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In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.
To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).
In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.
Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
In 2017, dicamba-resistant (DR) soybean was commercially available to farmers in the United States. In August and September of 2017, a survey of 312 farmers from 60 Nebraska soybean-producing counties was conducted during extension field days or online. The objective of this survey was to understand farmers’ adoption and perceptions regarding DR soybean technology in Nebraska. The survey contained 16 questions and was divided in three parts: (1) demographics, (2) dicamba application in DR soybean, and (3) dicamba off-target injury to sensitive soybean cultivars. According to the results, 20% of soybean hectares represented by the survey were planted to DR soybean in 2017, and this number would probably double in 2018. Sixty-five percent of survey respondents own a sprayer and apply their own herbicide programs. More than 90% of respondents who adopted DR soybean technology reported significant improvement in weed control. Nearly 60% of respondents used dicamba alone or glyphosate plus dicamba for POST weed control in DR soybean; the remaining 40% added an additional herbicide with an alternative site of action (SOA) to the POST application. All survey respondents used one of the approved dicamba formulations for application in DR soybean. Survey results indicated that late POST dicamba applications (after late June) were more likely to result in injury to non-DR soybean compared to early POST applications (e.g., May and early June) in 2017. According to respondents, off-target dicamba movement resulted both from applications in DR soybean and dicamba-based herbicides applied in corn. Although 51% of respondents noted dicamba injury on non-DR soybean, 7% of those who noted injury filed an official complaint with the Nebraska Department of Agriculture. Although DR soybean technology allowed farmers to achieve better weed control during 2017 than previous growing seasons, it is apparent that off-target movement and resistance management must be addressed to maintain the viability and effectiveness of the technology in the future.
Understanding the underlying mechanisms of recovery from insomnia is an important goal for improving existing treatments. In a randomised controlled trial, 57 participants with insomnia disorder were given either cognitive therapy (CT) or mindfulness-based therapy (MBT) following 4 sessions of CBT. Each participant was assessed on process measures related to CT and MBT. MBT resulted in improvement on mindfulness process measures and the size of the improvement was significantly greater than achieved in the CT condition. Interestingly, CT and MBT both resulted in significant improvement on the cognitive process measures. Treatment outcome on the primary outcome measure (Insomnia Severity Index) was not predicted by type of treatment but was predicted by posttreatment scores on the cognitive process measures. The results suggest that changes in cognitive processes are especially important in treating insomnia, and that there are different therapeutic modalities through which this can be achieved.
A few comments first on education in schools - this is a special worry here in the UK, where our international rankings are disappointing. An appreciation of science is vital not just for tomorrow's scientist and engineers, but for everyone who will live and work in a world even more underpinned by technology - and even more vulnerable to its failures and misapplications - than the present one. Even more important, the option of higher education in science and technology should not be foreclosed to them. There is widespread concern particularly about the 16-18 age group. Many of us put strong emphasis on broadening the curriculum for this group, which currently enforces unduly early specialisation here in England. Young people opting for humanities should not drop all science when they are 16.
Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.
Dementia is a neurodegenerative disorder with global impact, with the largest proportion of cases occurring in low- and middle-income countries. It is estimated that there are 46.8 million cases globally with approximately 10 million new cases each year or a new case occurring every 3 sec (Prince et al., 2015). For comparison there are 36.7 million HIV cases with an estimated 2 million new cases each year (WHO, 2017). The rise in dementia prevalence is largely due to population ageing, with the oldest being at highest risk. To date there are no diseases modifying medications for Alzheimer's disease or the other causes of dementia. Academics and research groups are increasingly focused on prevention or delay of dementia (Brayne and Miller, 2017) and a number of organizations now prioritize dementia, indicating a strong and coherent international effort to address this problem. Examples include the World Health Organisation (WHO), which has established a Global Dementia Observatory; the World Dementia Council; the Organisation for Economic Co-operation and Development (OECD); the U.S. National Alzheimer's Project Act (NAPA); and the Global Council on Brain Health.
Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.
About 107 L⊙ of luminosity, mainly in ionizing flux and infrared radiation, emerges from the central pc3 of our Galaxy. This exceeds the luminosity from the corresponding region of most nearby galaxies, though it is surpassed by M82 and NGC 253 (Reike and Lebofsky 1982), but perhaps involves nothing more exotic than a starburst 106 − 107 years ago. But the manifestations of activity at the Galactic Centre that are unambiguously non-thermal in character are at a much lower level: the γ-ray annihilation line (~ 1038 erg s−1) and the compact radio source (~ 1034 erg s−1). I shall comment briefly on these two phenomena, and also suggest an interpretation of the remarkable pseudo-spiral structures revealed by the NeII infrared and the radio-continuum maps. These phenomena relate to the old question (cf. Lynden-Bell and Rees 1971) of whether our Galaxy has ever experienced a more violent phase, leaving a massive collapsed remnant.
If primordial fluctuations were isothermal their amplitude at recombination would be non-linear on scales Mo ≃ 106÷9 M⊙. Since the Jeans mass after recombination is MJo ≃ 8 × 105 Ω−1/2 M⊙ the clouds of mass Mo would be able to form the first generation of compact objects, the so-called Population III. These clouds would acquire angular momentum via tidal interactions with their neighbours. The importance of rotation can be conveniently characterised by the spin parameter λ = Vrotation/Vfree-fall and tidal interactions lead to a spin λo = 0.07 ± 0.03. As the cloud collapses λ increases as r−1/2. Any fragment forming in a rotating cloud would have the same spin λ as the whole cloud. It could therefore collapse only by ≃ λo2 in radius before centrifugal forces intervened, thus leaving a large geometrical cross-section for coalescence to be important. At radii r ≲ λo8/5 (Mo/MJo)2/15 ro the coalescence time is shorter than the free-fall time and no fragmentation is possible below this radius. In the primordial clouds two major factors prevent fragmentation at larger radii. First, the background radiation is still ‘hot’ and the trapping of it would prevent fragmentation until the whole cloud has collapsed to a radius 10−2 x−2/3 ro. Here x = 10−2(M/107 M⊙)1/3 is the ionization fraction given by the balance between gravitational contraction and recombination cooling. Furthermore, any small density fluctuation would lead to fragmentation only after the paternal cloud had collapsed by a factor (δ/5)2/3 in radius. For these reasons fragmentation is unlikely until centrifugal forces halt the collapse and a disk forms. The disk will be initially at T ≃ 104K but after a small fraction of H2 forms it will cool to T3 ≃ T/103K ≃ 1 and the final fragments mass could be as low as ≃ 0.2(λo/0.07)4 T32(MJo/Mo)1/3 M⊙.
The observed superluminal components have (deprojected) lengths of ~ 1020 cm, and imply relativistic bulk motions on these scales. There are, however, persuasive reasons for attributing the primary energy production to scales 1014–1015 cm. Moreover, the initial bifurcation and collimation must also be imposed on these small scales if the long-term stability of the jet axis in extended sources is due to the gyroscopic effect of a spinning black hole (Rees 1978). The issues I shall address in this talk are: how the jet gets from ~ 1015cm to ~ 1019 cm; and what VLBI data can tell us about the properties of galactic nuclei on scales below ~ 1019 cm — scales where optical and X-ray studies provide some evidence, but where there is no short-term hope of achieving spatial resolution.
There still seem to be three serious contenders for the dark matter in galactic halos and groups of galaxies: (i) very low mass stars, (ii) black hole remnants of very massive stars or (iii) some species of particle (e.g. axions, photinos, etc.) surviving from the big bang. There are genuine prospects of detecting individual objects in all three of these categories, and thereby narrowing down the present range of options. If the Universe has the critical density (Ω = 1), rather than the lower value (Ω = 0.1–0.2) inferred from dynamical evidence, then the galaxies must be more clustered than the overall distribution even on scales 10–20 Mpc. “Biased” galaxy formation could account for this.
The clustering properties of galaxies are incompatible with a cosmological model with Ω = 1 unless the formation process for bright galaxies is ‘biased’ in the sense that their resultant distribution exaggerates the amplitude of large-scale inhomogeneities in the overall mass distribution. The mechanisms for such biasing are intimately connected with the nature of the dark matter. Various possibilities are summarised here.
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.