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The design and the early commissioning of the ELI-Beamlines laser facility’s 30 J, 30 fs, 10 Hz HAPLS (High-repetition-rate Advanced Petawatt Laser System) beam transport (BT) system to the P3 target chamber are described in detail. It is the world’s first and with 54 m length, the longest distance high average power petawatt (PW) BT system ever built. It connects the HAPLS pulse compressor via the injector periscope with the 4.5 m diameter P3 target chamber of the plasma physics group in hall E3. It is the largest target chamber of the facility and was connected first to the BT system. The major engineering challenges are the required high vibration stability mirror support structures, the high pointing stability optomechanics as well as the required levels for chemical and particle cleanliness of the vacuum vessels to preserve the high laser damage threshold of the dielectrically coated high-power mirrors. A first commissioning experiment at low pulse energy shows the full functionality of the BT system to P3 and the novel experimental infrastructure.
Nearly 1 in 5 children in the United States lives in a household whose income is below the official federal poverty line, and more than 40% of children live in poor or near-poor households. Research on the effects of poverty on children's development has been a focus of study for many decades and is now increasing as we accumulate more evidence about the implications of poverty. The American Academy of Pediatrics recently added “Poverty and Child Health” to its Agenda for Children to recognize what has now been established as broad and enduring effects of poverty on child development. A recent addition to the field has been the application of neuroscience-based methods. Various techniques including neuroimaging, neuroendocrinology, cognitive psychophysiology, and epigenetics are beginning to document ways in which early experiences of living in poverty affect infant brain development. We discuss whether there are truly worthwhile reasons for adding neuroscience and related biological methods to study child poverty, and how might these perspectives help guide developmentally based and targeted interventions and policies for these children and their families.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Colonialism came late to northern Guatemala. The Spanish began to establish missions in the Peten Lakes region in the early 1700s, nearly 200 years after initial contact with the Mayas. Excavations in 2011–2012 at the Mission San Bernabé revealed European goods, nonnative animal species, and burial patterns that marked a new lifestyle. Who lived at the Mission San Bernabé, and where did they come from? The Spanish resettled indigenous populations to facilitate the colonization process; however, isotopic data are inconsistent with large population movements. Instead, strontium and oxygen isotope values in the tooth enamel and bones of individuals buried at the mission suggest a mostly local population. The data suggest in-migration from Belize, a region under nominal Spanish control, but with pre-Hispanic ties to the Peten. Changes did not come from migrants crossing a border; instead, the border itself moved and brought the colonial world to the Peten Mayas.
This study aimed to assess whether increasing operative experience results in better surgical outcomes in endoscopic middle-ear surgery.
A retrospective single-institution cohort study was performed. Patients underwent endoscopic tympanoplasty between May 2013 and April 2019 performed by the senior surgeon or a trainee surgeon under direct supervision from the senior surgeon. Following data collection, statistical analysis compared success rates between early (learning curve) surgical procedures and later (experienced) tympanoplasties.
In total, 157 patients (86 male, 71 female), with a mean age of 41.6 years, were included. The patients were followed up for an average of 43.2 weeks. The overall primary closure rate was 90.0 per cent.
This study demonstrates an early learning curve for endoscopic ear surgery that improves with surgical experience. Adoption of the endoscopic technique did not impair the success rates of tympanoplasty.
Abnormal brain structure of frontal and temporal brain regions has been suggested to occur in patients with schizophrenia who have frequent auditory verbal hallucinations (AVH). However, it is unknown whether this is specific to this patient subgroup. In this study tested the hypothesis that frontotemporal gray matter volume changes would characterize patients with persistent AVH (pAVH) in contrast to healthy controls and patients without AVH. Using structural magnetic resonance imaging at 3T, we studied 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH, whereas the remaining 10 patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Using a multivariate statistical technique for structural data, i.e. 'source-based morphometry' (SBM), we investigated naturally grouping patterns of gray matter volume variation among individuals, the magnitude of their expression between-groups and the relationship between gray matter volume and AVH-specific measures. SBM identified a lower expression of medial and inferior frontal as well as bilateral temporal gray matter volume between pAVH and nAVH. This pattern did not differ between nAVH patients and controls and was associated with 'physical' AVH characteristics (such as symptom duration, location, frequency and intensity) in the pAVH patient group. These results suggest that a pattern of lower gray matter volume in medial frontal and bilateral temporal cortical regions differentiates between patients with persistent AVH and non-hallucinating patients. Moreover, the data support a specific role of this neural pattern in AVH symptom expression.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. Numerous structural magnetic resonance imaging (MRI) studies repeatedly revealed accentuated thinning of cortical mantle in schizophrenia. However, whether NSS are related to alterations of cortical thickness has so far remained mostly unexplored.
Whole brain high-resolution MRI at 3 Tesla was used to investigate cortical thickness in twenty five patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale after remission of acute symptoms and related to cortical thickness. Age, education, medication and duration of illness were considered as potential confounders.
Higher NSS scores were associated with decreased cortical thickness in multiple areas. Significant correlations were found in somatosensory and primary motor cortex, pre-motor area and temporal lobe. Our results confirm the hypothesis of significant relationship between alterations of cortical thickness and the extent of NSS in schizophrenia.
Our findings provide new insights into the association of NSS with brain morphometric alterations and an involvement of cortical thickness in schizophrenia.
Recently, John Doe, an undocumented immigrant who was detained by United States Immigration and Customs Enforcement (ICE), was admitted to a hospital off-site from a detention facility. Custodial officers accompanied Mr. Doe into the exam room and refused to leave as physicians examined him. In this analysis, we examine the ethical dilemmas this case brings to light concerning the treatment of patients in immigration detention and their rights to privacy. We analyze what US law and immigration detention standards allow regarding immigration enforcement or custodial officers’ presence in medical exams and documentation of detainee health information. We describe the ethical implications of the presence of officers in medical exam rooms, including its effects on the quality of the patient-provider relationship, patient privacy and confidentiality, and provider's ability to provide ethical care. We conclude that the presence of immigration enforcement or custodial officers during medical examination of detainees is a breach of the right to privacy of detainees who are not an obvious threat to the public. We urge ICE and the US Department of Homeland Security to clarify standards for and tighten enforcement around when officers are legally allowed to be stationed in medical exam rooms and document detainees’ information.
There is no evidence on influence of HBV/HCV co-infection on survival characteristics in population with dual disorders.
To determine the impact of HBV/HCV co-infection on the long-term survival of schizophrenic patients with co-occurring substance use disorders.
Charts of 223 subjects admitted from January 1, 2002 to May 31, 2006 were assessed. The Kaplan–Meier survival analysis was used to estimate the cumulative survival rates. The association between HBV/HCV and mortality was estimated using the Cox proportional-hazard regression models, with adjustments for potential confounders. The main outcome was all-cause mortality. Median observation time was 10.3 years.
Total all-cause 11 year, unadjusted mortality was 18.0% in population with no viral hepatitis (VH) infection (n = 185; 83.0%), 66.7% in population with HBV monoinfection (n = 3; 1.3%), 50.0% in population with HCV monoinfection (n = 28; 12.6%), and 64.3% in population with HBV/HCV co-infection (n = 7; 3.1%), P < 0.00001. In Cox regression, the adjusted hazard ratio was 4.22 (95% CI: 1.00–18.63; P < 0.05) for the HBV, 4.24 (95% CI: 2.13–8.47; P < 0.00001) for the HCV, 6.18 (95% CI: 2.01–19.01; P < 0.0015) for the HBV/HCV, all vs. no VH-infection.
The high mortality of schizophrenic dual disorders patients with HBV/HCV necessitates new approaches to secondary and tertiary prevention to reduce the burden of chronic liver disease and to improve survival. The strong adverse effect of HBV/HCV on survival should encourage clinical trials including schizophrenic dual disorders patients on whether patients benefit from treatment choices. It is essential that adequate resources and strategies are targeted to the schizophrenic dual disorders patients with HBV/HCV.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
Psychotropic prescription rates continue to increase in the United States (USA). Few studies have investigated whether social-structural factors may play a role in psychotropic medication use independent of mental illness. Food insecurity is prevalent among people living with HIV in the USA and has been associated with poor mental health. We investigated whether food insecurity was associated with psychotropic medication use independent of the symptoms of depression and anxiety among women living with HIV in the USA.
We used cross-sectional data from the Women's Interagency HIV Study (WIHS), a nationwide cohort study. Food security (FS) was the primary explanatory variable, measured using the Household Food Security Survey Module. First, we used multivariable linear regressions to test whether FS was associated with symptoms of depression (Center for Epidemiologic Studies Depression [CESD] score), generalised anxiety disorder (GAD-7 score) and mental health-related quality of life (MOS-HIV Mental Health Summary score; MHS). Next, we examined associations of FS with the use of any psychotropic medications, including antidepressants, sedatives and antipsychotics, using multivariable logistic regressions adjusting for age, race/ethnicity, income, education and alcohol and substance use. In separate models, we additionally adjusted for symptoms of depression (CESD score) and anxiety (GAD-7 score).
Of the 905 women in the sample, two-thirds were African-American. Lower FS (i.e. worse food insecurity) was associated with greater symptoms of depression and anxiety in a dose–response relationship. For the psychotropic medication outcomes, marginal and low FS were associated with 2.06 (p < 0.001; 95% confidence interval [CI] = 1.36–3.13) and 1.99 (p < 0.01; 95% CI = 1.26–3.15) times higher odds of any psychotropic medication use, respectively, before adjusting for depression and anxiety. The association of very low FS with any psychotropic medication use was not statistically significant. A similar pattern was found for antidepressant and sedative use. After additionally adjusting for CESD and GAD-7 scores, marginal FS remained associated with 1.93 (p < 0.05; 95% CI = 1.16–3.19) times higher odds of any psychotropic medication use. Very low FS, conversely, was significantly associated with lower odds of antidepressant use (adjusted odds ratio = 0.42; p < 0.05; 95% CI = 0.19–0.96).
Marginal FS was associated with higher odds of using psychotropic medications independent of depression and anxiety, while very low FS was associated with lower odds. These complex findings may indicate that people experiencing very low FS face barriers to accessing mental health services, while those experiencing marginal FS who do access services are more likely to be prescribed psychotropic medications for distress arising from social and structural factors.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
Compound-specific radiocarbon (14C) dating often requires working with small samples of < 100 µg carbon (µgC). This makes the radiocarbon dates of biomarker compounds very sensitive to biases caused by extraneous carbon of unknown composition, a procedural blank, which is introduced to the samples during the steps necessary to prepare a sample for radiocarbon analysis by accelerator mass spectrometry (i.e., isolating single compounds from a heterogeneous mixture, combustion, gas purification and graphitization). Reporting accurate radiocarbon dates thus requires a correction for the procedural blank. We present our approach to assess the fraction modern carbon (F14C) and the mass of the procedural blanks introduced during the preparation procedures of lipid biomarkers (i.e. n-alkanoic acids) and lignin phenols. We isolated differently sized aliquots (6–151 µgC) of n-alkanoic acids and lignin phenols obtained from standard materials with known F14C values. Each compound class was extracted from two standard materials (one fossil, one modern) and purified using the same procedures as for natural samples of unknown F14C. There is an inverse linear relationship between the measured F14C values of the processed aliquots and their mass, which suggests constant contamination during processing of individual samples. We use Bayesian methods to fit linear regression lines between F14C and 1/mass for the fossil and modern standards. The intersection points of these lines are used to infer F14Cblank and mblank and their associated uncertainties. We estimate 4.88 ± 0.69 μgC of procedural blank with F14C of 0.714 ± 0.077 for n-alkanoic acids, and 0.90 ± 0.23 μgC of procedural blank with F14C of 0.813 ± 0.155 for lignin phenols. These F14Cblank and mblank can be used to correct AMS results of lipid and lignin samples by isotopic mass balance. This method may serve as a standardized procedure for blank assessment in small-scale radiocarbon analysis.
Objectives: This study aimed to evaluate the influence of lower limb loss (LL) on mental workload by assessing neurocognitive measures in individuals with unilateral transtibial (TT) versus those with transfemoral (TF) LL while dual-task walking under varying cognitive demand. Methods: Electroencephalography (EEG) was recorded as participants performed a task of varying cognitive demand while being seated or walking (i.e., varying physical demand). Results: The findings revealed both groups of participants (TT LL vs. TF LL) exhibited a similar EEG theta synchrony response as either the cognitive or the physical demand increased. Also, while individuals with TT LL maintained similar performance on the cognitive task during seated and walking conditions, those with TF LL exhibited performance decrements (slower response times) on the cognitive task during the walking in comparison to the seated conditions. Furthermore, those with TF LL neither exhibited regional differences in EEG low-alpha power while walking, nor EEG high-alpha desynchrony as a function of cognitive task difficulty while walking. This lack of alpha modulation coincided with no elevation of theta/alpha ratio power as a function of cognitive task difficulty in the TF LL group. Conclusions: This work suggests that both groups share some common but also different neurocognitive features during dual-task walking. Although all participants were able to recruit neural mechanisms critical for the maintenance of cognitive-motor performance under elevated cognitive or physical demands, the observed differences indicate that walking with a prosthesis, while concurrently performing a cognitive task, imposes additional cognitive demand in individuals with more proximal levels of amputation.
To explore the use of fluorescence lifetime imaging microscopy in thyroid tissues, and to investigate how different thyroid lesions affect fluorescence lifetime.
Fluorescence lifetime measurements were taken of fresh frozen thyroid surgical specimens stained with fluorescein isothiocyanate tagged anti-thyroglobulin monoclonal antibodies.
The mean fluorescence lifetime measurements in 12 patients – 3 with multinodular goitre, 4 with follicular adenoma, 4 with papillary thyroid carcinoma and 1 with follicular carcinoma – were 3.16 ns (range, 2.66–3.52 ns), 3.75 ns (range, 2.99–4.57 ns), 2.97 ns (range, 2.57–3.21 ns) and 3.61 ns, respectively. The fluorescence lifetime of follicular adenoma patients was higher than that of papillary thyroid carcinoma patients by 26 per cent (p = 0.058). The fluorescence lifetime in the follicular carcinoma patient was similar to the follicular adenoma group, but higher than in the papillary thyroid carcinoma group by 22 per cent (p = 0.01).
Fluorescence lifetime measurements varied in different thyroid pathologies, possibly because of tissue-scale structural influences.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
In this chapter, we describe note-taking and its importance to student achievement. We include data from a new survey that reveals when students take notes and how they use them, and review the literature pertaining to whether taking notes improves student performance as well as individual differences in note-taking quantity and quality.
This chapter on the German Confederation examines the largest cornerstone of the new European security system, designed to stabilise the European centre and provide an institutional structure for the cooperation of the thirty-eight remaining German states in relation to the other powers. After addressing and commenting upon the (lack of) historiography on the Bund, the chapter squarely puts this analysis of the Confederation in the context of European collective security operations, with the Bund as one of the pillars of this new post-Napoleonic security edifice, especially tasked with securing a ‘double balance of power’. The chapter ultimately fleshes out the role of the Confederation as laid down in the Bundeskriegsverfassung: to provide security for the states of the German Confederation and at the same time be the ‘pacific state of Europe’ (Heeren).