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Abstract Objectives This in vitro work investigates the potential of ostrich eggshell as a substitute for extracted human teeth in preliminary screening studies on dental erosion. Additionally, it aims to demonstrate the potential of ostrich eggshell compared to human enamel in evaluating the efficacy of a preventive agent in protecting against dental erosion, using an artificial mouth model. Methods The experiment utilized 96 erosion testing specimens from each substrate, human enamel, and ostrich eggshell. The specimens were subjected to six different experimental regimens of increasing erosive challenge, simulating the consumption of an acidic drink. The acidic drink was delivered at a consistent volume and duration range. Both artificially stimulated and unstimulated saliva flowed throughout the experimental regimens. Surface hardness was measured using a Through‐Indenter Viewing hardness tester with a Vickers diamond, while surface profiling was done using a surface contacting profilometer with a diamond stylus. An automated chemistry analyzer system was used to detect calcium and phosphate ions. Results The study found that ostrich eggshell specimens demonstrated predictable surface loss, hardness drop, and ion loss due to the acidic challenge. Meanwhile, enamel appeared to fall short in terms of surface hardness predictability. The transient hardness loss phase, which manifests as an overlooked decrease in surface hardness despite significant ion and structural loss, may explain this phenomenon. Conclusions The experiment showed that assessing surface loss is essential in addition to hardness testing, particularly as certain experimental conditions may produce a false perception of tissue recovery despite the actual surface loss. By analyzing the response of ostrich eggshell specimens to erosive challenges, researchers were able to identify an “overlooked” reduction in hardness in enamel specimens. The differences in the structure, chemical composition, and biological response to erosion in the presence of artificial saliva between enamel and ostrich eggshell could explain their distinct behaviors.

ABSTRACTBackground The practice of Dentistry has adapted in the past after encountering transformational episodes with novel pathogens. This article highlights two examples of how dentists in California were granted privileges to expand their scope of practice into areas of diagnostics and prevention while at the same time incorporating new barriers to an airborne pathogen. The SARS-Cov-2 virus elevated the scope of universal precautions in dentistry with changes to acceptable PPE, administrative practices, airspace filtering and the screening of patients – including the use rapid testing for SARS-Cov-2. When a COVID-19 vaccine became available, dentists were approved to be vaccinators for the first time in California. Creation of opportunities to vaccinate at every entry point into the healthcare system, including dental offices, was vital for increased access to preventive care.Practical Implications Dentists can play a major role in disease prevention and continued advocacy for removing barriers to their role in pandemic response should continue. Coordinating with medical partners to provide testing and community vaccine confidence is necessary to help combat future flu seasons and Covid surges. With improvement in the technology of diagnostics, delivery of care, and improving patient outcomes, dental clinicians can effectively integrate disease prevention if system barriers are removed.

Shallow groundwater is vulnerable to faecal contamination, especially in low-income urban areas where use of on-site sanitation facilities is high. This paper explores statistical relationships between potential factors influencing contaminant pathways (i.e., variables) and observed faecal contamination of shallow groundwater, represented by nitrate concentrations and counts of Escherichia coli (i.e., response function) in a small, growing town in Uganda over dry and wet seasons in 2018 and 2019. A statistically significant (p = 0.004) multiple linear regression model from dry-season E. coli counts in 2018 identifies medium sanitary risk levels and modes of construction as significant pathways (p = 0.01). Water source depth (10 m) to a pit latrine were also significant (p

Introduction Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin’s lymphoma (NHL) receiving anthracycline-based chemotherapy.Methods and analysis PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects.Ethics and dissemination A favourable opinion was given following research ethics committee review by West Midlands—Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication.Trial registration number NCT03265574.

One major challenge facing farmers and other end users of weather and climate information (WCI) in Kenya is the linkage between their perceptions, needs, and engagements with producers of the information. This is highlighted by increased interest in understanding the constraints on appropriate use of weather information by farmers in decision-making. The choice between sub-seasonal and seasonal forecasts can enable better decisions by farmers if the forecast information is reliable and integrated through a coproduction process. This study analyzes user needs and perceptions of crop farmers, pastoralists, and agro-pastoralists in relation to sub-seasonal and seasonal forecasts for five counties in Kenya. A total of 258 peer-reviewed articles and gray literature were systematically analyzed using Search, Appraisal, Synthesis and Analysis (SALSA) to understand how the needs and perceptions of users of WCI shaped access and use in decision-making. The study also evaluated factors influencing use and uptake of sub-seasonal and seasonal forecasts as well as the barriers to use. Results show that farmers' perceptions shaped the choice of WCI that is used and also highlight how sub-seasonal and seasonal forecasts were used for diverse applications. Gender, availability of resources, access, and mode of communication were key factors influencing the use of seasonal forecasts. For example, access to seasonal forecasts of farmers in drier counties enabled them to manage floods and reduce risk. One lesson learned was that farmers combined WCI with other coping practices such as agronomic practices and water efficiency management. Despite a number of challenges by forecast users such as insufficient resources and lack of access to information, there is potential to improve forecasts according to user needs through a coproduction process. This study recommends stakeholder engagements with producers in the development and evaluation of forecast products and communication pathways to improve uptake and use of forecasts in decision-making.

Introduction Numbers of patients undergoing mitral valve repair (MVr) surgery for severe mitral regurgitation have grown and will continue to rise. MVr is routinely performed via median sternotomy; however, there is a move towards less invasive surgical approaches.There is debate within the clinical and National Health Service (NHS) commissioning community about widespread adoption of minimally invasive MVr surgery in the absence of robust research evidence; implementation requires investment in staff and infrastructure.The UK Mini Mitral trial will provide definitive evidence comparing patient, NHS and clinical outcomes in adult patients undergoing MVr surgery. It will establish the best surgical approach for MVr, setting a standard against which emerging percutaneous techniques can be measured. Findings will inform optimisation of cost-effective practice.Methods and analysis UK Mini Mitral is a multicentre, expertise based randomised controlled trial of minimally invasive thoracoscopically guided right minithoracotomy versus conventional sternotomy for MVr. The trial is taking place in NHS cardiothoracic centres in the UK with established minimally invasive mitral valve surgery programmes. In each centre, consenting and eligible patients are randomised to receive surgery performed by consultant surgeons who meet protocol-defined surgical expertise criteria. Patients are followed for 1 year, and consent to longer term follow-up.Primary outcome is physical functioning 12 weeks following surgery, measured by change in Short Form Health Survey (SF-36v2) physical functioning scale. Early and 1 year echo data will be reported by a core laboratory. Estimates of key clinical and health economic outcomes will be reported up to 5 years.The primary economic outcome is cost effectiveness, measured as incremental cost per quality-adjusted life year gained over 52 weeks following index surgery.Ethics and dissemination A favourable opinion was given by Wales REC 6 (16/WA/0156). Trial findings will be disseminated to patients, clinicians, commissioning groups and through peer reviewed publication.Trial registration number ISRCTN13930454.

Valiosas percepções podem ser extraídas de dados quantitativos,mesmo por historiadores não-quantitativos. Isto é particularmente verdadeiro porque tais dados freqüentemente sugerem padrões comuns de comportamento nem sempre vistos e muito menos compreendidos a seu tempo, bem como porque precisamente tais padrões gerais mostram a importância de desvios particulares. A informação quantitativa também pode levar os pesquisadores a formular questões que, de outra forma, não pensariam em levantar, especialmente quando ela é sujeita à análise comparativa. Neste artigo, ofereço exemplos extraídos das minhas próprias experiências ao estudar temas como a família escrava, o número de escravos nas embarcações que abasteciam Salvador com alimento e seu papel na guerra de Independência na Bahia, o consumo per capita de farinha de mandioca em Salvador na primeira metade do século XIX, a cultura política do clientelismo durante a segunda metade do mesmo século e o poder aquisitivo do mil-réis de 1780 a 1860.

Background: Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. Objectives: To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway. Design: A validating paired-cohort study and an economic evaluation using a decision-analytic model. Setting: Eleven NHS hospitals in England. Participants: Men at risk of prostate cancer undergoing a first prostate biopsy. Interventions: Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test). Main outcome measures: Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy. Results: Diagnostic study – a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation – the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer. Limitations: The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy. Conclusions: Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission. Trial registration: Current Controlled Trials ISRCTN16082556 and NCT01292291. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council’s Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK.

O trabalho analisa como os afro-brasi­leiros (descendentes de africanos) foram afetados pelas novas estruturas políticas e pela ideologia adotadas pelas elites políticas do século XIX. Durante o Im­pério, o Brasil apresentava uma tensão entre a ideologia do liberalismo e as an­tigas características de uma sociedade hierarquizada, onde os descendentes de africanos haviam construído certas for­mas de vida comunitária. A consolida­ção de valores individuais permitiu a as­censão política e social de algumas per­sonalidades entre os afro-brasileiros, mas a maioria continuava excluída. (Tradução Ana Maria Santos)

BackgroundSince red blood cells (RBCs) are the predominant cellular blood component interacting with the arterial wall, we explored the role of RBCs efferocytosis by vascular smooth muscle cells (vSMCs) in the initiation of human atheroma.Methods and resultsThe comparison of human healthy aortas with aortic fatty streaks or fibroatheromas revealed that RBC angiophagy is implicated from the earliest stages of atherogenesis, as documented by the concomitant detection of redox-active iron, hemoglobin, glycophorin A, and ceroids. RBCs infiltration in the arterial wall was associated with local lipid and protein oxidation, as well as vascular response (expression of heme oxygenase-1 and of genes related to iron metabolism as well as those encoding for phagocytosis). These effects were recapitulated in vitro when vSMCs were co-cultured with phosphatidyl-exposing senescent (s) RBCs but not with fresh RBCs. VSMCs engulfing sRBC increased their intracellular iron content, accumulated hemoglobin, lipids, and activated their phagolysosomes. Strikingly, injections of sRBCs into rats promoted iron accumulation in the aortic wall. In rabbits, hypercholesterolemia increased circulating senescent RBCs and induced the subendothelial accumulation of iron-rich phagocytic foam cells. RBCs bring cholesterol and iron/heme into the vascular wall and interact with vSMCs that phagocytize them.ConclusionThis study presents a previously unforeseen mechanism of plaque formation that implicates intimal RBC infiltration as one of the initial triggers for foam cell formation and intimal oxidation. Pathogenic effects exerted by several metabolic and hemodynamic factors may rely on their effect on RBC biology, thereby impacting how RBCs interact with the vascular wall.

É uma honra saber que meu artigo “Constructing a nation in nineteenth-century Brazil” (Construindo uma nação no Brasil do século 19) despertou comentários de dois historiadores tão importantes como Thomas Holloway e Lilia Schwarcz. No meu ensaio, concluí, entre outras coisas, que a criação do estado central brasileiro foi projeto de uma elite sócio-econômica de senhores de escravos e proprietários de terras. Através de suas instituições e liderança cultural esse estado atribuiu maior legitimidade aos fazendeiros para exercer seus poderes locais e regionais. Mas eu insisti que foram eles que criaram aquele estado, fazendo-o especificamente para proteger e incrementar seus interesses sociais e econômicos, especialmente a manutenção da escravatura, a subserviência dos que não possuíam terras, e o evitar uma revolução social. De fato, foi antes de mais nada o medo da desordem social que levou os proprietários a construir um governo central forte, e eles disseram isso. Também argumentei que foi através da criação e desenvolvimento daquele estado que os líderes de todo o país começaram a abandonar seus desejos de autonomia ou independência, local ou regional, e começaram a pensar seus destinos ligados à unidade brasileira. Desta maneira, a idéia de uma nação emergiu, ao menos no meio dessas elites, enquanto eles começaram a se identificar, verdadeira e profundamente, como brasileiros.

Neste ensaio, o autor contribui significativamente para com o estudo da formação do Estado e da construção das nações no Brasil e na América Espanhola, durante e depois do período de emancipação política no século XIX. Baseado num amplo conhecimento da literatura sobre os temas que desenvolve e pela notável familiaridade do autor com seu objeto, este ensaio contribui para o avanço no entendimento, bem como para discussões futuras entre historiadores, de importantes questões relacionadas aos interesses de classe, o desenvolvimento das instituições estatais e o senso de nacionalismo. Abstract. In this essay, the author addresses important issues in the comparative study of state formation and the contruction of nations in Brazil and Spanish America, during and after the period of political independence in the early nineteenth century. Informed by a wide-ranging assessment of the literature on the themes it addresses and by the author's close familiarity with the subject matter, this essay serves to advance understanding, as well as to further discussion among historians of important questions relating to the causal sequence of class interests, the development of state institutions, and a sense of nationalism.

The Long-Rains wet season of March–May (MAM) over Kenya in 2018 was one of the wettest on record. This paper examines the nature, causes, impacts, and predictability of the rainfall events, and considers the implications for flood risk management. The exceptionally high monthly rainfall totals in March and April resulted from several multi-day heavy rainfall episodes, rather than from distinct extreme daily events. Three intra-seasonal rainfall events in particular resulted in extensive flooding with the loss of lives and livelihoods, a significant displacement of people, major disruption to essential services, and damage to infrastructure. The rainfall events appear to be associated with the combined effects of active Madden–Julian Oscillation (MJO) events in MJO phases 2–4, and at shorter timescales, tropical cyclone events over the southwest Indian Ocean. These combine to drive an anomalous westerly low-level circulation over Kenya and the surrounding region, which likely leads to moisture convergence and enhanced convection. We assessed how predictable such events over a range of forecast lead times. Long-lead seasonal forecast products for MAM 2018 showed little indication of an enhanced likelihood of heavy rain over most of Kenya, which is consistent with the low predictability of MAM Long-Rains at seasonal lead times. At shorter lead times of a few weeks, the seasonal and extended-range forecasts provided a clear signal of extreme rainfall, which is likely associated with skill in MJO prediction. Short lead weather forecasts from multiple models also highlighted enhanced risk. The flood response actions during the MAM 2018 events are reviewed. Implications of our results for forecasting and flood preparedness systems include: (i) Potential exists for the integration of sub-seasonal and short-term weather prediction to support flood risk management and preparedness action in Kenya, notwithstanding the particular challenge of forecasting at small scales. (ii) We suggest that forecasting agencies provide greater clarity on the difference in potentially useful forecast lead times between the two wet seasons in Kenya and East Africa. For the MAM Long-Rains, the utility of sub-seasonal to short-term forecasts should be emphasized; while at seasonal timescales, skill is currently low, and there is the challenge of exploiting new research identifying the primary drivers of variability. In contrast, greater seasonal predictability of the Short-Rains in the October–December season means that greater potential exists for early warning and preparedness over longer lead times. (iii) There is a need for well-developed and functional forecast-based action systems for heavy rain and flood risk management in Kenya, especially with the relatively short windows for anticipatory action during MAM.

In this essay, the author addresses important issues in the comparative study of state formation and the contruction of nations in Brazil and Spanish America, during and after the period of political independence in the early nineteenth century. Informed by a wide-ranging assessment of the literature on the themes it addresses and by the author's close familiarity with the subject matter, this essay serves to advance understanding, as well as to further discussion among historians of important questions relating to the causal sequence of class interests, the development of state institutions, and a sense of nationalism.Neste ensaio, o autor contribui significativamente para com o estudo da formação do Estado e da construção das nações no Brasil e na América Espanhola, durante e depois do período de emancipação política no século XIX. Baseado num amplo conhecimento da literatura sobre os temas que desenvolve e pela notável familiaridade do autor com seu objeto, este ensaio contribui para o avanço no entendimento, bem como para discussões futuras entre historiadores, de importantes questões relacionadas aos interesses de classe, o desenvolvimento das instituições estatais e o senso de nacionalismo.

Neste meio tempo, entretanto, ocorreú um segundo incidente que tornou-se base das queixas futuras. Indicando que os tribunais brasileiros não mereciam ser reconhecidos pelas nações "civilizadas" o Govêrno Inglês propôs que um oficial britânico participasse das investigações do caso Prince of Wales. A recusa brasileira a esta proposta foi tomada co-mo um insulto à Marinha Britânica.