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Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
Methods
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Results
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
Conclusions
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Errors inherent in self-reported measures of energy intake (EI) are substantial and well documented, but correlates of misreporting remain unclear. Therefore, potential predictors of misreporting were examined. In Study One, fifty-nine individuals (BMI = 26·1 (sd 3·8) kg/m2, age = 42·7 (sd 13·6) years, females = 29) completed a 14-d stay in a residential feeding behaviour suite where eating behaviour was continuously monitored. In Study Two, 182 individuals (BMI = 25·7 (sd 3·9) kg/m2, age = 42·4 (sd 12·2) years, females = 96) completed two consecutive days in a residential feeding suite and five consecutive days at home. Misreporting was directly quantified by comparing covertly measured laboratory weighed intakes (LWI) with self-reported EI (weighed dietary record (WDR), 24-h recall, 7-d diet history, FFQ). Personal (age, sex and %body fat) and psychological traits (personality, social desirability, body image, intelligence quotient and eating behaviour) were used as predictors of misreporting. In Study One, those with lower psychoticism (P = 0·009), openness to experience (P = 0·006) and higher agreeableness (P = 0·038) reduced EI on days participants knew EI was being measured to a greater extent than on covert days. Isolated associations existed between personality traits (psychoticism and openness to experience), eating behaviour (emotional eating) and differences between the LWI and self-reported EI, but these were inconsistent between dietary assessment techniques and typically became non-significant after accounting for multiplicity of comparisons. In Study Two, sex was associated with differences between LWI and the WDR (P = 0·009), 24-h recall (P = 0·002) and diet history (P = 0·050) in the laboratory, but not home environment. Personal and psychological correlates of misreporting identified displayed no clear pattern across studies or dietary assessment techniques and had little utility in predicting misreporting.
The association between Clostridioides difficile colonization and C. difficile infection (CDI) is unknown in solid-organ transplant (SOT) patients. We examined C. difficile colonization and healthcare-associated exposures as risk factors for development of CDI in SOT patients.
Methods:
The retrospective study cohort included all consecutive SOT patients with at least 1 screening test between May 2017 and April 2018. CDI was defined as the presence of diarrhea (without laxatives), a positive C. difficile clinical test, and the use of C. difficile-directed antimicrobial therapy as ordered by managing clinicians. In addition to demographic variables, exposures to antimicrobials, immunosuppressants, and gastric acid suppressants were evaluated from the time of first screening test to the time of CDI, death, or final discharge.
Results:
Of the 348 SOT patients included in our study, 33 (9.5%) were colonized with toxigenic C. difficile. In total, 11 patients (3.2%) developed CDI. Only C. difficile colonization (odds ratio [OR], 13.52; 95% CI, 3.46–52.83; P = .0002), age (OR, 1.09; CI, 1.02–1.17; P = .0135), and hospital days (OR, 1.05; 95% CI, 1.02–1.08; P = .0017) were independently associated with CDI.
Conclusions:
Although CDI was more frequent in C. difficile colonized SOT patients, the overall incidence of CDI was low in this cohort.
Glyphosate-tolerant and glyphosate-resistant weeds are becoming increasingly problematic in cotton fields in Australia, necessitating a return from a glyphosate dominated system to a more integrated approach to weed management. The development of an integrated weed management system can be facilitated by identifying the critical period for weed control (CPWC), a model that enables cotton growers to optimize the timing of their weed control inputs. Using data from field studies conducted from 2003 to 2015, CPWC models using extended functions, including weed biomass in the relationships, were developed for the mimic weeds, common sunflower and Japanese millet, in high-yielding, fully irrigated cotton. A multispecies CPWC model was developed after combining these data sets with data for mungbean in irrigated cotton, using weed height and weed biomass as descriptors in the models. Comparison of observed and predicted relative cotton-lint yields from the multispecies CPWC model demonstrated that the model reasonably described the competition from these three very different mimic weeds, opening the possibility for cotton growers to use a multispecies CPWC model in their production systems.
Is support for democracy in the United States robust enough to deter undemocratic behavior by elected politicians? We develop a model of the public as a democratic check and evaluate it using two empirical strategies: an original, nationally representative candidate-choice experiment in which some politicians take positions that violate key democratic principles, and a natural experiment that occurred during Montana’s 2017 special election for the U.S. House. Our research design allows us to infer Americans’ willingness to trade-off democratic principles for other valid but potentially conflicting considerations such as political ideology, partisan loyalty, and policy preferences. We find the U.S. public’s viability as a democratic check to be strikingly limited: only a small fraction of Americans prioritize democratic principles in their electoral choices, and their tendency to do so is decreasing in several measures of polarization, including the strength of partisanship, policy extremism, and candidate platform divergence. Our findings echo classic arguments about the importance of political moderation and cross-cutting cleavages for democratic stability and highlight the dangers that polarization represents for democracy.
Research using the critical period for weed control (CPWC) has shown that high-yielding cotton crops are very sensitive to competition from grasses and large broadleaf weeds, but the CPWC has not been defined for smaller broadleaf weeds in Australian cotton. Field studies were conducted over five seasons from 2003 to 2015 to determine the CPWC for smaller broadleaf weeds, using mungbean as a mimic weed. Mungbean was planted at densities of 1, 3, 6, 15, 30, and 60 plants m−2 with or after cotton emergence and added and removed at approximately 0, 150, 300, 450, 600, 750, and 900 degree days of crop growth (GDD). Mungbean competed strongly with cotton, with season-long interference; 60 mungbean plants m−2 resulted in an 84% reduction in cotton yield. A dynamic CPWC function was developed for densities of 1 to 60 mungbean plants m−2 using extended Gompertz and exponential curves including weed density as a covariate. Using a 1% yield-loss threshold, the CPWC defined by these curves extended for the full growing season of the crop at all weed densities. The minimum yield loss from a single weed control input was 35% at the highest weed density of 60 mungbean plants m−2. The relationship for the critical time of weed removal was further improved by substituting weed biomass for weed density in the relationship.
From 2008, the UK’s National Diet and Nutrition Survey (NDNS) changed the method of dietary data collection from a 7-d weighed diary to a 4-d unweighed diary, partly to reduce participant burden. This study aimed to test whether self-reported energy intake changed significantly over the 4-d recording period of the NDNS rolling programme. Analyses used data from the NDNS years 1 (2008/2009) to 8 (2015/2016) inclusive, from participants aged 13 years and older. Dietary records from participants who reported unusual amounts of food and drink consumed on one or more days were excluded, leaving 6932 participants. Mean daily energy intake was 7107 kJ (1698 kcal), and there was a significant decrease of 164 kJ (39 kcal) between days 1 and 4 (P < 0·001). There was no significant interaction of sex or low-energy reporter status (estimated from the ratio of reported energy intake:BMR) with the change in reported energy intake. The decrease in reported energy intake on day 4 compared with day 1 was greater (P < 0·019) for adults with higher BMI (>30 kg/m2) than it was for leaner adults. Reported energy intake decreased over the 4-d recording period of the NDNS rolling programme suggesting that participants change their diet more, or report less completely, with successive days of recording their diet. The size of the effect was relatively minor, however.
Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia.
METHODS:
This phase 3, double-blind study (ClinicalTrials.gov: NCT02694328) enrolled adults 18–55 yo with stable schizophrenia, randomized 1:1 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension.
RESULTS:
561 patients were randomized: 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, −2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P<0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment.
DISCUSSION:
OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment.
A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.
Methods:
Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.
Results:
Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).
Conclusions:
In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.
The Grey Falcon Falco hypoleucos is one of the world’s rarest raptors, with an estimated population size of fewer than 1,000 individuals. Our knowledge of threats posed to the Grey Falcon remains scant. Understanding the genetic variation in this species would help to assess its conservation status more realistically and its prospects for survival in a changing environment. We amplified the cytochrome b region of mitochondrial DNA from the feathers of 26 individuals captured from the wild across the distribution of the species and assessed the genetic diversity and spatial genetic structuring of the species. Genetic diversity was low, with only six haplotypes identified, but there was no evidence of a recent genetic bottleneck. No population genetic structuring was detected, indicating that the Grey Falcon population is effectively continuous across the species’ entire distribution, covering much of Australia’s arid/semi-arid zone. Our results indicate that the Grey Falcon should be managed as a single population and suggest conservation efforts that benefit the species at a local level should be good for the species as a whole. Future studies should employ next generation sequencing approaches, which may provide finer-scale information on the extent these birds move among breeding sites. Further research into the species’ ecology is also required to identify effective conservation measures.
Previously, we showed that disinfection of sink drains is effective at decreasing bacterial loads. Here, we report our evaluation of the ideal frequency of sink-drain disinfection and our comparison of 2 different hydrogen peroxide disinfectants.
Field studies were conducted over five seasons from 2004 to 2015 to determine the critical period for weed control (CPWC) in high-yielding, irrigated cotton using a competitive mimic grass weed, Japanese millet. Japanese millet was planted with or after cotton emergence at densities of 10, 20, 50, 100, and 200 plants m−2. Japanese millet was added and removed at approximately 0, 150, 300, 450, 600, 750, and 900 degree days of crop growth (GDD). Data were combined over years. Japanese millet competed strongly with cotton, with season-long interference resulting in an 84% reduction in cotton yield with 200 Japanese millet plants m−2. The data were fit to extended Gompertz and logistic curves including weed density as a covariate, allowing a dynamic CPWC to be estimated for densities of 10 to 200 Japanese millet plants m−2. Using a 1% yield-loss threshold, the CPWC commenced at 65 GDD, corresponding to 0 to 7 d after crop emergence (DAE), and ended at 803 GDD, 76 to 98 DAE with 10 Japanese millet plants m−2, and 975 GDD, 90 to 115 DAE with 200 Japanese millet plants m−2. These results highlight the high level of weed control required throughout the cropping season in high-yielding cotton to ensure crop losses do not exceed the cost of weed control.
Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.
Method:
Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).
Results:
Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.
Conclusion:
Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
In analysing fluid forces on a moving body, a natural approach is to seek a component due to viscosity and an ‘inviscid’ remainder. It is also attractive to decompose the velocity field into irrotational and rotational parts, and apportion the force resultants accordingly. The ‘irrotational’ resultants can then be identified as classical ‘added mass’, but the remaining, ‘rotational’, resultants appear not to be consistent with the physical interpretation of the rotational velocity field (as that arising from the fluid vorticity with the body stationary). The alternative presented here splits the inviscid resultants into components that are unquestionably due to independent aspects of the problem: ‘convective’ and ‘accelerative’. The former are associated with the pressure field that would arise in an inviscid flow with (instantaneously) the same velocities as the real one, and with the body’s velocity parameters – angular and translational – unchanging. The latter correspond to the pressure generated when the body accelerates from rest in quiescent fluid with its given rates of change of angular and translational velocity. They are reminiscent of the added-mass force resultants, but are simpler, and closer to the standard rigid-body inertia formulae, than the developed expressions for added-mass force and moment. Finally, the force resultants due to viscosity also include a contribution from pressure. Its presence is necessary in order to satisfy the equations governing the pressure field, and it has previously been recognised in the context of ‘excess’ stagnation-point pressure. However, its existence does not yet seem to be widely appreciated.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
We employ global input–output analysis to quantify amplification of exogenous disturbances in compressible boundary layer flows. Using the spatial structure of the dominant response to time-periodic inputs, we explain the origin of steady reattachment streaks in a hypersonic flow over a compression ramp. Our analysis of the laminar shock–boundary layer interaction reveals that the streaks arise from a preferential amplification of upstream counter-rotating vortical perturbations with a specific spanwise wavelength. These streaks are associated with heat-flux striations at the wall near flow reattachment and they can trigger transition to turbulence. The streak wavelength predicted by our analysis compares favourably with observations from two different hypersonic compression ramp experiments. Furthermore, our analysis of inviscid transport equations demonstrates that base-flow deceleration contributes to the amplification of streamwise velocity and that the baroclinic effects are responsible for the production of streamwise vorticity. Finally, the appearance of the temperature streaks near reattachment is triggered by the growth of streamwise velocity and streamwise vorticity perturbations as well as by the amplification of upstream temperature perturbations by the reattachment shock.
Placental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.
For decades, the deceptive simplicity of the radius
$R_{\rm e}$
, enclosing an arbitrary 50% of a galaxy’s light, has hamstrung the understanding of early-type galaxies (ETGs). Half a century ago, using these ‘effective half-light’ radii from de Vaucouleurs’
$R^{1/4}$
model, Sérsic reported that bright ETGs follow the relation
$\mathfrak{M}_B\propto2.5\log R_{\rm e}$
; and consequently, one has that
$\langle\mu\rangle_{\rm e}\propto2.5\log R_{\rm e}$
and
$\mu_{\rm e}\propto2.5\log R_{\rm e}$
, where
$\mu_{\rm e}$
and
$\langle\mu\rangle_{\rm e}$
are the effective surface brightness at
$R_{\rm e}$
and the mean effective surface brightness within
$R_{\rm e}$
, respectively. Sérsic additionally observed an apparent transition which led him to advocate for a division between what he called dwarf and giant ETGs; a belief frequently restated to occur at
$\mathfrak{M}_B \approx -18$
mag or
$n\approx 2.5$
. Here, the location of this false dichotomy in diagrams using ‘effective’ parameters is shown to change by more than 3 mag simply depending on the arbitrary percentage of light used to quantify a galaxy’s size. A range of alternative radii are explored, including where the projected intensity has dropped by a fixed percentage plus a battery of internal radii, further revealing that the transition at
$\mathfrak{M}_B
\approx -18$
mag is artificial and does not demark a boundary between different physical processes operating on the ETG population.
The above understanding surrounding the effective radius
$R_{\rm e}$
is of further importance because quantities such as dynamical mass
$\sigma^2R/G$
, gravitational-binding energy
$GM^2/R$
, acceleration
$GM/R^2$
, and the ‘Fundamental Plane’ also depend on the arbitrary percentage of light used to define R, with implications for dark matter estimates, galaxy formation theories, compact massive galaxies, studies of peculiar velocity flows, and more. Finally, some of the vast literature which has advocated for segregating the ETG population at
$\mathfrak{M}_B \approx -18$
mag (
$M\approx1$
–
$2\times10^{10}\,{\rm M}_{\odot}$
) is addressed, and it is revealed how this pervasive mindset has spilled over to influence both the classical bulge versus pseudobulge debate and recently also correlations involving supermassive black hole masses.