We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.
To identify: 1) best practice aged care principles and practices for Aboriginal and Torres Strait Islander older peoples, and 2) actions to integrate aged care services with Aboriginal community-controlled primary health care.
Background:
There is a growing number of older Aboriginal and Torres Strait Islander peoples and an unmet demand for accessible, culturally safe aged care services. The principles and features of aged care service delivery designed to meet the unique needs of Aboriginal and Torres Strait Islander peoples have not been extensively explored and must be understood to inform aged care policy and primary health care planning into the future.
Methods:
The research was governed by leaders from across the Aboriginal community-controlled primary health care sector who identified exemplar services to explore best practice in culturally aligned aged care. In-depth case studies were undertaken with two metropolitan Aboriginal community-controlled services. We conducted semi-structured interviews and yarning circles with 46 staff members to explore key principles, ways of working, enablers and challenges for aged care service provision. A framework approach to thematic analysis was undertaken with emergent findings reviewed and refined by participating services and the governance panel to incorporate national perspectives.
Findings:
A range of principles guided Aboriginal community-controlled aged care service delivery, such as supporting Aboriginal and Torres Strait Islander identity, connection with elders and communities and respect for self-determination. Strong governance, effective leadership and partnerships, Aboriginal and Torres Strait Islander workforce and culturally safe non-Indigenous workforce were among the identified enablers of aged care. Nine implementation actions guided the integration of aged care with primary health care service delivery. Funding limitations, workforce shortages, change management processes and difficulties with navigating the aged care system were among the reported challenges. These findings contribute to an evidence base regarding accessible, integrated, culturally safe aged care services tailored to the needs of Aboriginal and Torres Strait Islander peoples.
Amorphous Mg-Fe silicates are produced from microwave-dried sol-gels and their thermal crystallisation is studied via in situ synchrotron X-ray powder diffraction. Mg-pyroxene crystallised to forsterite, enstatite and cristobalite. The inclusion of 10% Fe formed only forsterite at much higher temperature, while pure Mg-olivine crystallised at a lower temperature than Mg-pyroxene. Cristobalite is observed as a high-temperature crystallite in the pure-Mg compositions. Crystallisation activation energies are derived and discussed in relation to protoplanetary disks.
To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).
Methods
Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.
Results
Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.
Conclusion
The majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.
Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.
Methods
In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.
Results
The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction.
Conclusions
These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.
Within the growing field of publications on El Sistema and Sistema-inspired programmes around the world, a marked divide can be observed between the findings of critical academic studies and commissioned evaluations. Using evaluations of El Sistema in Venezuela and Aotearoa New Zealand as our principal case studies, we argue that this gulf can be explained at least partly by methodological problems in the way that some evaluations are carried out. We conclude that many Sistema evaluations display an alignment with advocacy rather than explorative research, and that the foundation for El Sistema's claims of social transformation is thus weak.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Novel multi-stage adaptive morphing of a hydrogel cube has been achieved by combining multi-metal ionoprinting and redox chemistry of iron. A demonstration of the two-stage deployment has been shown for (1) the selective opening and closing of the cube’s lid, where the hinge point has been ionoprinted with iron, and (2) the full unfolding and folding of the cube into its cruciform net, with remaining hinges ionoprinted with vanadium. The selective unfolding and folding is achieved by alternating the oxidation state of iron between +2 and +3. This is achieved using redox chemistry selective for iron. This approach could be applied, in principle, to more degrees of staging by adding additional redox responsive ionoprinted cations and appropriate selection of reducing agents.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
We argue that the claim that essence-based causal explanations emerge, hydra-like, from an inherence heuristic is incomplete. No plausible mechanism for the transition from concrete properties, or cues, to essences is provided. Moreover, the fundamental shotgun and storytelling mechanisms of the inherence heuristic are not clearly enough specified to distinguish them, developmentally, from associative or causal networks.
Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.
Aims
To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.
Method
A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10–30 mg/day) or aripiprazole once-monthly 50mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: clinicaltrials.gov, NCT00706654.)
Results
A total of 1118 patients were screened, and 662 responders to oral aripiprazole were randomised. Kaplan–Meier estimated impending relapse rates at week 26 were 7.12% for aripiprazole once-monthly 400mg and 7.76% for oral aripiprazole. This difference (−0.64%, 95% CI −5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to aripiprazole once-monthly 50mg (21.80%, P⩽0.001).
Conclusions
Aripiprazole once-monthly 400mg was non-inferior to oral aripiprazole, and the reduction in Kaplan–Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.
Background: Cognitive Behavioural Therapy (CBT) is not primarily conceptualized as operating via affective processes. However, there is growing recognition that emotional processing plays an important role during the course of therapy. Aims: The Emotional Processing Scale was developed as a clinical and research tool to measure emotional processing deficits and the process of emotional change during therapy. Method: Fifty-five patients receiving CBT were given measures of emotional functioning (Toronto Alexithymia Scale [TAS-20]; Emotional Processing Scale [EPS-38]) and psychological symptoms (Brief Symptom Inventory [BSI]) pre- and post-therapy. In addition, the EPS-38 was administered to a sample of 173 healthy individuals. Results: Initially, the patient group exhibited elevated emotional processing scores compared to the healthy group, but after therapy, these scores decreased and approached those of the healthy group. Conclusions: This suggests that therapy ostensibly designed to reduce psychiatric symptoms via cognitive processes may also facilitate emotional processing. The Emotional Processing Scale demonstrated sensitivity to changes in alexithymia and psychiatric symptom severity, and may provide a valid and reliable means of assessing change during therapy.