The aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members’ biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.

Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.

The Mediterranean diet offers a range of health benefits. However, previous studies indicate that the restricted consumption of red meat in the diet may affect long-term sustainability in non-Mediterranean countries. A 24-week randomised controlled parallel cross-over design compared a Mediterranean diet supplemented with 2–3 serves per week of fresh, lean pork (MedPork) with a low-fat control diet (LF). Thirty-three participants at risk of CVD followed each intervention for 8 weeks, with an 8-week washout period separating interventions. The primary outcome was home-measured systolic blood pressure. Secondary outcomes included diastolic blood pressure, fasting lipids, glucose, insulin, C-reactive protein (CRP), body composition and dietary adherence. During the MedPork intervention, participants achieved high adherence to dietary guidelines. Compared with the MedPork intervention, the LF intervention led to greater reductions in weight (Δ = −0·65; 95 % CI −0·04, −1·25 kg, P = 0·04), BMI (Δ = −0·25; 95 % CI −0·03, −0·47 kg/m2, P = 0·01) and waist circumference (Δ = −1·40; 95 % CI −0·45, −2·34 cm, P < 0·01). No significant differences were observed for blood pressure, lipids, glucose, insulin or CRP. These findings indicate that Australians are capable of adhering to a Mediterranean diet with 2–3 weekly serves of fresh, lean pork. Larger intervention studies are now required to demonstrate clinical efficacy of the diet in populations with elevated blood pressure.

In lifecourse studies that encompass the adolescent period, the assessment of pubertal status is important, but can be challenging. We aimed to identify current methods for pubertal assessment and assess their appropriateness for population-based research by combining a review of the literature with the views of experts in the field. We searched bibliographic databases, extracted data and assessed study quality to inform a workshop with 21 experts. Acceptability of different approaches was explored with a panel of ten adolescents. We screened 11,935 abstracts, assessed 157 articles and summarised results from 38 articles. Combining these with the opinions of experts, self-assessment was found to be a practical method for use in studies where agreement with the gold standard of clinical assessment by physical examination to within one Tanner stage was acceptable. Serial measures of height and foot size accurately indicated timing of the pubertal growth spurt and age at peak height velocity, and were seen as feasible within longitudinal studies. Hormonal and radiological methods did not offer a practical means of assessing pubertal status. Assessment of voice maturation was promising, but needed validation. Young people thought that self-assessment, foot size and voice assessments were acceptable, and preferred an assessor of the same sex for clinical assessment. This review thus informs researchers working in lifecourse and adolescent health, and identifies future directions in order to improve validity of the methods.

Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of −1.11 (95% credible interval −1.62 to −0.60) for face-to-face CBT, −1.06 (−2.05 to −0.08) for hybrid CBT, and −0.59 (−1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.

A power MOSFET-based push–pull configuration nanosecond-pulse generator has been designed, constructed, and characterized to permeabilize cells for biological and medical applications. The generator can deliver pulses with durations ranging from 80 ns up to 1 µs and pulse amplitudes up to 1.4 kV. The unit has been tested for in vitro experiments on a medulloblastoma cell line. Following the exposure of cells to 100, 200, and 300 ns electric field pulses, permeabilization tests were carried out, and viability tests were conducted to verify the performance of the generator. The maximum temperature rise of the biological load was also calculated based on Joule heating energy conservation and experimental validation. Our results indicate that the developed device has good capabilities to achieve well-controlled electro-manipulation in vitro.

Experiments were initiated to characterize a waterhemp population (CHR) discovered in a central Illinois corn field after it was not controlled by the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor topramezone. Field experiments conducted during 2014–2015 indicated that acetolactate synthase (ALS)-, protoporphyrinogen oxidase (PPO)-, photosystem II (PSII)-, and HPPD-inhibiting herbicides and the synthetic auxin 2,4-D did not control the CHR population. Laboratory experiments confirmed target site–based resistance mechanisms to ALS- and PPO-inhibiting herbicides. Herbicide doses required to reduce dry biomass 50% (GR50) were determined in greenhouse dose–response experiments, and indicated 16-fold resistance to the HPPD inhibitor mesotrione, 9.5-fold resistance to the synthetic auxin 2,4-D, and 252-fold resistance to the PSII inhibitor atrazine. Complementary results from field, laboratory, and greenhouse investigations indicate that the CHR population has evolved resistance to herbicides from five sites of action (SOAs): ALS-, PPO-, PSII-, and HPPD-inhibiting herbicides and 2,4-D. Herbicide use history for the field in which CHR was discovered indicates no previous use of 2,4-D.

The second order nonlinear optical (NLO) properties of two different ionic selfassembled multilayer (ISAM) films combined with Ag nanoparticles have been investigated. The plasmon resonances in the Ag particles concentrate the incident light, markedly increasing in the NLO efficiencies of the films. We find that the efficiency enhancement is significantly larger in conventional ISAM films compared to films made using a hybrid covalent ISAM technique (HCISAM), even though the intrinsic bulk second order non-linear susceptibility (χ (2)) is much larger for HCISAM films. We attribute this to the interfaces in HCISAM films being much easier to disrupt by external perturbations such as the metal deposition by which the nanoparticles are fabricated. We conclude that because the plasmon decay length is very short, the plasmonic enhancement of NLO effects primarily occurs at and near the film-particle interface. To discern the importance of the interfaces, we surrounded thin ISAM and HCISAM films with NLOinactive buffer layers, which confirmed this hypothesis, particularly in the case of HCISAM films.

This study examined the interplay between a polygenic composite and cortisol activity as moderators of the mediational pathway among family adversity, youth negative emotional reactivity to family conflict, and their psychological problems. The longitudinal design contained three annual measurement occasions with 279 adolescents (Mean age = 13.0 years) and their parents. Latent difference score analyses indicated that observational ratings of adversity in interparental and parent–child interactions at Wave 1 predicted increases in a multimethod, multi-informant assessment of youth negative emotional reactivity to family conflict from Waves 1 to 2. Changes in youth negative emotional reactivity, in turn, predicted increases in a multi-informant (i.e., parents, adolescent, and teacher) assessment of psychological problems from Waves 1 to 3. Consistent with differential susceptibility theory, the association between family adversity and negative emotional reactivity was stronger for adolescents who carried more sensitivity alleles in a polygenic composite consisting of 5-HTTLPR, DRD4 VNTR, and BDNF polymorphisms. Analyses of adolescent cortisol in the period surrounding a family disagreement task at Wave 1 revealed that overall cortisol output, rather than cortisol reactivity, served as an endophenotype of the polygenic composite. Overall cortisol output was specifically associated with polygenic plasticity and moderated the association between family adversity and youth negative emotional reactivity in the same for better or for worse manner as the genetic composite. Finally, moderator-mediated-moderation analyses indicated that the moderating role of the polygenic plasticity composite was mediated by the moderating role of adolescent cortisol output in the association between family adversity and their emotional reactivity.

We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.

Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term “antibiotic never events” to globally recognize and define the most inappropriate antibiotic use.

The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.

Diagnosing delirium superimposed on dementia (DSD) remains challenging because of a lack of specific tools, though motor dysfunction in delirium has been relatively under-explored. This study aimed to use dysfunction in balance and mobility (with the Hierarchical Assessment of Balance And Mobility: HABAM) to identify DSD. This is a cross-sectional multicenter study, recruiting consecutive patients ≥70 years admitted to five acute or rehabilitation hospitals in Ireland, Italy, Portugal, and Switzerland. Delirium was diagnosed using DSM-5 criteria; dementia was determined by the Mini-Mental State Examination and the Questionnaire of Cognitive Decline in the Elderly. HABAM score was recorded at admission. Out of 114 patients (mean age ± SD = 82 ± 7; 54% female), dementia alone was present in 24.6% (n = 28), delirium alone in 18.4% (n = 21) and DSD in 27.2% (n = 31). Patients with DSD had a mean HABAM score 7 points greater than those with dementia alone (19.8 ± 8.7 vs 12.5 ± 9.5; p < 0.001); 70% of participants with DSD were correctly identified using the HABAM at a cut off of 22 (sensitivity 61%, specificity 79%, AUC = 0.76). Individuals with delirium have worse motor function than those without delirium, even in the context of comorbid dementia. Measuring motor function using the HABAM in older people at admission may help to diagnose DSD.