High blood pressure predicts hippocampal atrophy rate in cognitively impaired elders

INTRODUCTION: Understanding relationships among blood pressure (BP), cognition, and brain volume could inform Alzheimer's disease (AD) management. METHODS: We investigated Alzheimer's Disease Neuroimaging Initiative (ADNI) participants: 200 controls, 346 mild cognitive impairment (MCI), and 154 AD. National Alzheimer's Co‐ordinating Center (NACC) participants were separately analyzed: 1098 controls, 2297 MCI, and 4845 AD. Relationships between cognition and BP were assessed in both cohorts and BP and atrophy rates in ADNI. Multivariate mixed linear‐regression models were fitted with joint outcomes of BP (systolic, diastolic, and pulse pressure), cognition (Mini‐Mental State Examination, Logical Memory, and Digit Symbol) and atrophy rate (whole‐brain, hippocampus). RESULTS: ADNI MCI and AD patients with greater baseline systolic BP had higher hippocampal atrophy rates ([r, P value]; 0.2, 0.005 and 0.2, 0.04, respectively). NACC AD patients with lower systolic BP had lower cognitive scores (0.1, 0.0003). DISCUSSION: Higher late‐life BP may be associated with faster decline in cognitively impaired elders

Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids

RP2 mutations cause a severe form of X-linked retinitis pigmentosa (XLRP). The mechanism of RP2-associated retinal degeneration in humans is unclear, and animal models of RP2 XLRP do not recapitulate this severe phenotype. Here, we developed gene-edited isogenic RP2 knockout (RP2 KO) induced pluripotent stem cells (iPSCs) and RP2 patient-derived iPSC to produce 3D retinal organoids as a human retinal disease model. Strikingly, the RP2 KO and RP2 patient-derived organoids showed a peak in rod photoreceptor cell death at day 150 (D150) with subsequent thinning of the organoid outer nuclear layer (ONL) by D180 of culture. Adeno-associated virus-mediated gene augmentation with human RP2 rescued the degeneration phenotype of the RP2 KO organoids, to prevent ONL thinning and restore rhodopsin expression. Notably, these data show that 3D retinal organoids can be used to model photoreceptor degeneration and test potential therapies to prevent photoreceptor cell death

Quantum anti-Zeno effect without wave function reduction

We study the measurement-induced enhancement of the spontaneous decay (called quantum anti-Zeno effect) for a two-level subsystem, where measurements are treated as couplings between the excited state and an auxiliary state rather than the von Neumann's wave function reduction. The photon radiated in a fast decay of the atom, from the auxiliary state to the excited state, triggers a quasi-measurement, as opposed to a projection measurement. Our use of the term "quasi-measurement" refers to a "coupling-based measurement". Such frequent quasi-measurements result in an exponential decay of the survival probability of atomic initial state with a photon emission following each quasi-measurement. Our calculations show that the effective decay rate is of the same form as the one based on projection measurements. What is more important, the survival probability of the atomic initial state which is obtained by tracing over all the photon states is equivalent to the survival probability of the atomic initial state with a photon emission following each quasi-measurement to the order under consideration. That is because the contributions from those states with photon number less than the number of quasi-measurements originate from higher-order processes.Comment: 7 pages, 3 figure

Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>The acellular fraction of epithelial ovarian cancer (EOC) ascites promotes <it>de novo </it>resistance of tumor cells and thus supports the idea that tumor cells may survive in the surrounding protective microenvironment contributing to disease recurrence. Levels of the pro-inflammatory cytokines IL-6 and IL-8 are elevated in EOC ascites suggesting that they could play a role in tumor progression.</p> <p>Methods</p> <p>We measured IL-6 and IL-8 levels in the ascites of 39 patients with newly diagnosed EOC. Commercially available enzyme-linked immunosorbent assay (ELISA) was used to determine IL-6 and IL-8 ascites levels. Ascites cytokine levels were correlated with clinicopathological parameters and progression-free survival.</p> <p>Results</p> <p>Mean ascites levels for IL-6 and IL-8 were 6419 pg/ml (SEM: 1409 pg/ml) and 1408 pg/ml (SEM: 437 pg/ml) respectively. The levels of IL-6 and IL-8 in ascites were significantly lower in patients that have received prior chemotherapy before the surgery (Mann-Whitney U test, <it>P </it>= 0.037 for IL-6 and <it>P </it>= 0.008 for IL-8). Univariate analysis revealed that high IL-6 ascites levels (<it>P </it>= 0.021), serum CA125 levels (<it>P </it>= 0.04) and stage IV (<it>P </it>= 0.009) were significantly correlated with shorter progression-free survival. Including these variables in a multivariate analysis revealed that elevated IL-6 levels (<it>P </it>= 0.033) was an independent predictor of shorter progression-free survival.</p> <p>Conclusion</p> <p>Elevated IL-6, but not IL-8, ascites level is an independent predictor of shorter progression-free survival.</p

An international comparative study of blood pressure in populations of European vs. African descent

Background: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. Methods: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). Results: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. Conclusions: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated

Dealing with Feelings: Characterization of Trait Alexithymia on Emotion Regulation Strategies and Cognitive-Emotional Processing

Background: Alexithymia, or "no words for feelings'', is a personality trait which is associated with difficulties in emotion recognition and regulation. It is unknown whether this deficit is due primarily to regulation, perception, or mentalizing of emotions. In order to shed light on the core deficit, we tested our subjects on a wide range of emotional tasks. We expected the high alexithymics to underperform on all tasks. Method: Two groups of healthy individuals, high and low scoring on the cognitive component of the Bermond-Vorst Alexithymia Questionnaire, completed questionnaires of emotion regulation and performed several emotion processing tasks including a micro expression recognition task, recognition of emotional prosody and semantics in spoken sentences, an emotional and identity learning task and a conflicting beliefs and emotions task (emotional mentalizing). Results: The two groups differed on the Emotion Regulation Questionnaire, Berkeley Expressivity Questionnaire and Empathy Quotient. Specifically, the Emotion Regulation Quotient showed that alexithymic individuals used more suppressive and less reappraisal strategies. On the behavioral tasks, as expected, alexithymics performed worse on recognition of micro expressions and emotional mentalizing. Surprisingly, groups did not differ on tasks of emotional semantics and prosody and associative emotional-learning. Conclusion: Individuals scoring high on the cognitive component of alexithymia are more prone to suppressive emotion regulation strategies rather than reappraisal strategies. Regarding emotional information processing, alexithymia is associated with reduced performance on measures of early processing as well as higher order mentalizing. However, difficulties in the processing of emotional language were not a core deficit in our alexithymic group

The JCMT Transient Survey: Identifying Submillimeter Continuum Variability over Several Year Timescales Using Archival JCMT Gould Belt Survey Observations

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.Investigating variability at the earliest stages of low-mass star formation is fundamental in understanding how a protostar assembles mass. While many simulations of protostellar disks predict non-steady accretion onto protostars, deeper investigation requires robust observational constraints on the frequency and amplitude of variability events characterized across the observable SED. In this study, we develop methods to robustly analyze repeated observations of an area of the sky for submillimeter variability in order to determine constraints on the magnitude and frequency of deeply embedded protostars. We compare 850 μm JCMT Transient Survey data with archival JCMT Gould Belt Survey data to investigate variability over 2–4 year timescales. Out of 175 bright, independent emission sources identified in the overlapping fields, we find seven variable candidates, five of which we classify as Strong, and the remaining two we classify as Extended to indicate that the latter are associated with larger-scale structure. For the Strong variable candidates, we find an average fractional peak brightness change per year of $| 4.0| \% \,{\mathrm{yr}}^{-1}$, with a standard deviation of $2.7 \% \,{\mathrm{yr}}^{-1}$. In total, 7% of the protostars associated with 850 μm emission in our sample show signs of variability. Four of the five Strong sources are associated with a known protostar. The remaining source is a good follow-up target for an object that is anticipated to contain an enshrouded, deeply embedded protostar. In addition, we estimate the 850 μm periodicity of the submillimeter variable source, EC 53, to be 567 ± 32 days, based on the archival Gould Belt Survey data.Steve Mairs was partially supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada graduate scholarship program. Doug Johnstone is supported by the National Research Council of Canada and by an NSERC Discovery Grant. Gregory Herczeg is supported by general grant 11473005 awarded by the National Science Foundation of China. Andy Pon received partial salary support from a Canadian Institute for Theoretical Astrophysics (CITA) National Fellowship. Miju Kang was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, & Future Planning (No. NRF-2015R1C1A1A01052160). J.-E. Lee was supported by the Basic Science Research Program through the National Research Foundation of Korea (grant No. NRF-2015R1A2A2A01004769) and the Korea Astronomy and Space Science Institute under the R&D program (Project No. 2015-1-320-18) supervised by the Ministry of Science and ICT. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Maunakea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. The James Clerk Maxwell Telescope is operated by the East Asian Observatory on behalf of the National Astronomical Observatory of Japan, Academia Sinica Institute of Astronomy and Astrophysics, the Korea Astronomy and Space Science Institute, the National Astronomical Observatories of China, and the Chinese Academy of Sciences (Grant No. XDB09000000), with additional funding support from the Science and Technology Facilities Council of the United Kingdom and participating universities in the United Kingdom and Canada. The James Clerk Maxwell Telescope has historically been operated by the Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the National Research Council of Canada, and the Netherlands Organisation for Scientific Research. Additional funds for the construction of SCUBA-2 were provided by the Canada Foundation for Innovation. The identification number for the JCMT Transient Survey data used in this paper is M16AL001. The identification numbers for the archival Gould Belt Survey data used in this paper are MJLSG31, MJLSG32, MJLSG33, MJLSG38, and MJLSG41. The authors thank the JCMT staff for their support of the data collection and reduction efforts. This research has made use of NASA's Astrophysics Data System and the facilities of the Canadian Astronomy Data Centre operated by the National Research Council of Canada, with the support of the Canadian Space Agency. The authors would especially like to thank Chang Won Lee and Harriet Parsons for their useful insights and suggestions, along with the extended JCMT Transient Team21 for their support. This research used the services of the Canadian Advanced Network for Astronomy Research (CANFAR), which in turn is supported by CANARIE, Compute Canada, University of Victoria, the National Research Council of Canada, and the Canadian Space Agency. This research made use of APLpy, an open-source plotting package for Python hosted at http://aplpy.github.com, and matplotlib, a 2D plotting library for Python (Hunter 2007)

The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.</p> <p>Methods</p> <p>High quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.</p> <p>Results</p> <p>Using the photographic method, the most commonly affected joints were the second DIP joints followed by the third DIP joints and second and third PIP joints. Both interobserver (ICC = 0.83) and intraobserver reading agreements (ICC = 0.89) were acceptable. On comparison with radiography and clinical examination, aggregate scores were significantly correlated (R_s0.35-0.69), more so in females (R_s0.53-0.72) than males. Hand pain in males showed very little association with HOA findings by the three methods but all methods showed a comparable moderate association with hand pain in females. The performance of photography in predicting pain on most days for at least a month in females was comparable to that of radiography and clinical examination (AUC 0.63 <it>p </it>= 0.004). Analysis of intermittent pain yielded similar results for in the DIP and PIP joints (OR 3.2-3.3, <it>p </it>< 0.01), but for the CMC1 joints, both radiography (OR 9.0, <it>p </it>< 0.0001), and clinical examination (OR 9.8, <it>p </it>< 0.0001), had higher predictive odds ratios for pain than photography (OR 3.6, <it>p </it>< 0.0001)., A shortened, rapidly performed form of reading photographs also showed a high degree of correlation with the other methods (R_s0.56-0.82).</p> <p>Conclusion</p> <p>High quality hand photographs can be used to diagnose and grade hand osteoarthritis. The method has the advantage of being inexpensive and easy to perform. By using a slightly simplified method of reading, it appears to be highly suitable for use in large studies.</p