434 research outputs found
HER2 overexpression of breast cancers in Hong Kong: Prevalence and concordance between immunohistochemistry and in-situ hybridisation assays
Objectives: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. Design: Retrospective study. Setting: Department of Clinical Oncology in a public hospital in Hong Kong. Patients: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). Results: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. Conclusions: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.published_or_final_versio
Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).
BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (ÎČ = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (ÎČ = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families
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Cognitive impairment in Parkinson's disease: impact on quality of life of carers.
BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36âmonths after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (nâ=â9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (nâ=â18) or normal cognition (nâ=â39) carers (pâ<â0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd
Cerebral glucose metabolism and cognition in newly diagnosed Parkinsonâs disease: ICICLE-PD study
This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1136/jnnp-2016-31391
Localization of hRad9 in breast cancer
<p>Abstract</p> <p>Background</p> <p><it>hRad9 </it>is a cell cycle checkpoint gene that is up-regulated in breast cancer. We have previously shown that the mRNA up-regulation correlated with tumor size and local recurrence. Immunohistochemical studies were made to better define the role of <it>hRad9 </it>in breast carcinogenesis.</p> <p>Methods</p> <p>Localisation of hRad9 protein were performed on paired tumor and normal breast tissues. Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells.</p> <p>Results</p> <p>Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. This nuclear protein existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1 complex.</p> <p>Conclusion</p> <p>Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth.</p
Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson's disease
We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (-1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: -0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and AÎČ42/AÎČ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD.This study was funded by a Parkinson's UK grant (J-0802) and supported by Parkinson's UK (CN), Lockhart Parkinson's Disease Research Fund (RAL, TKK, GWD), Michael J. Fox Foundation (AJY), the National Institute for Health Research (NIHR, RG64473) Cambridge Biomedical Research Centre, and Biomedical Research Unit in Dementia, the Wellcome Trust (JBR, 103838); the Medical Research Council of Cognition, and Brain Sciences Unit, Cambridge (JBR, MC-A060-5PQ30); the NIHR Newcastle Biomedical Research Unit based at Newcastle-upon-Tyne Hospitals NHS Foundation Trust and Newcastle University; the NIHR Dementia and Neurodegenerative Diseases Research Network (JTO), and Elijah Mak was in receipt of the Gates Cambridge studentship and Alzheimer's Research UK scholarship
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
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