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Background Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. Methods Cerebrospinal fluid was collected from children, Streptococcus pneumoniae was the predominant pathogen responsible for pediatric bacterial meningitis during longitudinal sentinel surveillance within Togo, from 2010 to 2016. However, pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction; from 59 cases prevaccine introduction to 7 cases postvaccine introduction.

At the same time, the contributors of this volume take up the theme of how particular ideas such as political wisdom and political leadership as well as the nature of political science itself have been addressed in the history of Western political philosophy—that is, in what ways the elements that constitute statesmanship have over the centuries undergone several transformations and ramifications to fit within certain contexts and historical developments. Hence, the volume neither ...

Summary Background Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. Methods In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. Results When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5–99.8) and specificity of 94% (95% CI: 89.3–96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9–100) sensitivity and 99% (95% CI: 98.2–100) specificity compared to 91.1% (95% CI: 86.1–96) sensitivity and 100% (95% CI: 98.2–100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1–100) but the lowest specificity 96% (95% CI: 92.6–98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Conclusion Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics.

SETTING Greater Banjul Area, The Gambia. OBJECTIVE To conduct a pragmatic evaluation of the Xpert(®) MTB/RIF assay in the diagnosis of tuberculosis (TB) among child contacts. DESIGN In this prospective study, one induced sputum sample was obtained from TB contacts aged

In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf- and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4(+) and CD8(+) T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf- compared with Mtb-infected patients. Purified protein derivative-specific polyfunctional CD4(+) T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3(+) CD11b(+) T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtb- compared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility.

BackgroundRoutine laboratory diagnostic methods for M. Tuberculosis complex (MTBC) in induced sputum samples such as smear microscopy, GeneXpert and liquid Mycobacteria growth indicator tube (MGIT) culture are often negative due to the paucibacillary nature of childhood tuberculosis. We hypothesise that prolonged incubation beyond routine culture time could potentially improve MTBC detection in specimens.MethodsOut of over 1000 induced sputum samples collected during our childhood TB contact tracing research programme, we randomly selected 102 MTBC-negative MGIT cultures that had either been reported as contaminated (n=35) or negative (n=67) and further incubated these at 37°C for the duration of one month. Ziehl-Neelsen microscopy, MPT64 Antigen secretion and GeneXpert tests were repeated on all samples to detect MTBC. Bacterial DNA was extracted by CTAB method and genotyped using spoligotyping analysis.ResultsOf the 1160 routinely collected induced-sputum samples 12 (1%) were smear-positives; 41 (3.5%) Xpert-positives and 51 (4.4%) MGIT culture MTBC-positives. The remaining MGIT cultures were flagged as contaminated 393 (33.9%) or MTBC-negative 644 (55.5%). After prolonged incubation and retesting of the randomly selected ones, 26/102 (25.5%) were now microscopy-positive, 2/55 (3.63%) were GeneXpert-positive, 8/102 (7.8%) MPT64-Antigen-positive, and 38/102 (37.2%) had readable spoligotyping patterns. The predominant lineages were Mtb-Euro-American 16 (42.1%), Mtb-Indo-Oceanic 11 (28.9%) and M. africanum West African type-2 8 (21%).ConclusionProlonged incubation of routinely MTBC-negative induced-sputum cultures yielded positive results upon retest, highlighting the low sensitivity of routine diagnosis tools on pauci-bacillary paediatric samples. Spoligotyping was more sensitive to detect MTBC compared to GeneXpert. However, prolonged incubation will cause diagnostic delays and thus better strategies are needed to improve timely childhood TB diagnosis.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Objectives/Background Mycobacterium africanum that causes 40% of tuberculosis (TB) in West Africa grows more slowly in culture and has similar transmission capacity compared with Mycobacterium tuberculosis, but M. africanum-exposed contacts progress more slowly to active disease. The presence of lipid body (LB) containing M. tuberculosis complex (MTBC) cells in sputum samples has been associated with mycobacterial transcriptomes indicating slow or no growth and persister-like antibiotic tolerance. Slow-growing bacilli have been found to display a persister-like phenotype with the accumulation of LBs and drug tolerance. Our previous study showed that the body mass index and lung damage resolution on chest X-ray were significantly improved slower in M. africanum-infected patients posttreatment than in M. tuberculosis-infected patients; however, the reason for this remains unclear. Therefore, we hypothesized that these differences could be either due to significant differences in drug resistance between the MTBC lineages or a difference in their content of persisters, as indicated by the percentage of LP-positive bacilli in sputum. Methods Sputum isolates collected before treatment from patients with TB were subjected to drug susceptibility testing using the BD BACTEC MGIT 960 SIRE kit. The percentage of acid-fast bacilli (AFB) and LB-positive bacilli in pretreatment sputum was determined by a dual staining procedure using Auramine O and LipidTOX Red neutral lipid stain, respectively, and fluorescence microscopy imaging. Results Out of the 77 isolates tested, 9 showed resistance to at least one drug and only 2 showed multidrug (rifampicin and isoniazid) resistance among M. tuberculosis-infected patients. The percentage of AFB-positive smears was similar between the two groups (p = 0.821), whereas that of LP-positive bacilli was significantly higher (p = 0.0059) in M. africanum-infected patients’ sputa (n = 24) than in M. tuberculosis-infected patients’ sputa (n = 36). In addition, the bacillary lengths were significantly higher in M. africanum-infected patients’ sputa than in M. tuberculosis-infected patients’ sputa (p = 0.0007). A high frequency of LP-positive bacilli in pretreatment sputum was associated with a poor body mass index and lung damage on chest X-ray improvement following anti-TB treatment in both the groups (r2 = 0.022; p = 0.017). Conclusion The slow clinical recovery of M. africanum-infected patients compared with M. tuberculosis-infected patients posttreatment may be at least partially associated with the persistence of drug-tolerant “fat and lazy” bacilli.

The predictive value of a combination of clinical and radiological features with interferon-γ release assay (IGRA) for diagnosis of active tuberculosis (TB) disease among TB-exposed children is unknown.150 symptomatic HIV-negative children (aged 3 months to 14 years), prospectively recruited through active contact tracing, were included. Backward stepwise logistic regression and bootstrapping techniques were used for the development and internal validation of a clinical prediction model for active TB disease. Model discrimination and incremental value of a positive IGRA test were assessed by area under the receiver operating characteristic curve (AUC).35 (23%) children were diagnosed with active TB disease and started on treatment and 115 (77%) had other respiratory tract infections. A final parsimonious clinical model, comprising age versus 0.70; p=0.644).A clinical algorithm, including age

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages.

At the same time, the contributors of this volume take up the theme of how particular ideas such as political wisdom and political leadership as well as the nature of political science itself have been addressed in the history of Western political philosophy—that is, in what ways the elements that constitute statesmanship have over the centuries undergone several transformations and ramifications to fit within certain contexts and historical developments. Hence, the volume neither...

This chapter traces some connections between Karl Marx and British politics and culture in the nineteenth century. It outlines Marx’s engagement with Chartism, contemporary politics (including his anti-Palmerston campaign), and the International Association. It explores Marx’s attitude towards socialism in Britain, using Robert Owen as a case study. Marx’s balanced view of ‘utopian socialism’ includes a positive assessment of Owen’s critique of capitalism and his vision of future socialist society. Moreover, Marx excused certain weaknesses in Owen’s social theory as unavoidably reflecting the undeveloped historical circumstances in which his intellectual formation had occurred. In addition, Marx credits Owen with a significant role in the histories of both ‘materialism’ and the cooperative movement. The chapter concludes with brief reflections on the need for accounts of Marx’s posthumous impact on British socialism in the nineteenth century to reflect an adequate appreciation of these various connections during his lifetime.

Pollen stratigraphy of an extrazonal palsa bog in the middle taiga of the West Siberian Plain is dated by radiocarbon at five levels. Local pollen assemblage zones (LPAZ) are the basis for palaeogeographical reconstructions. Tundra-steppe plant communities with shrub birch ( Betula nana) dominated in the latest Pleistocene. Warming after 10 000 14C yr BP caused the local thawing of permafrost, forming shallow lakes. Larixand then Picea spread along river valleys and depressions. Steppe plant communities existed on the dry interfluves. Further climatic warming and drying caused Picea to retreat, and Betula forest-steppe dominated 9500–8900 yr BP. Dense Pinus sylvestris and Pinus sibirica forests then spread over the whole area, and steppe communities decreased about 8300 yr BP. The Holocene climatic optimum (6000–5000 yr BP) was characterized by warm and wet conditions and Abies was widespread. Cooling then caused retreat of Abiesforests to the south and the expansion of Pinus sibirica forests on clay soils and Pinus sylvestris forests on sandy soils. Cooling about 4300 yr BP caused the peat to freeze and the palsa to form by bulging. Peat accumulation on the Bugristoye bog stopped at this time.

Edited book with Marc Stears, co-wrote the Introduction and also sole author of one of included chapters.

Pictures that spontaneously change in appearance, such as depth or figure-ground reversals, have always been thought of as powerful tools for understaning the nature of the perceptual system. The cause of the perceptual multistability that is experienced when viewing such figures most likely lies in the brain's physical organization; an organization that imposes several constraints on the processing of visual information. Why is it that our visual system fails to lock onto one aspect of an ambiguous figure? What accounts for the spontaneous changes of interpretation? What are the neural events that underlie such changes? Are there neurons in the visual pathways the activity of which reflects the visual awareness of the stimulus? In my paper I describe some combined psychophysical and physiological experiments that were motivated by these questions. In specific, we report on experiments in which neural activity in early visual cortex and in the inferior temporal cortex of monkeys was studied, while the animals experienced binocular rivalry. Our results provide us with new evidence not only on the neural mechanisms of binocular rivalry (one example of multistable perception), but also on the neural processes underlying image segmentation and perceptual grouping.

Binocular rivalry refers to the alternating perceptions experienced when two dissimilar patterns are stereoscopically viewed. To study the neural mechanism that underlies such competitive interactions, single cells were recorded in the visual areas V1, V2, and V4, while monkeys reported the perceived orientation of rivaling sinusoidal grating patterns. A number of neurons in all areas showed alternating periods of excitation and inhibition that correlated with the perceptual dominance and suppression of the cell"s preferred orientation. The remaining population of cells were not influenced by whether or not the optimal stimulus orientation was perceptually suppressed. Response modulation during rivalry was not correlated with cell attributes such as monocularity, binocularity, or disparity tuning. These results suggest that the awareness of a visual pattern during binocular rivalry arises through interactions between neurons at different levels of visual pathways, and that the site of suppression is unlikely to correspond to a particular visual area, as often hypothesized on the basis of psychophysical observations. The cell-types of modulating neurons and their overwhelming preponderance in higher rather than in early visual areas also suggests -- together with earlier psychophysical evidence -- the possibility of a common mechanism underlying rivalry as well as other bistable percepts, such as those experienced with ambiguous figures.

When stimuli presented to the two eyes differ considerably, stable binocular fusion fails, and the subjective percept alternates between the two monocular images, a phenomenon known as binocular rivalry. The influence of attention over this perceptual switching has long been studied, and although there is evidence that attention can affect the alternation rate, its role in the overall dynamics of the rivalry process remains unclear. The present study investigated the relationship between the attention paid to the rivalry stimulus, and the dynamics of the perceptual alternations. Specifically, the temporal course of binocular rivalry was studied as the subjects performed difficult nonvisual and visual concurrent tasks, directing their attention away from the rivalry stimulus. Periods of complete perceptual dominance were compared for the attended condition, where the subjects reported perceptual changes, and the unattended condition, where one of the simultaneous tasks was performed. During both the attended and unattended conditions, phases of rivalry dominance were obtained by analyzing the subject"s optokinetic nystagmus recorded by an electrooculogram, where the polarity of the nystagmus served as an objective indicator of the perceived direction of motion. In all cases, the presence of a difficult concurrent task had little or no effect on the statistics of the alternations, as judged by two classic tests of rivalry, although the overall alternation rate showed a small but significant increase with the concurrent task. It is concluded that the statistical patterns of rivalry alternations are not governed by attentional shifts or decision-making on the part of the subject.

An 105 Meerschweinchen und 24 Kaninchen wurden zunachst die Beziehungen zwischen Dosis und Infusionsgeschwindigkeit bzw. Applikationsform des INH einerseits und dem Intervall bis zum Auftreten von Krampfen andererseits untersucht. Mogliche Ursachen dieser Latenzzeit bis zur Ausbildung von Konvulsionen werden diskutiert. Der Isoniazidgehalt nach i.v.-Injektion war am hochsten in der Niere, es folgten Leber und Lunge. Die niedrigsten Werte wurden im Hirngewebe gefunden. Intracisternale Injektionen ergaben dagegen niedrige Isoniazid-Werte in Lunge, Leber, Niere und im Serum, aber sehr hohe in Gehirn und Liquor. Bei akuten Isoniazidintoxikationen (Dosen 50 mg/kg und daruber) konnten neben allgemeinen Organveranderungen Parenchymschaden, besonders an Leber und Niere, sowie mitunter seros-toxische Hepatitiden beobachtet werden, die jedoch Verlauf und Prognose der Intoxikation nicht mitbestimmen.

Ectopic teeth in the maxilla in eight patients were localised by roentgenstereo-photogrammetry and the findings confirmed at operation. This new method is likely to be useful in dental surgery.

Compilation of CTA contributions to the proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), which took place in 2-9 July, 2013, in Rio de Janeiro, Brazil, Comment: Index of CTA conference proceedings at the ICRC2013, Rio de Janeiro (Brazil). v1: placeholder with no arXiv links yet, to be replaced once individual contributions have been all submitted. v2: final with arXiv links to all CTA contributions and full author list

In 2015, there were an estimated 10.4 million new cases of tuberculosis (TB) globally, making it one of the leading causes of death due to an infectious disease. TB is caused by members of the Mycobacterium tuberculosis complex (MTBC), with human disease resulting from infection by M. tuberculosis sensu stricto and M. africanum. Recent progress in genotyping techniques, in particular the increasing availability of whole genome sequence data, has revealed previously under appreciated levels of genetic diversity within the MTBC. Several studies have shown that this genetic diversity may translate into differences in TB transmission, clinical manifestations of disease, and host immune responses. This suggests the existence of MTBC genotype-dependent host-pathogen interactions which may influence the outcome of infection and progression of disease. In this review, we highlight the studies demonstrating differences in innate and adaptive immunological outcomes consequent on MTBC genetic diversity, and discuss how these differences in immune response might influence the development of TB vaccines, diagnostics and new therapies.

Understanding how activity in the brain leads to a subjective percept is of great interest to philosophers and neuroscientists alike. In the last years, neurophysiological experiments have approached this problem directly by measuring neural signals in animals as they experience well-defined visual percepts. Stimuli in these studies are often inherently ambiguous, and thus rely upon the subjective report, generally from trained monkeys, to provide a measure of perception. By correlating the responses of a neuron or group of neurons to this report, one can speculate on the role of individual neurons and groups of neurons in the formation and maintenance of a particular percept. However, in order to draw valid conclusions from such experiments, it is critical that the responses accurately and reliably reflect what is perceived. For this reason, a number of behavioral paradigms have been developed to control and evaluate the truthfulness of responses from behaving animals. Here we describe several approaches to optimizing the reliability of a monkey's perceptual report, and argue that their combination provides an invaluable approach in the study of subjective visual perception.

In 2015, there were an estimated 10.4 million new cases of tuberculosis (TB) globally, making it one of the leading causes of death due to an infectious disease. TB is caused by members of the Mycobacterium tuberculosis complex (MTBC), with human disease resulting from infection by M. tuberculosis sensu stricto and M. africanum. Recent progress in genotyping techniques, in particular the increasing availability of whole genome sequence data, has revealed previously under appreciated levels of genetic diversity within the MTBC. Several studies have shown that this genetic diversity may translate into differences in TB transmission, clinical manifestations of disease, and host immune responses. This suggests the existence of MTBC genotype-dependent host-pathogen interactions which may influence the outcome of infection and progression of disease. In this review, we highlight the studies demonstrating differences in innate and adaptive immunological outcomes consequent on MTBC genetic diversity, and discuss how these differences in immune response might influence the development of TB vaccines, diagnostics and new therapies.

The educational Ecodesign game SuLi (Sustainable Living) aims at transferring basic knowledge about sustainability to young people onwards in a playful way. When playing the game, the impacts of producing and consuming goods are displayed. The importance of design and production decisions is transferred and the players are confronted with the consequences of their activities in an enjoyable but reasonable manner. This knowledge about the impacts of production and consumption along a products´ life cycle will help preferring environmentally sound products that were produced under fair conditions. The integration of the target group of the game takes place at an early stage of development so that their needs and wishes can be addressed and taken into account. During the testing phase the practical use of the game is also tested and evaluated on this high school.

This chapter assesses Karl Marx: His Life and Environment (1939), a book which offers an important snapshot of Berlin’s early understanding of topics that he continued to pursue: the nature of Enlightenment ideas, their impact on Marx’s thought, and the ‘counter-attack’ they provoked (from Hegel amongst others). The contrast with Berlin’s later views is sometimes striking. Marx is not treated as an archetypal Enlightenment thinker (but as having affinities and contrasts with Enlightenment thought); the Enlightenment influence on his writings is identified as broadly positive (responsible for its realism, clarity, and empirical insight); and Marx is not criticized for rejecting the truth of value pluralism (but for denying the historical importance of ideas and human agency).

This thesis will be concerned with the question of the relationship between Owenite socialists and religion. In this thesis I will seek to untangle and disambiguate existing scholarly accounts of the relationship between Owenite socialism and religion. I will then identify how Owenites offer a re-conception of the nature of ‘religion’ as advanced through knowledge of the natural and social world, as a prospective source of solidarity which could serve as the unifying bond for communities, and as constituted by ethical conduct. I will demonstrate how these Owenites’ critique of contemporary religion was shaped by the particular conditions of the early nineteenth century, conditions which represented a problem to which they offered a solution. I then show how this solution was formed by drawing upon the traditions of natural theology, popular religion, deism, and Rational Dissent. I show how this solution was formed through a sincere and considered reflection upon the problem of religious truth. I will then show the importance of this reimagination of religion to their understanding of socialism. I demonstrate that these Owenites understood their socialism to be, in part, a project of religious reform, as rivalling the Oxford Movement and as a successor to the Reformation. Their religious interests were not an eccentric adornment to their socialism, an outdated residue yet to be shed and encumbering the development of a mature socialism, or merely instrumental to their temporal goals. Instead, their ambitions of religious reform were grounded in the philosophical preoccupations which animated their socialism. They conceived theological falsehoods as an obstacle to the triumph of socialism. And they argued that one should become a socialist, in part, precisely because it created the conditions for the popularisation of religious virtue. I conclude by identifying some implications of the argument of this thesis.

This DPhil thesis is an attempt to provide a detailed account of Marx’s theory of history which relies on a quasi-Darwinian mechanism. Building on the debate around G.A. Cohen’s Karl Marx’s Theory of History: A Defence, I argue that a selective mechanism between societies can underpin some of the key theses of historical materialism. In societal selection, the view I propose, greater development of the forces of production leads to a competitive advantage for those wielding these forces. Therefore, societies which adopt more developed forces of production ̶ or relations of production which foster the development of the forces of production -̶ will tend to be those that succeed, expand and impose their practices on others, at the expense of societies with less developed forces. This, in a manner similar to natural selection, creates a broad tendency for forces of production to develop and for relations which enable further development of these forces to emerge. This thesis will not just be and account of this process, which has already been presented in a more limited form by others; it will also attempt to detail the mechanisms underlying this process in order to tease out what a historical materialism that is based on societal selection would look like. How do forces of production translate into advantage in (generally military) competition? What is the role of imitation and human intention in the theory? How do the mechanisms of historical materialism play themselves out? What account does this theory have of class struggle and human agency? What kinds of predictions would this theory yield? Answering these questions will not only provide a more complete view of historical materialism but also address the critiques levied against this selectionist view. The goal of this thesis is to propose a detailed theory which can provide a compelling account of human history.

The thesis roughly begins with the widespread belief that modern societies face and perhaps foster a problematic lack of commitment to moral objectivity. And it roughly ends with a blueprint for a utopian deliberative institution called U-Conservatism, which is my best go at attenuating the problem but has other important functions too. Moreover, the road to U-Conservatism establishes many independently weighty claims across practical philosophy; hence, the contributions of the thesis exceed its regulative aims. I interpret the social problem in terms of credences in nihilism, argue that we should try to weaken them, and identify visible, extensive, deep moral disagreement as a leading cause. However, in light of certain features of moral belief, I recommend shifting focus to an ostensibly different region of categorical value. Narrowing disagreement there would plausibly weaken nihilistic credences regarding categorical normativity tout court. U-Conservatism – the ‘U’ standing for unforced, unpolitical, and relatively metaphysically unpresumptuous – is the best vehicle I can imagine. It would achieve and publicly present a large measure of consensus among a demographically and philosophically diverse range of people about what objects possess non-functional value. U-Conservatism’s conservative element reflects that conserving is a categorically warranted response to objects of non-functional value, which encompasses, inter alia, aesthetic and historical value. Indeed, there’s a duty to maximise the conservation of objects of non-functional value – applying to all agents – with implications for practical ethics and public policy. Beyond weakening nihilistic credences, U-Conservatism would make the duty simpler and less demanding to discharge by indicating priorities for active schemes of conservation and showing what in or about the relevant objects should be maintained or altered during conservation. Given its epistemic credentials, U-Conservatism would also promote the fairness of conservationist schemes and ensure the legitimacy of state action to deter or punish wrongful violations of the duty.

This thesis examines the philosophy of aleatory materialism formulated by Louis Althusser. Aleatory materialism is an attempt to conceptualise history as open-ended but nevertheless amenable to scientific inquiry. Althusser argued that theories of history which supposed their object had a fixed direction or telos rested on unscientific premises. Such theories were premised on circular reasoning. By taking particular patterns of events to be universal and timeless, those particular patterns could only be explained by pre-existing themselves. Consequently, such ‘origin’ categories were exempt from requiring explanation. In this way, subjective values were introduced into supposedly objective theories to provide not scientific comprehension but legitimation for particular forms of social power. A scientific theory must dispense with first movers without simultaneously making itself unable to explain change at all. The way out of this impasse, Althusser argued, was to treat all social forms as contingent, rather than necessary, outcomes. Social structures included strategies and institutions to secure their continued reproduction. They were, however, unable to totally suppress the contingency that initially gave rise to them. It is because of contingency that the laws governing human behaviour can change. Social systems can transition into new systems comprised of new sets of laws. No particular configuration is destined to arise or persist indefinitely. Althusser showed that it is possible to accept both that history is amenable to scientific inquiry and that it is an open system, with a future that is not preordained but over which the actions of agents have a genuine influence. In doing so, this theory demonstrates how teleological theories are mechanisms of justification for prevailing forms of social power, by which they portray themselves as inevitable and natural outcomes, not accurate accounts of history.

This thesis sets out an interpretation of the value of community that I call communal reciprocity. It charts the history of that ideal, analyses its use in the work of an important academic proponent, G.A. Cohen, and develops a more comprehensive account of its main features. It also discusses the implications of communal reciprocity, including whether or not it conflicts with certain freedom-based concerns and its application, including in the assessment of market economies.