The Evolution of X-ray Clusters of Galaxies

Considerable progress has been made over the last decade in the study of the evolutionary trends of the population of galaxy clusters in the Universe. In this review we focus on observations in the X-ray band. X-ray surveys with the ROSAT satellite, supplemented by follow-up studies with ASCA and Beppo-SAX, have allowed an assessment of the evolution of the space density of clusters out to z~1, and the evolution of the physical properties of the intra-cluster medium out to z~0.5. With the advent of Chandra and Newton-XMM, and their unprecedented sensitivity and angular resolution, these studies have been extended beyond redshift unity and have revealed the complexity of the thermodynamical structure of clusters. The properties of the intra-cluster gas are significantly affected by non-gravitational processes including star formation and Active Galactic Nucleus (AGN) activity. Convincing evidence has emerged for modest evolution of both the bulk of the X-ray cluster population and their thermodynamical properties since redshift unity. Such an observational scenario is consistent with hierarchical models of structure formation in a flat low density universe with Omega_m=0.3 and sigma_8=0.7-0.8 for the normalization of the power spectrum. Basic methodologies for construction of X-ray-selected cluster samples are reviewed and implications of cluster evolution for cosmological models are discussed.Comment: 40 pages, 15 figures. Full resolution figures can be downloaded from http://www.eso.org/~prosati/ARAA

Preschool Teachers’ Perspectives About the Engagement of Immigrant and Non-Immigrant Parents in Their Children’s Early Education

The present study explores the perceptions of teachers about the engagement of immigrant and non-immigrant parents in preschool. Data were drawn from a larger evaluation study of a government initiative for preschools in Germany, which was designed to foster inclusive pedagogy and parent cooperation. In these analyses, teachers’ perceptions of the engagement of immigrant parents and non-immigrant parents were rated for each parent group, on a 10-item measure, to identify how teacher ratings varied for the different parent groups. Data from 1397 preschool teachers, employed across 203 preschools, were analyzed using multilevel modeling. This statistical approach takes account of the clustered nature of the data. Teacher ratings of engagement for immigrant and non-immigrant parent groups differed between preschools. Most variability in the ratings could be ascribed to preschool characteristics. In preschools, in which staff held a shared understanding of dealing with cultural diversity and in which the director of the preschool had a multicultural mindset, teachers perceived engagement of parents more positively, especially for immigrant parents. Overall, the findings identified the importance of self-efficacy for inclusion and more positive beliefs about multiculturalism among preschool teachers. Such qualities are important for working with all parents. However, unfavorable social structures, such as those found in disadvantaged areas, may present major challenges for parent cooperation and engagement

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebocontrolled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.TW Weickert, D Weinberg, R Lenroot, SV Catts, R Wells, A Vercammen, M O, Donnell, C Galletly, D Liu, R Balzan, B Short, D Pellen, J Curtis, VJ Carr, J Kulkarni, PR Schofield and CS Weicker

Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants

BACKGROUND: Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. METHODS: Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. RESULTS: Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6–26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than hospitalization of passively detected cases. CONCLUSION: While the current immigration screening program is unlikely to result in a large change in case rates, domestic follow-up of B-notification patients, including LTBI treatment, is highly cost-effective. If as many as three percent of screened individuals have active TB, and early detection reduces the rate of hospitalization, net savings may be expected

The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants.</p> <p>Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit.</p> <p>Methods/Design</p> <p>TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling".</p> <p>Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods.</p> <p>Sample size</p> <p>At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months.</p> <p>Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited.</p> <p>Primary outcome</p> <p>Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of:</p> <p>• Bayley mental developmental scale score less than 70</p> <p>• Gross Motor Function Classification System Levels III – V</p> <p>• Bilateral cortical visual impairments</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN89547571</p

The Relativistic Jet Orientation and Host Galaxy of the Peculiar Blazar PKS 1413+135

PKS 1413+135 is one of the most peculiar blazars known. Its strange properties led to the hypothesis almost four decades ago that it is gravitationally lensed by a mass concentration associated with an intervening galaxy. It exhibits symmetric achromatic variability, a rare form of variability that has been attributed to gravitational milli-lensing. It has been classified as a BL Lac object, and is one of the rare objects in this class with a visible counterjet. BL Lac objects have jet axes aligned close to the line of sight. It has also been classified as a compact symmetric object-objects that have jet axes not aligned close to the line of sight. Intensive efforts to understand this blazar have hitherto failed to resolve even the questions of the orientation of the relativistic jet and the host galaxy. Answering these two questions is important because they challenge our understanding of jets in active galactic nuclei and the classification schemes we use to describe them. We show that the jet axis is aligned close to the line of sight and PKS 1413+135 is almost certainly not located in the apparent host galaxy, but is a background object in the redshift range 0.247 z z = 0.247 provides a natural host for the putative lens responsible for symmetric achromatic variability and is shown to be a Seyfert 2 galaxy. We also show that, as for the radio emission, a "multizone" model is needed to account for the high-energy emission

New Tests of Milli-lensing in the Blazar PKS 1413+135

Symmetric achromatic variability (SAV) is a rare form of radio variability in blazars that has been attributed to gravitational milli-lensing by a similar to 10(2)-10(5) M (circle dot) mass condensate. Four SAVs have been identified between 1980 and 2020 in the long-term radio monitoring data of the blazar PKS 1413 + 135. We show that all four can be fitted with the same, unchanging, gravitational lens model. If SAV is due to gravitational milli-lensing, PKS 1413 + 135 provides a unique system for studying active galactic nuclei with unprecedented microarcsecond resolution, as well as for studying the nature of the milli-lens itself. We discuss two possible candidates for the putative milli-lens: a giant molecular cloud hosted in the intervening edge-on spiral galaxy, and an undetected dwarf galaxy with a massive black hole. We find a significant dependence of SAV crossing time on frequency, which could indicate a fast shock moving in a slower underlying flow. We also find tentative evidence for a 989 day periodicity in the SAVs, which, if real, makes possible the prediction of future SAVs: the next three windows for possible SAVs begin in 2022 August, 2025 May, and 2028 February

Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia

<p>Abstract</p> <p>Background</p> <p>Many critical maturational processes take place in the human brain during postnatal development. In particular, the prefrontal cortex does not reach maturation until late adolescence and this stage is associated with substantial white matter volume increases. Patients with schizophrenia and other major psychiatric disorders tend to first present with overt symptoms during late adolescence/early adulthood and it has been proposed that this developmental stage represents a "window of vulnerability".</p> <p>Methods</p> <p>In this study we used whole genome microarrays to measure gene expression in post mortem prefrontal cortex tissue from human individuals ranging in age from 0 to 49 years. To identify genes specifically altered in the late adolescent period, we applied a template matching procedure. Genes were identified which showed a significant correlation to a template showing a peak of expression between ages 15 and 25.</p> <p>Results</p> <p>Approximately 2000 genes displayed an expression pattern that was significantly correlated (positively or negatively) with the template. In the majority of cases, these genes in fact reached a plateau during adolescence with only subtle changes thereafter. These include a number of genes previously associated with schizophrenia including the susceptibility gene neuregulin 1 (NRG1). Functional profiling revealed peak expression in late adolescence for genes associated with energy metabolism and protein and lipid synthesis, together with decreases for genes involved in glutamate and neuropeptide signalling and neuronal development/plasticity. Strikingly, eight myelin-related genes previously found decreased in schizophrenia brain tissue showed a peak in their expression levels in late adolescence, while the single myelin gene reported increased in patients with schizophrenia was decreased in late adolescence.</p> <p>Conclusion</p> <p>The observed changes imply that molecular mechanisms critical for adolescent brain development are disturbed in schizophrenia patients.</p

Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.