Filler siphoning theory posits that the presence of fillers (known innocents) in a lineup protects an innocent suspect from being chosen by siphoning choices away from that innocent suspect. This mechanism has been proposed as an explanation for why simultaneous lineups  induces better performance than showups (one-person identification procedures). We implemented filler siphoning in a computational model , and explored the impact of the number of fillers (lineup size) and filler quality on simultaneous and sequential lineups (viewing lineups members in sequence), and compared both to showups. In limited situations, we found that filler siphoning can produce a simultaneous lineup performance advantage, but one that is insufficient in magnitude to explain empirical data. However, the magnitude of the empirical simultaneous lineup advantage can be approximated once criterial variability is added to the model. But this modification works by negatively impacting showups rather than promoting more filler siphoning. In sequential lineups, fillers were found to harm performance. Filler siphoning fails to clarify the relationship between simultaneous lineups and sequential lineups or showups. By incorporating constructs like filler siphoning and criterial variability into a computational model, and trying to approximate empirical data, we can sort through explanations of eyewitness decision-making, a prerequisite for policy recommendations.The online version of this article (doi:10.1186/s41235-017-0084-1) contains supplementary material, which is available to authorized users. We apply a formal model to the recently proposed filler siphoning explanation for why performance from simultaneous lineups is superior to showups. We show that, although fillers can produce a simultaneous lineup performance advantage, the magnitude of that advantage is insufficient to fit empirical data. Although the addition of criterial variability allows performance differences to be approximated, it is not because of a positive contribution from filler siphoning, but rather the greater adverse impact of criterial variability on showups. Theoretical understanding rooted in formal models is a prerequisite for policy recommendations in applied domains.Researchers have begun using receiver operating characteristic (ROC) analysis to assess the degree to which eyewitnesses distinguish innocent from guilty suspects when tested with simultaneous lineups, sequential lineups, and showups  by storing in memory a summary prototype (a depiction of the average bird), or do we instead store all the category exemplars that we experience? Posner and Keele  showed tIt is for reasons like this that it is necessary to explore filler siphoning theory using a formally specified model. We employ the WITNESS model to achieve this goal , and for the target-absent lineups, an innocent suspect. Parameters of the model govern how well the perpetrator is encoded into memory, and the degree to which the innocent suspect and fillers resemble the perpetrator. The decision stage specifies how these various elements are assessed and how a decision is made from the ID procedure. How these elements are constructed, and how the parameters determine ID rates, are described next.a, whereby a feature is correctly encoded into MEM (derived from PERP) with probability a, and noise, a new random value between − 1 and + 1, is encoded with probability (1 – a). For example, if a = .25, 25% of MEM will match the PERP and 75% will consist of random values. The creation of the innocent suspect and the fillers follows a similar logic whereby the parameters SSP (Similarity of the innocent Suspect to the PERP) and SSF (Similarity of the Suspect to the Fillers) govern the probability of the innocent suspect and filler features matching the PERP, respectively. For example, if SSP = .7, then 70% of the features match between the perpetrator and the innocent suspect. The closer SSP (or SSF) is to 1.0, the more the innocent suspect (or the fillers) resembles the perpetrator. When SSP = SSF, then the innocent suspect and fillers resemble the perpetrator to the same degree . In addition, the type of ID procedure, either a simultaneous or sequential lineup or showup, can be specified in the model. Lineups are modeled by compiling the proper number of vectors , which includes the guilty suspect (PERP) with five fillers in target-present lineups, or the innocent suspect with five fillers in target-absent lineups. A showup (a one-person lineup) is created by including only the PERP or the innocent suspect.In the model, a perpetrator (PERP) is specified as a vector of 100 random values between − 1 and + 1. Each element in the vector symbolizes a characteristic of the perpetrator . Once PERP is created, it is encoded into memory (MEM). The quality of encoding is governed by the parameter csim. If the best-match value fails to exceed csim, in either target-present or target-absent conditions, a rejection is recorded. If the best-match value exceeds csim, the model selects that lineup member. If the best match is the guilty suspect in a target-present lineup, then the selection is a correct ID, if not it is a filler ID. If the best match is the innocent suspect in a target-absent lineup, then the selection is a false ID, otherwise it is a filler ID. This is an implementation of an absolute decision rule.csu.csu, a correct ID (in target-present) or false ID (in target-absent) is recorded. If the match value falls below csu, a rejection is recorded.Once the vectors have been specified, the model makes a decision. For a simultaneous lineup, the model begins by computing the degree to which each lineup member matches memory for the perpetrator. These match values are computed by taking the dot product of each lineup member vector and MEM. A decision is made from the simultaneous lineup by comparing the highest match value  to a decision criterion, the value of which is governed by the parameter cseq  1 to 10:1 indicates that the witness is not confident at all, and 10 indicates the witness is highly confident in the decision. In the model, confidence ratings are apportioned by dividing the match strength dimension  into the number of bins that correspond to the confidence scale . When a selection is made from a lineup or showup, the selection’s match value is compared to the various confidence bins, and a tally is added to the bin in which the value falls. For instance, if the match value for the ID of a suspect was 2.0, the model will tally a confidence response of 8 if confidence bin 8 extends from 1.9 to 2.1.SSF), should induce more siphoning, and thereby provide more protection for innocent suspects .The present research explores the impact of fillers throughout WITNESS’ theory space. A theory space exploration varies the parameters over a wide range to see what the model can predict. According to filler siphoning theory, the presence of fillers is sufficient to produce a lineup advantage, which means that a lineup advantage should be apparent throughout the theory space. However, we expected to see that the magnitude of the lineup advantage would increase as the number of fillers (lineup size) increases, and as the competitiveness of the fillers  increases. This is because adding fillers that are close competitors to a guilty suspect . In this case, the innocent suspect and fillers are of equal similarity, which should result in the greatest amount of siphoning (protection for the innocent suspect). The second set of simulations also varied the competitiveness of the fillers, but in this case the simultaneous lineups were biased against the innocent suspect .The first set of simulations varied the competitiveness of the fillers by varying the value of a ranged from .11 to .33. We report results using a value of a = .3 for our simulations (the simulations were repeated with a = .2 and a = .5 and the pattern of results did not differ from those reported). The values for SSP and SSF varied over a wide range , reflecting the wide differences across experiments in the degree of match of innocent suspects and fillers to a perpetrator. The SSP and SSF values used in the current simulations were varied over comparable ranges (.3 to .75). There were no indications amongst the many simulations we conducted that the general patterns we report next were unique to the particular parameter values used. Moreover, to reiterate, there is nothing special about using WITNESS to perform these explorations – alternative signal detection and matching models should behave similarly.To begin, parameter values were selected based on values that have been used to fit empirical data . Filler siphoning theory predicts that when lineups are compared to the showups in this manner, lineups should exhibit an advantage. Additionally, we reasoned that as lineup size increases, more siphoning should occur (lineups should exhibit increasingly better performance than showups) because there are more viable options (more opportunities to siphon).For the first set of simulations, the match of the innocent suspect was set equal to the fillers to approximate a fair lineup  factorial was conducted. Figure SSP = SSF = .3 (panel A), where the innocent suspect and fillers share 30% of features with the PERP, SSP = SSF = .6 (panel B), where the innocent suspect and fillers share 60% of features with the PERP, and SSP = SSF = .75 (panel C), where the innocent suspect and fillers share 75% of features with the PERP. All guilty/innocent suspect, filler, and rejection rates for all simulations are available in Additional file A 4  × 3 .In panel A, there is no separation between the ROC curves for the showup, 3-, 6-, or 12-person lineups. This replicates the findings of Rotello and Chen , Fig. 1,In sum, as the degree to which the innocent suspect and the fillers resemble the perpetrator is increased, some separation can be seen in the ROC curves. However, contrary to filler siphoning theory, the impact of increasing the number of fillers beyond three did not affect discriminability ; rather, it truncated the ROC curves (because fillers are being selected instead of innocent or guilty suspects).SSP > SSF, the innocent suspect more closely resembled the perpetrator than did the fillers). The innocent suspect was set to be SSP = .75 and held constant while varying SSF. Across panels in Fig. SSF is increased, which should affect the degree of protection afforded to the innocent suspect. Once again, we varied the similarity of the fillers in a 4  × 3 (filler similarity (SSF): .0, .3, and .6) factorial. The three panels in Fig. SSF = 0 (panel A), SSF = .3 (panel B), and SSF = .6 (panel C).The second set of simulations also varied the competitiveness of fillers, but in this case the lineups were biased : .3, .6, and .75) factorial was conducted, as for simultaneous lineups. Suspect position was randomly assigned for each simulation and performance was averaged across simulations. Panel A of Fig. SSP = SSF = .3) shows that the ROC truncates as lineup size increases from 1 to 12. Panels B (SSP = SSF = .6) and C (SSP = SSF = .75) do exhibit larger effects of adding fillers, but in the opposite direction predicted by filler siphoning theory. In fair sequential lineups, as more fillers are added, discriminability decreases. This is most likely due to the increased probability that a filler will be chosen before the model gets to the guilty suspects later in the lineup.Figure SSF): .0, .3, and .6) factorial for biased sequential lineups. Innocent suspect similarity (SSP) was held constant at .75 for these simulations. The results of the biased sequential lineup exploration are similar to the fair sequential lineup. Panel A (SSF = .0) shows no effect of number of fillers; panels B (SSF = .3) and C (SSF = .6) show that as fillers are added, discriminability decreases. In sequential lineups, fillers do not differentially protect the innocent suspect from identification.Figure In sum, by using a computational model that implements filler siphoning theory, we find evidence that siphoning can occur in simultaneous lineups and, if the fillers are competitive, produce lineup ROCs that are superior to showup ROCs . We must hold the other parameters constant across lineup and showup conditions because the ID procedure manipulation takes place after encoding, and the same innocent suspect is used in both conditions. If WITNESS can approximate these data given these constraints , it suggests that filler siphoning theory is sufficient to explain the magnitude of the empirical performance differences between simultaneous lineups and showups.We fit WITNESS to the Wetmore et al.  data, a Table A report by the National Academy of Sciences  and biased  simultaneous lineups, compared to showups. For the lineups, we ran simulations where there was no criterion adjustment, a shift of + .01, + .025, or + .05. Figure We implemented this modification in WITNESS and explored its effect on fair (within-subject (and item) variability, whereas the eyewitness domain is concerned with between-subject variability, which could be more sizeable.Each participant only provides one decision in an eyewitness task, and each participant likely approaches the task with a different decision criterion. One eyewitness, for example, may be troubled by the possibility of a wrongful conviction and adopts a conservative criterion; the next might be seeking vengeance and be eager to make a lineup selection. Smith et al.  proposedcsim, or csu, σ = y * csim, or csu, where y is a scaling parameter, coupling the amount of variability to the value of csim, or, csu). The model fit improved quantitatively (RMSD = 0.012) with the inclusion of criterial variability. It also improved qualitatively because the magnitude of the lineup-showup difference is now comparable to empirical data , but lineups essentially stay the same . This is shown in Fig. Smith et al.  argued tFor the sake of completeness, we also examined the impact of criterial variability on sequential lineup performance. As with simultaneous lineups, adding increasing levels of criterial variability to a sequential lineup decision had little influence on discriminability, and the sequential ROCs were truncated. These results are a function of increased rates of early choices of fillers when the criterion is low, and lineup rejections when the criterion is high.The primary goal of the present research was to determine if filler siphoning theory can explain why simultaneous lineups result in superior performance compared to showups. The WITNESS model was used to explore situations where siphoning should appear . Although we found that the choice of fillers in simultaneous lineups can provide some protection for an innocent suspect, by siphoning more choices from an innocent than a guilty suspect, this mechanism was insufficient to approximate empirical data. Like Smith et al. , we founWe also explored how filler siphoning theory impacts fair and biased sequential lineups. Our simulations revealed that fillers can have a detrimental effect on sequential lineup performance, thereby restricting the generalizability of filler siphoning theory. Notably, our simulations provide a theoretical rationale supporting the empirical conclusion , from those that are specific to the perpetrator. For example, if all lineup members are Caucasian with short, brown hair, race and hair color are irrelevant for identifying the perpetrator. By shifting attention away from these non-diagnostic characteristics, an eyewitness can focus on diagnostic characteristics unique to the perpetrator . This comparison process is difficult in a showup because only one face is viewed, making it difficult for an eyewitness to determine which characteristics are diagnostic. The diagnostic feature hypothesis also can potentially explain why simultaneous lineups are superior to sequential lineups


Plasmodium falciparum are inadequate for eliminating malaria. To learn more about prevalence and genetic variability of P. malariae in Africa, we examined blood samples from 663 asymptomatic and 245 symptomatic persons from western Kenya during June–August of 2014 and 2015. P. malariae accounted for 5.3% (35/663) of asymptomatic infections and 3.3% (8/245) of clinical cases. Among asymptomatic persons, 71% (32/45) of P. malariae infections detected by PCR were undetected by microscopy. The low sensitivity of microscopy probably results from the significantly lower parasitemia of P. malariae. Analyses of P. malariae circumsporozoite protein gene sequences revealed high genetic diversity among P. malariae in Africa, but no clear differentiation among geographic populations was observed. Our findings suggest that P. malariae should be included in the malaria elimination strategy in Africa and highlight the need for sensitive and field-applicable methods to identify P. malariae in malaria-endemic areas.In Africa, control programs that target primarily  Plasmodium falciparum malaria still presents a major challenge for malaria elimination  than those with non–P. malariae infections   gene, which is known to be critical for plasmodia sporozoite motility and hepatocyte invasion , and each person who was willing to participate in the study.,During June–August of 2014 and 2015, blood samples were collected from persons in 4 villages at the Lake Victoria basin  of western Kenya . These vP. malariae prevalence in the adult population, we randomly selected 63 persons  >15 years of age from 18 households in Kombewa. We examined a total of 663 samples from the communities, which provided an estimation of 4% margin of error in parasite prevalence with 0.05 type I error. At the time of sampling, none of these persons exhibited fever or malaria-related symptoms.Community samples were collected from nonfebrile schoolchildren in 7 public primary schools . An equal number of boys and girls 6–15 years of age were randomly selected from each school. To determine Plasmodium spp. by microscopy at the time of sampling. Thick and thin blood smears were prepared for microscopic examination to determine the Plasmodium species, and ≈50 μL blood was blotted onto Whatman 3MM filter  papers. Filter papers were air dried and stored in zip-sealed plastic bags with silica gel absorbent at room temperature until DNA extraction.Clinical samples were collected from 113 male and 132 female patients, <1 to 76 years of age, in 3 district hospitals. This sample size provided an estimation of 6% margin of error in parasite prevalence with 0.05 type I error. These patients had fever or malaria-related signs or symptoms and were determined to be positive for We examined slides under microscopes at 100× magnification and counted the number of parasites per 200 leukocytes. A slide was considered negative when no parasites were observed after counting >100 microscopic fields. At the time of sample collection, all slides were read by 2 microscopists. If counts were discordant, the slides were examined by a third microscopist. The density of parasitemia was expressed as the number of asexual parasites per microliter of blood, assuming a leukocyte count of 8,000 cells/μL, according to World Health Organization guidelines.P. falciparum, P. vivax, P. malariae, and P. ovale) was used for parasite detection and species identification. As positive controls for all amplifications, we used DNA from P. falciparum isolates 7G8 (MR4-MRA-926) and HB3 (MR4-MRA-155), P. vivax Pakchong (MR4-MRA-342G) and Nicaragua (MR4-MRA-340G), P. malariae (MR4-MRA-179), and P. ovale (MR4-MRA-180). As negative controls, we used water and noninfected samples to ensure lack of contamination. Reaction was performed in a Bio-Rad MyCycler thermal cycler according to the published protocol , we calculated the mean value and standard deviations from triplicates in 2 independent assays. The parasite gene copy number in a sample was quantified according to Ct by using the equation (sample = e(E × ΔCtsample), where GCN stands for gene copy number; ΔCt, the difference in Ct between the negative control and the sample; e, exponential function; and E, amplification efficiency  qPCR detection method with ficiency .P. malariae csp gene region and used together with the published primers . Sequences were translated into protein sequences and analyzed together with all csp protein sequences available in GenBank of P. malariae from East Africa (Kenya and Uganda), West Africa (Cameroon), Central Africa (Côte d’Ivoire), and South America (Venezuela) and of P. brasilianum from South America (Brazil and Venezuela). It is noteworthy that although P. malariae and P. brasilianum coexist in Brazil, no csp sequence for P. malariae is available. Because of the potential for alignment errors associated with gaps in the nucleotide sequences, we used translated amino acid sequences with unambiguous indels in phylogenetic analyses. Sequence diversity, including measures of evolutionary distances and average pairwise divergence, were estimated and compared among geographic regions  for parasite gene copy number and age by using R (https://www.r-project.org/).A 1-tailed P. malariae was detected by PCR in 35 . Among these, 29 were mixed infections  and 6 were P. malariae monoinfections , followed by Kendu Bay . Prevalence of P. falciparum prevalence was relatively high at these 2 sites , which was significantly higher than the number of cases detected in older persons . Although P. falciparum infection was highest among patients >5 to <15 years of age, no P. malariae was detected in persons in this and older age groups despite smaller samples in these groups. No significant difference was detected between male and female patients.Among the 245 samples from symptomatic patients, 8 (3.3%) fections . When thP. malariae infections in the community , >2-fold higher than by microscopy  without differing significantly (p>0.05). Similar results were observed in the level of P. malariae parasitemia, for which samples from symptomatic and asymptomatic persons did not differ significantly  was significantly higher than the amount of P. malariae DNA , consistent with the difference in parasitemia according to microscopy  were polymorphic among the studied parasites of different taxa (n (the repeat codon unit in which n denotes the number of repeats) in P. malariae ranged from 49 to 85 units. These tandem repeats could be rapidly evolving through a different mechanism and may influence genetic relationships among the samples. To examine such effect, we constructed phylogenetic trees with 2 sets of data: the entire sequence (530 aa) and partial sequences without the central repeat region (225 aa).The ent taxa . To avoicsp gene showed a clear distinction between isolates from South America and those from the other geographic regions  closely associated with P. brasilianum from Brazil. Sequences of P. malariae from Venezuela were almost identical to those of P. brasilianum from the same area. Closely related to the clade from South America was a large monophyletic group that contained P. malariae from East, Central, and West Africa and from China (bootstrap >90%). The isolates from these regions were divided into 2 subclades: I and II  on the basis of PCR  of clinical P. malariae cases occurred in children <15 years of age and the mean incidence density was highest for those 5–9 years of age  than younger persons (P. falciparum malaria prevalence can be ≈60% during the rainy season (,P. malariae infections, the level of P. malariae parasitemia does not seem to be associated with age. Chronic nephrotic syndromes attributed to P. malariae have been reported (,,We found thatP. malariae–positive samples detected by PCR were undetected by microscopy. Such a low sensitivity of microscopy could be attributed to a significantly lower P. malariae than P. falciparum parasitemia, according to qPCRs. Because most P. malariae–positive samples had mixed infections, microscopists could have recorded only the dominant P. falciparum and overlooked the sparse P. malariae trophozoites. Also, the ring forms of P. falciparum and P. malariae are morphologically more similar to each other than to P. vivax and P. ovale (Our data indicate that ≈50% of P. malariae monoinfection is chloroquine, and for P. falciparum and mixed plasmodial infections it is artemisinin combination therapy (P. malariae infections even in cases of misdiagnosis. However, P. malariae increases production of P. falciparum gametocytes in mixed infections, and these gametocytes can persist without proper antimalarial treatment or monitoring (P. malariae diagnosis and provide accurate epidemiologic data for specific and effective management guidelines. Although PCR is a better diagnostic method, it uses a relatively small amount of blood from filter papers and could still underestimate P. malariae infections in samples with exceptionally low levels of parasitemia. More accurate prevalence data may be obtained from ultrasensitive PCR that targets multicopy regions of the parasite genome (In Africa, the standard treatment for csp gene were shown to be highly polymorphic among P. malariae isolates from western Kenya. The most polymorphic region was in the central repeat region, where mutations and length differences were detected (,P. malariae from East and Central/West Africa were genetically closely related and exhibited a comparable level of sequence variation. This variation could be attributed to positive selection, frequent recombination, and gene flow among the parasites, as follows. First, compared with msp1, dhfr, and dhps of P. malariae (–csp gene revealed a remarkably higher level of sequence diversity. It is possible that selection of csp genetic variants may confer immunogenic advantages to the pathogen during host invasion (,,Sequences of the P. malariae infections influences diagnostic sensitivity by microscopy. A more sensitive tool is needed to identify asymptomatic P. malariae and to improve control strategies, particularly among infants and children who are vulnerable to P. malariae infection.In summary, underestimation of the actual prevalence of asymptomatic infections hinders progress toward malaria elimination in Africa. The low parasitemia of Plasmodium circumsporozoite protein gene sequences.Detailed description of PCR-based diagnostic assays and phylogenetic analyses of Plasmodium malariae and P. brasilianum isolates.Additional information for


The objective of this study was to test the validity of the pragmatic criteria of the definitions of neonatal near miss, extending them throughout the infant period, and to estimate the indicators of perinatal care in public maternity hospitals. A cohort of live births from six maternity hospitals in the municipalities of São Paulo, Niterói, and Rio de Janeiro, Brazil, was carried out in 2011. We carried out interviews and checked prenatal cards and medical records. We compared the pragmatic criteria  of the definitions of near miss of Pileggi et al., Pileggi-Castro et al., Souza et al., and Silva et al. We calculated sensitivity, specificity , percentage of deaths among newborns with life-threatening conditions, and rates of near miss, mortality, and severe outcomes per 1,000 live births. A total 7,315 newborns were analyzed (completeness of information > 99%). The sensitivity of the definition of Pileggi-Castro et al. was higher, resulting in a higher number of cases of near miss, Souza et al. presented lower value, and Pileggi et al. and de Silva et al. presented intermediate values. There is an increase in sensitivity when the period goes from 0–6 to 0–27 days, and there is a decrease when it goes to 0–364 days. Specificities were high (≥ 97%) and above sensitivities (54% to 77%). One maternity hospital in São Paulo and one in Niterói presented, respectively, the lowest and highest rates of infant mortality, near miss, and frequency of births with life-threatening conditions, regardless of the definition. The definitions of near miss based exclusively on pragmatic criteria are valid and can be used for monitoring purposes. Based on the perinatal literature, the cutoff points adopted by Silva et al. were more appropriate. Periodic studies could apply a more complete definition, incorporating clinical, laboratory, and management criteria, including congenital anomalies predictive of infant mortality. The four of the largest maternity hospitals in São Paulo are: one philanthropic (A), the only one that is not a reference for high-risk pregnancies; one national reference in Women’s and Newborn’s Health (B); one belonging to a university hospital (C); and another reference for high-risk pregnancy and parturient and neonatal in the Metropolitan region of Greater São Paulo (D). The selected maternity hospital of the municipality of Rio de Janeiro (E), located in the Metropolitan Region I, covers the local population, and the maternity hospital of Niterói (F) is a reference for low- and high-risk pregnancy of the Metropolitan Region II of the state of Rio de Janeiro.This study is a result of the integration of research studies on the health of women hospitalized for abortion or delivery and their newborns in the municipalities of São Paulo (FAPESP – Notice PPSUS 2009), Rio de Janeiro, and Niterói . We used common instruments for data collection and study logistics.Primary data was collected in an interview with the parturient 12 hours after delivery by previously trained health students. In addition, we consulted hospital records, the pregnancy card, and the delivery room record. Particularly the information on birth weight and Apgar score were obtained from hospital records. In the maternity hospitals of São Paulo, information on gestational age was obtained mainly from hospital records without reference to the method of calculation or estimation, following the protocols of the physicians who cared for the parturient. In Rio de Janeiro, the method used to calculate or estimate gestational age followed an algorithm that prioritized different data sources, in this order: the date of the last period (DLP), when compatible with ultrasound (US) before 20 weeks; US, when the values of DLP were inconsistent or ignored; finally, neonatal clinical examination. The information was worked as complete weeks of gestation.We selected 7,362 LB for analysis, and approximately 1% of the records were excluded because they did not present any of the data on birth weight, gestational age, or fifth-minute Apgar score. Therefore, the study population consisted of 7,315 LB, of which 5,535, 1,222, and 557 LB were from the maternity hospitals of São Paulo, Rio de Janeiro, and Niterói, respectively.Data on infant mortality after hospital discharge were obtained from the Mortality Information Improvement Program (PRO-AIM) of the Municipality of São Paulo and from the Mortality Information System (SIM) of the State Department of Health of Rio de January (probabilistic relationship of databases).The pragmatic criteria – markers of life threatening conditions of the newborn – and the cutoff points that support each of the four selected definitions of near miss are based on birth weight, gestational age, and fifth-minute Apgar scores  .The validation of the definition of neonatal near miss with Brazilian data has been performed by Pileggi et al.The only definition of near miss based exclusively on pragmatic criteria is the one by Pileggi et al.In this study, we analyzed only the pragmatic criteria of each definition of near miss by the infant age component .We calculated the frequencies of the four life-threatening definitions evaluated (with the presence of at least one of the pragmatic criteria). The study population was described in relation to situations that threaten the lives of newborns, severe morbidity (near miss), and infant mortality. In addition, we estimated the frequencies of missing or ignored information of the variables: birth weight, gestational age, and fifth-minute Apgar score.For the validation of the definitions of near miss based only on pragmatic criteria, we calculated sensitivity, specificity , and respective confidence intervals (95%CI). Regarding the choice of the best set of criteria, we evaluated the combination of sensitivity and specificity, the performance in the evaluation of the quality of the care, and, based on the literature, the adequacy of cutoff points used in perinatology. The definitions of near miss were named in this comparative study by the surname of the first author.®, version 17, and Excel spreadsheet.Considering the proposal of Pileggi et al.This study has been approved by the Research Ethics Committee of the Instituto de Estudos em Saúde Coletiva of the Universidade Federal do Rio de Janeiro (Process 15/2010) and the Faculdade de Saúde Pública of the Universidade de São Paulo (Process 2188/11), the Department of Health and Civil Defense of the Municipality of Rio de Janeiro (Process 87/2011), and the participating hospitals.Information on birth weight was present in all research records in the population eligible for analysis, 7,362 LB . GestatiThen, we evaluated 7,315 LB that presented the three data: birth weight, gestational age, and fifth-minute Apgar score.The frequency ranking of the isolated pragmatic criteria and their possible combinations to characterize the life-threatening situation showed variation, according to the definitions of near miss . In all When presenting at least one of the pragmatic criteria of the definition of near miss, 150 (2.1%), 241 (3.3%), 117 (1.6%), and 174 (2.4%) LB were classified as newborns with life threatening conditions, according to Pileggi et al.There were 34 early neonatal deaths, 13 late neonatal deaths, and 21 post-neonatal deaths. Regardless of the infant age component, the sensitivity of the definition of near miss of Pileggi-Castro et al.The indicators of birth and death and perinatal care evaluation are presented in Using the definition of Silva et al.The validation of the pragmatic criteria of the four definitions of near miss in three different components of infant mortality, with data from this study, showed similar values of sensitivity and specificity. Based only on these results, we can infer that there is no statistically significant difference between the four definitions evaluated.,,,The cutoff points of the pragmatic criteria varied according to the definitions of near miss analyzed, mainly gestational age. Based on the strength of association with neonatal death, all were valid in the studies of neonatal near miss, including this study. However, we consider that the cutoff point at 32 weeks , the burden of severe newborns (rate of severe outcomes) and the proportion of deaths among newborns with life-threatening conditions for the period of 0–6 full days were high, 50.3‰ LB and 23.1%, respectively (definition by Silva et al.,,The main advantages of the pragmatic criteria for the definition of near miss are the availability of information on birth weight, gestational age, and Apgar scores in the maternity hospitals and the SINASC and the ease to use the classification for clinical and epidemiological purposes. The completeness of the information from the pragmatic criteria in this study was excellentAs in the study of Pileggi et al.In addition, health indicators based on neonatal near miss allow us to monitor the quality of care provided and the care demand of a contingent of risky births, as well as identify children who will demand greater care from the health services and their family members.,,One limitation of this study was the non-randomness of maternity hospitals and parturients, although the method used is similar to that used in the research of WHOAs sensitivity and specificity did not show significant differences, we recommend the use of the definition of Silva et al.We also recommend that, since individualized information can be obtained in the SINASC and SIM, for example, from the probabilistic relationship of the respective databases, or the hospital itself, indicators based on near miss should be monitored by a health establishment, contributing with the evaluation of the maternal and infant care.


The data were submitted to EVOC 2005software and to similarity analysis. care was the central core of the representational structure identified among thestudents of the first period. Among last-period students, knowledge stood out as acore element. The term responsibility was identified as common to both centralcores. regarding professional autonomy, the results point to an overlapping process ofthe reified and consensual universes during the undergraduate course. However,responsibility, inherent in the profession, remains cross-sectional. For the firstperiod students, autonomy is resignified in a practical and attitudinal way,whereas for the last period students, the knowledge acquired stimulates them toassign meaning to professional autonomy with a cognitive and attitudinalrepresentation. The data can support the use of innovative teaching practices innursing undergraduate courses. In the context of nursing, professional autonomy is a great challenge, characterized bya considerable complexity. Professional autonomy is defined in nursing literature as theautonomy to make decisions in each one’s professional area and to act according toitThis concept has been associated to the possibility and the capacity for autonomousdecision-making, carried out by a personal body of knowledge and ethical obligationswith the client. A study conducted with British nurses pointed out the importance ofmore than one type of knowledge in the daily practice of the participantsAutonomy is also seen as a fundamental aspect in the professional practice of the nurseand as a pillar of the quality of care, considering that autonomy in the professionalpractice provides a higher degree of satisfaction for the nurse, which directlyinterferes in patient safety. It is defined, therefore, as freedom to act and to makeindependent clinical decisions in the nursing sphere of practice and interdependentdecisions in interdisciplinary spheres, all based on scientific evidences according to its structural approach, the Central Core Theory(CCT). For the proposer of the theory, the representation is composed of a determinedset of information, beliefs, opinions and attitudes about a social objectData were collected from November to December 2015 in three federal public universitieslocated in the Rio de Janeiro Metropolitan Region, in the State of Rio de Janeiro,Brazil. Two of these universities were located in the city of Rio de Janeiro and one inthe city of Niterói. All of them have undergraduate courses in nursing (teachinglicense) and consolidated graduate programs, nationally and internationally recognizedand serving the vast majority of the students approved in a unified selection processfor public higher education in nursing.The study population consisted of 111 students from the first period and 60 studentsfrom the last period, totaling 171 participants who were engaged in student activitiesin the scenarios chosen for the research at the time of data collection. Thus, thisresearch encompasses two distinct subgroups, according to the stage they were in thecourse. The number of participants was the product of a convenience sample to obtain therequired number of participants in the universe of 100% of the students in each class,per academic period. The final sample number, therefore, meets the recommendationstudies based on the structural approach of social representations, which is at least100 individualsNursing undergraduate students attending the following inclusion criteria participatedin the study: minimum age of 18 years, without no age limit nor gender distinction. Theexclusion criteria were the presence of communication difficulties or inaccessibility ofthe participant after three consecutive attempts to reach out. No other attribute was ajustifiable exclusion criterion.The regulations from Resolution 466/2012 of the National Health Council (CNS) werefollowed. These regulations define the ethical and legal aspects of human research,which include the presentation and shared reading of an Informed Consent Form (TCLE),followed by free and conscientious acceptance to participate in the research. As it wasan inter-institutional project, the study was approved by the Research Ethics Committees(REC) of the Universidade Federal Fluminense (UFF) and of the Universidade Estadual doRio de Janeiro (UERJ), obtaining approval under the protocols numbers 924,334 (UFF) and939,676 (UERJ). The free associations technique for the object “professional nurse autonomy” was used,aiming to highlight the semantic universe and the imaginary dimension of therepresentations. In addition, a questionnaire with closed and open-ended questions wasapplied in order to characterize the socio-demographic profile of the studyparticipants. The use of the free associations technique preceded the collection ofsocio-demographic data, so that the latter did not interfere with the data produced. Thedata collections consisted in asking the students to speak the first five words orexpressions that came to mind when they heard the inducing terms. The words wererecorded in the order they were recalled. corpus with all the words was elaborated, divided by participantsand in the order they were recalled, and presented in the four-house boardEnsemble des programmes permettant l’analyse desevocations (EVOC) software, 2005 version, was used to calculate and informthe simple frequency of occurrence of each word, the mean occurrence of each word in theorder they were evoked, and the mean of the weighted mean orders of the set of termsevoked (rang)-As for the data analysis techniques used, a simple descriptive statistical analysis wasperformed on the data from the questionnaire. Regarding the free associations, a,In this table, the upper left quadrant, or central core, contains the words that wereevoked more frequent than the number set by the researcher, as well as the most readilyevoked, which constitute the possible central elements of the representation. In theupper right quadrant or first periphery are the words which were also very frequent, butnot so readily evoked, and which may be reinforcing the central core. In the lower leftquadrant, also called the contrast zone, are words that were evoked fewer times than thenumber set but were promptly evoked. This group may be reinforcing the central core orindicating the presence of a subgroup in the studied group. And in the lower rightquadrant or second periphery were the words less evoked and verbalized later, that is,they were mentioned in the last positionsContinuing the analysis of the data obtained, similarity analysis of the freeassociations was conducted in a complementary way. This technique is a procedure usedwithin the structural perspective of social representations, in order to check thenumber of ties or connections between one element of the representation and another. Itsresult consists in the construction of a figure called maximum tree or similarity tree.The starting points for the construction of this figure are the highest similarityindices, that is, the strongest connections between words. This technique does not allowconfirming the core elements, but it provides another indication of the elements thatare central in the representation. Based on the organization of the data on thefour-house board and on the similarity tree, the data were analyzed in light of theassumptions of the CCT.The participants who were in the first period were mostly females (81%), between 18 and20 years old (63%), Evangelical (30%), with no personal income (64%), with family incomebetween 1 and 6 minimum wages (62%), with no previous technical training (59%), with noemployment bond (94%), who were already attended by nurses when needed (94%) and hadaccess to information about nursing outside the university (86%), mainly via websites(27%). Of those who had prior professional technical training, 55% were nursingtechnicians. Among the students of the last period, the profile was also formed by women (97%),between 21 and 26 years old (90%), Catholic (33%), with personal income lower than onethousand reais (64%), with no previous technical training (62%), with no employment bond(97%), who were already attended to by nurses when needed (67%) and had access toinformation about nursing outside the university (93%), mainly through scientificjournals (52%). Of those who had prior professional technical training, 61% were nursingtechnicians.Regarding the results of the free associations referring to the object “professionalnurse autonomy”, among the students of the first period (n = 111), the EVOC softwarecounted 505 words, 238 not repeated. For the purpose of organizing the data, the minimumfrequency of 6 words was defined, excluding words with frequency lower than. The meanfrequency was 13. The mean of the Mean Recall Orders (MOA), also called rang, was 2.8,calculated by EVOC software on a scale of 1 to 5. Combined analysis of these dataresulted in the organization presented in -In the structure of the social representation of professional nurse autonomy, the terms“care”  and “responsibility”  were the probable centralcores for the group of first-period students. These terms, therefore, determine at thesame time the signification and the internal organization of the representation. Thus,they exert a generating and organizing function by creating or transforming the meaningof the other elements of the representation, as well as by determining the nature of theties that bind the elements of representation together (organizing function)In the peripheral system of the representation more characteristics of the immediatecontext of the group appear, that is, it is where the representation is anchored in thereality of the moment of the social groupThe first peripheral system is formed by the term “knowledge” ,indicating another cognitive dimension of the representation. In the second periphery,the elements “commitment”  and “ethics”  justify thepresence of the term “responsibility” in the probable central core of therepresentational structure and reinforce the interpretation of the attitudinal dimensionas a whole. “Love” , in turn, appears as the only affective element of thestructure, possibly linked to the term “care” of the central core. “Submission”  reinforces the attitude of the first-period students regarding the objectprofessional autonomy, belonging to their value system on the same object. “Team”  and “leadership”  indicate the imaginary dimension of therepresentation, where autonomy is expressed.According to The probable central core of the social representation of professional nurse autonomy,for last period students, is formed by the terms “knowledge”  and“responsibility” . The first is related to the cognitive dimension, offunctional nature, and the other to the attitudinal dimension, of normative nature. Theterms “limited”  and “difficult”  in the contrast zone and“necessary”  in the second periphery reinforce the meaning of the term“responsibility” in the probable central core and are within the evaluative dimension ofthe representation.It is possible to identify elements that are related to the praxis dimension of therepresentation, such as “procedure” , “team” ,“prescription” , “management” , “care” ,“education” , “decision”  and “leadership” .These terms, for the group, associate the object to their practices ininternship/residence/technical visits. The peripheral system of the representation hasprecisely this characteristic, which is to show how the group approaches the objectthrough their practices or how they establish their practices, from the way theyresignify the object.The terms “Cofen/Coren” reflect the imaginary dimension of the representation, based onthe professional inspection institutions in Brazil and in the State of Rio de Janeiro,the Federal Nursing Council (Cofen) and the Regional Nursing Council (Coren).The terms “competence” , “quality” , “safety” , “appreciation” , “freedom” , “respect” , “dedication”  and “ethics” , attitudinaldimensions of the representation appearing in the contrast zone and the in the secondperiphery, seem to reinforce ideas expressed by the presence of the terms “knowledge”and “responsibility” in the probable central core of the representation. The term“support” , a cognitive dimension present in the contrast zone, refers tothe deontological aspects of the nursing profession, which, from the perspective of thegroup, may be related to the prerequisites for professional autonomy.In order to confirm certain aspects of the representations produced by the social group,a similarity analysis was also conducted. This is calculated based on the number ofco-occurrences between two terms divided by the number of participants, simultaneously.The product of this calculation is the similarity index. For the term “professionalnurse autonomy”, 94 of the 171 participants simultaneously evoked two or more words fromthe four-house board. According to the similarity analysis, the cognems that present the highest number ofconnections in the similarity tree are “responsibility” and “knowledge”, terms alreadypointed out as possibly central in the four-house board. While not necessarily attestingto the centrality of a given term, the number of connections it establishes with othersreinforces the interpretation that such a term is, in fact, a central core in therepresentation. The term “care” presented only a connection with the term “knowledge”,which puts its centrality in question. Other techniques of collection and analysis,which imply returning to the study scenario, need to be applied to confirm itsnon-centrality in the structure of the representation.The terms “responsibility” and “knowledge”, therefore, form two distinct thematicblocks, one mostly attitudinal (responsibility) and the other cognitive (knowledge).This data demonstrates that the social thought of this group regarding professionalnurse autonomy is dichotomized between the cognitive/attitudinal dimensions and theactions/knowing/doing dimensions, which complement each other in the constitution of thesocial thought. The highest index of similarity in the representation, 0.12, was betweenthose two terms, indicating that, because they are inseparable in the social thought ofthe group, the terms “responsibility” and “knowledge” establish the connection betweenblocks. The cognem “responsibility” is directly or indirectly connected to the terms “limited”,“difficult” and “submission”, three elements of evaluative nature with negativeconnotation, which indicates the existence of a negative position of the group regardingsome of the aspects of the representation. The term “education” is linked to the term“responsibility”, suggesting the idea of a prerequisite for professional autonomy,since it is a great responsibility, in the participants’ opinion. The term“appreciation”, although not directly related to the term “responsibility”, expressesthe idea of opposition to the term “limited” , suggesting the existence of internaltension based on the fact that professional autonomy is limited and this can only bereversed through the social appreciation of nurses.The word “knowledge”, in turn, is strongly linked to terms that are mostly practical inthe understanding of the representation, such as “leadership”, “management”, “team”,“care” and “hospital”, the only term of imaginary nature. Here, there is a sense ofaccomplishment of the professional autonomy in the daily practices of nurses. The word “freedom” is strongly connected to the term “knowledge”, leading to theinterpretation that the acquisition of technical-scientific knowledge is a propellant tofree, independent or autonomous professional practice. The term “ethical” is linked tothe terms “responsibility” and “knowledge” by dashed lines so that there would be noclosure of these connections in the tree, which is in line with the theoreticalperspective of the similarity analysis. In addition, these connections lead to theinterpretation that, in the organization of the social thought of the group, the word“ethics” demonstrates a transversality in the two thematic blocks inherent in thereconstruction of autonomy. “Ethics”, therefore, can be expressed in knowledge, as longas there is a continuation of the prerogative of the existence of responsibility.When comparing the probable central core of the social representation of professionalautonomy for students of the first and last period, the permanence of the term“responsibility” is verified. Considering they are students aiming forprofessionalization, this indicates a challenge for the future care practice, regardingthe burden of responsibility of a nurse considered by them as professionally autonomous.This element has representational components of attitudes favorable to the object andcan be derived from the growing increase of the nurse’s professional space, althoughthis may be fragile in face of public policy or the profiles of managers in theirrespective governmental spheresIt should be noted that the results found in this study are partially different fromthose obtained from non-nursing health professionalsProfessional nurse autonomy is expressed by undergraduate nursing students, at least inthe first instance, as between cognition and attitude, later branching out into otherelements that qualify, regulate or clarify it. This is a characteristic of the socialthought about the object that hadn’t yet been identified in other studies. These are thetwo dimensions of the representation that, in addition to organizing the others aroundthemselves, give coherence and consistency to the knowledge regarding professionalautonomy contextualized in such an affective and relational profession.-,,(Studies of social representations such as this demonstrate the ability to reveal thecodes present in the social thought regarding various themes and, to that end, thestructural approach has been highly heuristic(-,-However, this research is more aligned with studies addressing the social visibility ofnursing and its autonomy. The study is in agreement with several national andinternational authors There is a strong influence of the nurses’ professional training on their practice inthe health work world, since their knowledge, skills and competencies are forged intheir undergraduate training. A worldwide trend of transition of nurses from providersof care to prescribers of care is observed and, with this transition, there is aconsiderable increase in their autonomy and responsibility within health care. This factis very positive, especially for beginners in nursing practice, such as the participantsof this studyThe social representations of professional nurse autonomy for undergraduate nursingstudents differ according to the period they are in and their academic experiences inthe university. For students of the first period, professional autonomy is resignifiedin a practical and attitudinal way. Among students of the last period, the knowledgeacquired in their know-how stimulate them to assign meaning to professional autonomyconditioning it to the acquisition of scientific knowledge, which contributes to a morecognitive and attitudinal representation. In the representational structure of both subgroups, the permanence of responsibility asinherent to the autonomous nursing profession was identified. This is an element thatseems to be transverse from the beginning to the end of the training process in theundergraduate nursing course.


Combined pulmonary fibrosis and emphysema (CPFE) is increasingly acknowledged as a separate syndrome with distinct clinical, physiological and radiological characteristics. We sought to identify physiologic and radiographic indices that predict mortality in CPFE.Data on clinical characteristics, pulmonary function, high-resolution computed tomography (HRCT) and treatment were compared between patients with usual interstitial pneumonia (UIP) plus emphysema (CPFE group) and those with IPF alone (IPF group). Composite physiologic index (CPI) and HRCT scores at diagnosis and during follow-up were assessed.N = 87) was characterized by the predominance of males and smokers, who were less likely to have viral infection prior to the diagnosis, and display basal crackles, finger clubbing and wheeze, as compared to that in the IPF group (N = 105). HRCT and CPI scores increased over time in both groups. Moreover, CPFE group had a poorer prognosis, lower 5-year survival rate , and higher mortality  as compared to that in the IPF group. All CPFE patients received oxygen therapy, antibiotics and oral N-acetylcysteine; > 50 % received bronchodilators, 40 % received corticosteroids and 14 % needed noninvasive mechanical ventilation. On survival analyses, pulmonary arterial hypertension (PAH) and ≥ 5-point increase in CPI score per year were predictors of mortality in the CPFE group .CPFE group (Patients with CPFE were predominantly male and smokers and exhibited distinct clinical, physiological and radiographic characteristics. They had a poorer prognosis than IPF. PAH and ≥ 5-point increase in CPI score per year were predictors of mortality in these patients. Future studies are needed to identify the optimal treatment approach to CPFE. Patients with idiopathic pulmonary fibrosis (IPF) combined with emphysema were first reported several decades ago –3. In 19In clinical practice, CPFE cases are not uncommon, and the estimated prevalence of emphysema is thought to range between one quarter and one half of all IPF patients , 6. In tIn this study, we retrospectively compared the clinical and radiographic characteristics, available therapeutic options, and prognostic indicators between patients with CPFE and those with IPF alone. Furthermore, we assessed the prognostic significance of quantitative physiologic and radiographic indices in patients with CPFE.Subjects were genetically unrelated ethnic Northern Han Chinese and from Heilongjiang and Harbin Province. All hospitalized patients were consecutively recruited from January 2001 to December 2013 in the Department of Respiratory Medicine at the First Affiliated Hospital of Harbin Medical University. We included two groups: patients with CPFE who had usual interstitial pneumonia (UIP) pattern according to HRCT, and patients with IPF alone. The patients in the CPFE group met the diagnostic criteria for IPF for patients not subjected to surgical lung biopsy (in accordance with the 2011 American Thoracic Society and European Respiratory Society (ATS/ERS) statement) . PatientMedical records, pulmonary function tests and HRCT scans at diagnosis and during the 60-month follow-up period, were analyzed. The composite physiologic index (CPI) that represents a combination of pulmonary ventilation and diffusing capacity, and chest HRCT score were obtained to evaluate the extent of disease at diagnosis and at 6 months intervals up to a total of 36 months. The formula for the CPI is as follows: CPI = 91.0−(0.65 × percent predicted diffusing capacity for carbon monoxide-DLCO])− + (0.34 × percentage of predicted forced expiratory volume in 1 s [FEV1]) .https://imagej.nih.gov/ij/download.html). The extent of emphysema was visually estimated bilaterally in HRCT sections at three anatomic levels: near the superior margin of the aortic arch (the upper lung field), the carina (the middle lung field), and at 1 cm above the right hemidiaphragm (the inferior lung field). A score was assigned to grade the emphysematous changes in each lung field as follows: score 0 (no emphysema), score 0.5 , score 1 , score 2 , score 3 , and score 4 . The severity of emphysema was graded based on the sum of the scores in all six lung fields as follows: score 0 (no emphysema), score 1–8 (mild); score 9–16 (moderate), score 17–24 (severe) [HRCT scans were evaluated separately by two radiologists using an image-processing program  . The finThe study endpoint was the completion of the 60-month follow-up, including all-cause deaths and loss to follow-up. Mortality of CPFE was calculated from the deaths that directly resulted from CPFE or CPFE-related causes.t-test. Intragroup variability was assessed by repeated Analysis of Variance (ANOVA). Categorical variables are presented as percentages and compared using the chi-square test and Fisher’s exact test. Univariate and multivariate survival analyses were performed to determine the relationship between clinical parameters, physiological indices, HRCT imaging scores and survival. Differences with an associated P value of < 0.05 were considered significant. All statistical analyses were performed using SAS version 9.1.3 software.Continuous variables are presented as mean ± standard deviation (SD); intergroup differences were assessed by performing A total of 87 patients were included in the CPFE group . The IPF group included 105 patients . The demographic, clinical characteristics and outcomes in both the groups are presented in Table P < 0.05 for all). Patients with CPFE had less frequent history of viral infection as compared to that in the IPF group (P < 0.05). CPFE patients were more likely to have concomitant cardiovascular and cerebrovascular diseases than IPF patients (P < 0.05). CPFE patients more frequently presented with wheeze , and less frequently with basal crackles, than IPF patients (P < 0.05 for both). These were more likely to show concomitant cardiovascular and cerebrovascular disease, wheeze (63.2 % vs. 11.4 %), and an increased level of carcinoembryonic antigen (CEA) as compared to patients in the IPF group (P < 0.05). There was no significant difference in the proportion of patients with BMI < 18 kg/m2 between the two groups (P > 0.05). At the completion of the 60-month follow-up period, 33 patients with CPFE were alive; 11 were lost to follow-up; 30 died from CPFE or CPFE-related causes (lung cancer excluded); 11 died from extrapulmonary diseases, and 2 died from lung cancer. The mean 5-year survival rate in the CPFE group was 43.42 %, with an all-cause mortality rate of 56.58 %, and CPFE-related mortality of 39.47 %. By comparison, 59 IPF patients were alive at the end of 60 months, 15 were lost to follow-up; 21 died from IPF or IPF-related causes, 18 from extrapulmonary diseases and 2 from lung cancer. The mean 5-year survival rate of IPF patients was 65.56 %, with a mean all-cause mortality rate of 34.44 %, and IPF-related mortality of 23.33 %. Compared to IPF, CPFE had a significantly lower 5-year survival rate, higher all-cause mortality and disease-related mortality (P < 0.05).The mean age at diagnosis, and the proportion of males and smokers in the CPFE was higher than that in the IPF (P < 0.05) (Table P < 0.05).The CPI and HRCT scores were used to evaluate the disease progression in both groups and were recorded at 6-month intervals for a total duration of 36 months. During follow-up, all-cause deaths were included in the analysis, whereas data pertaining to patients who were lost to follow-up were excluded. A total of 80 CPFE and 99 IPF completed the follow-up with complete data available for analyses Tables  and 2. TP < 0.0001). The rate of increase in CPI scores showed significant differences between the four different treatment groups, as well as the interaction effects of different time points during follow-up . The rate of increase in CPI score in the group treated with oxygen therapy, bronchodilators and corticosteroids was lower than that in the other groups, which suggests that this therapeutic regimen may be more effective, especially if administered within 24 months from diagnosis . The trend of HRCT and CPI among different treatment groups is shown in Fig. The effect of various therapeutic regimens on prognosis of CPFE patients were assessed by CPI and HRCT scores in sub-groups of patients receiving different treatment. All 87 patients with CPFE received oxygen therapy, antibiotics and oral N-acetylcysteine treatment. Out of these, 12 patients who experienced acute exacerbation or respiratory failure during the disease course were administered noninvasive mechanical ventilatory support; 36 received bronchodilators plus corticosteroids and 15 received bronchodilators but no corticosteroids. The treatment lasted for at least 2 months per year. Rare cases that received other treatments such as immunosuppressants and anti-fibrotic targeted therapy were excluded from the analyses. At the end of the 36-month follow-up, complete data on the CPIs and HRCT scores were available for 69 patients in the CPFE group. These were divided into four sub-groups based on the treatment regimen Tables  and 5. AUnivariate and multivariate survival analyses were performed to identify the clinical parameters associated with mortality in CPFE Table . After aEvidence suggests that a syndrome of CPFE, most frequently associated with IPF, deserves to be recognized as a separate clinical entity owing to the distinct clinical, functional, radiological, and pathological characteristics. In the present study, we compared the clinical characteristics, quantitative respiratory physiological index, radiographic scoring system, treatment and prognosis between patients with UIP plus emphysema (CPFE group) and IPF alone.Although controversies exist in the published literature mainly regarding the prognosis of CPFE patients, the clinical characteristics of CPFE remain consistent with those described by Cottin et al. . Most ofvs. 65.56 %; P < 0.05) and a higher mortality . However, evidence from recent studies that have compared the prognosis of CPFE with that of PF alone has largely been equivocal [vs. 34 months, P < 0.01). In contrast, others have reported either a better survival associated with CPFE as compared to that associated with IPF alone [In this study, the chest HRCT and CPI scores were used for the first time to assess and monitor the course of CPFE. Simultaneous review of these two quantitative indices allowed for an objective evaluation of pulmonary structural and functional damage over the follow-up period. HRCT score and CPI tended to increase over time in both CPFE and IPF groups. However, the clinical course of CPFE varied from that of IPF. The increase in HRCT scores and CPI was more dramatic in the CPFE group, which suggested a correlation of these two indices with clinical deterioration of CPFE. These findings appear to justify the categorization of CPFE as a distinct syndrome that is characterized by a much worse prognosis than that of IPF. Survival analyses showed lower 5-year survival rate and poorer prognosis compared to IPF patients  is increasingly acknowledged as a distinct syndrome with typical clinical, physiological and radiological characteristics. In clinical practice, CPFE cases are not uncommon. But the therapeutic and treatment options for patients with CPFE are limited.CPFE patients were predominantly male and smokers and exhibited distinct clinical, physiological and radiographic characteristics. They had a poorer prognosis than patients with idiopathic pulmonary fibrosis alone (IPF). Pulmonary arterial hypertension and ≥ 5-point increase in composite physiologic index (CPI) score per year were predictors of mortality in CPFE patients.


Thus, Mg2+ homeostasis is subject to tight regulation. Besides the fast and immediate regulation of plasma Mg2+, a major part of Mg2+ homeostasis is realized by a concerted action of epithelial molecular structures that tightly control intestinal uptake and renal absorption. This mechanism is provided by a combination of para- and transcellular pathways. Whereas the first pathway provides the organism with a maximal amount of vital substances by a minimal energy expenditure, the latter enables controlling and fine-tuning by means of local and regional regulatory systems and also, hormonal control. The paracellular pathway is driven by an electrochemical gradient and realized in principal by the tight junction (TJ), a supramolecular organization of membrane-bound proteins and their adaptor and scaffolding proteins. TJ determinants are claudins (CLDN), a family of membrane spanning proteins that generate a barrier or a pore between two adjacent epithelial cells. Many insights into molecular mechanisms of Mg2+ handling have been achieved by the identification of alterations and mutations in human genes which cause disorders of paracellular Mg2+ pathways . Also, in the distal convoluted tubule, a basolateral protein, CNNM2, causes if mutated, familial dominant and also recessive renal Mg2+ wasting, albeit its true function has not been clarified yet, but is assumed to play a key role in the transcellular pathway. Moreover, mutations in human genes that are involved in regulating these proteins directly or indirectly cause, if mutated human diseases, mostly in combination with comorbidities as diabetes, cystic renal disease, or metabolic abnormalities. Generation and characterization of animal models harboring the corresponding mutations have further contributed to the elucidation of physiology and pathophysiology of Mg2+ disorders. Finally, high-end crystallization techniques allow understanding of Mg2+ handling in more detail. As this field is rapidly growing, we describe here the principles of physiology and pathophysiology of epithelial transport of renal Mg2+ homeostasis with emphasis on recently identified mechanisms involved.Magnesium (Mg It is the eleventh most abundant element by mass in the human body. Mg2+ is indispensable for several vital functions, such as neurotransmission, cardiac conductance, blood glucose control, and blood pressure regulation. In muscle, Mg2+ regulates contraction by antagonizing calcium  and is present in every cell type and in every organism. In the blood and serum, Mg2+ is mostly bound to serum albumin  and stored in muscle fibers and in bone. The biologically active form is the ionized form and dietary sources rich of magnesium are plants . Clinically, deficiency of Mg2+ causes nausea, appetite loss, fatigue, and general weakness. At a later stage, patients present with numbness, tingling, muscle cramps, cerebral seizures, and cardiac arrhythmias. Moreover, Mg2+ deficiency can lead to hypocalcemia and hypokalemia  is the major source of cell energy, and must bind Mg and RNA . In planokalemia . On the okalemia . However disease .2+ storage (around 1000 g in adults), the whole body content of Mg2+ only sums up to 20 g. In addition, Mg2+ stores are not as readily accessible as Ca2+ stores by, e.g., PTH action. Therefore, the organisms’ intra- and extracellular Mg2+ levels are kept tightly within narrow limits. Likewise, the available, ionized, biologically active and relevant form (Mg2+) is dependent on a more or less a continuous nutritional supply. Mg2+ serum concentrations in adults range from 0.7 to 1.1 mmol/l, while newborns and toddlers can have lower limit serum concentrations . The daily need of Mg2+ in adults is around 300–350 mg/day and fractional intestinal uptake varies depending on the amount of intake. Fine et al. found that intestinal Mg2+ absorption increases with intake but also that fractional Mg2+ absorption fells progressively (from 65% at low to 11% at high intake)  .In both organs, the intestine and the kidney, Mgn Figure . The par2+ absorption is provided by a continuously maintained electrochemical gradient between the apical (tubular fluid) and the basolateral (blood) compartment. This process is realized by a battery of transcellular  and paracellular transport mechanisms. As a principle, paracellular transport mainly takes place where the transepithelial concentration gradient is high, i.e., the proximal jejunum in the gut and in the proximal tubule (PT) as well the thick ascending loop of Henle in the kidney. By contrast, transcellular transport takes place in the late ileum, colon, and the distal part of the renal tubule , more than 95% of filtered Mg2+ in the pro-urine is reabsorbed along the tubular system by several coordinated transport processes . With this newly proposed classification, we aim to focus on the current knowledge on Mg2+ handling toward a more interactive model, the magnesiome, and the Mg2+ interactome.After glomerular filtration, the non-protein-bound fraction, Mgrocesses . Besides2+ reabsorption are, besides the PT (10–20%), the thick ascending loop of Henle  and the distal convoluted tubule  , a protein family consisting of at least 24 members in Eukaryotes enabling the TJ to function as either (a) barrier, (b) fence, or (c) channel  where needed. As such, the PT has a low resistance (6–10 Ω × cm2) whereas downstream, toward TAL (11–34 Ω × cm2) and the Collecting Duct  TER is constantly increasing  and H20 absorption and is dependent on an existing electro-chemical gradient  or on the surplus of a molecule or substance over the epithelial layer. Although the TJ does not possess pumps or antiporters, transport can nevertheless be selective by the variation and regulation of TJ composition and protein expression  as well as the basolateral extrusion mechanisms  are essential for Na+ K+ and Cl− handling in the TAL (Bartter’s Syndrome types 1–4)  present in these patients. Thus, all the proteins are classified into Category 3  –33 Here, 3 Table . Interes 3 Table , 36. Alt+ K+ ATPase. Mutations in the gene (FYXD2) coding for the γ-subunit of this protein have been shown to cause dominant familial Hypomagnesemia. Thus, it has been shown that this protein is a “conditio-sine-qua-non” for generating the necessary transepithelial gradient for transport systems and, thus, also for renal Mg2+ handling . An important driving force in epithelial tissues and, therefore, also in the TAL, in order to maintain a transepithelial gradient is generated by the basolateral Nahandling , 12, 37,2+ absorption have been shown to cause rare human disorders. In the TAL, where significant Mg2+ and Ca2+ transcellular transport is absent, paracellular transport is of vital importance and is driven by a lumen-positive potential. Mutations in CLDN16 cause an autosomal-recessive disorder called “Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis” (FHHNC)  . Patientantation . A clinificiency . There ificiency . A similficiency , 46.2+ and Ca2+ wasting, clinically an almost phenocopy of patients with CLDN16 mutations  and their tissue distribution (Kidney and Uterus for Claudin-10a and ubiquitously for Claudin-10b)  in two unrelated families. Hadj-Rabia et al. reported mutations in six patients from two unrelated families , resulting in an absence of CLDN10 at the plasma membrane. Affected members had high serum Mg2+ levels and renal loss of K+, Na+ and Cl−. Of interest is that patients also suffered from a variety of skin and teeth disorders . A similar renal phenotype was reported by Klar and colleagues  in a patient by Terliesner was reported to have normomagnesemia  that contributes to Mgdin-10b) –52  . The expdin-10b) . Isolaten CLDN10 –57. Bonglleagues . They idInterestingly, the full CLDN10 knock-out mouse dies a few hours after birth, indicating that one or more organs different than the kidney and skin must be, if deficient for Claudin-10, vital for survival. Thus, the fact that human mutation does not lead to a lethal phenotype are intriguing in terms of compensatory mechanisms. However, the fact that Claudin-10 is expressed in the lung leads to spectate that the primary cause of postnatal death is caused by the absence of Claudin-10 in the lung , 59.−/−) with a hypermagnesemic model (kidney specific CLDN10−/−) resulted in a normomagnesemic mouse, thus a “restored” normal phenotype  molecular machinery that has been recently reviewed in Ref.   –67, onlyd CNNMs) , (2) thed CNNMs) , and (3)d CNNMs) , 65 , growth factors (EGF), (co)-transporters , or even ion-channels (Kir4.1 encoded by KCNJ10) , the chronic kidney disease and the hyperphenylinaemia a subordinated problem to the patient. However, identifying hypomagnesemia might be of value to identify the comorbidities at an early stage  , 81–84   . Mutatioand -A3) , diabeteand -A3) , and nepand -A3) . As in tand -A3) . SLC41A3d SLC41A . These r2+ transport mediator expressed in the DCT is CNNM2, which belongs to the Cyclin M family. This family encompasses four different members (CNNM1-4). Mutations in CNNM2 cause dominant familial hypomagnesemia  mice show lower Mg2+ levels in serum, thus suggesting defects in Mg2+ reabsorption in kidney. In addition, these animals showed lower blood pressure than compared to control mice. These results highlighted the importance of Mg2+ and its reabsorption in the kidney to maintain blood pressure  efflux  domain pair in their amino acid sequence –103. The) efflux ], and wi) efflux , 105. It) efflux , as theyThe second member of the Cnnm family, CNNM2, is abundant in brain and kidney , 65, and2+ transporters and channels, that so far was limited to the crystal structures of two prokaryotic proteins: (i) CorA from Thermotoga maritima  family 41 members . CorA represents the major transport machinery responsible for Mg2+ uptake in bacteria and it translocates Mg2+ by using an inwardly biased electrochemical gradient that serves as the driving force for Mg2+ permeation  the presence of an intracellular CBS domain pair  that are located at opposite ends of the central β-sheets of the CBS motifs. In contrast with S1, which is partially occluded and full of bulky residues, the site S2 is fully accessible and can accommodate phospho-nucleotides, such as AMP, ADP, or ATP , 121 Fi. Site S2 Figures B,C (106,2+ and in the absence of MgATP, the CBS module adopts a “twisted” shape (Figure 2+ ions through the basolateral cell membrane (At low concentrations of Mge Figure B, in whie Figure . These se Figure B toward e Figure C. The comembrane , 121 (Fimembrane .2+ homeostasis in bacteria (2+ ions, the complementary CBS2 motifs of MgtE subunits remain apart in the dimer due to the repulsion exerted by acidic clusters located at the interfacial helices of the CBS2 domains. In this state, the CBS module impairs the transport of Mg through the membrane and maintains the protein in an “open” state. While the intracellular concentration of Mg2+ is low, the CBS module remains open and allows the influx of Mg2+ ions toward the interior of the cell. Upon increasing the intracellular concentration of Mg2+, the pre-existing repulsive acidic clusters become sequentially neutralized by newly bound Mg2+ ions, thus allowing the approximation of the CBS2 motifs. The sequential binding of Mg atoms progressively causes a closure of the CBS module that, when completed, adopts a “flat” disk-like arrangement as that observed in the MgATP/Mg2+ bound form of CNNM2 (Interestingly, an ATP/Mg-mediated gating process ruled out by CBS domains has also been postulated as the mechanism by which the MgtE transporter senses and regulate the Mgbacteria . In contbacteria –115. In of CNNM2 . The newof CNNM2 .2+ handling in health and disease. On that basis, technologies, such as mouse genetic engineering as well as crystallography, have contributed in this field of physiology and pathophysiology. However, our current knowledge of the molecular mechanisms underlying magnesium transport through the cell membranes is very scarce, and represents an incipient field of research that will mature, as we are able to identify new molecular partners involved in this process. Proteins involved in trans- and paracellular pathways have the potential of being key players in Magnesium Homeostasis and also other disorders, such as diabetes, hypertension, and schizophrenia, thus being a potential target for pharmaceutical interventions.The identification of mutations in human genes has led to a deeper understanding of MgAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Many risk behaviours in adolescence are socially patterned. However, it is unclear to what extent socioeconomic position (SEP) influences adolescent drinking in various parts of Europe. We examined how alcohol consumption is associated with parental SEP and adolescents’ own SEP among students aged 14–17 years.Cross-sectional data were collected in the 2013 SILNE study. Participants were 8705 students aged 14–17 years from 6 European cities. The dependent variable was weekly binge drinking. Main independent variables were parental SEP  and adolescents’ own SEP (student weekly income and academic achievement). Multilevel Poisson regression models with robust variance and random intercept were fitted to estimate the association between adolescent drinking and SEP.Prevalence of weekly binge drinking was 4.2% (95%CI = 3.8–4.6). Weekly binge drinking was not associated with parental education or family affluence. However, weekly binge drinking was less prevalent in adolescents with high academic achievement than those with low achievement , and more prevalent in adolescents with >€50 weekly income compared to those with ≤€5/week . These associations were found to vary according to country, but not according to gender or age group.Across the six European cities, adolescent drinking was associated with adolescents’ own SEP, but not with parental SEP. Socio-economic inequalities in adolescent drinking seem to stem from adolescents’ own situation rather than that of their family.The online version of this article (doi:10.1186/s12889-017-4635-7) contains supplementary material, which is available to authorized users. Alcohol consumption ranks among the top five risk factors for disease, disability and death throughout the world . AdolescMany risk behaviours in adolescence are socially patterned. Several studies have assessed the possible association between parental socioeconomic position (SEP) and adolescent alcohol consumption. These studies yielded inconsistent results –12. AccoThe lack of a consistent association between the parental SEP and adolescent alcohol use could be due to adolescence being a period of decreasing parental influence on risk behaviours . Thus, mThe aim of this study was to estimate the association between adolescent drinking and parental SEP and adolescents’ own SEP among students aged 14–17 years, and to analyse which SEP indicator has a stronger association with adolescent drinking. We additionally explored whether the associations varied according to country, gender and age group. The particular value of this study lies in analysing multiple SEP indicators at parental and adolescent level at the same time, and in using a large dataset covering cities from six different European countries.n = 11,015; 79.4% response rate). All data were self-reported by the students. Ethical approval was obtained in all countries. Methodological details on the SILNE survey have been published elsewhere [n = 424) and those with missing information on both alcohol measures (n = 12), demographic variables (n = 178) and parental and adolescent SEP variables (n = 1696). The final sample size was of 8705 students.The study used a cross-sectional design with data from the SILNE  survey, conducted in 2013. The SILNE survey was primarily aimed at studying socioeconomic inequalities in smoking in different European cities , but it lsewhere . For thiThe dependent variable was weekly binge drinking, defined as drinking 5 or more alcoholic drinks on one occasion at least once a week in the previous 12 months (yes/no). Moreover, to describe adolescent alcohol consumption, weekly alcohol consumption  was also used to perform a sensitivity analysis. Information on weekly binge drinking and weekly alcohol consumption was available for 8541 and 8652 individuals, respectively.We measured two different indicators of parental SEP: parental education level and family affluence, which have been previously used , 12, 20.We measured two different indicators of adolescents SEP, the amount of money students had available to spend on themselves each week and the academic achievement, which have been used in previous studies , 23. StuWe measured confounders likely to predict adolescent drinking, such as age (in years), gender  and migrant background . We distr = 0.88), we decided to focus the study on weekly binge drinking and conduct a sensitivity analysis with weekly alcohol consumption as the dependent variable.First, we described the distribution of the independent variables in the sample and estimated the age-adjusted prevalence of weekly binge drinking and weekly alcohol consumption for all subgroups. We also tested for polychoric correlations between the dependent variables, as the variables were categorical . As we fWe calculated polychoric correlations between the different adolescent and parental SEP variables to assess potential multicollinearity in the regression model. We found that the correlations between these variables were weak (between −0.10 and +0.21). To estimate the associations between weekly binge drinking and parental education, family affluence, student weekly income and academic achievement, we fit multilevel Poisson regression models with robust variance and random intercept (2 levels: student and school). These models yielded Prevalence Ratios (PR) and their 95% confidence intervals (95%CI). We tried to fit a three-level model including the city as the highest level, but the model fit poorly due to the fact that school variability explained the differences between countries and also because there were few countries in the study. We used Poisson regression models with robust variance instead of logistic regression models as they yielded PR, which have the advantage over Odds Ratios to have a concrete interpretation even when prevalence rates are high .We fit several models in various steps. In each step, we adjusted for gender, age and migrant background. In step 1 we estimated the variance among schools. In step 2 we fit several models including in each model only one SEP measure . In step 3 we included all SEP measures in one model simultaneously. We conducted a sensitivity analysis using multiple imputation in addition to the complete-case analysis approach in order to assess whether the method used to deal with missing data influenced the results.To test whether the associations were consistent among gender, age and country, we also fit the same regression models per gender, age and country. All analyses were conducted using STATA 13.Table The results of the multilevel Poisson regression confirm the findings of the descriptive analysis Table . When adThe results stratified by gender and age group are presented in Additional file Table Finally, in a sensitivity analysis, we repeated these analyses using weekly alcohol consumption as the dependent variable. The results of the multilevel Poisson regression models for weekly alcohol consumption are shown in Additional file The main results of this study were: 1) Parental SEP measures  were not associated with adolescent drinking; 2) High student weekly income and low academic achievement were associated with higher likelihood of alcohol consumption; 3) The same associations were observed for different drinking measures , and for different sexes and age groups; and 4) Although the relationship between SEP indicators and binge drinking varied between countries, in most countries adolescent SEP was associated with alcohol consumption, while parental SEP was not.First, alcohol consumption measures were estimated based on self-reported data. As a result, prevalence rates of weekly binge drinking and alcohol consumption may be underestimated due to social desirability bias, as individuals drinking higher amounts of alcohol tend to underestimate their consumption . BesidesSecond, parental SEP was reported by students instead of parents themselves. As a consequence, we could not ask in detail about the family income or parental occupation status. Moreover, parental education level was the only variable with a relevant proportion of missing data (around 12%). This may introduce bias, as non-response rates tend to be higher among people with low SEP . HoweverWe found substantial differences in the prevalence of alcohol consumption between countries, with the highest age-adjusted prevalence of weekly binge drinking in Belgium (6.1%) and the lowest in Finland (1.1%). Although the lower prevalence of alcohol use in Finish adolescents may be explained by a steep decline in alcohol use and intoxication in adolescents after 2011 , factorsThe prevalence of alcohol use in all countries is lower than the one estimated in the HBSC survey of 2009–2010 . In ItalOur findings suggest that, in general, there is no association between parental SEP and adolescent drinking, which is in line with a review that found no clear pattern in this association . HoweverBesides, this lack of association between adolescent drinking and parental SEP in the overall sample did not change depending on the alcohol drinking measure. The results from a study in Slovak students were in agreement with ours: no association was found between parental education and both frequency of alcohol use and drunkenness .With respect to the student weekly income, we found a strong positive association: the more available money, the higher the risk of binge drank weekly. This finding is in line with previous studies , 37. In High academic achievement appears to be a protective factor for alcohol consumption. Students with higher achievement may be more oriented toward the future and, therefore, be more likely to protect their health. Previous studies found that having high academic goals, such as planning to graduate from university, is a protective factor for substance use among adolescents . FurtherOur results suggest the need for further research using longitudinal data to identify the causal mechanism driving the associations between adolescent drinking and student weekly income and academic achievement, respectively. Besides, research on socioeconomic inequalities in adolescent drinking should include measures of adolescents’ own SEP as they appear to be much more predictive of adolescent alcohol use than parental SEP indicators. A diminished alcohol availability and accessibility in adolescents should be reinforced through stricter alcohol policies, such as increasing alcohol taxes or higher control of alcohol selling, among other effective policies –47.Low academic achievement and high student weekly income are both strongly associated with higher adolescent drinking. Parental educational level and family affluence are not consistently associated with adolescent alcohol consumption. This suggests that socioeconomic inequalities in adolescent drinking may originate from adolescents’ own situation rather than that of their family. These results imply that health programmes to prevent adolescent drinking in schools should focus especially on children with school problems and low academic performers, just as it has been suggested for tobacco . The impAdditional file 1:Table S1. Prevalence ratios (PR) of weekly binge drinking by gender estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOC 66 kb)Additional file 2:Table S2. Prevalence ratios (PR) of weekly binge drinking by group of age estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOC 56 kb)Additional file 3:Table S3. Prevalence ratios (PR) of drinking at least one alcoholic beverage per week estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOCX 14 kb)Additional file 4:Table S4. Prevalence ratios (PR) of drinking at least one alcoholic beverage per week by gender estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOCX 15 kb)Additional file 5:Table S5. Prevalence ratios (PR) of drinking at least one alcoholic beverage per week by group of age estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOCX 15 kb)Additional file 6:Table S6. Prevalence of drinking at least one alcoholic beverage per week and prevalence ratios for the socioeconomic position (SEP) variables by country, estimated with multilevel Poisson regression models with robust variance among 14–17 years-old students from 6 European cities participating in the SILNE survey, 2013. (DOCX 16 kb)