The Impact of Almonds and Almond Processing On Gastrointestinal Physiology, Luminal Microbiology and Gastrointestinal Symptoms: a Randomized Controlled Trial and Mastication Study.

BACKGROUND: Almonds contain lipid, fiber and polyphenols and possess physicochemical properties that impact nutrient bioaccessibility, which are hypothesized to impact gut physiology and microbiota. OBJECTIVES: Investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition and transit time. DESIGN: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d) or an isocaloric control muffin in place of habitual snacks for 4 weeks. Gut microbiota composition and diversity (16S rRNA gene sequencing), short-chain fatty acids (gas-chromatography), volatile organic compounds (gas-chromatography mass-spectrometry), gut transit time (wireless motility capsule), stool output and gut symptoms (7-day diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured in a subgroup (n = 31). RESULTS: Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in abundance of fecal bifidobacteria following consumption of whole almonds (8.7%, SD 7.7%), ground almonds (7.8%, SD 6.9%) or control (13.0%, SD 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher butyrate (24.1 μmol/g, SD 15.0 μmol/g) in comparison to control (18.2 μmol/g, SD 9.1 μmol/g; p = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency or gut symptoms. Almond form (whole versus ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher predicted lipid release (10.4%, SD 1.8%) in comparison to whole almonds (9.3%, SD 2.0%; p = 0.017). CONCLUSIONS: Almond consumption has limited impact on gut microbiota composition but increases butyrate concentrations in adults, suggesting positive alterations to microbiota functionality. Almonds can be incorporated into the diet to increase fiber consumption without triggering gut symptoms. Clinical trial registry: ClinicalTrials.gov identifier - NCT03581812

Entanglement-free Heisenberg-limited phase estimation

Measurement underpins all quantitative science. A key example is the measurement of optical phase, used in length metrology and many other applications. Advances in precision measurement have consistently led to important scientific discoveries. At the fundamental level, measurement precision is limited by the number N of quantum resources (such as photons) that are used. Standard measurement schemes, using each resource independently, lead to a phase uncertainty that scales as 1/sqrt(N) - known as the standard quantum limit. However, it has long been conjectured that it should be possible to achieve a precision limited only by the Heisenberg uncertainty principle, dramatically improving the scaling to 1/N. It is commonly thought that achieving this improvement requires the use of exotic quantum entangled states, such as the NOON state. These states are extremely difficult to generate. Measurement schemes with counted photons or ions have been performed with N <= 6, but few have surpassed the standard quantum limit and none have shown Heisenberg-limited scaling. Here we demonstrate experimentally a Heisenberg-limited phase estimation procedure. We replace entangled input states with multiple applications of the phase shift on unentangled single-photon states. We generalize Kitaev's phase estimation algorithm using adaptive measurement theory to achieve a standard deviation scaling at the Heisenberg limit. For the largest number of resources used (N = 378), we estimate an unknown phase with a variance more than 10 dB below the standard quantum limit; achieving this variance would require more than 4,000 resources using standard interferometry. Our results represent a drastic reduction in the complexity of achieving quantum-enhanced measurement precision.Comment: Published in Nature. This is the final versio

Signal acquisition and analysis of ambulatory electromyographic recordings for the assessment of sleep bruxism : A scoping review

Background Ambulatory electromyographic (EMG) devices are increasingly being used in sleep bruxism studies. EMG signal acquisition, analysis and scoring methods vary between studies. This may impact comparability of studies and the assessment of sleep bruxism in patients. Objectives (a) To provide an overview of EMG signal acquisition and analysis methods of recordings from limited-channel ambulatory EMG devices for the assessment of sleep bruxism; and (b) to provide an overview of outcome measures used in sleep bruxism literature utilising such devices. Method A scoping review of the literature was performed. Online databases PubMed and Semantics Scholar were searched for studies published in English until 7 October 2020. Data on five categories were extracted: recording hardware, recording logistics, signal acquisition, signal analysis and sleep bruxism outcomes. Results Seventy-eight studies were included, published between 1977 and 2020. Recording hardware was generally well described. Reports of participant instructions in device handling and of dealing with failed recordings were often lacking. Basic elements of signal acquisition, for example amplifications factors, impedance and bandpass settings, and signal analysis, for example rectification, signal processing and additional filtering, were underreported. Extensive variability was found for thresholds used to characterise sleep bruxism events. Sleep bruxism outcomes varied, but typically represented frequency, duration and/or intensity of masticatory muscle activity (MMA). Conclusion Adequate and standardised reporting of recording procedures is highly recommended. In future studies utilising ambulatory EMG devices, the focus may need to shift from the concept of scoring sleep bruxism events to that of scoring the whole spectrum of MMA.Peer reviewe

Wideband THz time domain spectroscopy based on optical rectification and electro-optic sampling

We present an analytical model describing the full electromagnetic propagation in a THz time-domain spectroscopy (THz-TDS) system, from the THz pulses via Optical Rectification to the detection via Electro Optic-Sampling. While several investigations deal singularly with the many elements that constitute a THz-TDS, in our work we pay particular attention to the modelling of the time-frequency behaviour of all the stages which compose the experimental set-up. Therefore, our model considers the following main aspects: (i) pump beam focusing into the generation crystal; (ii) phase-matching inside both the generation and detection crystals; (iii) chromatic dispersion and absorption inside the crystals; (iv) Fabry-Perot effect; (v) diffraction outside, i.e. along the propagation, (vi) focalization and overlapping between THz and probe beams, (vii) electro-optic sampling. In order to validate our model, we report on the comparison between the simulations and the experimental data obtained from the same set-up, showing their good agreement

Differential effects of natural palm oil, chemically- and enzymatically-modified palm oil on weight gain, blood lipid metabolites and fat deposition in a pediatric pig model

<p>Abstract</p> <p>Background</p> <p>Increasing prevalence of obesity and overweight in the Western world, continue to be a major health threat and is responsible for increased health care costs. Dietary intervention studies show a strong positive association between saturated fat intake and the development of obesity and cardiovascular disease. This study investigated the effect of positional distribution of palmitic acid (Sn-1, 2 & 3) of palm oil on cardiovascular health and development of obesity, using weaner pigs as a model for young children.</p> <p>Methods</p> <p>Male and female weaner piglets were randomly allocated to 4 dietary treatment groups: 1) pork lard (LRD); 2) natural palm olein (NPO); 3) chemically inter-esterified PO (CPO) and 4) enzymatically inter-esterified PO (EnPO) as the fat source. Diets were formulated with 11% lard or with palm olein in order to provide 31% of digestible energy from fat in the diet and were balanced for cholesterol, protein and energy across treatments.</p> <p>Results</p> <p>From 8 weeks onwards, pigs on EnPO diet gained (P < 0.05) more weight than all other groups. Feed conversion efficiency (feed to gain) over the 12 week experimental period did not vary between treatment groups. Plasma LDL-C content and LDL-C/HDL-C ratio in pigs fed natural PO tended to be lower compared to all other diets. The natural PO lowered (P < 0.02) the plasma triglyceride (TG) content relative to the lard or EnPO diets, but was not different from the CPO diet. The natural PO diet was associated with lower (P < 0.05) saturated fat levels in subcutaneous adipose tissue than the CPO and EnPO diets that had lower saturated fat levels than the lard diet. Female pigs had lower lean and higher fat and fat:lean ratio in the body compared with male pigs. No difference in weight gain or blood lipid parameters was observed between sexes.</p> <p>Conclusions</p> <p>The observations on plasma TG, muscle and adipose tissue saturated fatty acid contents and back fat (subcutaneous) thickness suggest that natural palm oil may reduce deposition of body fat. In addition, dietary supplementation with natural palm oil containing palmitic acid at different positions in meat producing animals may lead to the production of meat and meat products with lower saturated fats. An increase in fat content and a decrease in lean content in female pigs resulted in an increased body fat:lean ratio but gender had no effect on blood lipid parameters or insulin concentrations.</p

The C313Y Piedmontese mutation decreases myostatin covalent dimerisation and stability

<p>Abstract</p> <p>Background</p> <p>Myostatin is a key negative regulator of muscle growth and development, whose activity has important implications for the treatment of muscle wastage disorders. Piedmontese cattle display a double-muscled phenotype associated with the expression of C313Y mutant myostatin. <it>In vivo</it>, C313Y myostatin is proteolytically processed, exported and circulated extracellularly but fails to correctly regulate muscle growth. The C313Y mutation removes the C313-containing disulphide bond, an integral part of the characteristic TGF-β cystine-knot structural motif.</p> <p>Results</p> <p>Here we present <it>in vitro </it>analysis of the structure and stability of the C313Y myostatin protein that reveals significantly decreased covalent dimerisation for C313Y myostatin accompanied by a loss of structural stability compared to wild type. The C313Y myostatin growth factor, processed from full length precursor protein, fails to inhibit C2C12 myoblast proliferation in contrast to wild type myostatin. Although structural modeling shows the substitution of tyrosine causes structural perturbation, biochemical analysis of additional disulphide mutants, C313A and C374A, indicates that an intact cystine-knot motif is a major determinant in myostatin growth factor stability and covalent dimerisation.</p> <p>Conclusions</p> <p>This research shows that the cystine-knot structure is important for myostatin dimerisation and stability, and that disruption of this structural motif perturbs myostatin signaling.</p

Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

<p>Abstract</p> <p>Background</p> <p>In recent years, quartet-based phylogeny reconstruction methods have received considerable attentions in the computational biology community. Traditionally, the accuracy of a phylogeny reconstruction method is measured by simulations on synthetic datasets with known "true" phylogenies, while little theoretical analysis has been done. In this paper, we present a new model-based approach to measuring the accuracy of a quartet-based phylogeny reconstruction method. Under this model, we propose three efficient algorithms to reconstruct the "true" phylogeny with a high success probability.</p> <p>Results</p> <p>The first algorithm can reconstruct the "true" phylogeny from the input quartet topology set without quartet errors in <it>O</it>(<it>n</it>²) time by querying at most (<it>n </it>- 4) log(<it>n </it>- 1) quartet topologies, where <it>n </it>is the number of the taxa. When the input quartet topology set contains errors, the second algorithm can reconstruct the "true" phylogeny with a probability approximately 1 - <it>p </it>in <it>O</it>(<it>n</it>⁴log <it>n</it>) time, where <it>p </it>is the probability for a quartet topology being an error. This probability is improved by the third algorithm to approximately <inline-formula><m:math name="1748-7188-3-1-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>1</m:mn><m:mo>+</m:mo><m:msup><m:mi>q</m:mi><m:mn>2</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mn>2</m:mn></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>4</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>16</m:mn></m:mrow></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>5</m:mn></m:msup></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaqcfa4aaSaaaeaacqaIXaqmaeaacqaIXaqmcqGHRaWkcqWGXbqCdaahaaqabeaacqaIYaGmaaGaey4kaSYaaSaaaeaacqaIXaqmaeaacqaIYaGmaaGaemyCae3aaWbaaeqabaGaeGinaqdaaiabgUcaRmaalaaabaGaeGymaedabaGaeGymaeJaeGOnaydaaiabdghaXnaaCaaabeqaaiabiwda1aaaaaaaaa@3D5A@</m:annotation></m:semantics></m:math></inline-formula>, where <inline-formula><m:math name="1748-7188-3-1-i2" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mi>q</m:mi><m:mo>=</m:mo><m:mfrac><m:mi>p</m:mi><m:mrow><m:mn>1</m:mn><m:mo>−</m:mo><m:mi>p</m:mi></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaGaemyCaeNaeyypa0tcfa4aaSaaaeaacqWGWbaCaeaacqaIXaqmcqGHsislcqWGWbaCaaaaaa@3391@</m:annotation></m:semantics></m:math></inline-formula>, with running time of <it>O</it>(<it>n</it>⁵), which is at least 0.984 when <it>p </it>< 0.05.</p> <p>Conclusion</p> <p>The three proposed algorithms are mathematically guaranteed to reconstruct the "true" phylogeny with a high success probability. The experimental results showed that the third algorithm produced phylogenies with a higher probability than its aforementioned theoretical lower bound and outperformed some existing phylogeny reconstruction methods in both speed and accuracy.</p

Efficiency of BRCAPRO and Myriad II mutation probability thresholds versus cancer history criteria alone for BRCA1/2 mutation detection

Considerable differences exist amongst countries in the mutation probability methods and thresholds used to select patients for BRCA1/2 genetic screening. In order to assess the added value of mutation probability methods, we have retrospectively calculated the BRCAPRO and Myriad II probabilities in 306 probands who had previously been selected for DNA-analysis according to criteria based on familial history of cancer. DNA-analysis identified 52 mutations (16.9%) and 11 unclassified variants (UVs, 3.6%). Compared to cancer history, a threshold ≥10% with BRCAPRO or with Myriad II excluded about 40% of the patients from analysis, including four with a mutation and probabilities <10% with both programs. All four probands had a BRCA2 mutation. BRCAPRO and Myriad II showed similar specificity at 10% threshold, overall BRCAPRO was more sensitive than Myriad II for the detection of mutations. Only two of the probands with an UV had probabilities >20% with BRCAPRO and Myriad II. In summary, BRCAPRO and Myriad II are more efficient than cancer history alone to exclude patients without a mutation. BRCAPRO performs better for the detection of BRCA1 mutations than of BRCA2 mutations. The Myriad II scores provided no additional information than the BRCAPRO scores alone for the detection of patients with a mutation. The use of thresholds excluded from analysis the majority of patients carrying an UV

Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014)

Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dose-finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale

Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires

peer-reviewedBackground: Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results: All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05). Conclusions Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow.Department of Agriculture, Food and Fisheries, Ireland - Research Stimulus Fund (RSF-06-0353; RSF-06-0409); Irish Dairy Research Trust; Teagasc Walsh Fellowshi