159 research outputs found
Electrocardiographic patch devices and contemporary wireless cardiac monitoring.
Cardiac electrophysiologic derangements often coexist with disorders of the circulatory system. Capturing and diagnosing arrhythmias and conduction system disease may lead to a change in diagnosis, clinical management and patient outcomes. Standard 12-lead electrocardiogram (ECG), Holter monitors and event recorders have served as useful diagnostic tools over the last few decades. However, their shortcomings are only recently being addressed by emerging technologies. With advances in device miniaturization and wireless technologies, and changing consumer expectations, wearable “on-body” ECG patch devices have evolved to meet contemporary needs. These devices are unobtrusive and easy to use, leading to increased device wear time and diagnostic yield. While becoming the standard for detecting arrhythmias and conduction system disorders in the outpatient setting where continuous ECG monitoring in the short to medium term (days to weeks) is indicated, these cardiac devices and related digital mobile health technologies are reshaping the clinician-patient interface with important implications for future healthcare delivery
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Secondary analyses of global datasets: do obesity and physical activity explain variation in diabetes risk across populations?
Copyright © 2021 The Author(s). Type 2 diabetes rates vary significantly across geographic regions. These differences are sometimes assumed to be entirely driven by differential distribution of environmental triggers, including obesity and insufficient physical activity (IPA). In this review, we discuss data which conflicts with this supposition. We carried out a secondary analysis of publicly available data to unravel the relative contribution of obesity and IPA towards diabetes risk across different populations. We used sex-specific, age-standardized estimates from Non-Communicable Disease Risk Factor Collaboration (NCD-RisC) on diabetes (1980–2014) and obesity (1975–2016) rates, in 200 countries, and from WHO on IPA rates in 168 countries in the year 2016. NCD-RisC and WHO organized countries into nine super-regions. All analyses were region- and sex-specific. Although obesity has been increasing since 1975 in every part of the world, this was not reflected in a proportional increase in diabetes rates in several regions, including Central and Eastern Europe, and High-income western countries region. Similarly, the association of physical inactivity with diabetes is not homogeneous across regions. Countries from different regions across the world could have very similar rates of diabetes, despite falling on opposite ends of IPA rate spectrum. The combined effect of obesity and IPA on diabetes risk was analyzed at the worldwide and country level. The overall findings highlighted the larger impact of obesity on disease risk; low IPA rates do not seem to be protective of diabetes, when obesity rates are high. Despite that, some countries deviate from this overall observation. Sex differences were observed across all our analyses. Overall, data presented in this review indicate that different populations, while experiencing similar environmental shifts, are apparently differentially subject to diabetes risk. Sex-related differences observed suggest that males and females are either subject to different risk factor exposures or have different responses to them.The work presented in this paper is part of a PhD project by the first author (Budour Alkaf); internal funding by Imperial College London Diabetes Centre is gratefully acknowledged. The authors are also grateful for The Medical Research Council, UK (grant numbers: MR/M013138/1, MRC/BBSRC MR/S03658X/1 (JPI HDHL H2020)) for their financial support during the authors time when conducting this piece of work and writing this paper
Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish medical birth register
© 2019 Rodriguez et al. Background Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies. Methods and findings This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006–December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm −61.26 g (±SE 24.12, P < 0.01), preterm −-232.90 g (±SE 17.24, P < .001), near term −171.50 g (±SE 17.52, P < .001), and at term −-101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm −61.54 g (±SE 28.62, P < .03), preterm −222.78 g (±SE 19.64, P < .001), near term −159.25 g (±SE 19.14, P < .001), and at term −91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: −220.18 g (±SE 21.43, P < .001), −140.68 g (±SE 23.09, P < .001), and −89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested. Conclusions In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.Swedish Research Council for Health, Working Life, and Welfare (FAS 20111483; https://forte.se/) and VINNOVA Sweden’s Innovation Agency (200801003; https://www.vinnova.se/), both to AR; Academy of Finland EGEA project (285547; https://www.aka.fi/en/) and EU H2020 LifeCycle Action (grant agreement 733206) to MRJ; and EU H2020 DynaHEALTH action (grant agreement 633595; https://ec.europa.eu/programmes/horizon2020/) to MRJ (PI) and AR (collaborator
Spin and Statistics and First Principles
It was shown in the early Seventies that, in Local Quantum Theory (that is
the most general formulation of Quantum Field Theory, if we leave out only the
unknown scenario of Quantum Gravity) the notion of Statistics can be grounded
solely on the local observable quantities (without assuming neither the
commutation relations nor even the existence of unobservable charged field
operators); one finds that only the well known (para)statistics of Bose/Fermi
type are allowed by the key principle of local commutativity of observables. In
this frame it was possible to formulate and prove the Spin and Statistics
Theorem purely on the basis of First Principles.
In a subsequent stage it has been possible to prove the existence of a
unique, canonical algebra of local field operators obeying ordinary Bose/Fermi
commutation relations at spacelike separations. In this general guise the Spin
- Statistics Theorem applies to Theories (on the four dimensional Minkowski
space) where only massive particles with finite mass degeneracy can occur. Here
we describe the underlying simple basic ideas, and briefly mention the
subsequent generalisations; eventually we comment on the possible validity of
the Spin - Statistics Theorem in presence of massless particles, or of
violations of locality as expected in Quantum Gravity.Comment: Survey based on a talk given at the Meeting on "Theoretical and
experimental aspects of the spin - statistics connection and related
symmetries", Trieste, Italy - October 21-25, 200
Lung function in adults born preterm
Very preterm birth, before the gestational age (GA) of 32 weeks,
increases the risk of obstructed airflow in adulthood. We examined
whether all preterm births (GA<37 weeks) are associated with poorer
adult lung function and whether any associations are explained by
maternal, early life/neonatal, or current life factors. Participants of
the ESTER Preterm Birth Study, born between 1985 and 1989 (during the
pre-surfactant era), at the age of 23 years participated in a clinical
study in which they performed spirometry and provided detailed medical
history. Of the participants, 139 were born early preterm (GA<34
weeks), 239 late preterm (GA: 34-<37 weeks), and 341 full-term (GA≥37
weeks). Preterm birth was associated with poorer lung function. Mean
differences between individuals born early preterm versus full-term were
-0.23 standard deviation (SD) (95% confidence interval (CI): -0.40,
-0.05)) for forced vital capacity z-score (zFVC), -0.44 SD (95% CI
-0.64, -0.25) for forced expiratory volume z-score (zFEV1), and -0.29 SD
(95% CI -0.47, -0.10) for zFEV1/FVC. For late preterm, mean differences
with full-term controls were -0.02 SD (95% CI -0.17, 0.13), -0.12 SD
(95% CI -0.29, 0.04) and -0.13 SD (95% CI -0.29, 0.02) for zFVC, zFEV1,
and zFEV1/FVC, respectively. Examination of finer GA subgroups suggested
an inverse non-linear association between lung function and GA, with
the greatest impact on zFEV1 for those born extremely preterm. The
subgroup means were GA<28 weeks: -0.98 SD; 28-<32 weeks: -0.29 SD;
32-<34 weeks: -0.44 SD; 34-<36 weeks: -0.10 SD; 36-<37weeks:
-0.11 SD; term-born controls (≥37weeks): 0.02 SD. Corresponding means
for zFEV1/FVC were -1.79, -0.44, -0.47, -0.48, -0.29, and -0.02.
Adjustment for maternal pregnancy conditions and socioeconomic and
lifestyle factors had no major impact on the relationship. Preterm birth
is associated with airflow limitation in adult life. The association
appears to be attributable predominantly to those born most immature,
with only a modest decrease among those born preterm at later
gestational ages.</p
Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis
Aims :
Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit
lipoprotein lipase (LPL) and represent emerging drug targets to lower
circulating triglycerides and reduce cardiovascular risk. To investigate
the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4
inhibition and compare them to the effects of genetic mimicry of LPL
enhancement.
Methods and results :
Associations of genetic variants in ANGPTL3 (rs11207977-T),
ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum
lipid and metabolite profile (208 measures) were characterized in six
cohorts of up to 61 240 participants. Genetic associations with
anthropometric measures, glucose-insulin metabolism, blood pressure,
markers of kidney function, and cardiometabolic endpoints via
genome-wide summary data were also explored. ANGPTL4 rs116843064-A and
LPL rs115849089-A displayed a strikingly similar pattern of associations
across the lipoprotein and lipid measures. However, the corresponding
associations with ANGPTL3 rs11207977-T differed, including those for
low-density lipoprotein and high-density lipoprotein particle
concentrations and compositions. All three genotypes associated with
lower concentrations of an inflammatory biomarker glycoprotein acetyls
and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also
associated with lower C-reactive protein. Genetic mimicry of ANGPTL4
inhibition and LPL enhancement were associated with a lower waist-to-hip
ratio, improved insulin-glucose metabolism, and lower risk of coronary
heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was
associated with improved kidney function.
Conclusions :
Genetic mimicry of ANGPTL4 inhibition and LPL enhancement have
very similar systemic metabolic effects, whereas genetic mimicry of
ANGPTL3 inhibition showed differing metabolic effects, suggesting
potential involvement of pathways independent of LPL. Genetic mimicry of
ANGPTL4 inhibition and LPL enhancement were associated with a lower
risk of coronary heart disease and type 2 diabetes. These findings
reinforce evidence that enhancing LPL activity (either directly or via
upstream effects) through pharmacological approaches is likely to yield
benefits to human health.
</p
The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size
Background
We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations.
Methodology/Principal Findings
We analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by −40.4 g, 95%CI −61.4, −19.5; birth length −0.14 cm, 95%CI −0.23, −0.05; head circumference −0.09 cm 95%CI −0.15, −0.02) and neighborhood disparity (birthweight −28.8 g, 95%CI −47.7, −10.0; birth length −0.12 cm, 95%CI −0.20, −0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles.
Conclusions/Significance
Social adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults
Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition
Cholesteryl ester transfer protein (CETP) inhibition reduces vascular
event risk, but confusion surrounds its effects on low-density
lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic
inhibition of CETP on detailed lipoprotein measures and compare those to
genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
(HMGCR). We used an allele associated with lower CETP expression
(rs247617) to mimic CETP inhibition and an allele associated with lower
HMGCR expression (rs12916) to mimic the well-known effects of statins
for comparison. The study consists of 65,427 participants of European
ancestries with detailed lipoprotein subclass profiling from nuclear
magnetic resonance spectroscopy. Genetic associations were scaled to 10%
reduction in relative risk of coronary heart disease (CHD). We also
examined observational associations of the lipoprotein subclass measures
with risk of incident CHD in 3 population-based cohorts totalling 616
incident cases and 13,564 controls during 8-year follow-up. Genetic
inhibition of CETP and HMGCR resulted in near-identical associations
with LDL cholesterol concentration estimated by the Friedewald equation.
Inhibition of HMGCR had relatively consistent associations on lower
cholesterol concentrations across all apolipoprotein B-containing
lipoproteins. In contrast, the associations of the inhibition of CETP
were stronger on lower remnant and very-low-density lipoprotein (VLDL)
cholesterol, but there were no associations on cholesterol
concentrations in LDL defined by particle size (diameter 18-26 nm)
(-0.02 SD LDL defined by particle size; 95% CI: -0.10 to 0.05 for CETP
versus -0.24 SD, 95% CI -0.30 to -0.18 for HMGCR). Inhibition of CETP
was strongly associated with lower proportion of triglycerides in all
high-density lipoprotein (HDL) particles. In observational analyses, a
higher triglyceride composition within HDL subclasses was associated
with higher risk of CHD, independently of total cholesterol and
triglycerides (strongest hazard ratio per 1 SD higher triglyceride
composition in very large HDL 1.35; 95% CI: 1.18-1.54). In conclusion,
CETP inhibition does not appear to affect size-specific LDL cholesterol
but is likely to lower CHD risk by lowering concentrations of other
atherogenic, apolipoprotein B-containing lipoproteins (such as remnant
and VLDLs). Inhibition of CETP also lowers triglyceride composition in
HDL particles, a phenomenon reflecting combined effects of circulating
HDL, triglycerides, and apolipoprotein B-containing particles and is
associated with a lower CHD risk in observational analyses. Our results
reveal that conventional composite lipid assays may mask heterogeneous
effects of emerging lipid-altering therapies.</p
Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence
BackgroundPregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood.MethodsDetailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24–49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status.ResultsCompared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters.ConclusionsPregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.</div
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