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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Reliably dated surficial deposits for reconstructing palaeoclimate are rare in the McMurdo Dry Valleys of Antarctica. While many tephra have been found and dated, none is well characterized. In the Wright Valley, the Hart Ash is poorly dated and described. This paper reports profiles through tephra, the chemical signature of the glass shards and new high-precision multi-crystal laser fusion of 40Ar/39Ar ages. Major and trace element analyses of glass shards indicate the tephra are phonolitic and most probably sourced from Mount Discovery in the Erebus volcanic province. Two chemically distinct and stratigraphically separate tephra layers within the Hart Ash were found in three closely spaced soil profiles. The complex stratigraphy between these profiles could not be delineated without the geochemistry of the tephra. Importantly, our data suggest that only one tephra may be an in situ fall-out deposit, which gave a robust age of 2.97 ± 0.02 Ma. This new age for the Hart Ash tephra, which is 10 cm thick and is preserved at the current surface, provides a maximum age for surface deposits in the lower Wright Valley. This study highlights that well-characterized tephra enhance stratigraphic correlations in the Dry Valleys and improve the accuracy of palaeoenvironmental interpretations.
In a rational world, scientific effort would reflect society's needs. We tested this hypothesis using the area of infectious diseases, where the research response to emerging threats has obvious potential to save lives through informing interventions such as vaccination and prevention policies. Pathogens continue to evolve, emerge and re-emerge and infectious diseases that were once common become less so or their global distribution changes. A question remains as to whether scientific endeavours can adapt. Here, we identified papers on infectious diseases published in the four highest ranking, health-related journals over the 118 years from 1900. Focussing on outbreak-related and burden of disease-related metrics over the two time periods, 1990 to 2017 and 1900 to 2017, our analyses suggest that there is little underrepresentation of important infectious diseases among top ranked journals. Encouragingly our results suggest the scientific process is largely self-correcting.
This article presents a case study of decision making in a drug court located the southwestern United States. This study seeks to fill a gap in research on decision making by attending to the ways that drug court officials navigate the demands of a court that is dedicated to both therapy and criminal justice. This analysis differs from previous research by viewing the drug court as a “hybrid organization” and asking how the staff members interact in the decision-making process. Additionally, this research provides an opportunity to investigate the concerns over collaborative decision making raised by critics. The data from this case study reveal that as a hybrid organization, the drug court staff often divides along institutional lines by allowing the counseling staff to manage treatment and the judge to manage punishment. When tensions arise, they are resolved by the structure of the court, which is hierarchical rather than collaborative.
Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
To assess, using standardised tools, the quality and readability of online tinnitus information that patients are likely to access.
A standardised review was conducted of websites relating to tinnitus and its management. Each website was scored using the DISCERN instrument and the Flesch Reading Ease scale.
Twenty-seven unique websites were evaluated. The mean DISCERN score of the websites was 34.5 out of 80 (standard deviation = 11.2). This would be considered ‘fair’ in quality. Variability in DISCERN score between websites was high (range, 15–57: ‘poor’ to ‘very good’). Website readability was poor, with a mean Flesch Reading Ease score of 52.6 (standard deviation = 7.7); this would be considered ‘difficult’ to read.
In general, the quality of tinnitus websites is fair and the readability is poor, with substantial variability in quality between websites. The Action on Hearing Loss and the British Tinnitus Association websites were identified as providing the highest quality information.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
Patient days and days present were compared to directly measured person time to quantify how choice of different denominator metrics may affect antimicrobial use rates. Overall, days present were approximately one-third higher than patient days. This difference varied among hospitals and units and was influenced by short length of stay.
Because the 14C calibration curves IntCal and SHCal are based on data from temperate latitudes, it remains unclear which curve is more suitable for archaeological and paleoenvironmental records from tropical South America. A review of climate dynamics reveals a significant influx of Northern Hemisphere air masses and moisture over a substantial part of the continent during the South American Summer Monsoon (SASM). Areas affected by the SASM receive unknown amounts of input from both hemispheres, where an argument could be made for either curve. Until localized tree-ring data can resolve this, we suggest using a mixed calibration curve, which accounts for inputs from both hemispheres, as a third calibration option. We present a calibration example from a crucial period of environmental and cultural change in the southern Lake Titicaca. Given our current lack of data on past ∆14C variation in South America, our calibrations and chronologies will likely change in the future. We hope this paper spurs new research into this topic and encourages researchers to make an informed and explicit choice of which curve to use, which is particularly relevant in research on past human–environmental relationships.
Healthcare-associated norovirus outbreaks increase later but have a more pronounced seasonality than nonhealthcare norovirus outbreaks. Healthcare-associated norovirus outbreaks had higher correlation with Google Trends activity than nonhealthcare outbreaks (R2=0.68 vs 0.39). Google Trends data may have the potential to supplement existing norovirus surveillance due to its real-time availability.
Azaperone can reduce stress caused by weaning and relocation of breeding sows, but its effects on reproductive processes are still poorly understood. The primary aim of this study was to describe and compare the endocrine and ovarian activity in ultrasonographically monitored second parity sows, with or without azaperone treatment at weaning (2 mg/kg BW i.m.). The intervals from weaning to the onset of estrus and ovulation were both greater (P<0.05) in azaperone-treated (n=12) than in control sows (n=12) by ~12 h. Mean daily growth rates of identified antral follicles were less (P<0.05) in azaperone-treated than in control sows (1.08±0.17 v.1.23±0.18 mm/day; mean±SD) and treated animals exceeded (P<0.05) controls in the mean ovulation rate (13.7±1.3 v. 12.6±1.2). A transient suppression of cortisol release was observed in the treatment group (at 10 and 30 min after azaperone injections) but circulating cortisol concentrations were variable in both groups of sows for the remainder of the study. The preovulatory rise in LH and estradiol secretion was delayed (P<0.05), and the duration of the LH surge was greater (P<0.001) in azaperone-treated sows compared with their control counterparts. The amplitude of episodic fluctuations in serum cortisol concentrations was correlated with the number of stillborn piglets in control sows (r=0.63, P=0.04). The amplitude and concentration of the preovulatory rise in estradiol secretion were negatively correlated with ovulatory response and litter size (r=−0.63 to −0.82, P<0.05), whereas the time at which the LH surge ended was directly related to the number of live-born piglets (r=0.82, P=0.002) in azaperone-treated animals. The present results indicate that administration of azaperone at weaning had a profound effect on preovulatory LH secretion as well as growth kinetics and estrogenicity of ovarian antral follicles. However, the causative associations among various characteristics of the preovulatory LH discharge, ovarian and adrenal steroid secretion post-weaning, and reproductive variables in sows remain equivocal.
Acute rheumatic fever (ARF) continues to produce a significant burden of disease in New Zealand (NZ) Māori and Pacific peoples. Serious limitations in national surveillance data mean that accurate case totals cannot be generated. Given the changing epidemiology of ARF in NZ and the major national rheumatic fever prevention programme (2012–2017), we updated our previous likely true case number estimates using capture–recapture analyses. Aims were to estimate the likely true incidence of ARF in NZ and comment on the changing ability to detect cases. Data were obtained from national hospitalisation and notification databases. The Chapman Estimate partially adjusted for bias. An estimated 2342 likely true new cases arose from 1997 to 2015, giving a mean annual incidence of 2·9 per 100 000 (95% CI 2·5–3·5). Compared with the pre-intervention (2009–2011) baseline incidence (3·4 per 100 000, 95% CI 2·9–4·0), the likely true 2015 incidence declined 44%. Large gaps in data completeness are slowly closing. During the period 2012–2015, 723 cases were identified; 83·8% of notifications were matched to hospitalisation data, and 87·2% of hospitalisations matched to notifications. Despite this improvement, clinicians need to remain aware of the need to notify atypical patients. A possible unintended consequence of the national ARF prevention programme is increased misdiagnosis.
The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.
Poor animal performance associated with low digestibility silages results partly from the reduced nutrient yield per unit intake, but also from the associated lower intakes which were presumed to be a consequence of rumen fill effects. Legume silages have a lower average digestibility than grass silages, and yet often have higher intake characteristics. The objective of this work was to compare rumen fill and rumen particle size distribution for animals fed grass silage or legume silage-based diets.