Can auditory objects be subitized?

In vision, humans have the ability to mentally 'tag' approximately four objects, allowing us to monitor, attend, and interact with them. As a consequence, we can rapidly and accurately enumerate up to four objects – a process known as subitizing. Here, we investigate whether a similar ability exists for tagging auditory stimuli and find that only two or three auditory stimuli can be enumerated with high accuracy. We assess whether this high accuracy indicates the existence of an auditory subitizing mechanism, and if it is influenced by factors known to influence visual subitizing. Based on accuracy, Experiments 1 and 2 reveal a potential auditory subitizing mechanism only when stimuli are spatially separated, as is the case for visual subitizing. Experiment 3 failed to show any evidence of auditory subitizing when objects were separated in time, rather than space. All three experiments provide only limited evidence for an age-related decline in auditory enumeration of small numbers of objects. This suggests that poor auditory tagging does not contribute significantly to older adults’ difficulties in multi-talker conversations. We hypothesize that although auditory subitizing might occur, it is restricted to approximately two spatially-separated objects due to the difficulty of parsing the auditory scene into its constituent parts

Cavity-mediated coherent coupling of magnetic moments

We demonstrate the long range strong coupling of magnetostatic modes in spatially separated ferromagnets mediated by a microwave frequency cavity. Two spheres of yttrium iron garnet are embedded in the cavity and their magnetostatic modes probed using a dispersive measurement technique. We find they are strongly coupled to each other even when detuned from the cavity modes, and investigate the dependence of the magnet-magnet coupling on the cavity detuning. Dark states of the coupled magnetostatic modes of the system are observed, and ascribed to mismatches between the symmetries of the modes and the drive field.We would like to acknowledge support from Hitachi Cambridge Laboratory, EPSRC Grant No. EP/K027018/1 and ERC Grant No. 648613. A.J.F. is supported by a Hitachi Research Fellowship. A.C.D. is supported by the ARC via the Centre of Excellence in Engineered Quantum Systems (EQuS), Project No. CE110001013.This is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevA.93.02180

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

FEN1 Blockade for Platinum Chemo-Sensitization and Synthetic Lethality in Epithelial Ovarian Cancers

\ua9 2021 by the authors. Licensee MDPI, Basel, Switzerland.FEN1 plays critical roles in long patch base excision repair (LP-BER), Okazaki fragment maturation, and rescue of stalled replication forks. In a clinical cohort, FEN1 overexpression is associated with aggressive phenotype and poor progression-free survival after platinum chemother-apy. Pre-clinically, FEN1 is induced upon cisplatin treatment, and nuclear translocation of FEN1 is dependent on physical interaction with importin β. FEN1 depletion, gene inactivation, or inhibition re-sensitizes platinum-resistant ovarian cancer cells to cisplatin. BRCA2 deficient cells exhibited synthetic lethality upon treatment with a FEN1 inhibitor. FEN1 inhibitor-resistant PEO1R cells were generated, and these reactivated BRCA2 and overexpressed the key repair proteins, POLβ and XRCC1. FEN1i treatment was selectively toxic to POLβ deficient but not XRCC1 deficient ovarian cancer cells. High throughput screening of 391,275 compounds identified several FEN1 inhibitor hits that are suitable for further drug development. We conclude that FEN1 is a valid target for ovarian cancer therapy

An exploratory study on the contribution of graduate entry students personality to the diversity of medical student populations

Studies conducted in medical education show that personality influences undergraduate medical students academic and clinical performances and also their career interests. Our aims with this exploratory study were: to assess the contribution of graduate entry students to the diversity of personality in medical student populations; to assess whether eventual differences may be explained by programme structure or student age and sex. We performed a cross-sectional study underpinned by the five-factor model of personality, with students attending three medical schools in Portugal. The five personality dimensions were assessed with the Portuguese version of the NEO-Five Factor Inventory. MANOVA and MANCOVA analyses were performed to clarify the contributions of school, programme structure, age and sex. Student personality dimensions were significantly different between the three medical schools [F (10,1026)  = 3.159, p < .001, [Formula: see text] = 0.03, π = 0.987]. However, taking sex and age into account the differences became non-significant. There were institutional differences in personality dimensions. However, those were primarily accounted for by sex and age effects and not by the medical school attended. Diversifying age and sex of the admitted students will diversify the personality of the medical student population

H. pylori Seropositivity before Age 40 and Subsequent Risk of Stomach Cancer: A Glimpse of the True Relationship?

Stomach carcinogenesis involves mucosal and luminal changes that favor spontaneous disappearance of Helicobacter pylori. Therefore, the association between the infection and cancer risk might typically be underestimated. As acquisition of the infection almost invariably occurs before adulthood, the serostatus at age 16–40 should best reflect the lifetime occurrence of the infection. We therefore conducted a case-control study nested within a historic cohort of about 400,000 individuals who donated sera before age 40 to either of two large Swedish Biobanks between 1968 and 2006, and whose records were linked to complete nationwide registers. For each stomach adenocarcinoma case occurring at least 5 years after serum donation 2 controls were selected matched on age, sex and year of donation and biobank. Serum immunoglobulin G antibodies against H. pylori cell-surface antigens (Hp-CSAs) were measured with an enzyme–linked immunosorbent assay and antibodies against CagA with an immunoblot assay. Conditional logistic regression models were used to estimate odds ratios (ORs) for stomach adenocarcinoma among H. pylori infected relative to uninfected. We confirmed 59 incident cases of stomach adenocarcinoma (41 non-cardia tumors) during follow-up. ORs for non-cardia stomach adenocarcinoma among subjects with Hp-CSA antibodies (regardless of CagA serostatus), antibodies against CagA (regardless of Hp-CSA serostatus), and antibodies to both, relative to those who were seronegative to both, were 17.1 (95% confidence interval [CI] 4.0–72.9), 10.9 (95% CI 3.2–36.9), and 48.5 (95% CI 5.8–407.4), respectively. H. pylori infection is a much stronger risk factor for non-cardia stomach adenocarcinoma than initially realized. However, further studies are needed to answer whether it is a necessary cause, as the possibility of misclassification of H. pylori status could not be ruled out in our study

Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study

BACKGROUND: Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. METHODS: Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. RESULTS: 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5-7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen's d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. CONCLUSIONS: It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as exposures, confounding factors or outcome variables in future analyses.The UK Biobank Activity Project and the collection of activity data from participants was funded by the Wellcome Trust (https://wellcome.ac.uk/) and the Medical Research Council (http://www.mrc.ac.uk/). The analysis was supported by the British Heart Foundation Centre of Research Excellence at Oxford (http://www.cardioscience.ox.ac.uk/bhf-centre-of-research-excellence) [grant number RE/13/1/30181 to AD], the Li Ka Shing Foundation (http://www.lksf.org/) [to AD], the UK Medical Research Council (http://www.mrc.ac.uk/) [grant numbers MC_UU_12015/1 and MC_UU_12015/3 to NW and SB], the RCUK Digital Economy Research Hub on Social Inclusion through the Digital Economy (SiDE) (http://www.rcuk.ac.uk/) [EP/G066019/1 to NH], the EPSRC Centre for Doctoral Training in Digital Civics (https://www.epsrc.ac.uk/)[EP/L016176/1 to DJ], and the National Institute for Health Research (http://www.nihr.ac.uk/) [SRF-2011-04-017 to MIT]. The MRC and Wellcome Trust played a key role in the decision to establish UK Biobank, and the accelerometer data collection. No funding bodies had any role in the analysis, decision to publish, or preparation of the manuscript

An Essential Role for the Proximal but Not the Distal Cytoplasmic Tail of Glycoprotein M in Murid Herpesvirus 4 Infection

Murid herpesvirus-4 (MuHV-4) provides a tractable model with which to define common, conserved features of gamma-herpesvirus biology. The multi-membrane spanning glycoprotein M (gM) is one of only 4 glycoproteins that are essential for MuHV-4 lytic replication. gM binds to gN and is thought to function mainly secondary envelopment and virion egress, for which several predicted trafficking motifs in its C-terminal cytoplasmic tail could be important. We tested the contribution of the gM cytoplasmic tail to MuHV-4 lytic replication by making recombinant viruses with varying C-terminal deletions. Removing an acidic cluster and a distal YXXΦ motif altered the capsid distribution somewhat in infected cells but had little effect on virus replication, either in vitro or in vivo. In contrast, removing a proximal YXXΦ motif as well completely prevented productive replication. gM was still expressed, but unlike its longer forms showed only limited colocalization with co-transfected gN, and in the context of whole virus appeared to support gN expression less well. We conclude that some elements of the gM cytoplasmic tail are dispensible for MuHV-4 replication, but the tail as a whole is not

The effect of crystalloid versus medium molecular weight colloid solution on post-operative nausea and vomiting after ambulatory gynecological surgery - a prospective randomized trial.

UNLABELLED: ABSTRACT: BACKGROUND: Intravenous fluid is recommended in international guidelines to improve patient post-operative symptoms, particularly nausea and vomiting. The optimum fluid regimen has not been established. This prospective, randomized, blinded study was designed to determine if administration of equivolumes of a colloid (hydroxyethyl starch 130/0.4) reduced post operative nausea and vomiting in healthy volunteers undergoing ambulatory gynecologic laparoscopy surgery compared to a crystalloid solution (Hartmann\u27s Solution). METHODS: 120 patients were randomized to receive intravenous colloid (N = 60) or crystalloid (N = 60) intra-operatively. The volume of fluid administered was calculated at 1.5 ml.kg-1 per hour of fasting. Patients were interviewed to assess nausea, vomiting, anti-emetic use, dizziness, sore throat, headache and subjective general well being at 30 minutes and 2, 24 and 48 hours post operatively. Pulmonary function testing was performed on a subgroup. RESULTS: At 2 hours the proportion of patients experiencing nausea (38.2 % vs 17.9%, P = 0.03) and the mean nausea score were increased in the colloid compared to crystalloid group respectively (1.49 ± 0.3 vs 0.68 ± 0.2, P = 0.028). The incidence of vomiting and anti-emetic usage was low and did not differ between the groups. Sore throat, dizziness, headache and general well being were not different between the groups. A comparable reduction on post-operative FVC and FEV-1 and PEFR was observed in both groups. CONCLUSIONS: Intra-operative administration of colloid increased the incidence of early postoperative nausea and has no advantage over crystalloid for symptom control after gynaecological laparoscopic surgery