Data-adaptive harmonic spectra and multilayer Stuart-Landau models

Harmonic decompositions of multivariate time series are considered for which we adopt an integral operator approach with periodic semigroup kernels. Spectral decomposition theorems are derived that cover the important cases of two-time statistics drawn from a mixing invariant measure. The corresponding eigenvalues can be grouped per Fourier frequency, and are actually given, at each frequency, as the singular values of a cross-spectral matrix depending on the data. These eigenvalues obey furthermore a variational principle that allows us to define naturally a multidimensional power spectrum. The eigenmodes, as far as they are concerned, exhibit a data-adaptive character manifested in their phase which allows us in turn to define a multidimensional phase spectrum. The resulting data-adaptive harmonic (DAH) modes allow for reducing the data-driven modeling effort to elemental models stacked per frequency, only coupled at different frequencies by the same noise realization. In particular, the DAH decomposition extracts time-dependent coefficients stacked by Fourier frequency which can be efficiently modeled---provided the decay of temporal correlations is sufficiently well-resolved---within a class of multilayer stochastic models (MSMs) tailored here on stochastic Stuart-Landau oscillators. Applications to the Lorenz 96 model and to a stochastic heat equation driven by a space-time white noise, are considered. In both cases, the DAH decomposition allows for an extraction of spatio-temporal modes revealing key features of the dynamics in the embedded phase space. The multilayer Stuart-Landau models (MSLMs) are shown to successfully model the typical patterns of the corresponding time-evolving fields, as well as their statistics of occurrence.Comment: 26 pages, double columns; 15 figure

Genotype-independent association between vitamin D deficiency and polycystic ovarian syndrome in Lahore, Pakistan.

Both vitamin D deficiency and single nucleotide polymorphisms (SNPs) in the gene encoding the vitamin D receptor (VDR) have been widely reported to associate with susceptibility to polycystic ovarian syndrome (PCOS). A case-control study was conducted to study the influence of vitamin D status and genotpye for 24 SNPs in four genes in the vitamin D pathway (VDR, DBP, CYP27B1, CYP24A1) on PCOS. Statistical analyses were conducted to identify phenotypic and genotypic factors associated with risk of PCOS and to test for interactions between genotype and vitamin D status. PCOS was independently associated with lower age, higher body mass index, lower waist-hip ratio, vitamin D deficiency (serum 25-hydroxyvitamin D concentration <10 ng/mL), lack of outdoor exercise, increased fasting glucose and a family history of PCOS in at least one first degree relative. No statistically significant association was observed between the genotype of any SNP investigated and risk of PCOS, either as a main effect or in interaction with vitamin D status. We report a strong and independent association between vitamin D deficiency and risk of PCOS in Pakistan, that was not modified by genetic variation in the vitamin D pathway

Anatomic and Cellular Niches for Mycobacterium tuberculosis in Latent Tuberculosis Infection.

Latent tuberculosis has been recognized for over a century, but discovery of new niches, where Mycobacterium tuberculosis resides, continues. We evaluated literature on M.tuberculosis locations during latency, highlighting that mesenchymal and hematopoietic stem cells harbor organisms in sensitized asymptomatic individuals.This work was supported by grants from the Medical Research Council (ref. MR/P024548/1; to A. R. M.) and the DELTAS Africa Initiative (ref. DEL-15-011 [to J. M.], via THRiVE-2). The DELTAS Africa Initiative is an independent funding scheme of the AAS’s Alliance for Accelerating Excellence in Science in Africa and supported by the NEPAD Agency with funding from the Wellcome Trust Grant No. 107742/Z/15/Z and the United Kingdom government

The projection score - an evaluation criterion for variable subset selection in PCA visualization

<p>Abstract</p> <p>Background</p> <p>In many scientific domains, it is becoming increasingly common to collect high-dimensional data sets, often with an exploratory aim, to generate new and relevant hypotheses. The exploratory perspective often makes statistically guided visualization methods, such as Principal Component Analysis (PCA), the methods of choice. However, the clarity of the obtained visualizations, and thereby the potential to use them to formulate relevant hypotheses, may be confounded by the presence of the many non-informative variables. For microarray data, more easily interpretable visualizations are often obtained by filtering the variable set, for example by removing the variables with the smallest variances or by only including the variables most highly related to a specific response. The resulting visualization may depend heavily on the inclusion criterion, that is, effectively the number of retained variables. To our knowledge, there exists no objective method for determining the optimal inclusion criterion in the context of visualization.</p> <p>Results</p> <p>We present the projection score, which is a straightforward, intuitively appealing measure of the informativeness of a variable subset with respect to PCA visualization. This measure can be universally applied to find suitable inclusion criteria for any type of variable filtering. We apply the presented measure to find optimal variable subsets for different filtering methods in both microarray data sets and synthetic data sets. We note also that the projection score can be applied in general contexts, to compare the informativeness of any variable subsets with respect to visualization by PCA.</p> <p>Conclusions</p> <p>We conclude that the projection score provides an easily interpretable and universally applicable measure of the informativeness of a variable subset with respect to visualization by PCA, that can be used to systematically find the most interpretable PCA visualization in practical exploratory analysis.</p

Evaluating probabilistic dengue risk forecasts from a prototype early warning system for Brazil

Open accessRecently, a prototype dengue early warning system was developed to produce probabilistic forecasts of dengue risk three months ahead of the 2014 World Cup in Brazil. Here, we evaluate the categorical dengue forecasts across all microregions in Brazil, using dengue cases reported in June 2014 to validate the model. We also compare the forecast model framework to a null model, based on seasonal averages of previously observed dengue incidence. When considering the ability of the two models to predict high dengue risk across Brazil, the forecast model produced more hits and fewer missed events than the null model, with a hit rate of 57% for the forecast model compared to 33% for the null model. This early warning model framework may be useful to public health services, not only ahead of mass gatherings, but also before the peak dengue season each year, to control potentially explosive dengue epidemics

Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)

BACKGROUND: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. METHODS: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. RESULTS: Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06–1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m(2) (1.24, 1.11–1.39), South Asian vs. White ethnicity (1.65, 1.10–2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with  lower risk (0.80, 0.70–0.93, for ≥ 10 vs. 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m(2) (aGMR 1.10, 1.02–1.19), South Asian vs. White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02–1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. CONCLUSIONS: Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02286-4

Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data.

“This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.”BACKGROUND: Randomised controlled trials (RCTs) of adjunctive vitamin D in pulmonary tuberculosis (PTB) treatment have yielded conflicting results. Individual participant data (IPD) meta-analysis could identify factors explaining this variation. METHODS: We meta-analysed IPD from RCTs of vitamin D in patients receiving antimicrobial therapy for PTB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified sub-group analyses were done according to baseline vitamin D status, age, sex, drug-susceptibility, HIV status, extent of disease, and vitamin D receptor genotype. RESULTS: IPD were obtained for 1850 participants in 8 studies. Vitamin D did not influence time to sputum culture conversion overall (aHR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant PTB (aHR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (aHR 1.02, 95% CI 0.88-1.19; Pinteraction=0.02). Vitamin D accelerated sputum smear conversion overall (aHR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. CONCLUSIONS: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant PTB.ARM and DAJ are supported by the Higher Education Funding Council for England (HEFCE)

Control of interjoint coordination during the swing phase of normal gait at different speeds

BACKGROUND: It has been suggested that the control of unconstrained movements is simplified via the imposition of a kinetic constraint that produces dynamic torques at each moving joint such that they are a linear function of a single motor command. The linear relationship between dynamic torques at each joint has been demonstrated for multijoint upper limb movements. The purpose of the current study was to test the applicability of such a control scheme to the unconstrained portion of the gait cycle – the swing phase. METHODS: Twenty-eight neurologically normal individuals walked along a track at three different speeds. Angular displacements and dynamic torques produced at each of the three lower limb joints (hip, knee and ankle) were calculated from segmental position data recorded during each trial. We employed principal component (PC) analysis to determine (1) the similarity of kinematic and kinetic time series at the ankle, knee and hip during the swing phase of gait, and (2) the effect of walking speed on the range of joint displacement and torque. RESULTS: The angular displacements of the three joints were accounted for by two PCs during the swing phase (Variance accounted for – PC1: 75.1 ± 1.4%, PC2: 23.2 ± 1.3%), whereas the dynamic joint torques were described by a single PC (Variance accounted for – PC1: 93.8 ± 0.9%). Increases in walking speed were associated with increases in the range of motion and magnitude of torque at each joint although the ratio describing the relative magnitude of torque at each joint remained constant. CONCLUSION: Our results support the idea that the control of leg swing during gait is simplified in two ways: (1) the pattern of dynamic torque at each lower limb joint is produced by appropriately scaling a single motor command and (2) the magnitude of dynamic torque at all three joints can be specified with knowledge of the magnitude of torque at a single joint. Walking speed could therefore be altered by modifying a single value related to the magnitude of torque at one joint