Milk production of cows grazing pasture supplemented with grain mixes containing canola meal or corn grain or both over the first 100 days of lactation.

Grain mixes varying in proportions of wheat grain, barley grain, canola meal, and corn grain were fed to grazing dairy cows in early lactation to determine the contribution of canola meal and corn grain to milk yield, BW, BCS, eating behavior, and blood serum metabolite concentrations. The experiment used 80 multiparous, seasonally calving Holstein-Friesian dairy cows during the first 100 d of lactation, the treatment period, and over the subsequent carryover period of 100 d, during which all cows were fed a common diet. Cows were divided into 4 cohorts (blocks) based on calving date and within each cohort, 5 cows were randomly allocated to each of the 4 treatments. Dietary treatments included disc-milled grain mixes comprising (on a DM basis) (1) a control treatment of wheat (25%) and barley (75%); (2) wheat (25%), barley (50%), and canola meal (25%); (3) wheat (25%), barley (50%), and corn (25%), and (4) wheat (25%), barley (25%), canola meal (25%), and corn (25%). Treatment diets were introduced at 19 DIM ± 4.7 d, which included a 7-d adaptation period and were applied up until 100 DIM. Each grain mix was fed at 9 kg of DM/cow per day, offered twice daily, in equal proportions in the parlor at milking times. In addition to the grain mix, all cows grazed perennial ryegrass pasture at a daily allowance of ∼35 kg of DM/cow per day (measured to ground level). Results were analyzed in terms of corn and canola presence or absence in the diet. Including canola meal in grain mixes increased grain intake and pasture intake by 0.6 and 2.1 kg of DM/cow per day, respectively, resulting in an increased milk yield of 2.6 kg/cow per day during the first 100 d of lactation. Including canola meal also increased yields of milk fat and protein, and concentrations of milk fat, as well as increasing mean BW and BCS over the 100 d. The inclusion of canola meal in the grain mixes also resulted in greater blood serum BHB and urea concentrations, compared with feeding grain mixes that did not contain canola meal. The inclusion of corn grain provided no milk production benefits and did not change BW, BCS, or any feeding behavior variables. There were no carryover effects on milk production from either canola meal or corn grain after the treatment period. In summary, the results demonstrate that the provision of canola meal in grain mixes can improve milk production and increase mean BCS. Further, there are no benefits to milk yield when a proportion of barley is substituted for corn, in a wheat and barley grain mix fed to grazing dairy cows in early lactation. However, these results are dependent on the level of inclusion and the feeding system employed.

The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Risk factors for persistent pain after breast cancer surgery: a multicentre prospective cohort study.

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.

Effect of forage type on swallowed bolus mass and a method for counting swallows in dairy cattle.

Dry matter intake (DMI) is a primary determinant of milk production in grazing dairy cows and an ability to measure the DMI of individual cows would allow herd managers to formulate supplementary rations that consider the amount of nutrients ingested from grass. The 2 related aims of this experiment were to define the mean number of swallowed boli and mass of the swallowed boli in Holstein-Friesian dairy cattle offered a variety of forages commonly fed in the dairy industry of southeastern Australia, and to evaluate 2 indirect methods for counting the number of swallows. Twelve ruminally-fistulated, lactating Holstein-Friesian cows were randomly assigned to 3 replicated 4 × 4 Latin square designs and offered 4 forages: fresh chicory (FC), fresh perennial ryegrass (RP), alfalfa hay (AH), and perennial ryegrass silage (RS). The experiment was conducted over 28 d with each of 4 periods consisting of 7 d with 3 d of measurement. Forage diets were offered to individual cows following the partial evacuation of the rumen. The first 20 min after forage was offered constituted the measurement period, during which all swallowed boli were manually captured by samplers who placed their hand through the ruminal fistula and over the cardia entrance of the rumen of each cow. Concurrently, microphones and video cameras were used for the indirect measurement of swallows. The average swallowed bolus mass overall was 17.4 g dry matter (DM) per bolus with the lowest mass observed in cows offered FC (8.9 g DM/bolus), followed by RP (14.9 g DM/bolus), compared with cows offered AH (23.6 g DM/bolus) and RS (22.3 g DM/bolus). The swallowing rate was greater in cows offered FC (78 swallows/20 min) than in cows offered RP, AH, and RS (62.3 swallows/20 min). The audio recording method showed greater concordance (Lin's concordance correlation coefficient = 0.90) with the physical capturing of the boli through the rumen, than the video recording method did (Lin's concordance correlation coefficient = 0.54). It is concluded that the mass of the swallowed boli is related to forage type and that using a microphone attached to the cow's forehead can provide an accurate measure of the number of swallows when verified against the actual number of swallows counted by manual interception of the boli at the rumen cardia.

Acoustics of thermoviscous fluids: The Kirchhoff-Helmholtz representation in generalized form.

The Kirchhoff-Helmholtz representation of linear acoustics is generalized to thermoviscous fluids, by deriving separate bounded-region equations for the acoustic, entropy, and vorticity modes in a uniform fluid at rest. For the acoustic and entropy modes we introduce modal variables in terms of pressure and entropy perturbations, and develop asymptotic approximations to the mode equations that are valid to specified orders in two thermoviscous parameters. The introduction of spatial windowing for the mode variables leads to surface source and dipole distributions as a way of representing boundary conditions for each mode. For the acoustic mode the boundary source distribution is expressible in terms of the fluid normal velocity, the normal heat flux, and the vector ω×n̂, where ω is the vorticity on the boundary and n̂ is the unit normal; only the first of these is present in the usual lossless-fluid version of the Kirchhoff-Helmholtz representation. Use of the generalized thermoviscous representation to project exterior sound fields from surface data, where the data may contain contributions from all three linear modes, is shown to be robust to cross-modal contamination. The asymptotic limitations of the thermoviscous modal equations are discussed in an appendix.

Using estimated nutrient intake from pasture to formulate supplementary concentrate mixes for grazing dairy cows.

In pasture-based dairy systems, feeding a complex concentrate mix in the parlor during milking that contains cereal grains and protein supplements has been shown to have milk production advantages over feeding straight cereal grain. This experiment had the aim of testing whether further milk production advantages could be elicited by adjusting the composition of the concentrate mix in an attempt to match the expected nutrient intake from pasture during late spring. The experiment used 96 lactating dairy cows, grazing perennial ryegrass pasture offered at a target allowance of 30 kg of dry matter/cow per day (to ground level) during late spring (mid October to November) in southeastern Australia. Cows were allocated into 3 replicates of 4 treatment groups, with 24 cows in each treatment. Each treatment group was offered 1 of 4 dietary treatments in the parlor at milking: control consisting of crushed wheat and barley grains; formulated grain mix (FGM) consisting of crushed wheat, barley, and corn grains and canola meal; designer grain mix 1 (DGM1) consisting of the same ingredients as the FGM grain mix but formulated using the CPM Dairy nutrition model to take into account the expected nutrient intake from pasture; and designer grain mix 2 (DGM2) consisting of the same ingredients as DGM1 but with canola meal replaced by urea and a fat supplement (Megalac, Volac Wilmar, Gresik, Indonesia). Concentrate mixes were offered at 8.0 kg of dry matter/cow per day, except for DGM2 cows, which were offered 7.5 kg of dry matter/cow per day. The experiment ran for a total of 28 d; after a 14-d adaptation period, nutrient intake, milk production, and body weight were measured over a 14-d measurement period. Milk yield (kg) of cows fed the FGM diet was greater than that of the control cows but was not different from that of the DGM1 and DGM2 cows. However, milk fat and protein yields (kg) were greater for cows fed the FGM diet than for all other diets. There was no difference in estimated daily pasture or total dry matter intakes between the 4 treatment groups, despite cows fed the DGM2 treatment consuming less of the concentrate mix (average 6.5 kg of dry matter/cow per day when offered 7.5 kg of dry matter/cow per day). This research has demonstrated the potential for using a nutrition model to take into account the expected nutrient intake from pasture to formulate a concentrate mix (DGM1) to achieve similar milk yields, but also highlighted the need for near real-time analyses of the pasture to be grazed so as to also capture benefits in terms of milk fat and protein yield.

A mobile telehealth program for behavioral treatment of urinary incontinence in women veterans: Development and pilot evaluation of MyHealtheBladder.

AIM: To develop and pilot test an interactive mobile telehealth program (mHealth) for behavioral treatment of women veterans with urinary incontinence (UI). METHODS: We developed an evidence-based 8-week behavioral mHealth program, MyHealtheBladder, with input from women veterans, behavioral medicine and health education experts, and clinical providers treating UI in the VA system. The program was story-based and included pelvic floor muscle exercises, bladder control strategies, fluid management, risk factor reduction, and self-monitoring. Participants were women veterans seeking outpatient treatment for UI occurring at least twice weekly. The primary efficacy estimate was the change in UI frequency, volume and impact on the quality of life as measured by the validated International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF; range: 0-21, 2.5 points for minimal clinically important difference [MCID]). RESULTS: We enrolled 29 women veterans (ages 29-77 years; mean = 54.4 ± 10.4), including 15 (52%) African-American women, 13 (45%) women with high school education, and 16 (55%) with a college degree. Twenty of 29 women (69%) completed all 8 weeks of the intervention with a 97% adherence rate to the daily sessions among completers. We found reductions in ICIQ-SF scores from a mean 12.6 ± 3.9 at baseline to 10.4 ± 4.11 at 5 weeks, to 8.7 ± 4.0 at the end of the 8-week intervention. CONCLUSIONS: Women veterans using an 8-week behavioral mHealth program for the treatment of UI had symptom improvements that exceeded the MCID for the ICIQ-SF. Our next step involves comparing the effectiveness of MyHealtheBladder to usual care in a larger clinical trial.

A patient and public involvement investigation into healthy eating and weight management advice during pregnancy.

OBJECTIVE: To conduct patient and public involvement (PPI) to gain insight into the experience of healthy eating and weight management advice during pregnancy. DESIGN: PPI in the planning and development of health interventions, aiming to ensure patient-centred care. Optimum nutrition and weight management are vital for successful pregnancy outcomes, yet many services report poor attendance and engagement. SETTING: Community venues in Liverpool and Ulster (UK). PARTICIPANTS: Two PPI representatives were involved in all aspects of the study: design, interview questions, recruitment and collection/analysis of feedback. INTERVENTION: Feedback was collected via note taking during group discussions, two in Liverpool (n = 10 & 5); two in Ulster (n = 7 & 9) and an interview (n = 1, in Ulster). MAIN OUTCOME MEASURES: Transcript data were collated and thematic analysis was applied in analysis. RESULTS: Thematic analysis identified three themes: (i) weight gain is inevitable in pregnancy; (ii) healthy eating advice is important but currently lacks consistency and depth and (iii) expectations regarding the type of knowledge/support. CONCLUSIONS: PPI provides opportunity to enhance research design and offers valuable insight towards the needs of healthcare users. Pregnant women want positive health messages, with a focus on what they can/should do, rather than what they should not do. Midwives need to consider their communication with pregnant women, to ensure that their unique relationship is maintained, especially when the topics of diet and weight management are addressed. A well-designed digital intervention could improve access to pregnancy-specific nutrition information; empowering midwives to communicate patient-centred, healthy eating messages with confidence. This has the potential to change dietary and weight management behaviour in pregnant women.

Cold-atom clock based on a diffractive optic.

Clocks based on cold atoms offer unbeatable accuracy and long-term stability, but their use in portable quantum technologies is hampered by a large physical footprint. Here, we use the compact optical layout of a grating magneto-optical trap (gMOT) for a precise frequency reference. The gMOT collects 107 87Rb atoms, which are subsequently cooled to 20 µK in optical molasses. We optically probe the microwave atomic ground-state splitting using lin⊥lin polarised coherent population trapping and a Raman-Ramsey sequence. With ballistic drop distances of only 0.5 mm, the measured short-term fractional frequency stability is 2×10-11/τ.

A direct test of the diathesis-stress model for depression.

The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.

Fibroblast-specific plasminogen activator inhibitor-1 depletion ameliorates renal interstitial fibrosis after unilateral ureteral obstruction.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) expression increases extracellular matrix deposition and contributes to interstitial fibrosis in the kidney after injury. While PAI-1 is ubiquitously expressed in the kidney, we hypothesized that interstitial fibrosis is strongly dependent on fibroblast-specific PAI-1 (fbPAI-1). METHODS: Tenascin C Cre (TNC Cre) and fbPAI-1 knockdown (KD) mice with green fluorescent protein (GFP) expressed within the TNC construct underwent unilateral ureteral obstruction and were sacrificed 10 days later. RESULTS: GFP+ cells in fbPAI-1 KD mice showed significantly reduced PAI-1 expression. Interstitial fibrosis, measured by Sirius red staining and collagen I western blot, was significantly decreased in fbPAI-1 KD compared with TNC Cre mice. There was no significant difference in transforming growth factor ß (TGF-ß) expression or its activation between the two groups. However, GFP+ cells from fbPAI-1 KD mice had lower TGF ß and connective tissue growth factor (CTGF) expression. The number of fibroblasts was decreased in fbPAI-1 KD compared with TNC Cre mice, correlating with decreased alpha smooth muscle actin (α-SMA) expression and less fibroblast cell proliferation. TNC Cre mice had decreased E-cadherin, a marker of differentiated tubular epithelium, in contrast to preserved expression in fbPAI-1 KD. F4/80-expressing cells, mostly CD11c+/F4/80+ cells, were increased while M1 macrophage markers were decreased in fbPAI-1 KD compared with TNC Cre mice. CONCLUSION: These findings indicate that fbPAI-1 depletion ameliorates interstitial fibrosis by decreasing fibroblast proliferation in the renal interstitium, with resulting decreased collagen I. This is linked to decreased M1 macrophages and preserved tubular epithelium.

Health state utility values measured using the EuroQol 5-dimensions questionnaire in adults with chronic hepatitis C: a systematic literature review and meta-analysis.

PURPOSE: Chronic hepatitis C infection and its treatment can considerably affect patients' health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire. METHODS: MEDLINE, Embase, the Cochrane Library and EconLit were searched from database inception through 31 August 2017. Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults with chronic hepatitis C infection. Study quality and risk of bias were assessed. RESULTS: Of 1480 records identified, 26 studies were included. The most commonly defined health states described different stages of chronic hepatitis C infection and specific liver-related disease states, including METAVIR score, compensated and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to patients with lower METAVIR scores. Patients that achieved sustained virologic responses tended to have higher EQ-5D scores compared to those that did not. A meta-analysis conducted on three studies confirmed that patients with decompensated cirrhosis have significantly lower HSUVs than patients with compensated cirrhosis [mean difference - 0.11 (95% CI - 0.19 to - 0.04)], implying worse HRQoL. However, there was not sufficient evidence to compare how different treatments for chronic hepatitis C infection affect EQ-5D scores. CONCLUSIONS: This study provides a summary of EQ-5D HSUVs for patients with chronic hepatitis C infection, and demonstrates that clinically important disease stages associated with treatment decisions are associated with differences in HRQoL.

Bioactive compounds sourced from Terminalia spp. in bacterial malodour prevention: an effective alternative to chemical additives.

OBJECTIVE: Recently, our group reported that extracts prepared from the Australian native plant Terminalia ferdinandiana Exell. are potent inhibitors of the growth malodorous bacteria with similar efficacy to triclosan and through these results, we highlighted a potential biological alternative to the current chemical additives. Other members of the genus Terminalia are also well documented for their antibacterial potential and tannin contents and thus were investigated as potential deodorant additives. METHODS: Solvent extractions prepared from of selected Indian, Australian and South African Terminalia spp. were screened by disc diffusion and liquid dilution assays against C. jeikeium, S. epidermidis, P. acnes and B. linens. The antibacterial activity was quantified by liquid dilution MIC assays. The extracts were screened for toxicity using Atremia franciscana nauplii and HDF cell viability bioassays. High-resolution time-of-flight (TOF) LC-MS and GC-MS headspace fingerprint analysis was used to detect tannin, flavonoid and terpenoid components in the extracts. RESULTS: Bacterial growth inhibition was observed in all Terminalia extracts with the methanolic T. chebula, T. carpenteriae and T. sericea extracts the most promising bacterial growth inhibitors, yielding MIC values as low as 200 µg mL-1 . Toxicity analyses of the extracts were favourable, and we determined that the methanolic T. chebula, T. carpenteriae and T. sericea extracts were all non-toxic. Using previously detected T. ferdinandiana antimicrobials as benchmarks, LC-MS and GC-MS fingerprint analyses revealed similar compounds in the methanolic T. chebula, T. carpenteriae and T. sericea extracts. CONCLUSION: Through these results, we propose that Terminalia spp. extracts may be useful deodorant additives to inhibit the growth of axillary and plantar malodorous bacteria, offering a biological alternative to their chemically synthesized counterparts.

OBJECTIF: notre groupe a récemment signalé que les extraits de la plante native d'Australie Terminalia ferdinandiana Exell sont de puissants inhibiteurs de croissance pour les bactéries responsables de mauvaises odeurs. Leur efficacité est comparable à celle du triclosan. Ces résultats nous ont permis de mettre en avant la possibilité d'une alternative biologique aux additifs chimiques utilisés aujourd'hui. D'autres membres du genre Terminalia, également bien connus pour leur potentiel antibactérien et leur taux de tanin, ont eux aussi été examinés comme additifs potentiels pour les déodorants. MÉTHODES: extractions par solvant préparées à partir de spécimens de Terminalia spp. d'Inde, d'Australie et d'Afrique du Sud, sélectionnés par diffusion (méthode des disques) et par des dosages de dilution liquide, contre C. Jeikeium, S. Epidermidis, P. Acnes et B. Linens. L'activité antibactérienne a été quantifiée à l'aide d'analyses de la CMI en dilution liquide. La toxicité des extraits a été recherchée à l'aide d'Atremia franciscana nauplii et de dosages biologiques de la viabilité cellulaire de fibroblastes dermiques humains (FDH). Pour détecter les composants tanniques, flavonoïdes et terpénoïdes dans les extraits, on a procédé à une analyse d'identification de l'espace de tête par LC-MS et GC-MS à temps de vol (TOF) à haute résolution. RÉSULTATS: On a observé une inhibition de la croissance bactérienne dans tous les extraits de Terminalia avec les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea, les inhibiteurs de croissance bactérienne les plus prometteurs, ayant des valeurs de CMI pouvant être aussi faibles que 200 µg/ml_ 1. Les analyses de toxicité des extraits ont donné des résultats favorables et nous avons pu établir que les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea étaient tous non toxiques. En utilisant les antimicrobiens déjà repérés T. Ferdinandiana comme des points de repère, les analyses d'identification par LC-MS et GC-MS ont révélé la présence de composés similaires dans les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea. CONCLUSION: D'après ces résultats, nous pensons que les extraits de Terminalia spp. peuvent constituer des additifs utiles pour les déodorants grâce à leur pouvoir d'inhibition de la croissance des bactéries responsables des mauvaises odeurs de pieds et d'aisselles, offrant ainsi une alternative biologique à leurs équivalents d'origine chimiosynthétique.

Genetic and Environmental Influences on Language Ability in Older Adults: Findings from the Older Australian Twins Study.

We used a sub-sample from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

This corrects the article DOI: 10.1038/mp.2017.42.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Eliciting preferences on secondary findings: the Preferences Instrument for Genomic Secondary Results.

PURPOSE: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences. METHODS: We conducted focus groups with 110 adults to understand patient perspectives on secondary genomic findings and the role that preferences should play. We then developed and refined a draft instrument and used it to elicit preferences from parents participating in a genomic sequencing study in children with intellectual disabilities. RESULTS: Patients preferred filtering of secondary genomic results to avoid information overload and to avoid learning what the future holds, among other reasons. Patients preferred to make autonomous choices about which categories of results to receive and to have their choices applied automatically before results are returned to them and their clinicians. The Preferences Instrument for Genomic Secondary Results (PIGSR) is designed to be completed by patients or research participants without assistance and to guide bioinformatic analysis of genomic raw data. Most participants wanted to receive all secondary results, but a significant minority indicated other preferences. CONCLUSIONS: Our novel instrument-PIGSR-should be useful in a wide variety of clinical and research settings.Genet Med 19 3, 337-344.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population.

Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few studies have examined the genetic overlap between cognitive ability and ASD/ADHD. The aim of this study was to examine the polygenic overlap between ASD/ADHD and cognitive ability in individuals from the general population. Polygenic risk for ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD conducted by the Psychiatric Genetics Consortium. Risk scores were created in three independent cohorts: Generation Scotland Scottish Family Health Study (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for ASD is positively correlated with general cognitive ability (beta=0.07, P=6 × 10(-7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was replicated in BATS as a positive association with full-scale intelligent quotient (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that polygenic risk for ADHD was associated with cognitive function; however, a negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was observed in the Lothian Birth Cohorts. These findings are in individuals from the general population, suggesting that the relationship between genetic risk for ASD and intelligence is partly independent of clinical state. These data suggest that common genetic variation relevant for ASD influences general cognitive ability.