Mineral-polymer composites found in nature exhibit exceptional structural properties essential to their function, and transferring these attributes to the synthetic design of functional materials ...holds promise across various sectors. Biomimetic fabrication of nanocomposites introduces new pathways for advanced material design and explores biomineralization strategies. This study presents a novel approach for producing single platelet nanocomposites composed of CaCO3 and biomimetic peptoid (N-substituted glycines) polymers, akin to the bricks found in the brick-and-mortar structure of nacre, the inner layer of certain mollusc shells. The significant aspect of the proposed strategy is the use of organic peptoid nanosheets as the scaffolds for brick formation, along with their controlled mineralization in solution. Here, we employ the B28 peptoid nanosheet as a scaffold, which readily forms free-floating zwitterionic bilayers in aqueous solution. The peptoid nanosheets were mineralized under consistent initial conditions (σcalcite = 1.2, pH 9.00), with variations in mixing conditions and supersaturation profiles over time aimed at controlling the final product. Nanosheets were mineralized in both feedback control experiments, where supersaturation was continuously replenished by titrant addition and in batch experiments without a feedback loop. Complete coverage of the nanosheet surface by amorphous calcium carbonate was achieved under specific conditions with feedback control mineralization, whereas vaterite was the primary CaCO3 phase observed after batch experiments. Thermodynamic calculations suggest that time-dependent supersaturation profiles as well as the spatial distribution of supersaturation are effective controls for tuning the mineralization extent and product. We anticipate that the control strategies outlined in this work can serve as a foundation for the advanced and scalable fabrication of nanocomposites as building blocks for nacre-mimetic and functional materials.
Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, ...could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother-child pairs, and 6,222 father-child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.
•Self-reporting of apathy for patients with psychosis is in concordance with clinician ratings.•Patients with schizophrenia reported higher levels of apathy than other diagnostic groups.•Controlling ...for level of depression altered some results.
Negative symptoms have traditionally been assessed based on clinicians’ observations. The subjective experience of negative symptoms in people with psychosis may bring new insight. The Apathy Evaluation Scale (AES) is commonly used to study apathy in psychosis and has corresponding self-rated (AES-S) and clinician-rated (AES-C) versions. The aim of the present study was to determine the validity and reliability of the AES-S by investigating its concordance with the AES-C. Eighty-four first-episode (FEP) patients completed the shortened 12-item AES-S and AES-C at baseline (T1) and 12 months (T2). Concordance was studied by degree of correlation, comparison of mean scores, and change and difference between diagnostic groups. The Positive and Negative Symptom Scale (PANSS) was used to study convergent and discriminative properties. High concordance was found between AES-S and AES-C at both T1 and T2 regarding mean values, change from T1 to T2, and the proportion with high levels of apathy. Both versions indicated high levels of apathy in FEP, while associations with PANSS negative symptoms were weaker for AES-S than AES-C. Controlling for depression did not significantly alter results. We concluded that self-rated apathy in FEP patients is in concordance with clinician ratings, but in need of further study.
AbstractObjectivesTo develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age.DesignAnalysis of ...genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa.SettingMultiple institutions that were members of international PRACTICAL consortium.ParticipantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.Main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.ResultsIn the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10−16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score.ConclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.
Glaciers are important indicators of climate change, and recent observations worldwide document increasing rates of mountain glacier recession. Here we present approximately 200 years of change in ...mountain glacier extent in northern Troms and western Finnmark, northern Norway. This was achieved through (1) mapping and lichenometric dating of major moraine systems within a subset of the main study area (the Rotsund Valley) and (2) mapping recent (post-1980s) changes in ice extent from remotely sensed data. Lichenometric dating reveals that the Little Ice Age (LIA) maximum occurred approximately 1814 (±41 years), which is before the early twentieth-century LIA maximum proposed on the nearby Lyngen Peninsula but younger than LIA maximum limits in southern and central Norway (mid-eighteenth century). Between LIA maximum and 1989, a small sample of measured glaciers (n = 15) shrank a total of 3.9 km
2
(39 percent), and those that shrank by more than 50 percent are fronted by proglacial lakes. Between 1989 and 2018, the total area of glaciers within the study area (n = 219 in 1989) shrank by approximately 35 km
2
. Very small glaciers (<0.5 km
2
) show the highest relative rates of shrinkage, and 90 percent of mapped glaciers within the study area were less than 0.5 km
2
in 2018.
BACKGROUND
Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, ...polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT.
METHODS
We conducted a Norwegian–Swedish case–parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case–control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing.
RESULTS
Five genetic variants across the ESR2 gene encoding estrogen receptor beta (ERβ) were statistically significantly associated with the risk of TGCT. In the case–parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case–parent/case–control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case–parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined.
CONCLUSIONS
Our findings provide support for ERβ and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.
We present a record of almost six years of data (2000–2006) from an automatic weather station (AWS) in the ablation zone of Midtdalsbreen, a glacier in southern Norway. Measured incoming longwave ...radiation is used to estimate cloudiness, revealing that high cloud fractions occur almost 50% of the time in all seasons. Measured wind speeds and humidity are higher for cloudy conditions, especially in winter. Net solar radiation dominates the surface energy balance in summer, contributing on average 75% of the melt energy. The turbulent fluxes supply 35% of the melt energy while net longwave radiation and the subsurface heat flux are energy sinks of 8% and 2%, respectively. Although the melt rate is generally larger under clear skies, almost 60% of the melt occurs under cloudy skies, a consequence of the prevailing cloudy conditions. Interannual variability in the total melt is found to be equally determined by variations in the date of ice reappearance and differences in the meteorological conditions during melt. Comparing the results for Midtdalsbreen with measurements from an AWS on Morteratschgletscher, Switzerland reveals that the larger ice ablation on Morteratschgletscher primarily results from an earlier start of the melt season and larger net solar radiation. The energy balance model used in this study is found to be more sensitive to changes in the stability correction than to an order‐of‐magnitude change in the roughness length for momentum.
Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to ...demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively.
Nonadherence to oral antipsychotic drugs is a major issue in clinical psychiatry giving rise to treatment failure. Further, polypharmacy is common in the treatment of psychotic disorders due to ...insufficient treatment effect during monotherapy. As a potential circuit problem, we hypothesized that antipsychotic polypharmacy is associated with increased risk of nonadherence. To investigate this, in terms of ‘complete’ nonadherence, the rates of undetectable serum drug concentrations during prescribing of doses used in psychotic disorders were compared during antipsychotic ‘monotherapy’ vs ‘polypharmacy’ treatment using therapeutic drug monitoring (TDM) data of 24,239 patients. A complete nonadherence patient was objectively defined as the detection of at least one event of undetectable serum concentration of a prescribed antipsychotic drug. The rate of complete nonadherence patients was compared between antipsychotic monotherapy and polypharmacy by multivariate logistic regression analyses. The overall rate of complete nonadherence in the population was 6.8% (n = 1,644; 95%CI: 6.5–7.1). Compared to monotherapy patients, the rate of nonadherence increased significantly with the number of co-prescribed antipsychotic drugs. After adjusting for sex (p = 0.091) and age (p < 0.001) as covariates, the rates of nonadherence vs monotherapy were 1.69-fold (95% CI: 1.48–1.92; p < 0.001) for two, 2.60-fold (95% CI: 1.88–3.59; p < 0.001) for three, and 3.54-fold (95% CI: 1.46–8.58; p = 0.005) for four or more co-prescribed antipsychotics, respectively. The present naturalistic study shows that antipsychotic polypharmacy significantly increases the rate of complete nonadherence, which is positively correlated with increasing number of concurrently used antipsychotic drugs. Thus, the intended clinical benefit of combining oral antipsychotic drugs may probably be reduced by increased nonadherence.
PDF
