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In the United States, science education has experienced substantial shifts in the last decade. For in-service teachers, professional development programs (PDPs) play an important role in reform success. Despite well-known core features of effective PDPs, research still suggests a range of results among programs that claim to use those features. An analysis of the nuances associated with these core features has emerged as an important step in bridging the gap between conceptual and actual effective PD. This article presents the validation of constructs for "responsive facilitation", which may serve as a source of these nuances. Using an adapted Delphi Method, constructs were validated by multiple expert groups. A 10-construct consensus is presented with an eleventh remaining under dispute. All constructs have connections to current literature and may support the gap noted above. Implications include a structure that may provide nuance to the core features and support more consistently effective PD.

Despite some progress, universal access to safe water, sanitation and hygiene (WASH) by 2030—a remit of Sustainable Development Goal 6—remains a distant prospect in many countries. Policy-makers and implementers of the WASH sector are challenged to track a new path. This research aimed to identify core orienting themes of the sector, as legacies of past processes, which can provide insights for its future. We reviewed global policy, science and programmatic documents and carried out 19 expert interviews to track the evolution of the global WASH sector over seven decades. We situated this evolution in relation to wider trends in global health and development over the same time period.With transnational flows of concern, expertise and resources from high-income to lower-income countries, the WASH sector evolved over decades of international institutionalisation of health and development with (1) a focus on technologies (technicalisation), (2) a search for generalised solutions (universalisation), (3) attempts to make recipients responsible for environmental health (responsibilisation) and (4) the shaping of programmes around quantifiable outcomes (metricisation). The emergent commitment of the WASH sector to these core themes reflects a pragmatic response in health and development to depoliticise poverty and social inequalities in order to enable action. This leads to questions about what potential solutions have been obscured, a recognition which might be understood as ‘uncomfortable knowledge’—the knowns that have had to be unknown, which resonate with concerns about deep inequalities, shrinking budgets and the gap between what could and has been achieved.

Background: The adoption of e-platforms for use in clinical and administrative processes within health facilities in many African countries has been slow. Objectives: To assess the opinion of physicians on the usefulness and impact of e-platforms in their practice. Materials and Methods: Information was obtained from 236 physicians using an online pre-tested and validated 29-item questionnaire. Results: The majority of the respondents, 57.2% agreed that information and communication technology (ICT) reduced errors in patient records in the clinics and emergency room and 22.8% disagreed, whereas 19.9% were neutral. On whether ICT helped to curb cases of missing medical records, 76.7% agreed and 9.7% disagreed, whereas 13.6% were neutral. Concerning ICT platforms being user-friendly and easy to understand, 64% agreed and 12.3% disagreed, whereas 23.7% were neutral. On whether the clinics experienced faster reviews and turnaround time, 48.4% agreed and 20.8% disagreed, whereas 30.9% were neutral. While 27.1% agreed that excess workload had been reduced in their clinic in the past 3 years because of these new platforms and 28.8% disagreed, 44.1% were neutral. On clinics being less crowded as a result, 28.8% agreed and 32.2% disagreed, whereas 39% were neutral. There was no difference in the responses obtained across the various cadres of physicians or their years of experience. Conclusion: Most respondents agreed that communication with other health facilities and ease of accessing patients′ clinical and laboratory details have been improved by using e-platforms. Responses obtained did not vary across the various cadre of physicians or with their years of experience. Translating these innovations to impact patients’ satisfaction, reduction in workload, and overcrowding are of major importance.

Abstract Analysis of environmental DNA (eDNA) has gained widespread usage for taxonomically based biodiversity assessment. While interest in applying noninvasive eDNA monitoring for population genetic assessments has grown, its usage in this sphere remains limited. One barrier to uptake is that the effectiveness of eDNA detection below the species level remains to be determined for multiple species and environments. Here, we test the utility of this emergent technology to obtain within‐species haplotypic variation of New Zealand (NZ) blackfoot pāua (Haliotis iris). We compare mitochondrial haplotype diversity recovered from marine eDNA samples against traditional tissue samples of blackfoot pāua collected at the same NZ coastal site. Targeting the ATP8‐ATP6 region, we recovered four mitochondrial haplotypes from eDNA versus six haplotypes from tissue samples. Three common haplotypes were recovered with both eDNA and tissue samples, while only one out of three rare haplotypes – represented in tissue samples by one individual each – was recovered with our eDNA methods. We demonstrate that eDNA monitoring is an effective tool for recovering common genetic diversity from pāua, although rare (

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems.

The mass production of antibiotics in the 1940s enabled their travel beyond Europe and America, but to date the significance of the ways in which these medicines co-constituted colonial regimes at the time has not been systematically described. Through a case study of yaws and syphilis, this research article traces arrivals of antibiotics in three countries of Eastern Africa—Malawi, Zimbabwe, and Uganda. We draw attention to the emergent roles of antibiotics at the intersection of colonial governance and humanitarianism in these different settings. Through this analysis of archival and ethnographic materials, we explore how antibiotics became ‘infrastructural’ in material, affective, and political ways. Achieving a better understanding of the entanglement of antibiotics with human systems and lives is crucial to address the pressing issue of antimicrobial resistance (AMR). With this article we join in the global multidisciplinary efforts to tackle AMR, pointing out the often-overlooked role of colonial history in the circulation of antibiotic drugs, and opening a line of research that will provide valuable insights for the development of effective measures to prevent and reduce the spread of antibiotic resistance.

Epigenetic mechanisms allow cells to fine-tune gene expression in response to environmental stimuli. For decades, it has been known that mitochondria have genetic material. Still, only recently have studies shown that epigenetic factors regulate mitochondrial DNA (mtDNA) gene expression. Mitochondria regulate cellular proliferation, apoptosis, and energy metabolism, all critical areas of dysfunction in gliomas. Methylation of mtDNA, alterations in mtDNA packaging via mitochondrial transcription factor A (TFAM), and regulation of mtDNA transcription via the micro-RNAs (mir 23-b) and long noncoding RNAs [RNA mitochondrial RNA processing (RMRP)] have all been identified as contributing to glioma pathogenicity. Developing new interventions interfering with these pathways may improve glioma therapy.

In Guillain-Barré syndrome (GBS), both axonal and demyelinating variants can be mediated by complement-fixing anti–GM1 ganglioside autoantibodies that target peripheral nerve axonal and Schwann cell (SC) membranes, respectively. Critically, the extent of axonal degeneration in both variants dictates long-term outcome. The differing pathomechanisms underlying direct axonal injury and the secondary bystander axonal degeneration following SC injury are unresolved. To investigate this, we generated glycosyltransferase-disrupted transgenic mice that express GM1 ganglioside either exclusively in neurons [GalNAcT–/–-Tg(neuronal)] or glia [GalNAcT–/–-Tg(glial)], thereby allowing anti-GM1 antibodies to solely target GM1 in either axonal or SC membranes, respectively. Myelinated-axon integrity in distal motor nerves was studied in transgenic mice exposed to anti-GM1 antibody and complement in ex vivo and in vivo injury paradigms. Axonal targeting induced catastrophic acute axonal disruption, as expected. When mice with GM1 in SC membranes were targeted, acute disruption of perisynaptic glia and SC membranes at nodes of Ranvier (NoRs) occurred. Following glial injury, axonal disruption at NoRs also developed subacutely, progressing to secondary axonal degeneration. These models differentiate the distinctly different axonopathic pathways under axonal and glial membrane targeting conditions, and provide insights into primary and secondary axonal injury, currently a major unsolved area in GBS research.

In the United States, science education has experienced substantial shifts in the last decade. For in-service teachers, professional development programs (PDPs) play an important role in reform success. Despite well-known core features of effective PDPs, research still suggests a range of results among programs that claim to use those features. An analysis of the nuances associated with these core features has emerged as an important step in bridging the gap between conceptual and actual effective PD. This article presents the validation of constructs for responsive facilitation, which may serve as a source of these nuances. Using an adapted Delphi Method, constructs were validated by multiple expert groups. A 10-construct consensus is presented with an eleventh remaining under dispute. All constructs have connections to current literature and may support the gap noted above. Implications include a structure that may provide nuance to the core features and support more consistently effective PD. [ABSTRACT FROM AUTHOR]

Research on science teaching and learning supports instructional sequences that are driven by phenomena, provide student agency, and are made relevant to students. The use of locally based, phenomenon-driven instruction that creates opportunities for students to engage in coherent investigations can provide opportunities to realize a vision of science for all students. The purpose of this article is to share a local, phenomenon-based instructional sequence that supported all students in connecting to their place, drawing from their experiences, and pursuing their curiosities to make sense of an intriguing event while learning about science ideas. By using local examples, our students were able to quickly connect to the material and focus on the concepts rather than trying to make sense of the landscape. They were able to use the local phenomenon as an anchor for understanding these abstract physical science concepts in meaningful ways. [ABSTRACT FROM AUTHOR]

Abstract Background There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. Methods Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. Results Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of

Drug resistant infections are increasing across the world and urgent action is required to preserve current classes of antibiotics. Antibiotic use practices in low-and-middle-income countries have gained international attention, especially as antibiotics are often accessed beyond the formal health system. Public awareness campaigns have gained popularity, often conceptualising antimicrobial resistance (AMR) as a problem of excess, precipitated by irrational behaviour. Insufficient attention has been paid to people's lived experiences of accessing medicines in low-income contexts. In Chikwawa District, Malawi, a place of extreme scarcity, our study aimed to understand the care and medicine use practices of households dependent on subsistence farming. Adopting an anthropological approach, we undertook medicine interviews (100), ethnographic fieldwork (six-month period) and key informant interviews (33) with a range of participants in two villages in rural Chikwawa. The most frequently used drugs were cotrimoxazole and amoxicillin, not considered to be of critical importance to human health. Participants recognised that keeping, sharing, and buying medicines informally was not the "right thing." However, they described using antibiotics and other medicines in these ways due to conditions of extreme precarity, the costs and limitations of seeking formal care in the public sector, and the inevitability of future illness. Our findings emphasise the need in contexts of extreme scarcity to equip policy actors with interventions to address AMR through strengthening health systems, rather than public awareness campaigns that foreground overuse and the dangers of using antibiotics beyond the formal sector.

Addressing antibiotic use is essential to tackle antimicrobial resistance, a major human and animal health challenge. This review seeks to inform stewardship efforts in companion animals by collating research insights regarding antibiotic use in this group and identifying overlooked avenues for future research and stewardship efforts. The development of population-based methods has established that antibiotics are frequently used in companion animal care. Research insights are also contributing toward an in-depth comprehension of the contexts to antibiotic use. Qualitative approaches, for example, have enabled a nuanced understanding in four key areas: interactions with owners, clinical and financial risk management, time pressures, and clinic dynamics. This review identifies that much of the existing research frames antibiotic use as the result of choices made by the individuals at the interface of their use. Future research and policy endeavours could look beyond the moment of prescribing to consider the societal structures and networks in which companion animal antibiotic use is entangled. A diversification in research approaches and frameworks through which antibiotic use is understood will facilitate the identification of additional targets for stewardship initiatives beyond providing information and awareness campaigns.

Environmental disturbances have long been theorized to play a significant role in shaping the diversity and composition of ecosystems. However, an inability to specify the characteristics of a disturbance experimentally has produced an inconsistent picture of diversity-disturbance relationships (DDRs). Here, using a high-throughput programmable culture system, we subjected a soil-derived bacterial community to dilution disturbance profiles with different intensities (mean dilution rates), applied either constantly or with fluctuations of different frequencies. We observed an unexpected U-shaped relationship between community diversity and disturbance intensity in the absence of fluctuations. Adding fluctuations increased community diversity and erased the U-shape. All our results are well-captured by a Monod consumer resource model, which also explains how U-shaped DDRs emerge via a novel ‘niche flip’ mechanism. Broadly, our combined experimental and modeling framework demonstrates how distinct features of an environmental disturbance can interact in complex ways to govern ecosystem assembly and offers strategies for reshaping the composition of microbiomes.

In Guillain-Barre syndrome (GBS), both axonal and demyelinating variants can be mediated by complement-fixing anti-GM1 ganglioside autoantibodies that target peripheral nerve axonal and Schwann cell (SC) membranes, respectively. Critically, the extent of axonal degeneration in both variants dictates long-term outcome. The differing pathomechanisms underlying direct axonal injury and the secondary bystander axonal degeneration following SC injury are unresolved. To investigate this, we generated glycosyltransferase-disrupted transgenic mice that express GM1 ganglioside either exclusively in neurons [[GalNAcT.sup.-/-]-Tg(neuronal)] or glia [[GalNAcT.sup.-/-]-Tg(glial)], thereby allowing anti-GM1 antibodies to solely target GM1 in either axonal or SC membranes, respectively. Myelinated-axon integrity in distal motor nerves was studied in transgenic mice exposed to anti-GM1 antibody and complement in ex vivo and in vivo injury paradigms. Axonal targeting induced catastrophic acute axonal disruption, as expected. When mice with GM1 in SC membranes were targeted, acute disruption of perisynaptic glia and SC membranes at nodes of Ranvier (NoRs) occurred. Following glial injury, axonal disruption at NoRs also developed subacutely, progressing to secondary axonal degeneration. These models differentiate the distinctly different axonopathic pathways under axonal and glial membrane targeting conditions, and provide insights into primary and secondary axonal injury, currently a major unsolved area in GBS research., Introduction Guillain-Barre syndrome (GBS) is a postinfectious autoimmune disorder affecting the peripheral nervous system (PNS) resulting in acute-onset paralysis (1). GBS comprises a spectrum of axonal and demyelinating variants that [...]

Abstract Background Intermittent preventive treatment (IPT) of malaria is recommended as policy for certain high-risk populations, but not currently for schoolchildren. A cluster-randomized trial was conducted to evaluate the effect of IPT with dihydroartemisinin–piperaquine (DP) on primary schoolchildren in Jinja, Uganda. Results of the impact of IPT of schoolchildren on community-level transmission have been reported previously. Here, secondary outcomes from a school-based survey are presented. Methods Eighty-four clusters (one primary school plus 100 households) were randomized to intervention and control (1:1 ratio). Participants from intervention schools received monthly IPT with DP for up to 6 rounds (June–December 2014). At endline (November–December 2014), randomly selected children from all 84 schools were surveyed (13 per school) and thick blood smears were done. Those with fever or history of fever were tested with rapid diagnostic tests (RDTs) for malaria. Haemoglobin was measured in every fifth participant. Outcome measures included prevalence of asexual parasites and gametocytes (by microscopy), and prevalence of anaemia. Prevalence outcomes were analysed using generalized linear Poisson models with log link function, incorporating a cluster-level random intercept and quantified using prevalence risk ratios. Results Among 23,280 students listed on the 42 intervention school registers, 10,079 (43.3%) aged 5–20 years were enrolled into the IPT intervention and received at least one dose of DP; of these, 9286 (92.1%) received at least one full (3-day) course. In total, 1092 children were enrolled into the final school survey (546 per arm) and had a thick blood smear done; of these, 255 had haemoglobin measured (129 intervention, 126 control). Children in the intervention arm were less likely to have asexual parasites (9.2% intervention vs 44.1% control, adjusted risk ratio [aRR] 0.22 [95% CI 0.16–0.30] p

Environmental stress can affect the outcome of ecological competition. Here, the authors use theory and experiments with a synthetic microbial community to show that a tradeoff between growth rate and competitive ability determines which species prevails when the population faces variable mortality rates.

Climatic changes and anthropogenic pressures affect biodiversity and community composition. These biodiversity shifts are recognized in marine ecosystems, but the underlying processes are barely understood so far. Importantly, human well-being highly relies on oceanic services, which are affected by anthropogenic pressures. Here, we review how interdisciplinary research approaches, with the incorporation of eDNA (environmental DNA) analyses, can help increase the understanding of complex ecosystem processes and dynamics, and how they affect ecosystem services. We discuss marine conservation issues in the light of life cycle aspects and conclude that eDNA can improve our ecological knowledge in some instances, for example, in tracking migration patterns. We also illustrate and discuss the application of eDNA analysis within the context of population genetics, epigenetics, geochemistry and oceanography. Embedded into an interdisciplinary context, eDNA can be exploited by a huge variety of methodological techniques, and can resolve spatio-temporal patterns of diversity, species, or even populations within ecological, evolutionary, and management frameworks.

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an ‘implementation gap’. At a policy level, the design of internationally salient solutions that are able to address AMR’s interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise ‘good’ antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.

The effect of environmental fluctuations is a major question in ecology. While it is widely accepted that fluctuations and other types of disturbances can increase biodiversity, there are fewer examples of other types of outcomes in a fluctuating environment. Here we explore this question with laboratory microcosms, using cocultures of two bacterial species, P. putida and P. veronii. At low dilution rates we observe competitive exclusion of P. veronii, whereas at high dilution rates we observe competitive exclusion of P. putida. When the dilution rate alternates between high and low, we do not observe coexistence between the species, but rather alternative stable states, in which only one species survives and initial species' fractions determine the identity of the surviving species. The Lotka-Volterra model with a fluctuating mortality rate predicts that this outcome is independent of the timing of the fluctuations, and that the time-averaged mortality would also lead to alternative stable states, a prediction that we confirm experimentally. Other pairs of species can coexist in a fluctuating environment, and again consistent with the model we observe coexistence in the time-averaged dilution rate. We find a similar time-averaging result holds in a three-species community, highlighting that simple linear models can in some cases provide powerful insight into how communities will respond to environmental fluctuations.

Understanding the prevalence and types of antibiotics used in a given human and/or animal population is important for informing stewardship strategies. Methods used to capture such data often rely on verbal elicitation of reported use that tend to assume shared medical terminology. Studies have shown the category ‘antibiotic’ does not translate well linguistically or conceptually, which limits the accuracy of these reports. This article presents a ‘Drug Bag’ method to study antibiotic use (ABU) in households and on farms, which involves using physical samples of all the antibiotics available within a given study site. We present the conceptual underpinnings of the method, and our experiences of using this method to produce data about antibiotic recognition, use and accessibility in the context of anthropological research in Africa and South-East Asia. We illustrate the kinds of qualitative and quantitative data the method can produce, comparing and contrasting our experiences in different settings. The Drug Bag method can produce accurate antibiotic use data as well as provide a talking point for participants to discuss antibiotic experiences. We propose it can help improve our understanding of antibiotic use in peoples’ everyday lives across different contexts, and our reflections add to a growing conversation around methods to study ABU beyond prescriber settings, where data gaps are currently substantial.

Kynurenine-3-monooxygenase (KMO) is an emerging clinical target for treatment of neurodegenerative diseases and acute pancreatitis. Here, the authors report potent inhibitors that bind KMO in an unexpected conformation, offering structural and mechanistic insights for future drug discovery ventures.

Background: Blindness from glaucoma is associated with socio-economic deprivation, presumed to reflect poor access to care and poor adherence to treatment. Objectives: To determine why people with glaucoma are presenting late for treatment and to understand access to glaucoma care. Additionally, we sought to identify what patients and the community know, do and think about the condition and why the poor are the most affected with glaucoma blindness. Design: Study participants were from four communities and two hospitals in Abuja-FCT and Kaduna State, Nigeria. A total of 120 participants were involved, including 8 focus group discussions, 7 in-depth interviews with blind/visually impaired glaucoma patients, 5 rapid direct observation visits with these patients and 13 exit interviews of glaucoma patients in the hospital. The data were analysed using content analysis, interpreting participant experiences in terms of three key steps conceptualised as important in the care pathway: what it takes to know glaucoma, to reach a diagnosis and to access continued care. Results: This article presents multiple narratives of accessing and maintaining glaucoma care and how people manage and cope with the disease. People may be presenting late due to structural barriers, which include lack of knowledge and awareness about glaucoma and not finding an appropriately equipped health care facility. What keeps glaucoma patients within the care pathway are a good hospital experience; a support structure involving family, counselling and shared patients’ experiences; and an informed choice of treatment, as well as agency. The high cost of purchasing care is a major factor for patients dropping out of treatment. Conclusion: The findings suggest the need to address economic and social structural drivers as glaucoma presents another case study to demonstrate that poverty is a strong driver for blindness. There is also a need for clear glaucoma care pathways with early case finding in the community, two-way referral/feedback systems, well-equipped glaucoma care hospitals and better eye health care financing.