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Purpose: To explore personal experiences of loss of foot sensation following stroke in order to inform the focus of clinical assessments and development of a vibrotactile insole. Methods: Qualitative design with an interpretive phenomenological approach to data collection and analysis. Eight community dwelling adults with stroke (>6 months) and sensory impairment in the feet participated. Data was collected via conversational style interviews which were transcribed and analyzed using a thematic framework. Themes were verified with co-researchers and a lay advisory group. Results: Data formed four themes: Sensory deficits are prevalent and constant, but individual and variable; Sensory deficits have a direct impact on balance, gait, mobility and falls; Sensory deficits have consequences for peoples' lives; Footwear is the link between function, the environment and identity. They embraced the concept of discrete vibrotactile insoles, their potential benefits and demonstrated a willingness to try it. Conclusions: Sensory deficit contributes to effects upon physical function, mobility and activity. Clinical outcome measures need to capture the emotional, psychological and social impacts of sensory deficit. Participants demonstrated a resilience and resourcefulness through adaption in daily living and self-management of footwear. The participants focus on footwear provides the opportunity to develop discrete and non-burdensome vibrotactile insoles for this patient group. IMPLICATIONS FOR REHABILITATION Sensory deficits are wide ranging and varied and are not distinct from motor deficits though contribute to the overall effect on physical function, mobility and activity. The physical effects impact on participants' lives emotionally, psychologically and socially. Measurement of outcomes need to capture specific activities that are valued by patients. The participants have revealed resilience and resourcefulness to create a "new normal" for their lives through adaption and self-management with a focus being on footwear as a solution. The participants have revealed the need for insole interventions to be discreet and non-burdensome, welcoming insole technology and contributing to the design and features of such insoles.

Background: The delivery of healthcare is changing and aligned with this, the podiatry profession continues to change with evidence informed practice and extending roles. As change is now a constant, this gives clinicians the opportunity to take ownership to drive that change forward. In some cases, practitioners and their teams have done so, where others have been reluctant to embrace change. It is not clear to what extent good practice is being shared, whether interventions to bring about change have been successful, or what barriers exist that have prevented change from occurring. The aim of this article is to explore the barriers to changing professional practice and what lessons podiatry can learn from other health care professions.\ud \ud \ud Main body: A literature search was carried out which informed a narrative review of the findings. Eligible papers had to (1) examine the barriers to change strategies, (2) explore knowledge, attitudes and roles during change interventions, (3) explore how the patients/service users contribute to the change process (4) include studies from predominantly primary care in developed countries.\ud \ud Ninety-two papers were included in the final review. Four papers included change interventions involving podiatrists. The barriers influencing change were synthesised into three themes (1) the organisational context, (2) the awareness, knowledge and attitudes of the professional, (3) the patient as a service user and consumer.\ud \ud \ud Conclusions: Minimal evidence exists about the barriers to changing professional practice in podiatry. However, there is substantial literature on barriers and implementation strategies aimed at changing professional practices in other health professions. Change in practice is often resisted at an organisational, professional or service user level. The limited literature about change in podiatry, a rapidly changing healthcare workforce and the wide range of contexts that podiatrists work, highlights the need to improve the ways in which podiatrists can share successful attempts to change practice.

Germ cells undergo mitotic expansion via incomplete cytokinesis, forming cysts of undifferentiated cells that remain interconnected prior to meiotic initiation, through mechanisms that are not well-defined. In somatic cells, Ras-related nuclear protein (Ran) spatiotemporally regulates mitotic spindle assembly, cleavage furrow formation and abscission. Here, we identify Ran and β-importins as critical regulators of cyst development in theDrosophilaovary. Depletion ofRanor the β-importinsTnpo-SRandcadmusdisrupts oocyte selection and results in egg chambers with variable numbers of germ cells, suggesting abnormal cyst development and cyst fragmentation. We demonstrate that Ran, Tnpo-SR, and Cadmus regulate key cellular processes during cyst formation, including cell cycle dynamics, fusome biogenesis, and ring canal stability, yet do so independently of mitotic spindle assembly. Further, Tnpo-SR and Cadmus control cyclin accumulation and suppress cytokinesis independent of Ran-GTP, suggesting that β-importins sequester protein cargos that normally promote the mitotic-to-meiotic transition. Our data demonstrates that Ran and β-importins are critical for germ cell cyst formation, a role that is likely conserved in other organisms.SUMMARY STATEMENTRan and two β-importins function coordinately to promote oocyte selection and cyst development in theDrosophilaovary.

Between 1884 and 1939 the Egypt Exploration Fund (later Society) and the British School of Archaeology in Egypt held a series of annual exhibitions in London to showcase the finds of each archaeological season. Displaying artefacts excavated just weeks before, alongside new archaeological interpretations and interpretive devices, and in varying locations across the capital, these temporary exhibitions functioned as network hubs for the circulation of disciplinary objects and knowledge. Established at a time when archaeology was emerging as a new, professional scientific discipline and the British occupation of Egypt was altering political dynamics, the practice reflected a period of considerable change in the display and reception of ancient Egyptian collections. The aim of this thesis is to centre the exhibitions in the theoretical framework of archaeological representation, addressing how the practice contributed to the construction and communication of knowledge about ancient and contemporary Egypt in the imperial metropole. The following discussion will argue that the annual exhibitions utilised their temporary, transient, and transitional nature to experiment with new ways of displaying Egypt and of shaping the visual culture and material products of Egyptian archaeology.

Eastern existential traditions focus on practices meant to increase one’s ability to observe what is true in one’s awareness of this existence. The accuracy of surveys depends on the ability of the respondents to observe truth. Practices that increase one’s ability to observe what is true are formalized in this paper through the methodology of Human-Centric Functional Modeling, so they can be used to pre-qualify survey respondents according to their ability to understand principles of truthful observation. These principles are namely, that truth is what is true within one's own experience (what one can observe directly or prove through "first principles", that is prove from such direct observations). Truth is not what is within one's beliefs, with the exception of what in one’s own observation those beliefs function to achieve. Nor is truth what any given academic tradition might assume, unless those assumption can be observed directly or deduced from first principles. In addition, this paper explores why the use of General Collective Intelligence or GCI is required to remove barriers to the complexity of observations that can be truthfully made. The justifications for these conclusions is presented, as is a methodology for using these conclusions to continuously and adaptively improve survey results.

The hypothesis that human intelligence represents a phase transition in animal intelligence is explored, as is the hypothesis that General Collective Intelligence (GCI), which has been defined as a system that organizes groups into a single collective cognition with the potential for vastly greater general problem-solving ability than that of any individual in the group, represents a phase transition in human intelligence. At these phase transitions, cognition can be demonstrated to gain the capacity for exponentially greater general problem-solving ability. If valid, then when generalized as an Nth order pattern, these N phase transitions represent successively more powerful super-intelligences, where each of these super-intelligences can potentially be implemented as an Artificial General Intelligence (AGI), or as a General Collective Intelligence (GCI).

This piece was commissioned as part of a collaboration between the Adelphi Contemporary Music Group here at the University of Salford, and the Beauty and the Beasts; Falling in love with Insects exhibition at the Manchester Museum. This project is part of the museum’s mission to build a sustainable world. Insects keep ecosystems working and are the food of the world, but many habitats and individual species are currently under threat of extinction. The project seeks to explore our complex relationship with insects and highlights the fact that the vast majority of insects are not only harmless to humans, but vital for maintaining the earth as we know it. A world without insects would, in the end, be a world without people. Art, and collaboration with artists is central to the storytelling and exploration of the project.

Background Appropriate footwear is important for those who stand for prolonged periods of time at work, enabling them to remain comfortable, healthy and safe. Preferences for different footwear cushioning or hardness are often person specific and one shoe or insole will not be the choice for all. The aim of this study was to develop a range of insole options to maintain comfort during long periods of standing at work and test insole material preferences in the workplace. Methods The study consisted of two parts. Part one evaluated 9 insoles of the same geometry that varied in hardness under 2 different plantar regions (n = 34). Insole preference, plantar pressure and selected anthropometric foot measures were taken. Three insole designs based on the most preferred options were identified from this part. In part two, these three insoles were evaluated with 22 workers immediately after trying them on (1 min) and after a working day. Foot anthropometric measures and subjective questions concerning material hardness preferences and self-reported foot characteristics were used to investigate whether either had a relationship with insole preference. Results Part one found insole preference predominantly varied according to material hardness under the medial arch rather than the heel/forefoot. Softer material under the heel and forefoot was associated with a reduction in peak pressures in these regions (p In part two, under real world conditions, insole preference changed for 65% of participants between the immediate assessment (1 min) and after a whole workday, with dorsum height related to the latter (p Conclusion Preference for material hardness varies underneath the medial arch of the foot and is time dependent. Simple foot measures and questions about comfort can guide selection of preferred insoles.

A recently developed Functional Modeling Framework (FMF) for defining models of consciousness and cognition proposes to have the capacity to represent all models of consciousness and cognition and proposes to define the criteria for a model of consciousness to have the potential for self awareness. The FMF provides a single mathematical framework for defining models of consciousness that is human-centric in being independent of assumptions made by any specific model. This human-centric approach enables different models to be more easily compared so research on consciousness can reliably converge on a single understanding, enabling the possibility of massively collaborative interdisciplinary projects to research, and implement a model of consciousness and cognition where not possible before. Some functional components of the FMF remain to be validated. However even without validating the entire framework using some subset of the framework is still useful as a common basis for comparing models of consciousness. This paper demonstrates the comparison of three leading model of consciousness within the subset of this framework that has been validated by many years of tradition.

This paper addresses the question of how current group decision-making systems, including collective intelligence algorithms, might be constrained in ways that prevent them from achieving general problem solving ability. And as a result of those constraints, how some collective issues that pose existential risks such as poverty, the environmental degradation that has linked to climate change, or other sustainable development goals, might not be reliably solvable with current decision-making systems. This paper then addresses the question that assuming specific categories of such existential problems are not currently solvable with any existing group decision-systems, how can decision-systems increase the general problem solving ability of groups so that such issues can reliably be solved? In particular, how might a General Collective Intelligence, defined here to be a system of group decision-making with general problem solving ability, facilitate this increase in group problem-solving ability? The paper then presents some boundary conditions that a framework for modeling general problem solving in groups suggests must be satisfied by any model of General Collective Intelligence. When generalized to apply to all group decision-making, any such constraints on group intelligence, and any such system of General Collective Intelligence capable of removing those constraints, are then applicable to any process that utilizes group problem solving, from design, to manufacturing or any other life-cycle processes of any product or service, or whether research in any field from the arts to the basic sciences. For this reason these questions are important to a wide variety of academic disciplines. And because many of the issues impacted represent existential risks to human civilization, these questions may also be important by to all by definition.

Borrowing techniques from complex systems and software engineering, this paper defines a Functional Modeling Framework to provide a simple common mechanism for representing models of consciousness or cognition that is independent of assumptions made by any specific model. All models of consciousness or cognition should of course fit into the complete set of functions of what consciousness, or cognition can do. Through attempting to represent all such functions (both computable and non-computable), this framework attempts to gain the capacity to represent all models of consciousness or cognition, even where the implementation mechanisms of those functions are unknown. Enabling different models of consciousness or cognition to be more easily compared is intended to enable research on consciousness and cognition to more reliably converge on a single understanding, even across massively collaborative research projects spanning multiple disciplines. Furthermore, if biological functionality can be considered as dynamically stable where it is persistent, then in aiming to provide a common approach for representing and comparing the functionalities of consciousness or cognition as dynamically stable systems, this framework provides a set of features through which it may be possible to see commonality between the functional components of a wide range of other dynamically stable biological or non-biological systems. If such commonality does exist, and if, as proposed, that commonality reflects deeper underlying physical and mathematical principles, then representing any researcher’s model of consciousness or cognition within this framework might help reveal applications of that researcher’s model across a wide range of other domains of study.

Background: This study explores the factors constraining group decision-making, where those factors might tend to restrict groups from selecting optimal solutions with regards to sustainability or sustainable development. This study also explores the factors constraining group decision-making from framing problems in the optimal way (choosing the optimal problem to solve), and how together these factors constraining groups from choosing the optimal problem to solve or the optimal solution to solve it with, might tend to bar groups from achieving optimal outcomes. To address the first set of constraints, collective intelligence algorithms aim to use the intelligence of crowds to select optimal solutions. To address the second set of constraints, General Collective Intelligence solutions, as defined in this paper, aim to further improve outcomes by selecting the optimal problem to solve.Results: In the absence of General Collective Intelligence fundamental economic forces are suggested to drive a continual increase in the alignment of group decision-making with the interests of decision-makers rather than with optimizing collective impact. And while sustainability and sustainable development might be achieved locally in the face of this misalignment, globally this misalignment is suggested to compete directly against that achievement. For this reason, maximizing collective outcomes such as impact on sustainability or sustainable development is suggested to require General Collective Intelligence in order to reliably increase the forces driving groups towards prioritizing collective impact until those forces are greater than the forces driving this misalignment. As a result, without General Collective Intelligence this misalignment of group decision-making in a direction other than optimal collective impact is suggested to be a hidden "bug" that may prevent sustainability and sustainable development from being reliably achievable globally through current sustainability or sustainable development programs.Conclusions: General Collective Intelligence is a pattern of biomimicry that potentially replicates the robust and stable multi-cellular cooperation nature has evolved over more than a billion years to enable cells in organisms to cooperate to sustainably achieve outcomes. Platforms organizing groups into such a General Collective Intelligence are suggested to be required in order for sustainability or the sustainable development goals to be reliably achievable globally.

Importance The National COVID Cohort Collaborative (N3C) is a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools and inform clinical care and policy. Objectives To evaluate COVID-19 severity and risk factors over time and assess the use of machine learning to predict clinical severity. Design, Setting, and Participants In a retrospective cohort study of 1 926 526 US adults with SARS-CoV-2 infection (polymerase chain reaction >99% or antigen Main Outcomes and Measures Patient demographic characteristics and COVID-19 severity using the World Health Organization COVID-19 severity scale and differences between groups over time using multivariable logistic regression. Results The cohort included 174 568 adults who tested positive for SARS-CoV-2 (mean [SD] age, 44.4 [18.6] years; 53.2% female) and 1 133 848 adult controls who tested negative for SARS-CoV-2 (mean [SD] age, 49.5 [19.2] years; 57.1% female). Of the 174 568 adults with SARS-CoV-2, 32 472 (18.6%) were hospitalized, and 6565 (20.2%) of those had a severe clinical course (invasive ventilatory support, extracorporeal membrane oxygenation, death, or discharge to hospice). Of the hospitalized patients, mortality was 11.6% overall and decreased from 16.4% in March to April 2020 to 8.6% in September to October 2020 (P = .002 for monthly trend). Using 64 inputs available on the first hospital day, this study predicted a severe clinical course using random forest and XGBoost models (area under the receiver operating curve = 0.87 for both) that were stable over time. The factor most strongly associated with clinical severity was pH; this result was consistent across machine learning methods. In a separate multivariable logistic regression model built for inference, age (odds ratio [OR], 1.03 per year; 95% CI, 1.03-1.04), male sex (OR, 1.60; 95% CI, 1.51-1.69), liver disease (OR, 1.20; 95% CI, 1.08-1.34), dementia (OR, 1.26; 95% CI, 1.13-1.41), African American (OR, 1.12; 95% CI, 1.05-1.20) and Asian (OR, 1.33; 95% CI, 1.12-1.57) race, and obesity (OR, 1.36; 95% CI, 1.27-1.46) were independently associated with higher clinical severity. Conclusions and Relevance This cohort study found that COVID-19 mortality decreased over time during 2020 and that patient demographic characteristics and comorbidities were associated with higher clinical severity. The machine learning models accurately predicted ultimate clinical severity using commonly collected clinical data from the first 24 hours of a hospital admission.

A recently developed model of collective intelligence (CI) has been proposed to have the capacity for general collective intelligence (GCI), that is, the capacity for general problem-solving ability that can be reapplied across any domain. This paper explores the relationship between this model of GCI and a model proposed to describe existing CI solutions that are conventional in the sense of accomplishing a single function. The properties required for GCI in this model, and how they make this model unique from other approaches to CI, as well as the implications of these differences, are also explored. In addition, the implications of GCI are explored in terms of the capacity to drive societal impact at transformative scale, where that impact is suggested not to be reliably possible with other approaches to CI.

This presentation will focus on the research that has significantly influenced both the foot health interventions that are now provided to people with inflammatory joint conditions and the development of guidelines that directly impact on patient care. Aligned with this has been the increasing profile of podiatry within rheumatology and also the recognition within podiatry of rheumatology as a specialisation. However, the podiatrist’s role within rheumatology is currently under threat as services are driven to focus on other patient groups. This is happening despite recommendations from guidelines and support from rheumatologists. The risks associated with this decline in specialist foot care will be explored and some solutions suggested in relation to the diagnosis, assessment and management of foot problems.

Background: Along with its skin manifestations, SLE can present with\ud a variety of musculoskeletal signs and symptoms and vascular\ud problems that can affect the feet. Furthermore, there is the potential\ud for reduced tissue viability, leading to thinning of the skin and/or callus\ud formation. Further, systemic resistance to viral, bacterial and fungal\ud infections may be reduced and, together with poor tissue viability,\ud create the opportunity for these infections to proliferate in the feet. A\ud recent survey by the same authors (unpublished) has shown a high\ud prevalence of these infections, with many experiencing the impact of\ud vascular and musculoskeletal problems. To date there is no research\ud that has explored the impact of foot problems on people’s lives.\ud Methods: Following ethical approval, 12 participants who fulfilled the\ud inclusion criteria were recruited: diagnosed with SLE (ACR diagnosis),\ud current and/or past experience of foot/lower limb problems and age\ud �18 years. Consent was obtained and then conversational-style\ud interviews were carried out with an interpretivistic phenomenological\ud approach. The interviews were digitally recorded and complemented\ud by field notes. An opening question was used for all participants: ‘Tell\ud me about your experiences of having foot problems?’ If necessary,\ud further trigger questions were used in order to maintain the conversation\ud and the focus on foot problems. Data were transcribed verbatim\ud and analysed using a thematic framework approach. The transcripts\ud were verified by the participants and were analysed by a second\ud researcher in order to add to the credibility of the analyses.\ud Results: The data was organized into seven themes: Foot problems\ud and symptoms—what they are and the feeling associated with them;\ud Experiences of foot problems being diagnosed; Impact of foot\ud problems on activities; Treatment of foot symptoms/problems;\ud Perceived obstacles to professional foot care; Unanswered questions\ud about feet and foot care; and Recognition of the need for professional\ud foot care and foot care advice. These people experienced a wide\ud variety of foot problems that impact significantly on activities. Some\ud reported working through the pain in order to achieve visible normality\ud while experiencing the negative emotions of anger, frustration and\ud anxiety. Although some had experienced professional foot care, there\ud were obstacles to the foot problems being diagnosed, resulting in\ud many unanswered questions and some inappropriate selfmanagement.\ud Conclusion: Despite reporting foot pain, negative emotions and\ud activity restrictions related to their foot symptoms, people with SLE\ud tend to get on with it and self-treat rather than seeking professional\ud foot care. The lack of focus on the feet in the medical consultation is\ud caused by the participants’ belief that it is not the consultant’s role.\ud There is a clear need for foot assessments to be included in the\ud medical consultation and for professional foot care to be provided.

Background: SLE can affect many tissues throughout the body.\ud Anecdotally, it is suggested that people with SLE experience a range of\ud complications in the foot and lower limb, including vascular impairment\ud (e.g. RP), neurological impairment, poor tissue viability (e.g. ulceration),\ud infection and foot pain. However, to date, the precise prevalence of foot\ud complications experienced by people with SLE has not been described.\ud The aim of this survey was to determine self-reported foot and lower\ud limb complications experienced by people with SLE.\ud Methods: The survey was developed via patient and practitioner focus\ud groups. A consensus approach was used to generate items and to\ud formulate themes, categories, question format and survey structure.\ud The survey was checked for face and content validity prior to cognitive\ud debriefing to ensure usability and understanding. Consecutive patients\ud with a confirmed diagnosis of SLE meeting the inclusion criteria\ud attending any of seven UK clinical sites or members of Lupus UK were\ud invited to participate. Ethical approval and participant informed\ud consent was obtained.\ud Results: A total of 182 survey responses were completed. For all\ud responders, the most frequent age range was 40–49 years, mean BMI\ud was 27 (S.D. 7) and mean disease duration was 15 years (S.D. 10). A\ud number of vascular complications were reported, including intermittent\ud claudication [n ¼ 100 (55%)], RP [n ¼ 94 (52%)] and splinter\ud haemorrhage [n ¼ 39 (21%)]. Overall, 164 patients (90%) reported\ud experiencing symptoms of peripheral vascular complications.\ud Symptoms of peripheral neuropathy were reported by 30 patients\ud (16%), while a fall as a consequence of neuropathic symptoms was\ud reported by 45 patients (25%). A range of skin and nail complications\ud were reported, including callus or corns [n ¼ 130 (71%)], onychocryptosis\ud [n ¼ 69 (38%)], rashes or blistering [n ¼ 62 (34%)] and ulceration\ud [n ¼ 45 (25%)]. A high prevalence of infection was reported; a history of\ud viral infection (verrucae pedis) or fungal infection (tinea pedis) was\ud reported by 77 patients (42%), bacterial infection by 28 patients (15%)\ud and onychomycosis by 65 patients (36%). Overall, 170 patients (93%)\ud reported having experienced some form of tissue viability complication.\ud Foot joint pain, stiffness and swelling was reported by 145 (80%), 136\ud (75%) and 94 (52%) patients, respectively. Foot-related walking\ud impairment was reported by 67 patients (37%). Only 60 patients\ud (33%) reported having ever been asked about their feet by a medical\ud professional. Seventy-seven patients (42%) reported that they would\ud benefit from the provision of general foot health care advice.\ud Conclusion: A large number of people with SLE report vascular\ud complications, impaired tissue viability, musculoskeletal problems and\ud foot pain, as well as a range of infections and conditions of the skin\ud and nails. Despite this, foot health assessment by professionals was\ud infrequent. These results highlight the need to undertake clinical\ud studies investigating lower limb pathologies in SLE.

Arteriovenous fistula is a rare complication of peripheral venous cannulation. We report a case of a 79-year-old male who presented with a subcutaneous swelling on the anterio-lateral aspect of his right forearm. The ‘lump’ developed at the same site as the insertion of a previous peripheral venous cannula. Careful clinical examination and later radiological confirmation diagnosed an arteriovenous fistula. The patient was referred to a vascular surgeon for advice regarding further management. This case demonstrates the importance of clinical examination for the accurate diagnosis of ‘Lumps and Bumps’ prior to surgical treatment.

This was one of the invited lectures delivered at the 2014 Simposium for Postgraduate Students in Music in Brazil (SIMPOM), held at the Federal University of the State of Rio de Janeiro, Brazil. The lecture described a variety of collaborative approaches in music composition demonstrated in my work as a composer.

This paper examines how audiences experience live opera performance and the behaviours they exhibit during live-streaming of the performance. It aims to contribute to our understanding of how audiences, who increasingly inhabit an environment saturated with digital media, respond to contemporary opera performance. Based on a comparative study of audience experiences and behaviours during a live opera performance and the streamed opera screening, we investigate whether digital mediation affects audience appreciation, and whether streaming live opera means the same thing to an audience as the unmediated performance. We firstly outline the conception, design and performance of a contemporary opera and its simultaneous streaming to nearby digital screens. Then, we report the evaluation of the project as measured by a mix of qualitative and quantitative methods during the rehearsals, the live performance and the screening. As one of the few social studies of contemporary classical music in Britain, our study of opera audience behaviours sheds light on the challenges and opportunities afforded by digital technologies for opera companies. Understanding how audiences appreciate digital operas offers practical advice on how theatres and opera companies could respond to new forms of digital activities.

The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal. Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci prone to spontaneous activation. Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.