Making use of definitive new lattice computations of the Standard Model thermodynamics during the quantum chromodynamic (QCD) phase transition, we calculate the enhancement in the mass distribution of primordial black holes (PBHs) due to the softening of the equation of state. We find that the enhancement peaks at approximately 0.7M⊙, with the formation rate increasing by at least two orders of magnitude due to the softening of the equation of state at this time, with a range of approximately 0.3M⊙ < M < 1.4M⊙ at full width half-maximum. PBH formation is increased by a smaller amount for PBHs with masses spanning a large range, 10 −3 M⊙ < MPBH < 10 3 M⊙, which includes the masses of the BHs that LIGO detected. The most significant source of uncertainty in the number of PBHs formed is now due to unknowns in the formation process, rather than from the phase transition. A near scale-invariant density power spectrum tuned to generate a population with mass and merger rate consistent with that detected by LIGO should also produce a much larger energy density of PBHs with solar mass. The existence of BHs below the Chandresekhar mass limit would be a smoking gun for a primordial origin and they could arguably constitute a significant fraction of the cold dark matter density. They also pose a challenge to inflationary model building which seek to produce the LIGO BHs without overproducing lighter PBHs. * C.Byrnes@sussex.ac.uk † m.b.hindmarsh@sussex.ac.uk ‡ S.M.Young@sussex.ac.uk

Abstract. In this paper we report the discovery of a new class of active galactic nucleus in which although the nucleus is viewed directly, no broad emission lines are present. The results are based on a survey for AGN in which a sample of about 800 quasars and emission line galaxies were monitored yearly for 25 years. Among the emission line galaxies was the expected population of Seyfert 2 galaxies with only narrow forbidden lines in emission, and no broad lines. However, from the long term monitoring programme it was clear that some 10% of these were strongly variable with strong continuum emission. It is argued that these objects can only be Seyfert 1 galaxies in which the nucleus is viewed directly, but in which broad emission lines are completely absent. We compare these observations with other cases from the literature where the broad line region is reported to be weak or variable, and investigate the possibility that the absence of the broad line component is due to reddening. We conclude that this does not account for the observations, and that in these AGN the broad line region is absent. We also tentatively identify more luminous quasars from our sample where the broad emission lines also appear to be absent. The consequences of this for AGN models are discussed, and a case is made that we are seeing AGN in a transition stage between the fuel supply from a surrounding star cluster being cut off, and the nucleus becoming dormant.

Recent research indicates that approximately 60% of children diagnosed with cancer in Britain are cured and as a result, about 1 in a 1000 of the general population will soon be survivors of childhood cancer. Unfortunately some elements of the therapies which are responsible for this remarkable success are associated with serious complications, sometimes decades after their administration. Therefore, a comprehensive knowledge of the risks and benefits of different therapies will only be obtained by monitoring the health of survivors indefinitely. With such therapeutic success, increasingly the composition of future treatment protocols will be influenced by knowledge of the risks of long term morbidity and mortality associated with past therapies. An awareness of the long term risks of complications of treatment is also important for estimating the future demand on the health services of this increasing proportion of the general population who together represent many life years of care. This chapter reviews what is known concerning the long term risks of complications of different treatments. Appropriate strategies for future clinical and epidemiological follow-up of the survivor population are discussed and the need for indefinite follow-up of the survivor population is emphasised.

A registry including information about nearly 1,600 cases of retinoblastoma diagnosed in Britain has been created at the Childhood Cancer Research Group. Cases have been classified as 'old germ cell mutation', 'new germ cell mutation' or 'sporadic non-hereditary'. For a population-based group of 918 cases diagnosed between 1962 and 1985 we have calculated the proportions of unilateral/bilateral and hereditary/non-hereditary cases. Bilateral cases represent 40% of the total number over this period; the proportion known to be hereditary is 44%, a higher proportion than has been reported elsewhere. By following up selected groups of cases, an estimate has been made of the proportions of siblings of retinoblastoma patients and offspring of survivors from retinoblastoma who are themselves affected with the disease. Where there is no previous family history, the risk for siblings of retinoblastoma patients of developing the disease is approximately 2% if the disease in the affected child is bilateral and 1% if it is unilateral, assuming that there are no other siblings; if there are unaffected siblings the risks for subsequent children are lower. Children of patients with hereditary retinoblastoma have a one in two chance of carrying the germ cell mutation and for those who are carriers the probability of developing retinoblastoma is very close to the accepted figure of 90% if the parents have bilateral retinoblastoma but probably less if they have the unilateral form. For children of patients not known to be carriers, the probability of developing retinoblastoma is estimated to be about 1%, considerably lower than the previously accepted figure of about 5%. Retinoblastoma kindreds consist mainly of bilateral cases but there is evidence that some kindreds have a high proportion of unilateral cases. The ways in which these findings may be used in conjunction with modern techniques of molecular biology for prenatal and postnatal genetic counselling are discussed.

Background COVID-19 causes significant morbidity and mortality. Despite the high prevalence of delirium and delirium-related symptoms in COVID-19 patients, data and evidence-based recommendations on the pathophysiology and management of delirium are limited. Objective We conducted a rapid review of COVID-19-related delirium literature to provide a synthesis of literature on the prevalence, pathoetiology, and management of delirium in these patients. Methods Systematic searches of Medline, Embase, PsycInfo, LitCovid, WHO-COVID-19, and Web of Science electronic databases were conducted. Grey literature was also reviewed, including preprint servers, archives, and websites of relevant organizations. Search results were limited to the English language. We included literature focused on adults with COVID-19 and delirium. Papers were excluded if they did not mention signs or symptoms of delirium. Results 229 studies described prevalence, pathoetiology, and/or management of delirium in adults with COVID-19. Delirium was rarely assessed with validated tools. Delirium affected >50% of all patients with COVID-19 admitted to the ICU. The etiology of COVID-19 delirium is likely multifactorial, with some evidence of direct brain effect. Prevention remains the cornerstone of management in these patients. To date, there is no evidence to suggest specific pharmacological strategies. Discussion Delirium is common in COVID-19 and may manifest from both indirect and direct effects on the central nervous system. Further research is required to investigate contributing mechanisms. As there is limited empirical literature on delirium management in COVID-19, management with non-pharmacological measures and judicious use of pharmacotherapy is suggested.