The Cochlear Amplifier as a Standing Wave: Squirting Waves Between Rows of Outer Hair Cells?

This paper draws attention to symmetric Lloyd-Redwood (SLR) waves-known in ultrasonics as "squirting" waves-and points out that their distinctive properties make them well-suited for carrying positive feedback between rows of outer hair cells. This coul

Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma

Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132's strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS

Weak localization effect on thermomagnetic phenomena

The quantum transport equation (QTE) is extended to study weak localization (WL) effects on galvanomagnetic and thermomagnetic phenomena. QTE has many advantages over the linear response method (LRM): (i) particle-hole asymmetry which is necessary for the Hall effect is taken into account by the nonequilibrium distribution function, while LRM requires expansion near the Fermi surface, (ii) when calculating response to the temperature gradient, the problem of WL correction to the heat current operator is avoided, (iii) magnetic field is directly introduced to QTE, while the LRM deals with the vector potential and and special attention should be paid to maintain gauge invariance, e.g. when calculating the Nernst effect the heat current operator should be modified to include the external magnetic field. We reproduce in a very compact form known results for the conductivity, the Hall and the thermoelectric effects and then we study our main problem, WL correction to the Nernst coefficient (transverse thermopower).Comment: 20 pages 2 figure

Modes of coastal precipitation over southwest India and their relationship to intraseasonal variability

The west coast of India, dominated by the Western Ghats mountain range, is among the rainiest places in the tropics. The interaction between the land-sea contrast of the coast, the monsoonal westerlies, and the oblique mountains is subject to complex intraseasonal variability, which has not previously been explored in depth. This study investigates that variability from the perspective of the land-sea contrast, using empirical orthogonal function analysis to discern regimes of onshore and offshore rainfall over southwest India and the eastern Indian Ocean. Locally, it is found that the rainfall is most sensitive to mid-tropospheric humidity: when this is anomalously high, deep convection is encouraged; when this is anomalously low, it is suppressed. A moisture tracking algorithm is employed to determine the primary sources of the anomalously wet and dry mid-tropospheric air. There are important secondary contributions from low-level vorticity and cross-shore moisture flux. The dominant control on intraseasonal variability in coastal precipitation is found to be the BSISO: over 75% of the strongest offshore events occur during phases 3 and 4; and about 40% of the strongest onshore events occur during phases 5 and 6. The location of monsoon low-pressure systems is also shown to be important in determining the magnitude and location of coastal rainfall

Experience of clinical services shapes attitudes to mental health data sharing: findings from a UK-wide survey

BACKGROUND: Routinely-collected mental health data could deliver novel insights for mental health research. However, patients’ willingness to share their mental health data remains largely unknown. We investigated factors influencing likelihood of sharing these data for research purposes amongst people with and without experience of mental illness. METHODS: We collected responses from a diverse sample of UK National Health Service (NHS) users (n = 2187) of which about half (n = 1087) had lifetime experience of mental illness. Ordinal logistic regression was used to examine the influence of demographic factors, clinical service experience, and primary mental illness on willingness to share mental health data, contrasted against physical health data. RESULTS: There was a high level of willingness to share mental (89.7%) and physical (92.8%) health data for research purposes. Higher levels of satisfaction with the NHS were associated with greater willingness to share mental health data. Furthermore, people with personal experience of mental illness were more willing than those without to share mental health data, once the variable of NHS satisfaction had been controlled for. Of the mental illnesses recorded, people with depression, obsessive-compulsive disorder (OCD), personality disorder or bipolar disorder were significantly more likely to share their mental health data than people without mental illness. CONCLUSIONS: These findings suggest that positive experiences of health services and personal experience of mental illness are associated with greater willingness to share mental health data. NHS satisfaction is a potentially modifiable factor that could foster public support for increased use of NHS mental health data in research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12694-z

Characterizing Magnetized Turbulence in M51

We use previously published high-resolution synchrotron polarization data to perform an angular dispersion analysis with the aim of characterizing magnetized turbulence in M51. We first analyze three distinct regions (the center of the galaxy, and the northwest and southwest spiral arms) and can clearly discern the turbulent correlation length scale from the width of the magnetized turbulent correlation function for two regions and detect the imprint of anisotropy in the turbulence for all three. Furthermore, analyzing the galaxy as a whole allows us to determine a two-dimensional Gaussian model for the magnetized turbulence in M51. We measure the turbulent correlation scales parallel and perpendicular to the local mean magnetic field to be, respectively, δ_ǁ = 98±5 pc and δ_⊥ = 54±3 pc, while the turbulent-to-ordered magnetic field strength ratio is found to be B_t/B_0 = 1.01 ± 0.04. These results are consistent with those of Fletcher et al., who performed a Faraday rotation dispersion analysis of the same data, and our detection of anisotropy is consistent with current magnetized turbulence theories

Using a knowledge exchange event to assess study participants’ attitudes to research in a rapidly evolving research context

Grant information: DJP, IJD and AMM are supported by Wellcome Trust Grant 104036. IJD, DJP, JPB and AMM, IB, EJK and SFW are supported by MRC Mental Health Data Pathfinder Grant MC_PC_17209. AMM and SML are supported by MRC Grant MC_PC_MR/R01910X/1. AMM is supported by MRC Grant MR/S035818/1. Theirworld Edinburgh Birth Cohort is funded by the charity Theirworld (www.theirworld.org), and is undertaken in the MRC Centre for Reproductive Health, which is funded by MRC Centre Grant (G1002033). CB and DJP are supported by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities.Peer reviewedPublisher PD

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014