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Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Small angle X-ray scattering curves have been obtained for a series of Na Wyoming Bentonite clay samples containing 10% clay by weight and NaPO3 in concentrations ranging from 0 to 100 meq/1. From the scattering data, the relative probability of spacings between parallel clay platelets was computed. For the sample containing no NaPO3, the probability distribution showed a relatively broad maximum at an interparticle spacing of about 180Å. As the concentration of NaPO3 increased, the maximum became sharper and occurred for smaller interparticle distances. At NaPO3 concentrations between 25 and 100 meq/1, the position d of the maximum was given approximately by the equation d = 21 + 18.4c-1/2, where d is in angstroms, and c is the NaPOs concentration in eq/1. The similarity of this relation to the dependence of d on the concentration of NaCl (Norrish and Rausell-Colom, 1963; Norrish, 1954) suggests that the interparticle spacing depends primarily on the sodium ion concentration and not on the concentration of the anion. The value of d appears to be independent of whether the gel was prepared by the method of Norrish and Rausell-Colom, in which a dried flake was allowed to come to equilibrium with an electrolyte solution, or whether, as in this investigation, the gel was obtained by centrifuging a dilute suspension. Since the Na ions act to reduce the double-layer repulsion between platelets, while the anions tend to be adsorbed on the platelet edges and thus reduce the edge-to-face linkages (H. van Olphen, 1962), the value of the most probable interparticle distance appears to be determined primarily by the magnitude of the double-layer repulsion, even though other properties of the clay gels, such as the rheological behavior, are governed mainly by edge-to-face attractions.
The small angle X-ray scattering data obtained in an earlier investigation of a series of Na-montmorillonite clay samples containing varying concentrations of sodium metaphosphate have been used to calculate the potential energy φ(x) of the interaction between two isolated parallel clay platelets separated by a distance x. All φ(x) curves have the form expected for Na-montmorillonite. In each curve there is a potential well for a platelet separation approximately equal to the most probable separation distance determined in the earlier study. Because the depth of the potential well is of the order of 0·01 eV for all samples, the attractive forces are relatively weak. While the calculated φ(x) functions are not highly accurate, in future investigations precautions can be taken to increase the reliability of the computed potential energy functions. This preliminary study suggests that determination of φ(x) from small angle X-ray scattering data can be a useful method for quantitative study of interparticle forces in Na-montmorillonite clays.
Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.
The long-standing assumption that aboveground plant litter inputs have a substantial influence on soil organic carbon storage (SOC) and dynamics has been challenged by a new paradigm for SOC formation and persistence. We tested the importance of plant litter chemistry on SOC storage, distribution, composition, and age by comparing two highly contrasting ecosystems: an old-growth coast redwood (Sequoia sempervirens) forest, with highly aromatic litter, and an adjacent coastal prairie, with more easily decomposed litter. We hypothesized that if plant litter chemistry was the primary driver, redwood would store more and older SOC that was less microbially processed than prairie. Total soil carbon stocks to 110 cm depth were higher in prairie (35 kg C m−2) than redwood (28 kg C m−2). Radiocarbon values indicated shorter SOC residence times in redwood than prairie throughout the profile. Higher amounts of pyrogenic carbon and a higher degree of microbial processing of SOC appear to be instrumental for soil carbon storage and persistence in prairie, while differences in fine-root carbon inputs likely contribute to younger SOC in redwood. We conclude that at these sites fire residues, root inputs, and soil properties influence soil carbon dynamics to a greater degree than the properties of aboveground litter.
Verbal fluency tasks evaluate executive functioning by requiring a person to provide words within a certain time period that start with a certain letter (phonemic fluency) or category (semantic fluency). Research shows that age impacts test takers’ phonemic and semantic verbal fluency performance. In fact, it has been suggested that phonemic verbal fluency peaks around age 30 to 39 and begins to decline at older ages. In contrast to phonemic fluency, research suggests that semantic fluency increases steadily between test takers until age 12 and begins declining around age 20. A generation is a cohort of people born within a certain period who share age and experiences. Studies show that Generation X individuals (persons born between 1965-1980) outperform Generation Y (persons born between 19811995) and Generation Z individuals (persons born between 1965-1980) on the Cordoba Naming Test. To our knowledge, no study has investigated verbal fluency performance across generational groups. We predicted that Generation X individuals would outperform individuals from Generation Y and Z on both verbal fluency measures.
Participants and Methods:
The sample of the present study consisted of 107 participants with a mean age of 27.39 (SD = 9.16). Participants were divided into three groups: Generation X (n = 19), Generation Y (n = 52), and Generation Z (n = 36). The phonemic verbal fluency task consisted of three trials and the semantic verbal fluency task consisted of one trial, one minute each. A series of ANCOVAs with Bonferroni post-hoc tests were used to evaluate verbal fluency performance between generational groups. All participants passed performance validity testing.
Results:
We found significant differences between our generational groups on both verbal fluency tasks. Post-hoc tests revealed that the Generation Y group outperformed both Generation X and Z groups on both verbal fluency tasks, p’s <.05, np2 =.11 -.16. No significant differences were found on either verbal fluency task between the Generation X and Z groups.
Conclusions:
Contrary to our hypothesis, Generation Y individuals possessed better phonemic and semantic fluency than both Generation X and Z individuals. Meanwhile, Generation X individuals did not significantly differ on any of the verbal fluency tasks compared to Generation Z individuals. Speaking multiple languages has been shown to impact verbal fluency performance. In our sample, the Generation X and Z groups consisted primarily of bilingual speakers compared to the Generation Y group. Examining generational differences is essential to understand the unique characteristics and impact of the times in which various individuals have grown up. Future research, for instance, should evaluate the influence of bilingualism across generational groups on verbal fluency performance.
The Cordoba Naming Test (CNT) is a 30-item lexical retrieval task that was developed to be administered in multiple languages. Research shows that self-identifying Mexicans residing in Mexico outperform self-identifying Mexicans that reside in the United States on the CNT. Studies indicate that the process of acculturation can influence cognitive performance. Previous studies demonstrated that Generation Z individuals (i.e., people born between 1997 and 2012) have underperformed on the CNT compared to Generation Y individuals (i.e., people born between 1981 and 1996). To our knowledge, no study has examined the influence of acculturation on Generation Z Mexicans’ CNT performance. We expected Mexicans residing in Mexico (MRM) to outperform Mexicans residing in the United States on the CNT and to report higher acculturation traits. We also predicted that acculturation would correlate with CNT performance.
Participants and Methods:
The present study sample consisted of 285 Generation Z psychologically and neurologically healthy Mexicans with a mean age of 20.32 (SD = 1.60). Participants were divided into three groups: MRM, Mexicans residing in the United States, and Mexican-Americans residing in the United States (MARUS). All participants completed the CNT and acculturation measure in Spanish. Acculturation traits were measured by the Abbreviated Multidimensional Acculturation Scale (AMAS). ANCOVAs were used to evaluate differences in the CNT and AMAS (i.e., Spanish language, Latino competency, Latino identity). Pearson’s correlation coefficient was used to evaluate the relationship between acculturation on CNT performance.
Results:
MRM outperformed the Mexicans residing in the United States and MARUS on the CNT, p = .000, np2 = .49. The MRM group reported better Spanish language abilities compared to Mexicans residing in the United States and the MARUS groups, p = .000, np2 = .10. Additionally, MRM reported better Latino competency than the MARUS group, p = .000, np2 = .08. Pearson’s correlation coefficient revealed that the MARUS’s Spanish language abilities impacted CNT performance, p = .000, r = .48. In addition, we found that Latino competency correlated with CNT performance, p’s < .05, r’s = .20-.47, in both the MRM and Mexicans residing in the United States groups. Latino identity did not significantly correlate with CNT performance in any group.
Conclusions:
Results confirmed that MRM individuals perform better on the CNT than Mexicans residing in the United States and MARUS. Additionally, we found that several acculturation traits correlated with Mexican groups’ CNT performance. Our research indicates that while all Generation Z individuals of Mexican heritage feel strongly connected to their Latino identity regardless of where they live, MARUS feel less competent in Spanish and Latinx culture than MRM and Mexicans residing in the United States. Future work should further explore these differences for better insight into how acculturative factors influence lexical retrieval performance. Future work with bigger sample sizes can additionally examine CNT performance and acculturation in Generation Z first-generation and non-first-generation Mexicans (e.g., second-generation, third-generation) residing in the United States.
The Boston Naming Test (BNT) is a 60-item confrontation naming task requiring participants to name a series of pictures. Prior research has shown that bilingual children have smaller vocabularies than monolinguals and that this effect continues into adulthood. Numerous studies have confirmed that bilingual adults name fewer pictures correctly than monolinguals on the BNT. Research also shows that self-reported workload correlates with neuropsychological test performance and that estimates of workload provide additional information regarding cognitive outcomes. Hardy and Wright (2018) conditionally validated a measure of perceived mental workload called the NASA Task Load Index (NASA-TLX; Hart & Staveland 1988) with healthy adults on a neuropsychological test (i.e., the Tower of Hanoi). Research also shows that bilinguals report higher perceived workloads on cognitive tasks compared to monolinguals. Although this work has recently extended to other tests, to our knowledge, the workload profile of the BNT remains relatively unexplored. We evaluated BNT performance and perceived workload via the NASA-TLX in monolinguals and bilinguals. We predicted that monolinguals would outperform bilinguals on the BNT, but that bilinguals would report higher workloads.
Participants and Methods:
The study sample consisted of 84 healthy participants (36 monolinguals, 48 bilinguals) with a mean age of 28.94 (SD = 10.76). Participants completed the standard 60-item BNT in English. The NASA-TLX scale was utilized to evaluate perceived workload across six subscales. The NASA-TLX was also completed in English after the completion of the BNT. ANOVAs were used to test BNT performance and perceived workload ratings between our language groups.
Results:
We found that monolinguals performed better on the BNT compared to bilinguals, p =.001, np2 = 24. However, bilinguals reported exerting more effort when completing the BNT compared to monolinguals, p =.002, np2 = .11. Additionally. bilinguals also experienced more frustration when completing the BNT compared to monolinguals, p =.034, np2 = .05.
Conclusions:
As expected, results revealed that monolinguals outperformed bilingual participants on the BNT. However, bilinguals exerted more effort on the BNT and reported the BNT to be more frustrating. A possible reason for bilinguals underperforming and reporting higher perceived workloads on the BNT may be because correct responses were only accepted in English. This may have caused bilingual speakers to exert increased effort to complete the task in a non-native language. In turn, this increased effort likely increased cognitive load and led to higher frustration levels. Further research is needed to confirm our findings and support the idea that bilingualism leads to perceiving greater effort and frustration, and to determine whether there are subgroup differences in BNT performances among bilingual individuals (e.g., English learned as a first language compared to English learned as a second language).
Individuals with overweight or obesity are at a high risk for so-called ‘atypical’ or immunometabolic depression, with associated neurovegetative symptoms including overeating, fatigue, weight gain, and a poor metabolic profile evidenced e.g. by dyslipidemia or hyperglycemia. Research has generated preliminary evidence for a low-calorie diet (LCD) in reducing depressive symptoms. The aim of the current systematic review and meta-analysis is to examine this evidence to determine whether a LCD reduces depressive symptoms in people with overweight or obesity.
Methods
Eligible studies were identified through PubMed, ISI Web of Science, and PsycINFO until August 2023. Standardized mean differences (SMDs) were derived using random-effects meta-analyses for (1) pre-post LCD comparisons of depression outcomes, and (2) LCD v. no-diet-control group comparisons of depression outcomes.
Results
A total of 25 studies were included in the pre-post meta-analysis, finding that depression scores were significantly lower following a LCD (SMD = −0.47), which was not significantly moderated by the addition of exercise or behavioral therapy as a non-diet adjunct. Meta-regressions indicated that a higher baseline BMI and greater weight reduction were associated with a greater reduction in depression scores. The intervention-control meta-analysis (n = 4) found that overweight or obese participants adhering to a LCD showed a nominally lower depression score compared with those given no intervention (SMD = −0.29).
Conclusions
There is evidence that LCDs may reduce depressive symptoms in people with overweight or obesity in the short term. Future well-controlled intervention studies, including a non-active control group, and longer-term follow-ups, are warranted in order to make more definitive conclusions.
Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.
Methods:
This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.
Results:
Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).
Conclusions:
Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.
Identifying youths most at risk to COVID-19-related mental illness is essential for the development of effective targeted interventions.
Aims
To compare trajectories of mental health throughout the pandemic in youth with and without prior mental illness and identify those most at risk of COVID-19-related mental illness.
Method
Data were collected from individuals aged 18–26 years (N = 669) from two existing cohorts: IMAGEN, a population-based cohort; and ESTRA/STRATIFY, clinical cohorts of individuals with pre-existing diagnoses of mental disorders. Repeated COVID-19 surveys and standardised mental health assessments were used to compare trajectories of mental health symptoms from before the pandemic through to the second lockdown.
Results
Mental health trajectories differed significantly between cohorts. In the population cohort, depression and eating disorder symptoms increased by 33.9% (95% CI 31.78–36.57) and 15.6% (95% CI 15.39–15.68) during the pandemic, respectively. By contrast, these remained high over time in the clinical cohort. Conversely, trajectories of alcohol misuse were similar in both cohorts, decreasing continuously (a 15.2% decrease) during the pandemic. Pre-pandemic symptom severity predicted the observed mental health trajectories in the population cohort. Surprisingly, being relatively healthy predicted increases in depression and eating disorder symptoms and in body mass index. By contrast, those initially at higher risk for depression or eating disorders reported a lasting decrease.
Conclusions
Healthier young people may be at greater risk of developing depressive or eating disorder symptoms during the COVID-19 pandemic. Targeted mental health interventions considering prior diagnostic risk may be warranted to help young people cope with the challenges of psychosocial stress and reduce the associated healthcare burden.
We compare radiocarbon (14C) ages of coexisting planktonic foraminifera species from sediment cores VM12-107 and KNR166-2-26JPC from the Equatorial Atlantic Ocean for three time periods (Holocene, Heinrich Stadial 1, last glacial maximum). We find a maximum inter-species difference of 1200 14C yr. On average, the 14C ages deviate by ∼300 yr between Globigerinoides ruber and other species. In most cases, this exceeds the analytical uncertainty range of the measurements and thus renders the choice of species for generating age models as important as sample weight. While modern stratified water-column profiles imply an increase in 14C ages with water depth, we observe an expected parallel increase of 14C ages and δ18O only at VM12-107. The mismatch between 14C ages and δ18O at KNR166-2-26JPC likely results from the effects of bioturbation and the hydrographic setting. The largest difference in 14C ages between mixed-layer versus thermocline-calcifying planktonic foraminifera are observed during Heinrich Stadial 1 despite a decrease in upper-ocean stratification at that time. This difference is likely the result of inconsistent increases in 14C reservoir ages during times of reduced overturning circulation masking the potential of 14C ages of coexisting planktonic foraminifera to reflect the density stratification of the water column.
Peer-support groups for stroke survivors are often organized and facilitated by health authorities and disability related organizations within rehabilitation programs. However, the benefits of peer-led, peer-support groups have not yet been evaluated. The purpose of this study was to explore participants’ experiences in a community-based, peer-led, peer-support group for stroke survivors.
Materials and Methods:
Semi-structured interviews were conducted and analyzed following constructivist grounded theory with 11 participants who attended a peer-led, peer-support group for people with stroke. The data were also complemented with one quantitative rating question regarding their experience attending the group.
Results:
Three themes were identified. Meeting unmet needs after stroke captured how the group was created by stroke survivors to address life in the community post-stroke. Buddies helping buddies highlighted that stroke recovery is a shared process at the group, where members help and encourage each other to contribute what they can. Creating authentic friendships revealed how people experienced social connection and developed relationships in the peer-led, peer-support group.
Conclusions:
Peer-led, peer-support groups may provide opportunities for stroke survivors to connect with like-minded people in their community to have fun while exploring their abilities.
Recent estimates suggest that 40% of dementia cases could be avoided by treating recognised cardiovascular risk factors such as hypertension, diabetes, smoking and physical inactivity. Whether diet is associated with dementia remains largely unknown. We tested if low adherence to established dietary guidelines is associated with elevated lipids and lipoproteins and with increased risk of Alzheimer's disease and non-Alzheimer's dementia – a dementia subtype with a high frequency of cardiovascular risk factors.
Methods
We used the prospective Copenhagen General Population Study including 94 184 individuals with dietary information and free of dementia at baseline. Mean age at study entry was 58 years, and 55% (N = 51 720) were women and 45% (N = 42 464) were men. Adherence to dietary guidelines was grouped into low, intermediate and high adherence based on food frequency questionnaires. Main outcomes were non-Alzheimer's dementia and Alzheimer's disease.
Results
Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and plasma triglyceride levels were higher in individuals with intermediate and low adherence to dietary guidelines compared with individuals with high adherence (all p for trends <0.001). Age and sex-adjusted hazard ratios (HRs) for non-Alzheimer's dementia v. individuals with high adherence were 1.19 (95% confidence interval 0.97–1.46) for intermediate adherence, and 1.54 (1.18–2.00) for low adherence. Corresponding HRs in multivariable-adjusted models including APOE genotype were 1.14 (0.92–1.40) and 1.35 (1.03–1.79). These relationships were not observed in individuals on lipid-lowering therapy.
Conclusions
Low adherence to national dietary guidelines is associated with an atherogenic lipid profile and with increased risk of non-Alzheimer's dementia – the subtype of dementia with a high frequency of vascular risk factors. This study suggests that implementation of dietary guidelines associated with an anti-atherogenic lipid profile could be important for prevention of non-Alzheimer's dementia.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Over the past century and a half, Americans have contested the meaning of civil rights. The term first emerged as a distinctive, salient, and meaningful category of American political discourse at the end of the Civil War during a national debate over the rights due to America’s four million newly emancipated black men, women, and children. It became a focal point for a generation of struggle over the meaning of freedom, the boundaries of racial equality, and the responsibilities of the federal government. As a category of law, it helped open the door to some of the most ambitious constitutional and legal transformations in American history, even as it served to contain the scope of those changes.