To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
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.
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.
The classes CS and DCS of context-sensitive and deterministic contextsensitive languages were defined in 2.2.18 as the languages accepted by (deterministic) linearly bounded Turing machines. We saw in Theorem 2.8.2 that CS is also the class of languages generated by a context-sensitive grammar.
It follows from the closure properties of CS and DCS (2.8.3) and the results in Section 3.4 that the classes of finitely generated groups G with (deterministic) context-sensitive word problem are closed under finite extension and finitely generated subgroups. These classes have been systematically studied by Lakin  (see also [175, 176]), who proved in particular that they are closed under free and direct products; we leave these proofs as exercises for the reader.
Lakin observed that all finitely generated linear groups are deterministic context-sensitive. In fact a stronger result is true: their word problems are soluble in logspace. The class of linear groups includes the classes of finitely generated free groups, virtually polycyclic groups and their holomorphs, and torsion-free metabelian groups.
Shapiro had previously proved  that automatic groups are deterministic context-sensitive, and we included this result as Corollary 5.2.12. Hence all finitely generated subgroups of automatic groups are deterministic contextsensitive. An example of Lakin that is not of this form is described briefly in the next section.
It is unknown whether there exist groups that are context-sensitive but not deterministic context-sensitive. Indeed it is unknown whether there exists a language of any kind in CS\DCS, although there is no reason at all to believe that these language classes should be equal.
It is not easy to produce examples of finitely presented groupsG with soluble word problem for which it can be proved that. It can be shown that, if WP(G) is soluble in linearly bounded space, then it is soluble in time for any constant, and so one way of producing examples of the type we are looking for is to use the method of Avenhaus and Madlener mentioned in Section 10.2 to construct groups in which the time complexity of WP(G) is a primitive recursive function not bounded by any exponential function.
The class of hyperbolic groups was introduced and studied in Gromov's paper . In that paper a not necessarily finitely generated group is called hyperbolic if it is hyperbolic as a metric space, in the sense that the space has a hyperbolic inner product, which we define in 6.2.1 below. The group is called word-hyperbolic if it is finitely generated and hyperbolic with respect to the word metric. Since we are only concerned with finitely generated groups in this book, we shall from now on refer to such groups simply as hyperbolic groups.
The fact that there is a large variety of apparently different conditions on a finitely generated group that turn out to be equivalent to hyperbolicity (we present a list of several such conditions in Section 6.6) is itself a strong indication of the fundamental position that these groups occupy in geometric group theory. We have already encountered two of these conditions: groups having a Dehn presentation (or algorithm) in Section 3.5, and strongly geodesically automatic groups in Section 5.8.
Gromov's paper is generally agreed to be difficult to read, but there are several accessible accounts of the basic properties of hyperbolic groups, including those by Alonso et al. , Ghys and de la Harpe , Bridson and Haefliger [39, Part II, Section Γ] and Neumann and Shapiro .
We begin by comparing various notions of hyperbolicity. The definitions that we consider here apply to an arbitrary geodesic metric space, as defined in Section 1.6, but we are mainly interested in the case when the space is the Cayley graph of a finitely generated group.
Let be a geodesic metric space. A geodesic triangle xyz in Γ consists of three points x, y, z together with geodesic paths [xy], [yz] and [zx]. We can define hyperbolicity of Γ in terms of ‘thinness’ properties of geodesic triangles.
In contrast to the previous chapters, where the languages we dealt with were languages over a symmetric generating set for a group, we will now use automata to define group elements. The basic idea, which dates back at least to Alěshin , is that certain mappings from A* to itself can be described by automata with output capabilities, so called Mealy machines.
The real starting point for a systematic study of such groups was the discovery of the first groups of intermediate growth in this class of groups by Grigorchuk  and Gupta and Sidki . These groups naturally act on homogeneous rooted trees and many of them reflect the self-similar structure of the tree (see 9.3.13), which often allows for inductive arguments.
The realisation of iterated monodromy groups of partial self-coverings of orbispaces as automata groups by Nekrashevych  has given the subject another boost. This strongly links dynamical systems of post-critically finite rational functions and their Julia sets to contracting self-similar automata groups and their limit dynamical systems; see Section 9.3.16. Their study from a more automata theoretic point of view is a more recent development; see Sections 9.4 and 9.6.
Introducing permutational transducers
Finite state transducers A finite state transducer is a finite state automaton with an output function. So besides the input alphabet A there is now also an output alphabet B whose letters will be written to an auxiliary write-only output-tape. Also, each transition must now specify a finite, possibly empty, output string over B that will be written to the output-tape when the transition is made. We shall abbreviate finite state transducer and its plural by fst.
An fst simply translates strings over A into strings over B. As such, it does not accept input words, and so there is no need for accepting states. However, it may sometimes be useful to allow accepting states in order to validate the input and/or output; see 9.1.4.
In this chapter, we consider the class of automatic groups and some related classes, including the important subclass of (word-)hyperbolic groups, which are studied in more detail in Chapter 6. In the class of automatic groups, the two requirements for a normal form specified at the beginning of Chapter 4 are met. There is a normal form for group elements with the property that the set of words in normal form constitutes a regular set, and for which an arbitrary word can be reduced to normal form in quadratic time. The most comprehensive reference on automatic groups is the six-author book , by D.B.A. Epstein and co-authors and we refer the reader there for any necessary further information and references. For an alternative, more rapid, treatment, see the account by Baumslag, Gersten, Shapiro and Short [19, Part II].
A procedure is described by Epstein, Holt and Rees , and by Holt  and Holt et al. [144, Chapter 16], that starts with a finite presentation of a group and, if successful, outputs a set of fsa that between them define an automatic structure for that group; one fsa defines the normal form and the others enable the definition (and implementation) of an algorithm that reduces any input word to normal form. The most recent implementation of the procedure forms part of Holt's KBMAG package . There is an alternative implementation by Alun Williams  which performs better on many examples,
In view of the multitude of existing descriptions, we present only a summary of this procedure here, and we concentrate on the fact that it makes heavy use of logical operations applied to regular languages, such as those described in Proposition 2.5.10, 2.10.5 and 2.10.8. It involves the use of the Knuth–Bendix completion process described in Chapter 4, but can be successful even in cases where this process fails to terminate.