but H2T high, 9% of all cases) was aligned with concordant positive (HR=0.41, P=0.105), but showed a significantly shorter OS than concordant negative (HR=41, P<0.0001). Quantitative HER2 measurement by HERmark is highly sensitive, accurately quantifies HER2 protein expression and correlates well with routine HER2 testing. When HERmark and local HER2 results were discordant, HERmark more accurately predicted overall survival.

A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma.

PubMed

Catteau, Aurélie; Girardi, Hélène; Monville, Florence; Poggionovo, Cécile; Carpentier, Sabrina; Frayssinet, Véronique; Voss, Jesse; Jenkins, Robert; Boisselier, Blandine; Mokhtari, Karima; Sanson, Marc; Peyro-Saint-Paul, Hélène; Giannini, Caterina

2014-06-02

Mutations in isocitrate dehydrogenase genes IDH1 or IDH2 are frequent in glioma, and IDH mutation status is a strong diagnostic and prognostic marker. Current IDH mutation screening is performed with an immunohistochemistry (IHC) assay specific for IDH1 R132H, the most common mutation. Sequencing is recommended as a second-step test for IHC-negative or -equivocal cases. We developed and validated a new real-time quantitative polymerase chain reaction (PCR) assay for single-step detection of IDH1 R132H and 11 rare IDH1/2 mutations in formalin-fixed paraffin-embedded (FFPE) glioma samples. Performance of the IDH1/2 PCR assay was compared to IHC and Sanger sequencing. The IDH1/2 PCR assay combines PCR clamping for detection of 7 IDH1 and 5 IDH2 mutations, and Amplification Refractory Mutation System technology for specific identification of the 3 most common mutations (IDH1 R132H, IDH1 R132C, IDH2 R172K). Analytical sensitivity of the PCR assay for mutation detection was <5% for 11/12 mutations (mean: 3.3%), and sensitivity for mutation identification was very high (0.8% for IDH1 R132H; 1.2% for IDH1 R132C; 0.6% for IDH2 R172K). Assay performance was further validated on 171 clinical glioma FFPE samples; of these, 147 samples met the selection criteria and 146 DNA samples were successfully extracted. IDH1/2 status was successfully obtained in 91% of cases. All but one positive IDH1 R132H-IHC cases were concordantly detected by PCR and 3 were not detected by sequencing. Among the IHC-negative cases (n = 72), PCR detected 12 additional rare mutations (10 IDH1, 2 IDH2). All mutations detected by sequencing (n = 67) were concordantly detected by PCR and 5/66 sequencing-negative cases were PCR-positive (overall concordance: 96%). Analysis of synthetic samples representative of the 11 rare IDH1/2 mutations detected by the assay produced 100% correct results. The new IDH1/2 PCR assay has a high technical success rate and is more sensitive than Sanger sequencing. Positive concordance was 98% with IHC for IDH1 R132H detection and 100% with sequencing. The PCR assay can reliably be performed on FFPE samples and has a faster turnaround time than current IDH mutation detection algorithms. The assay should facilitate implementation of a comprehensive IDH1/2 testing protocol in routine clinical practice.

Electroplated Fe-Co-Ni films prepared in ammonium-chloride-based plating baths

NASA Astrophysics Data System (ADS)

Yanai, T.; Koda, K.; Kaji, J.; Aramaki, H.; Eguchi, K.; Takashima, K.; Nakano, M.; Fukunaga, H.

2018-05-01

We electroplated Fe-Co-Ni films in ammonium-chloride-based plating baths, and investigated the effect of the Co content on the magnetic properties and the structural ones of the as-plated films. The coercivity increased abruptly when the Co content become more than 60 at.%. As the rough surfaces were observed in the high Co content region, we considered that degradation of the surface is a factor of the abrupt increase in the coercivity. From the XRD analysis, we found that another factor of the abrupt increase is fcc-bcc phase transformation, and concluded that we need to keep the fcc structure to obtain Fe-Co-Ni films with low coercivity.

Coercivity degradation caused by inhomogeneous grain boundaries in sintered Nd-Fe-B permanent magnets

NASA Astrophysics Data System (ADS)

Chen, Hansheng; Yun, Fan; Qu, Jiangtao; Li, Yingfei; Cheng, Zhenxiang; Fang, Ruhao; Ye, Zhixiao; Ringer, Simon P.; Zheng, Rongkun

2018-05-01

Quantitative correlation between intrinsic coercivity and grain boundaries in three dimensions is critical to further improve the performance of sintered Nd-Fe-B permanent magnets. Here, we quantitatively reveal the local composition variation across and especially along grain boundaries using the powerful atomic-scale analysis technique known as atom probe tomography. We also estimate the saturation magnetization, magnetocrystalline anisotropy constant, and exchange stiffness of the grain boundaries on the basis of the experimentally determined structure and composition. Finally, using micromagnetic simulations, we quantify the intrinsic coercivity degradation caused by inhomogeneous grain boundaries. This approach can be applied to other magnetic materials for the analysis and optimization of magnetic properties.

Exploring Variations Within Situational Couple Violence and Comparisons With Coercive Controlling Violence and No Violence/No Control.

PubMed

Nielsen, Samantha K; Hardesty, Jennifer L; Raffaelli, Marcela

2016-02-01

We examined variations within situational couple violence among 23 divorcing mothers and compared them with mothers with coercive controlling violence and no violence/no control. Situational couple violence had great variability in frequency and severity of violence, fear, harassment, and protective strategies. In some cases, situational couple violence was frequent and severe and resembled coercive controlling violence in its consequences. The dynamics of fear and harassment in situational couple violence and in the divorce process in general warrant attention. Finally, mothers reported mental health symptoms that did not differ by group, which is likely due to the stresses of divorce. © The Author(s) 2015.

High-sensitivity GMR with low coercivity in top-IrMn spin-valves

NASA Astrophysics Data System (ADS)

Liu, H. R.; Qu, B. J.; Ren, T. L.; Liu, L. T.; Xie, H. L.; Li, C. X.; Ku, W. J.

2003-12-01

Top-IrMn spin-valves with a structure of Ta/NiFe/CoFe/Cu/CoFe/IrMn/Ta have been investigated. The spin-valves were deposited by high vacuum DC magnetron sputtering at room temperature. The magnetoresistance ratio reaches 9.12% at room temperature. The coercivity of the free layer and the exchange bias field is 1.04 and 180 Oe, respectively. The maximum sensitivity of the spin-valves is 8.36%/Oe. A reduction of 33.2% of the coercivity was obtained after a 2-min RIE process. Utilizing standard integrated circuit (IC) process, mass production of robust giant magnetoresistance sensors can be achieved with these spin-valve thin films.

High-coercivity FePt nanoparticle assemblies embedded in silica thin films.

PubMed

Yan, Q; Purkayastha, A; Singh, A P; Li, H; Li, A; Ramanujan, R V; Ramanath, G

2009-01-14

The ability to process assemblies using thin film techniques in a scalable fashion would be a key to transmuting the assemblies into manufacturable devices. Here, we embed FePt nanoparticle assemblies into a silica thin film by sol-gel processing. Annealing the thin film composite at 650 degrees C transforms the chemically disordered fcc FePt phase into the fct phase, yielding magnetic coercivity values H(c)>630 mT. The positional order of the particles is retained due to the protection offered by the silica host. Such films with assemblies of high-coercivity magnetic particles are attractive for realizing new types of ultra-high-density data storage devices and magneto-composites.

Initiation, desistance, and persistence of men's sexual coercion.

PubMed

Hall, Gordon C Nagayama; DeGarmo, David S; Eap, Sopagna; Teten, Andra L; Sue, Stanley

2006-08-01

Patterns of sexually coercive behavior were examined among 266 Asian American and 299 European American men over 1 year. Noncoercer (n = 358), desister (n = 120), initiator (n = 39), and persistent (n = 48) sexually coercive groups were identified. The strongest predictor of sexual coercion was past sexual coercion. Persistent sexual coercers were higher than the other groups in delinquency and hostile masculinity and were nearly twice as likely to engage in laboratory sexual harassment. Loss of face attenuated self-reported sexual coercion and laboratory sexual harassment risk among Asian Americans and attenuated only laboratory sexual harassment risk among European Americans. These findings suggest that the heterogeneity of sexually coercive behavior and ethnicity are important research and clinical considerations.

Validation of Acceptance of Coercive Sexual Behavior (ACSB). A Multimedia Measure of Adolescent Dating Attitudes

ERIC Educational Resources Information Center

Teten, Andra L.; Hall, Gordon C. Nagayama; Pacifici, Caesar

2005-01-01

The psychometric properties of the Acceptance of Coercive Sexual Behavior (ACSB), a multimedia measure of adolescent dating attitudes, were examined. The ACSB is an interactive instrument that uses video vignettes to depict adolescent dating situations. Analyses of the measure's factor structure, internal consistency, test-retest reliability, and…

Adolescent Resource Control: Associations with Physical and Relational Aggression, Prosocial and Withdrawn Behaviors, and Peer Regard

ERIC Educational Resources Information Center

Findley, Danielle; Ojanen, Tiina

2013-01-01

This study examined adolescent coercive and prosocial resource control strategies in relation to various indices of peer-reported behaviors and peer regard ("N" = 384; 12-14 years). Coercive control was uniquely positively related to physical and relational aggression and peer disliking, and negatively to prosocial behaviors when…

Coercion in the Evolution of Plant-Microbe Communication: A Perspective.

PubMed

Rowe, S L; Norman, J S; Friesen, M L

2018-06-06

Plants and microbes are dependent on chemical signals as a means of interkingdom communication. There are two predicted paths for the evolution of these signals. Ritualization is the oft-assumed pathway for the evolution of plant-microbe communication systems. In this process, chemical signals, which benefit both receiver and sender, evolve from chemical cues, which benefit only the receiver. However, plant-microbe signaling may evolve from coercive interactions as well, a process known as sensory manipulation. Here, we aim to highlight the prevalence of coercive interactions and discuss sensory manipulation in the context of plant-microbe interactions. We present two examples of stabilized coercion: microbial coercion of plants via the release of phytohormones and plant coercion of microbes via manipulation of quorum-sensing compounds. Furthermore, we provide an evolutionary framework for the emergence of signaling from coercive plant-microbe interactions through the process of sensory manipulation. We hope that researchers will recognize the relevance of coercive interactions in plant-microbe systems and consider sensory manipulation as a plausible evolutionary trajectory for the emergence of plant-microbe signaling.

What do potential jurors know about police interrogation techniques and false confessions?

PubMed

Leo, Richard A; Liu, Brittany

2009-01-01

Psychological police interrogation methods in America inevitably involve some level of pressure and persuasion to achieve their goal of eliciting confessions of guilt from custodial suspects. In this article, we surveyed potential jurors about their perceptions of a range of psychological interrogation techniques, the likelihood that such techniques would elicit a true confession from guilty suspects, and the likelihood that such techniques could elicit a false confession from innocent suspects. Participants recognized that these interrogation techniques may be psychologically coercive and may elicit true confessions, but believed that psychologically coercive interrogation techniques are not likely to elicit false confessions. The findings from this survey study indicate that potential jurors believe that false confessions are both counter- intuitive and unlikely, even in response to psychologically coercive interrogation techniques that have been shown to lead to false confessions from the innocent. This study provides empirical support for the idea that expert witnesses may helpfully inform jurors about the social science research on psychologically coercive interrogation methods and how and why such interrogation techniques can lead to false confessions. (c) 2009 John Wiley & Sons, Ltd.

Impact of parental emotional support and coercive control on adolescents' self-esteem and psychological distress: results of a four-year longitudinal study.

PubMed

Boudreault-Bouchard, Anne-Marie; Dion, Jacinthe; Hains, Jennifer; Vandermeerschen, Jill; Laberge, Luc; Perron, Michel

2013-08-01

This study aims at investigating the impact of parental practices on youths' adjustment. In all, 605 adolescents completed questionnaires at ages 14, 16 and 18. Self-esteem, psychological distress as well as parental emotional support and coercive control were measured. Analyses based on individual growth models revealed that self-esteem increased with age, but psychological distress remained stable over time. Boys reported higher levels of self-esteem and lower levels of psychological distress than girls. Maternal and paternal emotional support reinforced self-esteem over time. Maternal coercive control undermined self-esteem, but only at ages 16 and 18. Psychological distress decreased with parental emotional support but increased with parental coercive control at ages 14, 16 and 18. Overall, these results indicate that positive parental practices are related to youths' well-being. These findings support the importance of establishing intervention strategies designed to promote best practices among parents of teenagers to help them develop into well-adjusted adults. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Stress remagnetization in pyrrhotite-calcite synthetic aggregates

NASA Astrophysics Data System (ADS)

Robion, Philippe; Borradaile, Graham J.

2001-01-01

Stress-induced remagnetization has been applied to multidomain pyrrhotite-calcite synthetic aggregates in a triaxial rig. Experimental deformation used 150MPa confining pressure, a constant strain rate of 10-5 s-1 and applied differential stresses of up to 70MPa. New components of magnetization, parallel to the direction of the pressure vessel field, were added to the pre-deformational magnetization. The intensity of remagnetization (M'-M0) increases with the intensity of the applied differential stress and affects the coercivity fraction below 15mT. Bulk shortening is less than 8 per cent, thus grain rotation cannot explain selective remagnetization of the low-coercivity fraction. Remagnetization is thus attributed to deformational viscous remanent magnetization (DVRM). It is observed that high-coercivity (>15mT) grains do not remagnetize. There is, however, slight progressive rotation of pre-deformational magnetization with increasing strain up to 8 per cent of bulk shortening. The lack of piezoremanent magnetization in the high-coercivity range may be due to defects introduced in pyrrhotite during sample preparation. Experiments using synthetic pyrrhotite, expected to show low dislocation densities, would be necessary to test this effect.

Adolescent mental health and subsequent parenting: a longitudinal birth cohort study

PubMed Central

Byford, M; Abbott, R A; Maughan, B; Richards, M; Kuh, D

2014-01-01

Background Adolescent mental health problems are associated with a range of adverse outcomes in adulthood but little is known about the effects on adult parenting practices. This study aimed to examine prospective associations between adolescent conduct and emotional problems and subsequent parenting behaviours in adulthood. Methods The study sample comprised 1110 members from the MRC National Survey of Health and Development. Prospective data were collected from teacher reports of conduct and emotional problems at age 13 and 15 years and adult outcome measures of parenting included intellectual environment, cognitive stimulation, coercive discipline, parental interest and parental aspiration. Results In regression models adjusted for the confounding effects of social background, cognition and education, adolescent conduct problems predicted coercive parenting behaviours in adulthood. The effects of adolescent emotional problems on the development of coercive discipline practices were explained by covariates. Likewise, the inability of parents who displayed conduct problems in adolescence to provide an intellectually stimulating home environment was fully explained by the adjustment for education. Conclusions Adolescents who exhibit conduct problems are more likely to develop coercive styles of parenting. PMID:24357583

Adolescent mental health and subsequent parenting: a longitudinal birth cohort study.

PubMed

Byford, M; Abbott, R A; Maughan, B; Kuh, D; Richards, M

2014-05-01

Adolescent mental health problems are associated with a range of adverse outcomes in adulthood but little is known about the effects on adult parenting practices. This study aimed to examine prospective associations between adolescent conduct and emotional problems and subsequent parenting behaviours in adulthood. The study sample comprised 1110 members from the MRC National Survey of Health and Development. Prospective data were collected from teacher reports of conduct and emotional problems at age 13 and 15 years and adult outcome measures of parenting included intellectual environment, cognitive stimulation, coercive discipline, parental interest and parental aspiration. In regression models adjusted for the confounding effects of social background, cognition and education, adolescent conduct problems predicted coercive parenting behaviours in adulthood. The effects of adolescent emotional problems on the development of coercive discipline practices were explained by covariates. Likewise, the inability of parents who displayed conduct problems in adolescence to provide an intellectually stimulating home environment was fully explained by the adjustment for education. Adolescents who exhibit conduct problems are more likely to develop coercive styles of parenting.

High coercivity in large exchange-bias Co/CoO-MgO nano-granular films

NASA Astrophysics Data System (ADS)

Ge, Chuan-Nan; Wan, Xian-Gang; Eric, Pellegrin; Hu, Zhi-Wei; Wen-I, Liang; Michael, Bruns; Zou, Wen-Qin; Du, You-Wei

2015-03-01

We present a detailed study on the magnetic coercivity of Co/CoO-MgO core-shell systems, which exhibits a large exchange bias due to an increase of the uncompensated spin density at the interface between the CoO shell and the metallic Co core by replacing Co by Mg within the CoO shell. We find a large magnetic coercivity of 7120 Oe around the electrical percolation threshold of the Co/CoO core/shell particles, while samples with a smaller or larger Co metal volume fraction show a considerably smaller coercivity. Thus, this study may lead to a route to improving the magnetic properties of artificial magnetic material in view of potential applications. Project supported by the National Basic Research Program of China (Grant No. 2012CB932304), the National Natural Science Foundation of China (Grant Nos. U1232210, 91122035, 11174124, and 11374137), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 14KJB140003), and the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.

Using the ferroelectric/ferroelastic effect at cryogenic temperatures for set-and-hold actuation

NASA Astrophysics Data System (ADS)

Steeves, J. B.; Golinveaux, F. S.; Lynch, C. S.

2018-06-01

The ferroelectric and ferroelastic properties of lead-zirconate-titanate (PZT) based stack actuators have been characterized at temperatures down to 25 K and under various levels of constant compressive stress. Experiments indicate that the coercive field and magnitude of strain at the coercive field display an inverse relationship with temperature. A factor of 5.5 increase in coercive field, and a factor of 4.3 increase in strain is observed at 25 K in comparison to the room-temperature conditions. This information was used to induce non-180° domain wall motion in the material through the application of electric fields at or near the coercive field. The change in remanent strain accompanying these effects was shown to increase in magnitude as temperature decreased, reaching values of 2000 ppm at 25 K. This behavior was also shown to be temporally stable even under compressive loads. Additionally, it was demonstrated that the material can be returned to its original strain state through a repolarizing electric field. This switchable behavior could be exploited for future set-and-hold type actuators operating at cryogenic temperatures.

Organizing the Cellular and Molecular Heterogeneity in High Grade Serous Ovarian Cancer by Mass Cytometry

DTIC Science & Technology

2015-10-01

expressed and the intensity by IHC and CyTOF (E-cadherin, vimentin, CD45, pAKT, FAP and p53). The examples show Figure 1: IHC of E-cadherin and...into CyTOF panels. Markers CD45, FAP and CD31 from the tumor antibody panel allow us to enumerate tumor, immune and stroma/angiogenic compartments...compartment as CD45-/CD31-/ FAP -, the immune compartment as CD45+/CD31-/ FAP . Data analysis of tumor compartment As with our pilot experiments from years 1 and

[Comparison of Aggressive Behavior, Compulsory Medication and Absconding Behavior Between Open and Closed door Policy in an Acute Psychiatric Ward].

PubMed

Cibis, Mara-Lena; Wackerhagen, Carolin; Müller, Sabine; Lang, Undine E; Schmidt, Yvonne; Heinz, Andreas

2017-04-01

Objective According to legal requirements coercive treatment must be limited to acts necessary for the protection of patients and cannot be used for institutional interests. Here, we aimed to test the hypothesis that opening psychiatric wards can reduce the number of aggressive assaults and of coercive treatment without increasing absconding rates. Methods Numbers of absconding, coercive medication, fixation and special security actions were collected retrospectively and compared between phases of closed (N total = 409; N legally committed = 64) and 90 % of daytime opened (N total = 571; N legally committed = 99) doors in an acute psychiatric ward. Results During the phase of opened doors we observed significantly reduced aggressive assaults (p < 0,001) and coercive medication (p = 0,006) compared to the closed setting, while the absconding rate did not change (p = 0,20). Limitation Given the retrospective non-experimental design, no causal interpretations can be drawn. Conclusion The results suggest that open door is associated with reduction of aggressive assaults and coercive medication without increasing absconding rates. This speaks for a stronger implementation of open door policies in acute wards in order to preserve human rights in psychiatry. To collect more robust evidence for this thesis, longer phases should be monitored and moderating variables such as atmosphere and social cohesion should be assessed. © Georg Thieme Verlag KG Stuttgart · New York.

Synergetic Effect of Dy2O3 and Ca Co-Dopants towards Enhanced Coercivity of Rare Earth Abundant RE-Fe-B Magnets.

PubMed

Li, Yingfei; Tian, Na; Fan, Xiaodong; You, Caiyin; Pei, Wenli; Cheng, Zhenxiang

2017-12-13

Low coercivity is the main disadvantage of RE-Fe-B permanent magnets containing highly abundant rare earths (RE: La, Ce) from the application point of view, even though they exhibit many cost and resource advantages. In this work, an industrial mixed rare earth alloy (RE 100  = La 30.6 Ce 50.2 Pr 6.4 Nd 12.8 ) with a high amount of the more abundant elements was adopted to fabricate RE-Fe-B permanent magnets by means of mechanical alloying accompanied by post-annealing. A synergetic effect towards enhancing the coercivity was observed after co-doping with Dy 2 O 3 and Ca, with the coercivity increasing from 2.44 kOe to 11.43 kOe for co-dopant percentages of 7 wt.% Dy 2 O 3  + 2.3 wt.% Ca. Through analysis of the phase constituents and microstructure, it was determined that part of the Dy atoms entered the matrix of RE 2 Fe 14 B phase to enhance the magnetocrystalline anisotropy; due to the reductive effect of Ca on Dy 2 O 3 , nanocrystals of Dy-rich RE 2 Fe 14 B were present throughout the matrix, which could increase the resistance to domain wall movement. These are the dominant factors behind the improvement of the coercivity of the RE-Fe-B magnets with highly abundant RE elements.