Breath biomarkers of pediatric malaria: reproducibility and response to antimalarial therapy.

BACKGROUND: Many insect-borne pathogens appear to manipulate the odors of their hosts in ways that influence vector behaviors. In our prior work, we identified characteristic changes in volatile emissions of cultured Plasmodium falciparum parasites in vitro and during natural human falciparum malaria. In the current study, we prospectively evaluate the reproducibility of these findings in an independent cohort of children in Blantyre, Malawi. METHODS: We enrolled febrile children under evaluation for malaria and collected breath from children with and without malaria, as well as healthy controls. Using gas-chromatography/mass spectrometry, we characterized breath volatiles associated with malaria. By repeated sampling of children with malaria before and after antimalarial use, we determined how breath profiles respond to treatment. In addition, we investigated the stage-specificity of biomarkers through correlation with asexual and sexual stage parasitemia. RESULTS: Our data provide robust evidence that P. falciparum infection leads to specific, reproducible changes in breath compounds. While no individual compound served as adequate classifier in isolation, selected volatiles together yielded high sensitivity for diagnosis of malaria. Overall, the results of our predictive models suggest the presence of volatile signatures that reproducibly predict malaria infection status and determine response to therapy, even in cases of low parasitemia.

Background TV and infant-family interactions: Insights from home observations.

Background television has been found to negatively impact children's language development and self-regulatory skills, possibly due to decreased parent-child interactions. Most of the research on the relationship between background TV and caregiver-child interactions has been conducted in laboratory settings. In the current study, we conducted home observations and investigated whether infants engage in fewer interactions with family members in homes where background TV is more prevalent. We observed 32 infants at the ages of 8, 10, and 18 months in their home environments, coding for dyadic interactions (e.g., parent talking to and/or engaging with the child), triadic interactions (e.g., parent and infant play with a toy together), and infants' individual activities. Our findings revealed that background TV was negatively associated with the time infants spent in triadic interactions, positively associated with time spent engaging in individual activities, and not significantly related to the time spent in dyadic interactions. Apart from the relationship between background TV and individual activity time at 8 months, these associations remained significant even after accounting for families' socioeconomic status. These findings imply a correlation between background TV exposure and caregiver-infant-object interactions, warranting a longitudinal analysis with larger sample sizes.

Analogy is indispensable but rule is a must: Insights from Turkish.

Inflectional morphology provides a unique platform for a discussion of whether morphological productivity is rule-based or analogy-based. The present study testing 140 children (range = 29 to 97 months; M(SD) = 64.1(18.8)) on an elicited production task investigated the acquisition of the irregular distribution in the Turkish aorist. Results suggested that to discover the allomorphs of the Turkish aorist, children initially carried out similarity comparisons between analogous exemplars, which helped them tap into phonological features to induce generalizations for regulars and irregulars. Thereafter to tackle the irregularity, children entertained competing hypotheses yielding overregularizations and irregularizations. While the trajectory of overregularizations implicated the gradual formulation of an abstraction based on type-frequency, irregularizations suggested both intrusion of analogous exemplars and children's attempts to default to an erroneous micro-generalization. Our findings supported a model of morphological learning that is driven by analogy at the outset and that invokes rule-induction in later stages.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.

The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy.

We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. IMPACT STATEMENT What is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group. What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.

The acquisition and use of relative clauses in Turkish-learning children's conversational interactions: a cross-linguistic approach.

Using a cross-linguistic approach, we investigated Turkish-speaking children's acquisition and use of relative clauses (RCs) by examining longitudinal child-caregiver interactions and cross-sectional peer conversations. Longitudinal data were collected from 8 children between the ages of 8 and 36 months. Peer conversational corpus came from 78 children aged between 43 and 64 months. Children produced RCs later than in English (Diessel, 2004) and Mandarin (Chen & Shirai, 2015), and demonstrated increasing semantic and structural complexity with age. Despite the morphosyntactic difficulty of object RCs, and prior experimental findings showing a subject RC advantage, preschool-aged children produced object RCs, which were highly frequent in child-directed speech, as frequently as subject RCs. Object RCs in spontaneous speech were semantically less demanding (with pronominal subjects and inanimate head nouns) than the stimuli used in prior experiments. Results suggest that multiple factors such as input frequency and morphosyntactic and semantic difficulty affect the acquisition patterns.

The relationship between responsiveness to social and monetary rewards and ADHD symptoms.

Alterations in reward processing are frequently reported in attention deficit hyperactivity disorder (ADHD). One important factor affecting reward processing is the quality of reward as social and monetary rewards are processed by different neural networks. However, the effect of reward type on reward processing in ADHD has not been extensively studied. Hence, in the current study, an exploratory research was conducted to investigate the effect of reward type (i.e., social or monetary) on different phases of reward processing. We recorded event-related potentials (ERPs) during a spatial attention paradigm in which cues heralded availability and type of the upcoming reward and feedbacks informed about the reward earned. Thirty-nine (19 males) healthy individuals (age range: 19-27 years) participated in the study. ADHD symptoms were assessed by using ADHD self-report scale (ASRS). Our results revealed a consistent negative correlation between the hyperactivity subscale of ASRS and almost all social-feedback related ERPs (P2, P3, and FRN). ERP amplitudes after social feedbacks were less positive for P2 and P3 and more negative for FRN for individuals with greater hyperactivity levels. Our findings suggest that hyporesponsiveness to social feedbacks may be associated with hyperactivity. However, the results have to be confirmed with clinical populations.

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

INTRODUCTION: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). METHODS: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. RESULTS: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). CONCLUSIONS: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

Children's referential communication skills: The role of cognitive abilities and adult models of speech.

Referential communication is effective when speakers describe a specific entity in a way that leads to accurate identification of that referent among competitors. Young children's initial referential expressions are often inadequate, and this state of miscommunication needs to be repaired in subsequent communicative attempts. Exposure to adults' effective descriptions of referents is beneficial for children to develop referentially clear initial descriptions. Here, we examined whether adult models of speech also provide benefits for children's communicative repair behavior. Furthermore, we assessed the relation between children's cognitive abilities and referential communication skills. We tested 59 children (aged 4 years to 5 years 9 months) on their ability to request specific stickers among similar distractors in a pretest-modeling-posttest design. In the modeling phase, 30 children heard more informative descriptions of stickers with relative clauses (e.g., "you selected the horse that the boy is riding") and 29 children heard less informative descriptions with demonstrative noun phrases (e.g., "you selected that horse"). In a second session, we measured children's short-term memory, executive functions (working memory and cognitive flexibility), and theory of mind. Children who heard more informative expressions showed a greater increase in uniquely identifying initial descriptions than children who heard less informative expressions. Hearing more informative expressions did not provide an additional benefit in repairing ambiguous messages, an ability we found to be related to cognitive flexibility and memory. Results indicate that informative language structures that uniquely identify referents provide limited benefits to children for effective communication where children's short-term memory and executive functions also matter.

Ovarian reserve after internal iliac artery ligation.

AIM: Ligation of major vessels supplying ovaries may alter hormones and ovarian reserve due to disturbances of vascular circulation. Our purpose is to measure serum anti-Müllerian hormone (AMH) levels and ovarian volume in patients who had internal iliac artery ligation (IIAL) and/or IIAL plus hysterectomy due to uterine atony. METHODS: Patients who underwent IIAL and IIAL+ hysterectomy were evaluated 6 months after their operations and were compared with the control group. The hormones, ovarian volume and antral follicle count (AFC) were measured in each group. RESULTS: Serum AMH levels in the post-partum 6th month interval were lower in the IIAL group than in the control group and were the lowest in the IIAL+ hysterectomy group. Similar to AMH results, AFC and ovarian volumes were also lowest in the IIAL+ hysterectomy group. CONCLUSION: IIAL and hysterectomy are lifesaving interventions during peripartum hemorrhage; however, they might alter ovarian reserve in the short term.

Functions of Turkish evidentials in early child-caregiver interactions: a growth curve analysis of longitudinal data.

In languages with evidential marking, utterances consist of an informational content and a specification of the mode of access to that information. In this first longitudinal study investigating the acquisition of the Turkish evidential marker -mIs in naturalistic child-caregiver interactions, we examined six children between 8 and 36 months of age. We charted individual differences in child and caregiver speech over time by conducting growth curve analyses. Children followed a similar course of acquisition in terms of the proportion of the marker in overall speech. However, children exhibited differences with respect to the order of emergence of different evidential functions (e.g., inference, hearsay), where each child showed a unique pattern irrespective of the frequency in caregiver input. Nonfactual use of the marker was very frequent in child and caregiver speech, where high-SES caregivers mostly produced the marker during story-telling and pretend play, and low-SES caregivers for regulating the child's behavior.

The effects of active worrying on working memory capacity.

According to the attentional control theory, worry, a crucial component of anxiety, impairs task performance through its direct effect on working memory capacity (WMC) by using up the limited resources available for performance thus reducing attentional control. We tested this hypothesis in the current study by examining the causal influence of active worrying on WMC in a sample of undergraduate university students (n = 64) assigned either to a worry condition or to a non-worry control condition. Participants performed a change detection task before and after the worry/control manipulation. Mediation analyses showed that the level of self-reported worry mediated the effects of condition on change in WMC as demonstrated by the significant indirect effect of worry and the resulting non-significant direct effect of condition on change in WMC. Similar results were obtained when using state anxiety measures as mediating factors. Results of the current study are amongst the first to demonstrate that worry impairs WMC and as such have important implications for understanding the impact of worry.

Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer.

OBJECTIVES: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer. METHODS: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed. RESULTS: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS. CONCLUSIONS: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.

[Understanding/acceptance of radiotherapy: An ethical dilemma resolved by an ethics of care]. / Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude.

PURPOSE: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. MATERIALS AND METHODS: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. RESULTS: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. CONCLUSION: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

Membrane fluidity determines sensitivity of filamentous fungi to chitosan.

The antifungal mode of action of chitosan has been studied for the last 30 years, but is still little understood. We have found that the plasma membrane forms a barrier to chitosan in chitosan-resistant but not chitosan-sensitive fungi. The plasma membranes of chitosan-sensitive fungi were shown to have more polyunsaturated fatty acids than chitosan-resistant fungi, suggesting that their permeabilization by chitosan may be dependent on membrane fluidity. A fatty acid desaturase mutant of Neurospora crassa with reduced plasma membrane fluidity exhibited increased resistance to chitosan. Steady-state fluorescence anisotropy measurements on artificial membranes showed that chitosan binds to negatively charged phospholipids that alter plasma membrane fluidity and induces membrane permeabilization, which was greatest in membranes containing more polyunsaturated lipids. Phylogenetic analysis of fungi with known sensitivity to chitosan suggests that chitosan resistance may have evolved in nematophagous and entomopathogenic fungi, which naturally encounter chitosan during infection of arthropods and nematodes. Our findings provide a method to predict the sensitivity of a fungus to chitosan based on its plasma membrane composition, and suggests a new strategy for antifungal therapy, which involves treatments that increase plasma membrane fluidity to make fungi more sensitive to fungicides such as chitosan.

Modeling of the process of moisture loss during the storage of dried apricots.

Moisture content is a reference parameter for dried food because the growth of most microorganisms is inhibited below certain water activity levels. In addition, it has a determining influence on the evolution of important parameters, such as color and flavor, and on other properties and deterioration reactions, such as texture, oxidation processes and nutritional value. During the storage of some dried fruits, moisture is produced due to Maillard reactions and exchanged with the surrounding environment through the packaging. The evolution of dried foods during their shelf life depends on the storage conditions. The aim of this study is to analyze the evolution of the moisture content in dried apricots packaged in different types of containers, namely glass and thermosealed polypropylene trays. The samples were stored at constant temperatures: 5, 15, 25 and 35 °C and were analyzed periodically over a period of 12 months. The sorption isotherms of apricots used in this study were also determined. In order to model how the moisture evolved, an empirical kinetic model was tested. This model considers both water transfer from the fruit and also water production as a result of the Maillard processes. The explained variance was higher than 95% in the samples stored in trays, which were thermosealed with film.

Number and type of toys affect joint attention of mothers and infants.

Establishing joint attention with a caregiver on a physical object provides an optimal environment for language learning for infants. In the present study, we investigated whether 12-month-olds and their mothers establish higher quality joint attention interactions in the presence of fewer compared to more toys. As a secondary goal, we investigated how different types of toys affect how mother-infant dyads establish joint attention. In a five-minute free play setting, mothers and infants participated in either Five Toy (n = 48) or Twelve Toy (n = 33) groups. They were given organizational (i.e., toys that require arrangement of parts), responsive (i.e., toys that emit sounds via manipulation), and symbolic toys (i.e., toys that elicit pretend play). Results showed that compared to the Twelve Toy group, joint attention interactions in the Five Toy group were less frequent, lasted longer, were more likely to be initiated by maternal following than by maternal directing of infants' attention, and more likely to be coordinated in which infants demonstrated awareness of the mothers' simultaneous attentional focus by looking at their mothers, vocalizing, or turn-taking. We further found longer joint attention durations on organizational compared to symbolic toys, which were preferred to a lesser extent by the dyads. With responsive toys, mothers were more likely to initiate joint attention by following their infants' attention. Joint attention interactions lasted longer and were more likely to be coordinated in the second half compared to the first half of the play session, suggesting that over time it became easier for the mothers and infants to settle on certain toys for more elaborate play. In sum, mothers and infants establish higher-quality joint attention with fewer toys in general and with organizational toys in particular.

Cultural differences in performance on Eriksen's flanker task.

Eriksen's zoom model of attention implies a trade-off between the breadth and resolution of representations of information. Following this perspective, we used Eriksen's flanker task to investigate culture's influence on attentional allocation and attentional resolution. In Experiment 1, the spatial distance of the flankers was varied to test whether people from Eastern cultures (here, Turks) experienced more interference than people from Western cultures (here, Americans) when flankers were further from the target. In Experiment 2, the contrast of the flankers was varied. The pattern of results shows that congruency of the flankers (Experiment 1) as well as the degree of contrast of the flankers compared with the target (Experiment 2) interact with participants' cultural background to differentially influence accuracy or reaction times. In addition, we used evidence accumulation modeling to jointly consider measures of speed and accuracy. Results indicate that to make decisions in the Eriksen flanker task, Turks both accumulate evidence faster and require more evidence than Americans do. These cultural differences in visual attention and decision-making have implications for a wide variety of cognitive processes.