Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines

The Citation Field of Evolutionary Economics

Evolutionary economics has developed into an academic field of its own, institutionalized around, amongst others, the Journal of Evolutionary Economics (JEE). This paper analyzes the way and extent to which evolutionary economics has become an interdisciplinary journal, as its aim was: a journal that is indispensable in the exchange of expert knowledge on topics and using approaches that relate naturally with it. Analyzing citation data for the relevant academic field for the Journal of Evolutionary Economics, we use insights from scientometrics and social network analysis to find that, indeed, the JEE is a central player in this interdisciplinary field aiming mostly at understanding technological and regional dynamics. It does not, however, link firmly with the natural sciences (including biology) nor to management sciences, entrepreneurship, and organization studies. Another journal that could be perceived to have evolutionary acumen, the Journal of Economic Issues, does relate to heterodox economics journals and is relatively more involved in discussing issues of firm and industry organization. The JEE seems most keen to develop theoretical insights

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

First report on dung beetles in intra-Amazonian savannahs in Roraima, Brazil

This is the first study to address the dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae) diversity in intra-Amazonian savannahs in the state of Roraima, Brazil. Our aim was to survey the dung beetle fauna associated with these savannahs (regionally called 'lavrado'), since little is known about the dung beetles from this environment. We conducted three field samples using pitfall traps baited with human dung in savannah areas near the city of Boa Vista during the rainy seasons of 1996, 1997, and 2008. We collected 383 individuals from ten species, wherein six have no previous record in intra-Amazonian savannahs. The most abundant species were Ontherus appendiculatus (Mannerheim, 1829), Canthidium aff. humerale (Germar, 1813), Dichotomius nisus (Olivier, 1789), and Pseudocanthon aff. xanthurus (Blanchard, 1846). We believe that knowing the dung beetles diversity associated with the intra-Amazonian savannahs is ideal for understanding the occurrence and distribution of these organisms in a highly threatened environment, it thus being the first step towards conservation strategy development

Resposta terapêutica e profilática com ferro e ácido fólico na anemia em crianças de creches públicas em Goiânia, Goiás, Brasil: ensaio clínico randomizado

The objective of this study was to assess the prevalence of anemia and the therapeutic and prophylactic response to ferrous sulfate and folic acid. A double-blind, randomized, controlled clinical trial was conducted with 196 children 6 to 24 months of age enrolled in municipal daycare centers in Goiânia, Goiás State, Brazil. The children were assigned to two treatment groups that received a daily dose (5 times a week) of either 4.2mg/kg/day of ferrous sulfate + folic acid (50µg) or 4.2mg/kg/day of ferrous sulfate + folic acid placebo. One of the prevention groups received 1.4mg/kg/day of ferrous sulfate + folic acid (50µg/day) and the other 1.4mg/kg/day of ferrous sulfate + folic acid placebo. Supplementation lasted approximately three months. Baseline anemia prevalence was 56.1% (95%CI: 48.9-63.1). After treatment, anemia prevalence in the folic acid group (14%) was lower than in the placebo group (34.9%) (p = 0.02). After prophylaxis in the non-anemic children, the incidence of anemia did not differ between the groups, but there was an increase in hemoglobin level in the folic acid group (p = 0.003). Iron plus folic acid was effective for the treatment of anemia and improvement of hemoglobin level in non-anemic children.Avaliar a prevalência de anemia e a resposta terapêutica e profilática do sulfato ferroso e ácido fólico. Realizou-se um ensaio clínico controlado randomizado, duplo-cego, com 196 crianças de 6 a 24 meses, dos Centros Municipais de Educação Infantil de Goiânia, Goiás, Brasil. As crianças foram alocadas em dois grupos de tratamento que receberam dose diária (5x/semana) com 4,2mg/kg/dia de sulfato ferroso + ácido fólico (50µg) ou 4,2mg/kg/dia de sulfato ferroso + placebo de ácido fólico. Um dos grupos de prevenção recebeu 1,4 mg/kg/dia de sulfato ferroso + ácido fólico (50µg/dia) e o outro 1,4mg/kg/dia de sulfato ferroso + placebo de ácido fólico. A suplementação durou cerca de três meses. A prevalência de anemia inicial foi de 56,1% (IC95%: 48,9-63,1). Após o tratamento, a prevalência de anemia no grupo ácido fólico (14%) foi menor que no grupo placebo (34,9%; p = 0,02). Após profilaxia dos não anêmicos, a incidência de anemia não diferiu entre os grupos, porém, houve incremento da hemoglobina no grupo ácido fólico (p = 0,003). O ferro associado com ácido fólico foi eficaz no tratamento da anemia e na melhoria da hemoglobina nos não anêmicos.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de Goiás Faculdade de NutriçãoUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de Goiás Instituto de Patologia Tropical e Saúde PúblicaVila São José Bento CotolengoUNIFESPSciEL

Effect of propolis gel on the in vitro reduction of dentin permeability

OBJECTIVE: The aim of this study was to evaluate the capacity of potassium oxalate, fluoride gel and two kinds of propolis gel to reduce the hydraulic conductance of dentin, in vitro. MATERIAL AND METHODS: The methodology used for the measurement of hydraulic conductance of dentin in the present study was based on a model proposed in literature. Thirty-six 1-mm-thick dentin discs, obtained from extracted human third molars were divided into 4 groups (n=9). The groups corresponded to the following experimental materials: GI-10% propolis gel, pH 4.1; GII-30% propolis gel; GIII-3% potassium oxalate gel, pH 4,1; and GIV-1.23% fluoride gel, pH 4.1, applied to the dentin under the following surface conditions: after 37% phosphoric acid and before 6% citric acid application. The occluding capacity of the dentin tubules was evaluated using scanning electron microscopy (SEM) at ×500, ×1,000 and ×2,000 magnifications. Data were analyzed statistically by two-way ANOVA and Tukey's test at 5% significance level. RESULTS: Groups I, II, III, IV did not differ significantly from the others in any conditions by reducing in hydraulic conductance. The active agents reduced dentin permeability; however they produced the smallest reduction in hydraulic conductance when compared to the presence of smear layer (P<0.05). The effectiveness in reducing dentin permeability did not differ significantly from 10% or 30% propolis gels. SEM micrographs revealed that dentin tubules were partially occluded after treatment with propolis. CONCLUSIONS: Under the conditions of this study, the application of 10% and 30% propolis gels did not seem to reduce the hydraulic conductance of dentin in vitro, but it showed capacity of partially obliterating the dentin tubules. Propolis is used in the treatment of different oral problems without causing significant great collateral effects, and can be a good option in the treatment of patients with dentin sensitivity

Effects of 3 Topical Plant Extracts on Wound Healing in Beef Cattle

Eleven heifers of the Purun&#227; cattle breed were used to evaluate wound healing by second intention. An experimental wound excision model in bovines was created by means of a skin punch of diameter 2cm. The animals were topically treated for 17 days with a saline control or decoctions of Schinus terebinthifolius Raddi (Aroeira mansa), Tabebuia avellanedae Lorentz ex Griseb (Ip&#234; Roxo), and Casearia sylvestris Sw.(Gua&#231;atonga) mixed with carboxymethyl cellulose. Centripetal retraction, clinical, and histological aspects of the wounds were observed until complete healing. Decoctions of T. avellanedae and S. terebinthifolius, but not C. sylvestris, had a beneficial effect on wound healing by second intention

Statistical process control of mortality series in the Australian and New Zealand Intensive Care Society (ANZICS) adult patient database: implications of the data generating process

for the ANZICS Centre for Outcome and Resource Evaluation (CORE) of the Australian and New Zealand Intensive Care Society (ANZICS)BACKGROUND Statistical process control (SPC), an industrial sphere initiative, has recently been applied in health care and public health surveillance. SPC methods assume independent observations and process autocorrelation has been associated with increase in false alarm frequency. METHODS Monthly mean raw mortality (at hospital discharge) time series, 1995–2009, at the individual Intensive Care unit (ICU) level, were generated from the Australia and New Zealand Intensive Care Society adult patient database. Evidence for series (i) autocorrelation and seasonality was demonstrated using (partial)-autocorrelation ((P)ACF) function displays and classical series decomposition and (ii) “in-control” status was sought using risk-adjusted (RA) exponentially weighted moving average (EWMA) control limits (3 sigma). Risk adjustment was achieved using a random coefficient (intercept as ICU site and slope as APACHE III score) logistic regression model, generating an expected mortality series. Application of time-series to an exemplar complete ICU series (1995-(end)2009) was via Box-Jenkins methodology: autoregressive moving average (ARMA) and (G)ARCH ((Generalised) Autoregressive Conditional Heteroscedasticity) models, the latter addressing volatility of the series variance. RESULTS The overall data set, 1995-2009, consisted of 491324 records from 137 ICU sites; average raw mortality was 14.07%; average(SD) raw and expected mortalities ranged from 0.012(0.113) and 0.013(0.045) to 0.296(0.457) and 0.278(0.247) respectively. For the raw mortality series: 71 sites had continuous data for assessment up to or beyond lag ₄₀ and 35% had autocorrelation through to lag ₄₀; and of 36 sites with continuous data for ≥ 72 months, all demonstrated marked seasonality. Similar numbers and percentages were seen with the expected series. Out-of-control signalling was evident for the raw mortality series with respect to RA-EWMA control limits; a seasonal ARMA model, with GARCH effects, displayed white-noise residuals which were in-control with respect to EWMA control limits and one-step prediction error limits (3SE). The expected series was modelled with a multiplicative seasonal autoregressive model. CONCLUSIONS The data generating process of monthly raw mortality series at the ICU level displayed autocorrelation, seasonality and volatility. False-positive signalling of the raw mortality series was evident with respect to RA-EWMA control limits. A time series approach using residual control charts resolved these issues.John L Moran, Patricia J Solomo

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD