To send 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 sending content to .
To send content items to your Kindle, first ensure email@example.com
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 sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent 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.
Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children.
Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577).
ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score.
Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.
Ocean warming and acidification are expected to influence the biology of the ecologically and economically important red king crab, Paralithodes camtschaticus. We investigated transcriptome responses of adult, larval and juvenile red king crab to assess sensitivity to reduced pH and elevated temperature. In adults, gill tissue (but not heart or cuticle) responded to reduced pH by differentially regulating many genes involved in metabolic, membrane and cuticular processes, but not ionic or acid/base regulation. In larval crabs, we found little evidence for a strong transcriptomic response to pH, but did observe large differences in the transcriptomes of newly hatched and one-week old larvae. In juvenile crabs, we found that there was a strong transcriptomic response to temperature across all pH conditions, but that only extreme low pH caused transcriptomic shifts. Most of the genes in juveniles that were differentially expressed were for cuticular and calcification processes. While inferences regarding the specific biological responses associated with changes in gene expression are likely to change as resources for red king crab genomics enabled studies continue to improve (i.e. better assemblies and annotation), our inferences about general sensitivities to temperature and pH across the life stages of red king crab are robust and unlikely to shift. Overall, our data suggest that red king crab are more sensitive to warming than acidification, and that responses to acidification at the transcriptomic level occur at different levels of pH across life stages, with juveniles being less pH sensitive than adults.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.
Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.
Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.
The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.
Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy.
Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions.
One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit.
If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.
Decades of research have highlighted the significance of parenting in children's development, yet few studies have focused specifically on the development of parental monitoring strategies in diverse families living in at-risk neighborhoods. The current study investigated the development of active (i.e., parental discussions and curfew rules) and passive (i.e., child communication with parents) parental monitoring strategies across different developmental periods (middle childhood and adolescence; Grades 4–5 and 7–11) as well as individual (child, parent), family, and contextual antecedents (measured in kindergarten) of this parenting behavior. Using an ecological approach, this study evaluated longitudinal data from 753 participants in the Fast Track Project, a multisite study directed at the development and prevention of conduct problems in at-risk children. Latent trajectory modeling results identified little to no mean growth in these monitoring strategies over time, suggesting that families living in at-risk environments may engage in consistent levels of monitoring strategies to ensure children's safety and well-being. Findings also identified several kindergarten antecedents of the growth factors of these parental monitoring strategies including (a) early child conduct problems; (b) parental warmth/involvement, satisfaction, and efficacy; and (c) parent–child relationship quality. These predictive effects largely highlighted the important role of early parenting behaviors on later levels of and growth in parental monitoring strategies. These findings have important implications for potential prevention and intervention targets to promote the development of parental monitoring strategies among families living in more at-risk contexts.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos.
Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders.
In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02).
It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.
The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply.
To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid.
A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study.
Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes.
The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.
Replicate radiocarbon (14C) measurements of organic and inorganic control samples, with known Fraction Modern values in the range Fm = 0–1.5 and mass range 6 μg–2 mg carbon, are used to determine both the mass and radiocarbon content of the blank carbon introduced during sample processing and measurement in our laboratory. These data are used to model, separately for organic and inorganic samples, the blank contribution and subsequently “blank correct” measured unknowns in the mass range 25–100 μg. Data, formulas, and an assessment of the precision and accuracy of the blank correction are presented.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
To determine the association between excess body fat, assessed by skinfold thickness, and the incidence of type 2 diabetes mellitus (T2DM) and hypertension (HT).
Data from the ongoing PERU MIGRANT Study were analysed. The outcomes were T2DM and HT, and the exposure was skinfold thickness measured in bicipital, tricipital, subscapular and suprailiac areas. The Durnin–Womersley formula and SIRI equation were used for body fat percentage estimation. Risk ratios and population attributable fractions (PAF) were calculated using Poisson regression.
Rural (Ayacucho) and urban shantytown district (San Juan de Miraflores, Lima) in Peru.
Adults (n 988) aged ≥30 years (rural, rural-to-urban migrants, urban) completed the baseline study. A total of 785 and 690 were included in T2DM and HT incidence analysis, respectively.
At baseline, age mean was 48·0 (sd 12·0) years and 47 % were males. For T2DM, in 7·6 (sd 1·3) years, sixty-one new cases were identified, overall incidence of 1·0 (95 % CI 0·8, 1·3) per 100 person-years. Bicipital and subscapular skinfolds were associated with 2·8-fold and 6·4-fold risk of developing T2DM. On the other hand, in 6·5 (sd 2·5) years, overall incidence of HT was 2·6 (95 % CI 2·2, 3·1) per 100 person-years. Subscapular and overall fat obesity were associated with 2·4- and 2·9-fold risk for developing HT. The PAF for subscapular skinfold was 73·6 and 39·2 % for T2DM and HT, respectively.
We found a strong association between subscapular skinfold thickness and developing T2DM and HT. Skinfold assessment can be a laboratory-free strategy to identify high-risk HT and T2DM cases.
Tribology—the study of contacting, sliding surfaces—seeks to explain the fundamental mechanisms underlying friction, adhesion, lubrication, and wear, and to apply this knowledge to technologies ranging from transportation and manufacturing to biomedicine and energy. Investigating the contact and sliding of materials is complicated by the fact that the interface is buried from view, inaccessible to conventional experimental tools. In situ investigations are thus critical in visualizing and identifying the underlying physical processes. This article presents key recent advances in the understanding of tribological phenomena made possible by in situ experiments at the nanoscale. Specifically, progress in three key areas is highlighted: (1) direct observation of physical processes in the sliding contact; (2) quantitative analysis of the synergistic action of sliding and chemical reactions (known as tribochemistry) that drives material removal; and (3) understanding the surface and subsurface deformations occurring during sliding of metals. The article also outlines emerging areas where in situ nanoscale investigations can answer critical tribological questions in the future.