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Background Incidence estimates of Staphylococcus aureus infections rarely include the full spectrum of clinically relevant disease from both community and healthcare settings. Methods We conducted a prospective study capturing all S aureus infections in Fulton County, Georgia, during 2017. Medical records of patients with any incident infection (clinical cultures growing S aureus from any site, without prior positive culture in previous 14 days) were reviewed. Estimates of disease incidence were calculated using age-, race-, and sex-specific population denominators accounting for weighted sampling methods. Multivariable logistic regression models were used to identify risk factors for hospitalization among patients with skin and soft tissue infections (SSTIs). Results The overall incidence of clinically relevant S aureus infection was 405.7 cases per 100 000 people (standard error [SE], 5.62 [range, 400.1–411.3]). Overall incidence for those of Black race was 500.84 cases per 100 000 people (SE, 14.55), whereas White patients had overall incidence of 363.67 cases per 100 000 people (SE, 13.8). SSTIs were the most common infection (2351; 225.8 cases per 100 000 people [SE, 7.1]), and 30% required hospitalization. Among SSTIs, after adjusting for invasive disease, cellulitis, diabetes, and demographics, independent predictors of hospitalization included methicillin-resistant S aureus (adjusted odds ratio [aOR], 1.6 [95% confidence interval {CI}, 1.0–2.7]) and homelessness (aOR, 4.9 [95% CI, 1.1–22]). Conclusions The burden of clinically relevant S aureus infections is high, particularly among the Black population, and risks for hospitalization among SSTIs include isolate factors and factors related to patients' vulnerability. [ABSTRACT FROM AUTHOR]

The authors blend archaeological data with ethnographic, archival, and historical accounts to tell the story of a post-Famine stone cabin in County Cork, Ireland that was inhabited between 1860 and 1915. Research reveals the stories of the two families that once lived in the cabin and connects them to broader issues of land ownership, politics, and social dynamics. These issues came to a head in 1915, when one family was evicted from the property and the cabin was set ablaze. Artefacts found in situ speak to the complexities of everyday life and reveal localized expressions of identity and belonging. [ABSTRACT FROM AUTHOR]

This article reviews the most recent volume in the series of archival document collections on the history Australia's external affairs, Documents on Australian Foreign Policy, covering the years 1920 to 1930. It focuses upon two main themes of central importance to the Australian global presence in that decade: the organisation and purposes of the Empire-Commonwealth and the impact of the League of Nations. [ABSTRACT FROM AUTHOR]

This Special Issue of Information, Communication and Society explores what can be understood as 'digital landscapes'. The term draws our attention to the complex and overlapping contours of off- and on-line information flows, exchanges and meanings, and how these embody cultural, political and epistemic processes. The term also points to the ways in which social actors navigate the geographies of this landscape, and whether and how they have the resources to do so, indeed, whether they can create new geographies, and so new maps, in the process. This agency has therefore to be seen as highly contextual, a mix of both local and global dynamics. The papers brought together here examine the discursive, ethical, legal and infrastructural aspects of the digital landscape. In doing so, they open up for discussion on how we are best to understand, map, critique and importantly differentiate and contextualise the diverse forms of social engagement found within this landscape and its off-line instantiation. [ABSTRACT FROM AUTHOR]

This paper explores and develops the concept of 'readiness' as it relates to the adoption of innovation. In particular, the paper discusses readiness in regard to the notion of 'technology readiness' levels, widely used today by both producers and users to monitor and manage emergent innovation. The paper argues that, while useful, this notion needs to be informed by and subsumed within a broader concept of 'institutional readiness'. The latter is especially important in conceptualising how new technologies are actually adopted in organisational settings. The paper develops a model of institutional readiness that recognises the saliency of technology readiness but which embeds it within a broader socio-technical framework. This is illustrated with reference to the emerging field of regenerative medicine. [ABSTRACT FROM AUTHOR]

Pathogenic variants in BEST1 can cause autosomal dominant or autosomal recessive dystrophy, typically associated with distinct retinal phenotypes. In heterozygous cases, the disorder is commonly characterized by yellow sub-macular lesions in the early stages, known as Best vitelliform macular dystrophy (BVMD). Biallelic variants usually cause a more severe phenotype including diffuse retinal pigment epithelial irregularity and widespread generalized progressive retinopathy, known as autosomal recessive bestrophinopathy (ARB). This study describes three cases with clinical changes consistent with BVMD, however, unusually associated with autosomal recessive inheritance. Detailed ophthalmic workup included comprehensive ophthalmologic examination, multimodal retinal imaging, full-field and pattern electroretinography (ERG; PERG), and electrooculogram (EOG). Genetic analysis of probands and segregation testing and fundus examination of proband relatives was performed where possible. Three unrelated cases presented with a clinical phenotype typical for BVMD and were found to have biallelic disease-causing variants in BEST1. PERG P50 and ERG were normal in all cases. The EOG was subnormal (probands 1 and 3) or normal/borderline (proband 2). Probands 1 and 2 were homozygous for the BEST1 missense variant c.139C>T, p.Arg47Cys, while proband 3 was homozygous for a deletion, c.536_538delACA, p.Asn179del. The parents of proband 1 were phenotypically normal. Parents of proband 1 and 2 were heterozygous for the same missense variant. Individuals with biallelic variants in BEST1 can present with a phenotype indistinguishable from BVMD. The same clinical phenotype may not be evident in those harboring the same variants in the heterozygous state. This has implications for genetic counselling and prognosticationA. [ABSTRACT FROM AUTHOR]

Purpose: GPR158 is a newly characterized family C G-protein-coupled receptor, previously identified in functional screens linked with biological stress, including one for susceptibility to ocular hypertension/glaucoma induced by glucocorticoid stress hormones. In this study, we investigated GPR158 function in the visual system. Methods: Gene expression and protein immunolocalization analyses were performed in mouse and human brain and eye to identify tissues where GPR158 might function. Gene expression was perturbed in mice, and in cultures of human trabecular meshwork cells of the aqueous outflow pathway, to investigate function and mechanism. Results:GPR158 is highly expressed in the brain, and in this study, we show prominent expression specifically in the visual center of the cerebral cortex. Expression was also observed in the eye, including photoreceptors, ganglion cells, and trabecular meshwork. Protein was also localized to the outer plexiform layer of the neural retina. Gpr158 deficiency in knockout (KO) mice conferred short-term protection against the intraocular pressure increase that occurred with aging, but this was reversed over time. Most strikingly, the pressure lowering effect of the acute stress hormone, epinephrine, was negated in KO mice. In contrast, no disruption of the electroretinogram was observed. Gene overexpression in cell cultures enhanced cAMP production in response to epinephrine, suggesting a mechanism for intraocular pressure regulation. Overexpression also increased survival of cells subjected to oxidative stress linked to ocular hypertension, associated with TP53 pathway activation. Conclusions: These findings implicate GPR158 as a homeostatic regulator of intraocular pressure and suggest GPR158 could be a pharmacological target for managing ocular hypertension. [ABSTRACT FROM AUTHOR]

Water soluble “vital” dyes are commonly used clinically to evaluate health of the ocular surface; however, staining mechanisms remain poorly understood. Recent evidence suggests that sublethal damage stimulates vital dye uptake by individual living cells. Since cell damage can also stimulate reparative plasma membrane remodeling, we hypothesized that dye uptake occurs via endocytic vesicles. In support of this idea, we show here that application of oxidative stress to relatively undifferentiated monolayer cultures of human corneal epithelial cells stimulates both dye uptake and endocytosis, and that dye uptake is blocked by co-treatment with three different endocytosis inhibitors. Stress application to stratified and differentiated corneal epithelial cell cultures, which are a better model of the ocular surface, also stimulated dye uptake; however, endocytosis was not stimulated, and two of the endocytosis inhibitors did not block dye uptake. The exception was Dynasore and its more potent analogue Dyngo-4a, both small molecules developed to target dynamin family GTPases, but also having off-target effects on the plasma membrane. Significantly, while Dynasore blocked stress-stimulated dye uptake at the ocular surface of ex vivo mouse eyes when treatment was performed at the same time as eyes were stressed, it had no effect when used after stress was applied and the ocular surface was already damaged. Thus, Dynasore could not be working by inhibiting endocytosis. Employing cytotoxicity and western blotting assays, we went on to demonstrate an alternative mechanism. We show that Dynasore is remarkably protective of cells and their surface glycocalyx, preventing damage due to stress, and thus precluding dye entry. These unexpected and novel findings provide greater insight into the mechanisms of vital dye uptake and point the direction for future study. Significantly, they also suggest that Dynasore and its analogues might be used therapeutically to protect the ocular surface and to treat ocular surface disease. [ABSTRACT FROM AUTHOR]

An introduction to articles in the special issue of the "Australian Journal of Politics and History" on Europe's history, is presented, with topics such as link of British history with the definition of the European continent and the division of Europe into western and eastern parts.

The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to “accelerate” innovation. This article examines in detail one such agency, the United Kingdom’s Cell and Gene Therapy Catapult (CGTC). We describe CGTC’s role as an accelerator agency and its value narrative, which combines both “health and wealth.” Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field. [ABSTRACT FROM AUTHOR]

Rocks laid down during the Jurassic Period (201–143 Ma) in southern England are almost exclusively marine, but are sandwiched between continental deposits of the Late Triassic and Early Cretaceous. The transitions from fully continental to marine then back to continental, in response to continent movements and sea level change, mirror each other in important respects, taking place via intermediate environments which, although separated by approximately 60 million years, show remarkable similarities in their rocks and faunas. [ABSTRACT FROM AUTHOR]

Background: Despite a steady stream of headlines suggesting they will transform the future of healthcare, high-tech regenerative medicines have, to date, been quite inaccessible to patients, with only eight having been granted an EU marketing licence in the last 7 years. Here, we outline some of the historical reasons for this paucity of licensed innovative regenerative medicines. We discuss the challenges to be overcome to expedite the development of this complex and rapidly changing area of medicine, together with possible reasons to be more optimistic for the future.Discussion: Several factors have contributed to the scarcity of cutting-edge regenerative medicines in clinical practice. These include the great expense and difficulties involved in planning how individual therapies will be developed, manufactured to commercial levels and ultimately successfully delivered to patients. Specific challenges also exist when evaluating the safety, efficacy and cost-effectiveness of these therapies. Furthermore, many treatments are used without a licence from the European Medicines Agency, under "Hospital Exemption" from the EC legislation. For products which are licensed, alternative financing approaches by healthcare providers may be needed, since many therapies will have significant up-front costs but uncertain benefits and harms in the long-term. However, increasing political interest and more flexible mechanisms for licensing and financing of therapies are now evident; these could be key to the future growth and development of regenerative medicine in clinical practice.Conclusions: Recent developments in regulatory processes, coupled with increasing political interest, may offer some hope for improvements to the long and often difficult routes from laboratory to marketplace for leading-edge cell or tissue therapies. Collaboration between publicly-funded researchers and the pharmaceutical industry could be key to the future development of regenerative medicine in clinical practice; such collaborations might also offer a possible antidote to the innovation crisis in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Regenerative medicine (RM) is championed as a potential source of curative treatments for a variety of illnesses, and as a generator of economic wealth and prosperity. Alongside this optimism, however, is a sense of concern that the translation of basic science into useful RM therapies will be laboriously slow due to a range of challenges relating to live tissue handling and manufacturing, regulation, reimbursement and commissioning, and clinical adoption. This paper explores the attempts of stakeholders to overcome these innovation challenges and thus facilitate the emergence of useful RM therapies. The paper uses the notion of innovation niches as an analytical frame. Innovation niches are collectively constructed socio-technical spaces in which a novel technology can be tested and further developed, with the intention of enabling wider adoption. Drawing on primary and secondary data, we explore the motivation for, and the attempted construction of, niches in three domains which are central to the adoption of innovative technologies: the regulatory, the health economic, and the clinical. We illustrate that these niches are collectively constructed via both formal and informal initiatives, and we argue that they reflect wider socio-political trends in the social management of biomedical novelty. [ABSTRACT FROM AUTHOR]

In this paper, we examine processes of standardization and their role in helping to stabilize human embryonic stem cells as biological objects and in building the stem cell field itself. Drawing on empirical data from the emerging embryonic stem cell field, we explore the various arenas within which standardizing work goes on and how these relate to each other as different types of labour within and beyond the lab, one to do with stabilizing the bio-object and a second to do with its comparability and identity within a wider domain. Standardizing work reflects the recursive relation between these processes which are discussed via the concepts of bio-objectification and bio-identification. [ABSTRACT FROM PUBLISHER]

The identification of new biomarkers that help understand the epidemiological basis of patterns of malignancy at a population level is reshaping conceptions of health, disease and normality. These developments create new challenges for clinicians and the ways in which they work with scientists and engage with patients. Bioclinical collectives, an assemblage of laboratory and clinical evidence and practice, comprise different expert groups of scientists and clinicians who typically enact their expertise through boundary work to establish some degree of jurisdictional authority over their practice. Serra (2010) has argued for the existence of ‘medical technocracies’ wherein each speciality involved defines the boundaries between themselves in daily medical practices and use technology as a resource to construct their particular strategies. In this article we explore these two aspects of biomedical expertise – the collective and the boundaried domains of diagnostic practice (especially in regard to clinical utility) – to understand how haematological malignancy and disease are perceived and managed. The empirical data for the article are based on extensive primary research in hospitals based in the north of the UK, and among clinicians and laboratory scientists working in haematological malignancies. Our chosen field of inquiry – a haematological malignancy diagnostic service in the UK – is a particularly rich site through which to explore these twin aspects. [ABSTRACT FROM PUBLISHER]

Objective: Patient pathways to presentation to health care professionals and initial management in primary care are key determinants of outcomes in cancer. Reducing diagnostic delays may result in improved prognosis and increase the proportion of early stage cancers identified. Investigating diagnostic delay could be facilitated by use of a robust theoretical framework. We systematically reviewed the literature reporting the application of Andersen's Model of Total Patient Delay (delay stages: appraisal, illness, behavioural, scheduling, treatment) in studies which assess cancer diagnosis. Methods: We searched four electronic databases and conducted a narrative synthesis. Inclusion criteria were studies which: reported primary research, focused on cancer diagnosis and explicitly applied one or more stages of the Andersen Model in the collection or analysis of data. Results: The vast majority of studies of diagnostic delay in cancer have not applied a theoretical model to inform data collection or reporting. Ten papers (reporting eight studies) met our inclusion criteria: three studied several cancers. The studies were heterogeneous in their methods and quality. The review confirmed that there are clearly identifiable stages between the recognition of a symptom, first presentation to a health care professional, subsequent diagnosis and initiation of treatment. There was strong evidence to support the existence and importance of appraisal and treatment delay as defined in the Andersen Model, although treatment delay requires expansion. There was some evidence to support scheduling delay which may be contributed to by both patient and the health service. Illness delay was often difficult to distinguish from appraisal delay. It was less clear whether behavioural delay exists as a separate significant stage. Conclusions: Greater consistency is required in the conduct and reporting of studies of diagnostic delay in cancer. We propose refinements to the Andersen Model which could be used to increase its validity and improve the consistency of reporting in future studies. [ABSTRACT FROM AUTHOR]

This article examines developments in the field of regenerative medicine with respect to two quite distinct models of therapeutic development, a medical innovation model and a 'cells-as-drugs' model. It seeks to contribute to our understanding of regenerative medicine clinical trials, by exploring the ways in which the contingencies that shape all trial processes are given particular expression in stem cell trials. Drawing on both primary and secondary data, the article examines the two main trajectories taken by biomedical innovation, one based on patient-specific therapies, the other more akin to the innovation path seen in the pharmaceutical sector. Each path raises distinct scientific, regulatory and commercial challenges and uncertainties for those involved. We analyse the implications of these two paths for our understandings of regenerative medicine and the innovation process more generally. [ABSTRACT FROM AUTHOR]

How do patients make sense of their medication, how do they link it to their own state of health, and how do they cope with it within the context of their daily life? Such questions represent significant gaps in traditional medical sociology, which has to date been dominated by research into the role of producers and intermediaries in shaping the social world of medicines. This paper examines the social construction of the meaning of medicine through a detailed exploration of patients who have been prescribed warfarin, an anticoagulant (blood thinning) drug, to treat various chronic cardiovascular disorders. Through the development of the concept of 'lay pharmacology' we locate these meanings within wider collectivities of other patients, family and the anticoagulation clinic itself. We ask whether we can anchor these meanings within the patients' own understanding of their condition and of their treatment, and how in light of both they make sense of the anticoagulation regime they are asked to follow. We compare clinical notions of the safety, efficacy and side effects of drugs with lay versions of the same in order to suggest how the latter may be drawn on in clinical settings to help inform clinical dialogue with patients more directly, while, at a more general level help inform clinical trials and allow for a constructive dialogue with those in public policy who are tasked with ensuring the delivery of safe and cost-effective medicines. More broadly, in an era of so-called 'translational medicine' how expert and lay understandings are actually brought together is a public policy issue that should be given much greater priority. [ABSTRACT FROM AUTHOR]

Created in early 1921, the Temporary Mixed Commission on Armaments was a committee of eminent figures formed by the League of Nations to consider the problem of international disarmament in its widest aspects and to suggest potential initiatives, plans and solutions. What made it unique was that its members were specifically appointed as private individuals, unrestrained by formal instructions from governments. They were intended to be free to put forward ideas and opinions that seemed most likely to produce real progress but which might have created political turmoil if they had come from official representatives. To some contemporary observers this extraordinary degree of independence was tremendously appealing; to others, the lack of accountability on an issue of supreme importance to the national security of member states was desperately objectionable. In practice, much of the commission's work resolved into a battle between interventionist British members and resistant French members, led respectively by Lord Robert Cecil and Colonel Edouard Réquin, with its most prominent outcome being the failed 1923 draft Treaty of Mutual Assistance. A fascinating experiment in the possibilities of transnationalism within an international organization, the Temporary Mixed Commission on Armaments both exemplified the fluidity of the League of Nations in its early years and showed the limited results a transnational approach could achieve on as contentious an issue as disarmament. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the natural history of Sorsby fundus dystrophy and the effect of various treatment methods for choroidal neovascularization (CNV) in this dystrophy. Design: Historical cohort study. Methods: A cohort of 42 patients with the Ser181 Cys TIMP3 mutation were identified from the electronic database of genetic retinal diseases in Moorfields Eye Hospital. Retrospective analyses of case records were carried out. Serial best-corrected visual acuity, fundus findings, age at onset of CNV, initial location of CNV, time taken for CNV to progress to subfoveal location, and the interval between development of CNV in the first and second eye were recorded. The time taken for CNV to recur to a subfoveal location in patients in whom argon laser photocoagulation was carried out for extrafoveal CNV also was documented. In cases where photodynamic therapy (PDT) was carried out for subfoveal CNV, the visual outcome, number of PDT treatments, and progression of lesion size were noted. Results: The median age at onset of CNV in the first eye was 46.1 years and in the second eye was 50.3 years. The mean interval between the development of CNV in the first and second eye was 4.5 years. The median age at which vision fell to 20/200 or below was 48 years (first eye) and 54 years (second eye). Argon laser therapy and PDT are not effective in treating CNV of patients with this dystrophy. Antiangiogenic agents may be more effective in this condition. Conclusions: The main cause of blindness resulting from this dystrophy is CNV. Antiangiogenic agents may be useful in preventing visual loss as a result of this condition. [Copyright &y& Elsevier]

This paper explores the role of the International Stem Cell Initiative (ISCI) in its attempt to develop biological standards and experimental protocols for the embryonic field as a whole. Drawing on empirical research derived from UK and other labs and fieldwork within ISCI meetings, we describe the way standards have emerged and the difficulties in stabilizing them at the local level. The paper discusses the ways in which this form of governance-by-standards acts to manage uncertainty - to a degree - and suggests that this requirement to manage uncertainty is becoming a key characteristic of what we call “basic innovation”. We conclude by drawing out the implications of this for the management of uncertainty and the increasingly diverse regulatory space that will be needed to oversee the eventual clinical application of hESC. [ABSTRACT FROM AUTHOR]

This paper explores the role of the International Stem Cell Initiative (ISCI) in its attempt to develop biological standards and experimental protocols for the embryonic field as a whole. Drawing on empirical research derived from UK and other labs and fieldwork within ISCI meetings, we describe the way standards have emerged and the difficulties in stabilizing them at the local level. The paper discusses the ways in which this form of governance-by-standards acts to manage uncertainty – to a degree – and suggests that this requirement to manage uncertainty is becoming a key characteristic of what we call "basic innovation". We conclude by drawing out the implications of this for the management of uncertainty and the increasingly diverse regulatory space that will be needed to oversee the eventual clinical application of hESC. [ABSTRACT FROM AUTHOR]

To standardize human embryonic stem cells is an exercise in standardizing different kinds of unknowns. Such standards, currently being developed in the field, can change the understanding of what a stem cell is. In the influential International Stem Cell Initiative (ISCI), scientists in a fiercely competitive field are prepared to exchange research material and data that would normally be highly confidential. ISCI participants understand the particular unknown that they are seeking to standardize as a 'known unknown' and hope that their collaborative work will serve to move the field forward and thus enable both competition and comparable data. Such known unknowns are seen to be of vital importance, yet of a different epistemic currency than the types of unknowns that could lead to scientific fame and fortune. Furthermore, while the notion of 'pluripotency' is of pivotal importance as a discursive resource when demarcating the abilities of embryonic stem cells from those of adult stem cells, it can also present a practical problem. A more flexible definition allowing for different stem cell 'niches' could render the cell lines less pluri but more potent. The reconfiguration of pluripotency may serve to transport human embryonic stem cells into a clinical and 'doable' future. [ABSTRACT FROM AUTHOR]

This short article provides a response to Nowotny and Wynne's commentary on an earlier article by the author that examined the relation between science and technology studies (STS) and science policy. The article offers a reply with respect to understanding the domain of science policy; how Nowotny and Wynne seek to broaden the scope and so critical leverage of STS beyond the ‘policy room’; and the implications this has for the ways in which an STS/non-STS nexus might be configured in the future. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between a deconstructivist method in science and technology studies (STS) and the more recent moves towards a reconstructivist engagement with science and science policy making. Drawing on examples from the author's own research, the article identifies three forms of engagement and their relative utility and limitations. The article argues that these are typical of STS work that seeks direct engagement with science policy making and which could form the basis for a more ‘serviceable STS’ that retains its critical and independent perspective on science. The paper concludes by arguing that the analysis has important implications for the ways in which STS expertise can articulate with science policy making. [ABSTRACT FROM AUTHOR]

This article examines the six distinct varieties of disarmament pursued in the aftermath of the First World War, each of which had a meaningful impact upon international relations during the interwar period: the arms restrictions imposed upon the defeated powers; the unilateral cuts to armaments and military budgets made by the victors; the limitation of naval arms through ‘private’ treaties among the key maritime powers; the League's limited initiatives to establish regimes of control over armaments during 1920–25; the League's attempt to link arms reductions to the simultaneous creation of new systems of security during 1922–25; and the League's ‘general disarmament’ process of 1926–34, covering all nations and all spheres of armaments. It concludes that the success or failure of all these varieties was always ultimately determined by the political will and the self-interest of the major powers. [ABSTRACT FROM AUTHOR]

This article argues that, despite the eventual failure of the League to deliver the international disarmament that may believed would create peace, the early inter-war years showed signs of great promise. The League's early, often modest, efforts to establish the foundations of international disarmament, deserve greater credit than they are usually afforded because they have been overshadowed by the collapse of the World Disarmament Conference in 1934. [ABSTRACT FROM AUTHOR]

This paper explores competing discourses that envision different socio-technical landscapes opened up by the completion of the map of the human genome in 2003. It examines the ways in which the map, and its organising principle and very rationale—the gene as the sole or prime agent through which to understand the body and its disordering (as disease)—has been interpreted in quite distinct ways. It suggests how the sequences of a genomic map have post-genomic con-sequences that depend on a social rather than simply biological reading of genomic agency. Various accounts of the map and genetic agency or described, within science, science policy and social science, especially across science and technology studies (STS). The paper concludes with a comparative summary of these positions and asks whether a deconstructive reading of genomic agency by STS analysts might be the basis for a critical re-constructive engagement with post-genomic policy discourse that avoids the over-determination of agency one often finds in the latter. [ABSTRACT FROM AUTHOR]

There has been considerable scientific, corporate and policy interest in the more effective use of genetics in both drug development and delivery. Pharmacogenetics-the study of the relationship between an individual's genetic makeup and response to medicinal drugs-has attracted global interest, but will it live up to its promise? Looking beyond the hype that has accompanied much of the commentary in the area, the future of pharmacogenetics will depend on how competing interests and options are resolved. [ABSTRACT FROM AUTHOR]

This article provides a review of recent work in social science exploring the meaning of risk in contemporary society and its relation to science and science policy-making. The article argues that we have seen a reflexive turn in policy-making though this is limited and yet to fully embrace the discourse of uncertainty and lay engagement with science that will be required for a more socially robust and legitimated management of risks. It locates risk in a wider political culture and calls for new research that adopts a more sophisticated approach to the social framing of the science-risk-policy nexus. [ABSTRACT FROM AUTHOR]

This paper offers an introduction to the three themes that organise the papers in this special issue of Health, Risk & Society. These relate to the calculus, interpretation and regulation of health risk. The papers describe in differing ways the interface between the social and the biological, and the introduction suggests how this leads to a consideration of constructivist and realist approaches towards risk and the need to bridge the two, not only for methodological but also practical (regulatory) purposes. [ABSTRACT FROM AUTHOR]

The relationship between any new - however embryonic - health technologies and those already established will depend on how they are received in the present and this in turn depends on whether they are regarded as making sense and if they can be translated into the more everyday world of the technology user. This articulation between technologies and the context of use through which their meaning and utility are constructed is, of course, a key theme within science and technology studies. The scope and richness of such studies reflect the fact that medicine has itself become more and more dependent on increasingly sophisticated technologies that have been drawn from bioscience, engineering, information technologies and elsewhere. Medical science is a site particularly laden with risk and uncertainty today. As a result, the long-standing sociological argument that society is subject to the power of "medicalization" suddenly seems open to question, or at least overstates the degree of control that medicine currently enjoys.

: ObjectiveAge-related macular degeneration (AMD) is the most common cause of blindness in industrialized countries. There has been considerable interest in the genetics of early age-related maculopathy (ARM) and AMD, because they have phenotypes similar to inherited diseases where mutations have been identified, but the heritability of ARM and AMD is unknown.: DesignA classical twin study was performed to compare the concordance in monozygotic (MZ) and dizygotic (DZ) twins in an unselected sample of female volunteer twins.: ParticipantsFive hundred six twin pairs, 226 MZ and 280 DZ, with a mean age of 62 years, were examined.: MethodsARM was graded from stereoscopic macular photographs of 501 of the twin pairs (99%) according to the International ARM Epidemiologic Study Group grading system. The casewise concordance was calculated for twin pairs from 2 × 2 contingency tables of affected/unaffected twins, and these tables were used in maximum likelihood genetic modeling to estimate the heritabilities of phenotypes graded.: Main outcome measuresPrevalence of ARM; concordance in MZ and DZ twins of the phenotypes of ARM, soft drusen >63 μm and ≥125 μm diameter, pigmentary changes and hard drusen (<20 and ≥20 in number); heritability of ARM and subphenotypes.: ResultsThe overall prevalence of ARM was 14.6% (95% confidence interval [CI], 12.4%–16.8%). The concordance for ARM in MZ twins was 0.37 compared with 0.19 in DZ twins, suggesting a role for genes. Modeling confirmed a genetic effect for phenotypes of ARM, soft drusen, pigmentary changes, and ≥20 hard drusen, although there was little genetic effect for scattered (<20) hard drusen. The heritability of ARM was estimated as 45% (95% CI, 35%–53%). The most heritable phenotypes were soft drusen ≥125 μm (57%) and ≥20 hard drusen (81%), with the latter being dominantly inherited.: ConclusionsThis study confirms a significant genetic influence in ARM and suggests that future genetic studies should examine phenotypes of large (≥125 μm) soft drusen and ≥20 hard drusen, because these seem to be the most heritable components. [Copyright &y& Elsevier]

Provides information on Air Commission of the World Disarmament Conference of 1932 to 1934. Application of air armaments; Degree of potential attractiveness of women; Allurement exercised by a woman forming part of a group of women and considered individually.

To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults. Single-center retrospective, consecutive, observational study. Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene. Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed. Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters. Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3–84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti–vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His). BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype–genotype correlations allow for more accurate prognostication and counselling. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non‐syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726‐1G>C and p.(Tyr289Cys). Electroretinography indicated a rod‐cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra‐ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non‐null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood. [ABSTRACT FROM AUTHOR]

This paper explores the impact of a new IT system on the knowledge claims and occupational boundaries made by professional groups within a hospital laboratory setting. Within organizational settings professional groups enjoy considerable power and status through the specialised knowledge claims they make, deploying a variety of material and discursive resources to secure these. However, when organizations introduce new technologies to manage information needs, professional boundaries and claims to expertise may be threatened. This paper examines the strategies deployed by two key professional groups -- Medical Laboratory Scientific Officers and medics -- to secure their knowledge claims and statuses within the new organizational context shaped in part by an IT system. Though medics were more successful here, they had to accommodate to new demands within the organization. The professional identity and organizational space of the MLSOs were also redefined but, in contrast, by being narrowed. The different experiences and strategies of the two groups reflect their unequal holding of cultural capital and their differential capacity to define their status relative to the organization itself. [ABSTRACT FROM AUTHOR]

In this article, we examine the changing terms on which genetics-based technologies in two areas—agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics)—have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself. [ABSTRACT FROM AUTHOR]

Describes divorce trends and patterns in Australia. Examination of marriage duration-specific proportions divorcing and cumulative rates of divorce; Re-evaluation of normative sanctions against divorce; Adoption of objectively sounder mate selection and marriage timing practices.

The growing commercialisation of university science has often led to claims that research is being distorted by corporate influence. This paper develops a methodology for exploring the construction of research agendas associated with university-corporate ties. It examines in detail a form of collaboration that is increasingly common, the long-term research alliance funded by single companies. The study relates agenda construction to the organisational setting in which it occurs and argues that the latter needs to be given more attention in the sociological analysis of contemporary science. [ABSTRACT FROM AUTHOR]

This is a Comment on Greg Myers' paper on the writing and rewriting of patent applications by two biological scientists. It draws on data from our own study of patenting in UK public sector biosciences. While agreeing with much that Myers says, we place the issues in a wider context of developing relationships between industry and academe. The emergence of new networks blurs boundaries, and makes apparently separate arenas less distinct. [ABSTRACT FROM AUTHOR]

Examines the regulatory mechanisms and negotiation processes involved in the commercialization of intellectual property in industrial-academic collaborations. Intellectual property as a feature of commercialization of knowledge; Regimes of appropriation and governance; Implication of commercialization policies for intellectual property; Case of a university spin-off.

Focuses on the establishment of Great Britain's White Paper on Science and Technology. Measures of effective exploitation on scientific research; Establishment of Technology Foresight Steering Group; Presentation of the White Paper's policy for science and technology.

Discusses the emergence of a patenting culture in university science in Great Britain. Exploration of the translation of academic credits into patents; Questions raised by the process in regard to the understanding of scientific recognition and scientists' network; Recommendations for scientists to move between the two distinct social worlds.

To describe a patient with a history of obesity, retinal dystrophy, type II diabetes, and mild cognitive impairment; found to harbour biallelic splice-site variants in VPS13B. A complete ophthalmic evaluation was performed at Moorfields Eye Hospital (London, United Kingdom), consisting of measurement of best-corrected visual acuity (BCVA), slit lamp and dilated fundus evaluation, colour, autofluorescence and near-infrared retinal imaging, spectral domain-optical coherence tomography, and electroretinogram (ERG). Whole-genome sequencing was performed as part of the UK's 100,000 Genomes Project. A 26-year-old Pakistani man with normal appearance, stature, and head size presented with decreased BCVA and severely constricted visual fields to our Ophthalmic Genetics clinic. He had a history of obesity, type II diabetes, and mild cognitive impairment. His evaluation showed retina-wide, severe photoreceptor dysfunction in both eyes, with undetectable scotopic and photopic ERG waveforms. Genomic analysis identified a homozygous rare splice donor variant in the VPS13B gene (c.5024+2T>C) that was demonstrated to lead to skipping of the in-frame exon 31 (p.Gln1607_Ser1675delinsHis). Exon 31 skipping in VPS13B may lead to a hypomorphic change, with partial gene function and an incomplete, mild Cohen syndrome-like phenotype. [ABSTRACT FROM AUTHOR]

The article shares the story of a Swedish couple who ventured to China in quest for the treatment of their child's disease. It discusses the flourishing of yet to prove stem cell therapies derived from an in vitro fertilization (IVF) embryo to explore the mechanisms of the disease. It also mentions the collaborative effort in developing a conceptual repertoire of processes for bio-objects and their boundaries wherein life scientists and researchers lunched "Action."

A 19-year-old female presented with a 4-month history of bilateral, para-central flickering lights, stable over that time after a sudden onset. Examination revealed isolated, bilateral, reproducible and incongruent para-central scotomata. Conventional imaging of the retina and OCT of the macula were not conclusive. Infrared imaging of the fundi showed typical lesions of acute macular neuroretinopathy. The unique physical properties of the near infrared waves recently widened the field of retinal imaging and are of particular interest in the diagnosis of deep retinal layers. [ABSTRACT FROM AUTHOR]