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Follow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999–November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12–24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data.
We present an actuarial claims reserving technique that takes into account both claim counts and claim amounts. Separate (overdispersed) Poisson models for the claim counts and the claim amounts are combined by a joint embedding into a neural network architecture. As starting point of the neural network calibration, we use exactly these two separate (overdispersed) Poisson models. Such a nested model can be interpreted as a boosting machine. It allows us for joint modeling and mutual learning of claim counts and claim amounts beyond the two individual (overdispersed) Poisson models.
Introduction: Biphasic anaphylactic reactions are a concern in emergency medicine. Risk factors associated with this type of reaction remain ill-defined. The aim of this study was to investigate elements associated with biphasic anaphylactic reactions and to determine the impact of anaphylaxis treatments on biphasic reactions. Methods: From the multicenter Cross-Canada Anaphylaxis Registry prospective cohort, we selected adults (≥18 years) with a visit to the emergency department (ED) of Sacré-Cœur Hospital, an urban tertiary-care hospital. Then, a structured chart review was done to collect additional information on types and timing of treatments for the initial anaphylactic reaction, presence and treatment of biphasic reactions during the initial ED visit or upon patients’ return. Biphasic reactions were defined by the recurrence of any anaphylaxis symptoms within 72 hours of a resolved anaphylaxis episode. Potential factors associated with biphasic reactions were studied using Chi-Square and Mann-Whitney tests. Results: Patients with anaphylaxis were enrolled between April 2014 and February 2018. From the cohort, 401 adult patients were identified. We found 37 patients who developed a biphasic reaction. Amongst them, 33 received treatments and 9 required more than one dose of intramuscular epinephrine. None of the biphasic reaction patients required intravenous epinephrine, other vasopressors, ICU admission, or endotracheal intubation. Biphasic reactions appeared in a median time of 13.3h after the initial reaction ranging from 1.1h to 69.6h (IQR 30.2). There was no difference in age or gender of patients who developed a biphasic reaction compared those who did not. Pertinent past medical history, daily medications, mean of arrival to the ED, allergen type, ingestion route, or initial symptoms during the anaphylaxis episode were not significantly different in the two groups. Treatment with corticosteroids was similar in the two groups (9.0% vs. 8.1% p = 0.82). Treatment, dose and route of administration of epinephrine was not different in the two groups but longer delays before treatment with the first dose of epinephrine was more frequent in biphasic reaction patients (median delay of 64 minutes, p = 0.015). Conclusion: No patient characteristic, allergen, route of ingestion, symptom, nor treatment with corticosteroids has shown to be significantly different in patients with and without biphasic reactions. Delayed treatment with epinephrine is significantly associated with biphasic reactions.
Autism spectrum disorder (ASD) subjects can present temporary behaviors of acute agitation and aggressiveness, named problem behaviors. They have been shown to be consistent with the self-organized criticality (SOC), a model wherein occasionally occurring “catastrophic events” are necessary in order to maintain a self-organized “critical equilibrium.” The SOC can represent the psychopathology network structures and additionally suggests that they can be considered as self-organized systems.
The chain-ladder method is one of the most popular claims reserving techniques. The aim of this study is to back-test the chain-ladder method. For this purpose, we use a stochastic scenario generator that allows us to simulate arbitrarily many upper claims reserving triangles of similar characteristics for which we also know the corresponding lower triangles. Based on these simulated triangles, we analyse the performance of the chain-ladder claims reserving method.
Data on the impact of the recently recommended maternal pertussis vaccination are promising, but still insufficient to universalise this approach. We thus compared the epidemiological data prior to the implementation of this vaccination strategy in Argentina (2012) with the figures reported after 2012. During that 2010–2016 period, two outbreaks occurred, one in 2011 and another in 2016. In the former, the incidence was 6.9/100 000 inhabitants and the case-fatality rate 2.6%. Thereafter, a decline in incidence was detected until 2014. During 2015 and 2016 an increase in the incidence transpired, but this rise was fortunately not accompanied by one in the case fatality ratio. Indeed, in 2016 the case fatality ratio was the lowest (0.6%). Moreover, during the 2016 outbreak, the incidence (3.9/100 000 inhabitants) and the case severity detected in the most vulnerable population (infants 0–2 months) were both lower than those in 2011. Consistent with this pattern, in 2016, in the most populated province of Argentina (Buenos Aires), the case percentage with laboratory-positive results indicating a high number of symptoms (59.1% of the total cases) diminished compared with that detected in the 2011 outbreak without maternal immunisation (71.9%). Using the mathematical model of pertussis transmission we previously designed, we assessed the effect of vaccination during pregnancy on infant incidence. From comparisons between the epidemiological data made through calculations, emerged the possibility that vaccinating women during pregnancy would benefit the infants beyond age 2 months, specifically in the 2–12-month cohort.
In order to describe the molecular epidemiology of Blastocystis infection in Italy, 189 isolates, which had been collected during the years 2012–2014 from mildly symptomatic patients, or those affected by inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) or chronic diarrhoea, or otherwise immunosuppressed, were subtyped by sequence analysis of the SSU rRNA gene (536 bp). Six subtypes (STs) were detected: ST1 (15·3%), ST2 (13·8%), ST3 (46·0%), ST4 (21·7%), ST6 (3·2%) and ST8 (0·5%). They clustered in distinct clades, as inferred from Bayesian inference phylogenetic and median joining network analyses. A high genetic differentiation was found at the inter-subtype level; it ranged from Jukes–Cantor (JC) distance = 0·02 (between ST1 and ST4) to JC = 0·11 (between ST6 and ST2). At the intra-ST level, a high genetic homogeneity was registered in ST4, whereas higher genetic variation was found in isolates corresponding to ST1 and ST2. Accordingly, high values of haplotype and nucleotide diversity were observed in ST1, ST2 and ST3. No association was found between patient gender and ST, whereas ST3 and ST1 were significantly more prevalent in patients aged 15–50 years. A significant occurrence of Blastocystis ST4 in patients suffering from IBS, IBD or chronic diarrhoea was observed; in addition, a slight significant association between ST1 and ST3 and IBS patients was found. Multiple correspondence analysis showed some significant contribution of different variables (subtypes, haplotypes, age) in the observed pattern of ordination of the 189 patients in the symptom categories.
The genus Micipsella comprises three species of filariae to date identified in lagomorphs only, whereas the other genera belonging to the subfamily Splendidofilariinae are described as parasites of birds, reptiles and mammals. In the present study seven specimens of Micipsella numidica (Seurat, 1917), collected from the hare Lepus europaeus in Italy, were characterized genetically by molecular amplification of the mitochondrial genes (12S rDNA; cox1) and the 5S rDNA gene spacer region. Phylogenetic trees inferred using available sequences from filariae and those identified in this study evidenced a close relationship between M. numidica and Splendidofilariinae of other mammals and reptiles (Rumenfilaria andersoni and Madathamugadia hiepei). The present findings, apart from adding new data about the hosts in Italy, support the taxonomic position of M. numidica and highlight the substantial biological and molecular differences existing between Splendidofilariinae and other Onchocercidae. The study also contributes to our knowledge of the molecular/genetic diagnosis of filarial parasites of veterinary and medical concern in any vertebrate or invertebrate host.
We present novel results of pollen analyses performed on a 10 m firn core retrieved from Alto dell’Ortles glacier (3840 m a.s.l.), Eastern Italian Alps, in 2009. The objective was to identify and quantify pollen grains retained in the ice to detect annual and interannual variations in the pollen spectra, thus enabling construction of an accurate pollen-based timescale. Up to now, this has been achieved by pollen diagram interpretation. Here we present a statistical approach developed to extract the seasonal/annual signal contained in the pollen spectra of an ice core. The method is based on principal component analyses of pollen assemblages obtained by high-level taxonomical identification. We apply this approach to the Ortles samples, demonstrating that seasonal and yearly variations of the pollen spectra are easily detectable and provide valuable information that can help improve the chronological model of the firn core. This approach can potentially be used for deeper cores as well as other types of archives (e.g. varved sediments), allowing faster, more objective estimation of yearly and seasonal variations than with classical percentage pollen diagrams.
This paper presents findings from interviews conducted with editors of catalogue raisonné projects in various stages of development combined with the author’s work on the Catalogue Raisonné of the Drawings of Jasper Johns. A summary is presented of the common mission and challenges in preparing the catalogue raisonné as well as the considerations for, and benefits of, publishing online. The result is a concise reference tool of best practices and suggestions for future catalogues raisonnés and online catalogue projects, including features available if publishing online; staff recommendations; workflow; database options; data migration; research; storage of research assets; and long-term maintenance.
Where very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This ‘new’ burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4–5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended ‘dose pole’ has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution.
The recent implementation of mass drug administration (MDA) for control of uro-genital schistosomiasis has identified an urgent need for molecular markers to both directly monitor the impact of MDA, for example to distinguish re-infections from uncleared infections, as well as understand aspects of parasite reproduction and gene flow which might predict evolutionary change, such as the development and spread of drug resistance. We report the development of a novel microsatellite tool-kit allowing, for the first time, robust genetic analysis of individual S. haematobium larvae collected directly from infected human hosts. We genotyped the parasite populations of 47 children from 2 schools in the Ségou region of Mali, the first microsatellite study of this highly neglected parasite. There was only limited evidence of population subdivision between individual children or between the two schools, suggesting that few barriers to gene flow exist in this population. Complex relationships between parasite reproductive success, infection intensity and host age and gender were identified. Older children and boys harboured more diverse infections, as measured by the number of unique adult genotypes present. Individual parasite genotypes had variable reproductive success both across hosts, a pre-requisite for evolutionary selection, and, phenotypically, in hosts of different ages and genders. These data serve as a baseline against which to measure the effect of treatment on parasite population genetics in this region of Mali, and the tools developed are suitable to further investigate this important pathogen, and its close relatives, throughout their range.
This chapter discusses two roles for capnography in the assessment and treatment of patients in cardiac arrest. It evaluates the efficacy of cardiopulmonary resuscitation (CPR), and cessation of resuscitation. A number of animal studies have shown an excellent correlation between end-tidal carbon dioxide (PETCO2) and cardiac output during states of low flow and during CPR. An animal model with ultrasound flow probes and radioactive microspheres was used to examine the relationships between PETCO2 and cardiac output, cerebral perfusion, and renal perfusion. A number of studies have found that PETCO2 values may change transiently after the administration of intravenous epinephrine or sodium bicarbonate. One of several studies that examined the active compression/decompression CPR (active compression/decompression (ACD)/CPR) technique used PETCO2 as a marker for cardiac output to compare the hemodynamics generated by the ACD/CPR method to standard CPR in the out-of-hospital setting.
This section provides an overview of some of the statistical tools and concepts which are useful for data analysis and the study of complex networks. Our emphasis will be on the practical application of probability theory, rather than its mathematical foundations, which is why we will confine ourselves to self-consistent definitions of the basic ingredients of applied statistics, rather than their derivation from first principles. For those who desire a more rigorous and more detailed treatment of the material, a celebrated introduction to probability theory can be found in, which discusses the contents of this chapter in much greater detail.
Events and probabilities
Tossing a coin – with an outcome of ‘heads’ or ‘tails’ – is one of the simplest examples of a probabilistic event. More complicated examples could be to obtain ‘five’ and ‘two’ when throwing a pair of dice, the ball landing on a red number in a game of roulette, or the spreading of an infection from an infected individual to a healthy one. In all these cases the set of all possible outcomes of an experiment is the sample space. An event can be defined as any member (or subset) of the sample space.
Technical part In set theory we can write that very simply: Ω is the sample space and any set A ⊂ Ω is an event in the following sense.[…]
Ortles mountain (3905 m a.s.l.), South Tyrol, Italy, is the highest mountain of the Eastern European Alps, and its upper glacier, Alto dell’Ortles, presents a unique opportunity to obtain the first paleoenvironmental record from an ice core in this area. To study the suitability of this glacier as a drilling site, in 2009 we performed the first preliminary study of its glaciological characteristics at ˜3830 m a.s.l. The maximum thickness is ˜75 m, and lamination of the exposed ice layers is excellent down to bedrock. Firn and ice lenses were observed in a 10 m shallow core, and the firn/ice transition was below ˜24m. The seasonal chemical signal is clearly preserved only within the uppermost 2008 and 2009 snow/firn. A simple mass-balance model, the incipient ‘smoothing’ of the chemical record, and the observed ice lenses provide evidence that melting, infiltration and refreezing cycles occurred within the firn layers formed before 2008. Nevertheless, the mass balance of the upper part of Alto dell’Ortles was positive (˜800mma_1) during the last few years. We suggest that an environmental history is likely to be well preserved only within the ice layers formed before ˜1980, when summer air temperature was ˜2°C colder than today in this area. Clearly the continued warming trend predicted to occur over the next few decades, and the consequent increase in frequency and/or intensity of infiltration processes, will endanger the preservation of the glacial archive conserved in the deep ice layers of Ortles mountain.
Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using ‘preventive chemotherapy’ can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.