1,750 research outputs found
Biomineralization mediated by anaerobic methane-consuming cell consortia
published_or_final_versio
The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation
Aims: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. Results: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all-cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i
Structure of hadron resonances with a nearby zero of the amplitude
We discuss the relation between the analytic structure of the scattering
amplitude and the origin of an eigenstate represented by a pole of the
amplitude.If the eigenstate is not dynamically generated by the interaction in
the channel of interest, the residue of the pole vanishes in the zero coupling
limit. Based on the topological nature of the phase of the scattering
amplitude, we show that the pole must encounter with the
Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the
dynamical component of the eigenstate is small if a CDD zero exists near the
eigenstate pole. We show that the line shape of the resonance is distorted from
the Breit-Wigner form as an observable consequence of the nearby CDD zero.
Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma
amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio
Reactor mixing angle from hybrid neutrino masses
In terms of its eigenvector decomposition, the neutrino mass matrix (in the
basis where the charged lepton mass matrix is diagonal) can be understood as
originating from a tribimaximal dominant structure with small deviations, as
demanded by data. If neutrino masses originate from at least two different
mechanisms, referred to as "hybrid neutrino masses", the experimentally
observed structure naturally emerges provided one mechanism accounts for the
dominant tribimaximal structure while the other is responsible for the
deviations. We demonstrate the feasibility of this picture in a fairly
model-independent way by using lepton-number-violating effective operators,
whose structure we assume becomes dictated by an underlying flavor
symmetry. We show that if a second mechanism is at work, the requirement of
generating a reactor angle within its experimental range always fixes the solar
and atmospheric angles in agreement with data, in contrast to the case where
the deviations are induced by next-to-leading order effective operators. We
prove this idea is viable by constructing an -based ultraviolet
completion, where the dominant tribimaximal structure arises from the type-I
seesaw while the subleading contribution is determined by either type-II or
type-III seesaw driven by a non-trivial singlet (minimal hybrid model).
After finding general criteria, we identify all the symmetries
capable of producing such -based minimal hybrid models.Comment: 18 pages, 5 figures. v3: section including sum rules added, accepted
by JHE
A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease
BACKGROUND:
Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.
METHODS:
Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.
RESULTS:
A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.
CONCLUSIONS:
These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.
TRIAL REGISTRATION:
ISRCTN Registry 48776874
De facto exchange rate regime classifications: an evaluation
There exist several statistically-based exchange rate regime classifications that disagree with one another to a disappointing degree. To what extent is this a matter of the quality of the design of these schemes, and to what extent does it reflect the need to supplement statistics with other information (as is done in the IMF’s de facto classification)? It is shown that statistical methods are good at the basics (distinguishing some type of peg from some type of float), but less helpful in other respects, such as determining whether a float is managed, particularly for countries that are not very remote from their main trading partners. Different measures of exchange rate volatility have been used but are not primarily responsible for differences between classifications. The theoretical underpinning of particular classification schemes needs to be more explicit
Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes
Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable
Large Anomalous Hall effect in a silicon-based magnetic semiconductor
Magnetic semiconductors are attracting high interest because of their
potential use for spintronics, a new technology which merges electronics and
manipulation of conduction electron spins. (GaMn)As and (GaMn)N have recently
emerged as the most popular materials for this new technology. While Curie
temperatures are rising towards room temperature, these materials can only be
fabricated in thin film form, are heavily defective, and are not obviously
compatible with Si. We show here that it is productive to consider transition
metal monosilicides as potential alternatives. In particular, we report the
discovery that the bulk metallic magnets derived from doping the narrow gap
insulator FeSi with Co share the very high anomalous Hall conductance of
(GaMn)As, while displaying Curie temperatures as high as 53 K. Our work opens
up a new arena for spintronics, involving a bulk material based only on
transition metals and Si, and which we have proven to display a variety of
large magnetic field effects on easily measured electrical properties.Comment: 19 pages with 5 figure
Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer
Background Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development
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