1,777 research outputs found
Explainable Machine Learning for Real-Time Hypoglycemia and Hyperglycemia Prediction and Personalized Control Recommendations
BACKGROUND: The occurrences of acute complications arising from hypoglycemia and hyperglycemia peak as young adults with type 1 diabetes (T1D) take control of their own care. Continuous glucose monitoring (CGM) devices provide real-time glucose readings enabling users to manage their control proactively. Machine learning algorithms can use CGM data to make ahead-of-time risk predictions and provide insight into an individual’s longer term control. METHODS: We introduce explainable machine learning to make predictions of hypoglycemia (270 mg/dL) up to 60 minutes ahead of time. We train our models using CGM data from 153 people living with T1D in the CITY (CGM Intervention in Teens and Young Adults With Type 1 Diabetes)survey totaling more than 28 000 days of usage, which we summarize into (short-term, medium-term, and long-term) glucose control features along with demographic information. We use machine learning explanations (SHAP [SHapley Additive exPlanations]) to identify which features have been most important in predicting risk per user. RESULTS: Machine learning models (XGBoost) show excellent performance at predicting hypoglycemia (area under the receiver operating curve [AUROC]: 0.998, average precision: 0.953) and hyperglycemia (AUROC: 0.989, average precision: 0.931) in comparison with a baseline heuristic and logistic regression model. CONCLUSIONS: Maximizing model performance for glucose risk prediction and management is crucial to reduce the burden of alarm fatigue on CGM users. Machine learning enables more precise and timely predictions in comparison with baseline models. SHAP helps identify what about a CGM user’s glucose control has led to predictions of risk which can be used to reduce their long-term risk of complications
The Molecular Clockwork of the Fire Ant Solenopsis invicta
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication
Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK
Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based
studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a
proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly
used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed
for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate
current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly
selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases
of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised
for diagnosis, and which management or treatment protocols are used.
Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing
pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months.
Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural
sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52%
of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents
reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged
mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on
duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability
and previous history.
Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and
severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt
pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment
protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in
spayed and entire bitches has been made, further studies are warranted
Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea
Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates
Lack of trust in maternal support is associated with negative interpretations of ambiguous maternal behavior
Attachment theory assumes that children who lack trust in maternal availability for support are more inclined to interpret maternal behavior in congruence with their expectation that mother will remain unavailable for support. To provide the first test of this assumption, early adolescents (9-13 years old) were asked to assess whether ambiguous interactions with mother should be interpreted in a positive or a negative way. In our sample (n = 322), results showed that early adolescents' lack of trust in their mother's availability for support was related to more negative interpretations of maternal behavior. The associations remained significant after controlling for depressive mood. The importance of these findings for our understanding of attachment theory, attachment stability, and clinical practice are discussed
Weakened magnetic braking as the origin of anomalously rapid rotation in old field stars
A knowledge of stellar ages is crucial for our understanding of many
astrophysical phenomena, and yet ages can be difficult to determine. As they
become older, stars lose mass and angular momentum, resulting in an observed
slowdown in surface rotation. The technique of 'gyrochronology' uses the
rotation period of a star to calculate its age. However, stars of known age
must be used for calibration, and, until recently, the approach was untested
for old stars (older than 1 gigayear, Gyr). Rotation periods are now known for
stars in an open cluster of intermediate age (NGC 6819; 2.5 Gyr old), and for
old field stars whose ages have been determined with asteroseismology. The data
for the cluster agree with previous period-age relations, but these relations
fail to describe the asteroseismic sample. Here we report stellar evolutionary
modelling, and confirm the presence of unexpectedly rapid rotation in stars
that are more evolved than the Sun. We demonstrate that models that incorporate
dramatically weakened magnetic braking for old stars can---unlike existing
models---reproduce both the asteroseismic and the cluster data. Our findings
might suggest a fundamental change in the nature of ageing stellar dynamos,
with the Sun being close to the critical transition to much weaker magnetized
winds. This weakened braking limits the diagnostic power of gyrochronology for
those stars that are more than halfway through their main-sequence lifetimes.Comment: 25 pages, 3 figures in main paper, 6 extended data figures, 1 table.
Published in Nature, January 2016. Please see https://youtu.be/O6HzYgP5uyc
for a video description of the resul
The efficacy of semi-quantitative urine protein-to-creatinine (P/C) ratio for the detection of significant proteinuria in urine specimens in health screening settings
Long term time variability of cosmic rays and possible relevance to the development of life on Earth
An analysis is made of the manner in which the cosmic ray intensity at Earth
has varied over its existence and its possible relevance to both the origin and
the evolution of life. Much of the analysis relates to the 'high energy' cosmic
rays () and their variability due to the changing
proximity of the solar system to supernova remnants which are generally
believed to be responsible for most cosmic rays up to PeV energies. It is
pointed out that, on a statistical basis, there will have been considerable
variations in the likely 100 My between the Earth's biosphere reaching
reasonable stability and the onset of very elementary life. Interestingly,
there is the increasingly strong possibility that PeV cosmic rays are
responsible for the initiation of terrestrial lightning strokes and the
possibility arises of considerable increases in the frequency of lightnings and
thereby the formation of some of the complex molecules which are the 'building
blocks of life'. Attention is also given to the well known generation of the
oxides of nitrogen by lightning strokes which are poisonous to animal life but
helpful to plant growth; here, too, the violent swings of cosmic ray
intensities may have had relevance to evolutionary changes. A particular
variant of the cosmic ray acceleration model, put forward by us, predicts an
increase in lightning rate in the past and this has been sought in Korean
historical records. Finally, the time dependence of the overall cosmic ray
intensity, which manifests itself mainly at sub-10 GeV energies, has been
examined. The relevance of cosmic rays to the 'global electrical circuit'
points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics
Correlation Functions of Large N Chern-Simons-Matter Theories and Bosonization in Three Dimensions
We consider the conformal field theory of N complex massless scalars in 2+1
dimensions, coupled to a U(N) Chern-Simons theory at level k. This theory has a
't Hooft large N limit, keeping fixed \lambda = N/k. We compute some
correlation functions in this theory exactly as a function of \lambda, in the
large N (planar) limit. We show that the results match with the general
predictions of Maldacena and Zhiboedov for the correlators of theories that
have high-spin symmetries in the large N limit. It has been suggested in the
past that this theory is dual (in the large N limit) to the Legendre transform
of the theory of fermions coupled to a Chern-Simons gauge field, and our
results allow us to find the precise mapping between the two theories. We find
that in the large N limit the theory of N scalars coupled to a U(N)_k
Chern-Simons theory is equivalent to the Legendre transform of the theory of k
fermions coupled to a U(k)_N Chern-Simons theory, thus providing a bosonization
of the latter theory. We conjecture that perhaps this duality is valid also for
finite values of N and k, where on the fermionic side we should now have (for
N_f flavors) a U(k)_{N-N_f/2} theory. Similar results hold for real scalars
(fermions) coupled to the O(N)_k Chern-Simons theory.Comment: 49 pages, 16 figures. v2: added reference
Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells
Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer
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