Mixed T cell CHIMERISM in bone marrow at day+30 after allogeneic stem cell transplantation: Correlation with acute GVHD grades III-IV and no impact on relapse and overall survival.

OBJECTIVES: Early chimerism analysis is important to assess engraftment in allogeneic hematopoietic stem cell transplantations. METHODS: We retrospectively investigated the impact of T-cell chimerism at day 30 in bone marrow on acute graft-versus-host disease (aGVHD), relapse, and overall survival in 142 adult allo-transplanted patients. RESULTS: The majority of patients (89%) received myeloablative conditioning and 90% have undergone T-cell replete donor graft. At day 30, 103 patients showed T-complete chimerism with prevalence in haploidentical transplants, whereas 39 cases had CD3+ mixed chimerism, including 30 patients transplanted with HLA identical donors, and 21 with T-cell donors<90%. T-cell chimerism at day 30 was weakly inversely related to aGVHD grades II-IV (p = .078) with no cases of grades III-IV aGVHD in patients with CD3+ <95%. Mixed T-cell chimerism did not impact on relapse (p = .448) and five of the seven patients who relapsed had T-cell chimerism ≤90%. Older age and active disease at transplant had a statistically significant negative effect on overall survival (p = .01 and p = .0001, respectively), whereas mixed CD3+ chimerism did not. CONCLUSIONS: T lymphocyte chimerism analysis at day +30 in bone marrow could identify allo-transplanted patients at major risk of aGVHD grades III-IV (CD3+ donors >95%) mainly post-myeloablative conditioning regimen.

Bayesian inference for quantiles of the log-normal distribution.

The log-normal distribution is very popular for modeling positive right-skewed data and represents a common distributional assumption in many environmental applications. Here we consider the estimation of quantiles of this distribution from a Bayesian perspective. We show that the prior on the variance of the log of the variable is relevant for the properties of the posterior distribution of quantiles. Popular choices for this prior, such as the inverse gamma, lead to posteriors without finite moments. We propose the generalized inverse Gaussian and show that a restriction on the choice of one of its parameters guarantees the existence of posterior moments up to a prespecified order. In small samples, a careful choice of the prior parameters leads to point and interval estimators of the quantiles with good frequentist properties, outperforming those currently suggested by the frequentist literature. Finally, two real examples from environmental monitoring and occupational health frameworks highlight the improvements of our methodology, especially in a small sample situation.

Evaluation of factors affecting total nucleated cells in umbilical cord blood collected for the Calabria cord blood bank.

BACKGROUND: Total nucleated cell (TNC) count is the most important biological feature to consider in assessing the quality of umbilical cord blood (UCB) for haematopoietic stem cell (HSC) transplantation. Certain obstetric factors have been reported to increase TNC count in UCB units collected for transplantation. The aim of our study was to analyze how various maternal, neonatal and obstetric factors affected TNC count in the UCBs we collected for our cord blood bank in southern Italy. MATERIAL AND METHODS: We performed a retrospective analysis of 634 medical records of UCBs collected by Calabria Cord Blood Bank (CCBB), between January 1, 2010 and December 31, 2016. We analyzed various maternal, neonatal and obstetric variables factors and related this factor with the characteristic of TNC. RESULTS: We found that the average number of TNCs was significantly greater in vaginal delivery than in caesarean delivery. We also found that TNCs were higher in the 40th week of pregnancy and when Apgar 1' scores were ≤ 9. The effect of a newborn's gender was less evident on TNC count. CONCLUSIONS: Knowledge of factors predictive of a higher TNC count would help cord blood banks more efficiently identify donors likely to yield high-quality UCBs for transplantation.

The Effects of Air Pollution on COVID-19 Related Mortality in Northern Italy.

Long-term exposure to ambient air pollutant concentrations is known to cause chronic lung inflammation, a condition that may promote increased severity of COVID-19 syndrome caused by the novel coronavirus (SARS-CoV-2). In this paper, we empirically investigate the ecologic association between long-term concentrations of area-level fine particulate matter (PM2.5) and excess deaths in the first quarter of 2020 in municipalities of Northern Italy. The study accounts for potentially spatial confounding factors related to urbanization that may have influenced the spreading of SARS-CoV-2 and related COVID-19 mortality. Our epidemiological analysis uses geographical information (e.g., municipalities) and negative binomial regression to assess whether both ambient PM2.5 concentration and excess mortality have a similar spatial distribution. Our analysis suggests a positive association of ambient PM2.5 concentration on excess mortality in Northern Italy related to the COVID-19 epidemic. Our estimates suggest that a one-unit increase in PM2.5 concentration (µg/m3) is associated with a 9% (95% confidence interval: 6-12%) increase in COVID-19 related mortality.

Outlier robust model-assisted small area estimation.

Small area estimation with M-quantile models was proposed by Chambers and Tzavidis (). The key target of this approach to small area estimation is to obtain reliable and outlier robust estimates avoiding at the same time the need for strong parametric assumptions. This approach, however, does not allow for the use of unit level survey weights, making questionable the design consistency of the estimators unless the sampling design is self-weighting within small areas. In this paper, we adopt a model-assisted approach and construct design consistent small area estimators that are based on the M-quantile small area model. Analytic and bootstrap estimators of the design-based variance are discussed. The proposed estimators are empirically evaluated in the presence of complex sampling designs.

Factors correlated with hearing aids adherence in older adults: a prospective controlled study.

OBJECTIVE: To investigate which factors influence the adherence to hearing aid (HA) use in elderly patients with moderate-to-severe hearing loss. METHODS: This observational, prospective, single-centre study enrolled patients with moderate-to-severe hearing loss. They were evaluated before and 1 year after having either one or two HAs fitted. RESULTS: A total of 86 patients were enrolled in the study and of these 69.8% (60 of 86; USER group) continued to use their HA at 1 year after fitting; six patients had not continued their use (NON-USERS). The USER group was younger than the NON-USER group, but the difference was not significant. The USER group had a significantly better unaided auditory threshold at baseline than the NON-USER group. HA use resulted in improvements in speech audiometry and auditory threshold. There was also a maintenance of cognitive function in the USER group. CONCLUSION: Use of HA for 1 year resulted in improved auditory performance and an absence of a deterioration of cognitive function.Trial registration: This research was retrospectively registered under no. NCT04333043 at ClinicalTrials.gov (http://www.clinicaltrials.gov/) on the 26 March 2020. This research has been registered with the Ethics Committee of the Area Vasta Emilia Nord under number 104, date of approval 17/07/2017.

Do Different Types of Microphones Affect Listening Effort in Cochlear Implant Recipients? A Pupillometry Study.

BACKGROUND: It is known that subjects with a cochlear implant (CI) need to exert more listening effort to achieve adequate speech recognition compared to normal hearing subjects. One tool for assessing listening effort is pupillometry. The aim of this study is to evaluate the effectiveness of adaptive directional microphones in reducing listening effort for CI recipients. METHODS: We evaluated listening in noise and listening effort degree (by pupillometry) in eight bimodal subjects with three types of CI microphones and in three sound configurations. RESULTS: We found a correlation only between sound configurations and listening in noise score (p-value 0.0095). The evaluation of the microphone types shows worse scores in listening in noise with Opti Omni (+3.15 dB SNR) microphone than with Split Dir (+1.89 dB SNR) and Speech Omni (+1.43 dB SNR). No correlation was found between microphones and sound configurations and within the pupillometric data. CONCLUSIONS: Different types of microphones have different effects on the listening of CI patients. The difference in the orientation of the sound source is a factor that has an impact on the listening effort results. However, the pupillometry measurements do not significantly correlate with the different microphone types.

An Adaptation and Validation Study of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) in Italian Normal-Hearing Children.

This study aimed to translate and adapt the English version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children and for parents into the Italian language; validate SSQ for hearing children and their parents; and evaluate the discriminant validity of the instrument. A group of 102 normal-hearing Italian children, aged between 9 and 16 years, and their parents were included in this study. A group of 31 parents of normal-hearing Italian children aged between 6 and 8 years was also included. A group of 57 hearing-impaired Italian children aged between 9 and 16 years, and their parents were also included, as well as a group of 30 parents of hearing-impaired Italian children aged between 6 and 8 years. Cronbach's alpha in the SSQ for parents was 0.92; it was 0.95 in the SSQ for children. Guttmann's split-half coefficient in SSQ for children for both λ4 and λ6 was 0.98; in SSQ for parents in λ4 was 0.96 and λ6 was 0.95. These data provide evidence for the discriminant validity of the SSQ scale (p-value < 0.001). Italian SSQ scales for children and for parents are now available.

Nutritional Treatment in a Cohort of Pediatric Patients with Familial Hypercholesterolaemia: Effect on Lipid Profile.

Background and aims: Familial Hypercholesterolaemia (FH) is characterised by a genetic alteration in the transport and metabolism of cholesterol that leads to elevated levels of total cholesterol (CT) and low-density lipoprotein cholesterol (LDL-C) and early onset of atherosclerosis. According to the current guidelines, diet and promotion of healthy habits are first-line treatments. Little is known about the effectiveness of cholesterol-lowering diet and healthy lifestyle habits on plasma cholesterol and lipid profile in children and adolescents with FH. The aim of the study is to investigate the effect of the nutritional counseling on plasma lipid profile in FH children at the first step of treatment. Methods: 115 FH children (2−17 years) were included in the study; dietary habits were evaluated through a Food Frequency Questionnaire (FFQ) and blood samples for lipid profile were collected at the enrollment (T0) and six months later (T1). Results: the lipid profile at T0 and T1, expressed as mean ± standard deviation in mg/dL, was, respectively: total cholesterol 285.9 ± 51.1 and 276.6 ± 46.8 (paired test difference p value < 0.01), LDL-cholesterol 214.9 ± 47.7 and 206.4 ± 46.6 (p value < 0.01), HDL-cholesterol 52.9 ± 13 and 54.4 ± 11.5 (p value 0.07), triglycerides 87 ± 46.7 and 82.2 ± 38.4 (p value 0.4), non-HDL cholesterol 233 ± 51.4 and 222.2 ± 47.4 (p < 0.01). In the dietary habits (weekly portions) we observed an improvement (p ≤ 001) for fruit and vegetables, fish, pulses, whole foods, and a reduction (p < 0.01) for meat, sausages, cheese, junk foods consumption. Conclusions: In FH children we have highlighted an improvement of the plasma lipid profile and in healthy dietary habits after nutritional counseling.

From the Triage to the Intermediate Area: A Simple and Fast Model for COVID-19 in the Emergency Department.

INTRODUCTION: The early identification of patients with SARS-CoV-2 infection is still a real challenge for emergency departments (ED). First, we aimed to develop a score, based on the use of the lung ultrasonography (LUS), in addition to the pre-triage interview, to correctly address patients; second, we aimed to prove the usefulness of a three-path organization (COVID-19, not-COVID-19 and intermediate) compared to a two-path organization (COVID-19, non-COVID-19). METHODS: We retrospectively analysed 292 patients admitted to our ED from 10 April to 15 April 2020, with a definite diagnosis of positivity (93 COVID-19 patients) or negativity (179 not-COVID-19 patients) for SARS-COV-2 infection. Using a logistic regression, we found a set of predictors for infection selected from the pre-triage interview items and the LUS findings, which contribute with a different weight to the final score. Then, we compared the organization of two different pathways. RESULTS: The most informative factors for classifying the patient are known nasopharyngeal swab positivity, close contact with a COVID-19 patient, fever associated with respiratory symptoms, respiratory failure, anosmia or dysgeusia, and the ultrasound criteria of diffuse alveolar interstitial syndrome, absence of B-lines and presence of pleural effusion. Their sensitivity, specificity, accuracy, and AUC-ROC are, respectively, 0.83, 0.81, 0.82 and 0.81. The most significant difference between the two pathways is the percentage of not-COVID-19 patients assigned to the COVID-19 area, that is, 10.6% (19/179) in the three-path organization, and 18.9% (34/179) in the two-path organization (p = 0.037). CONCLUSIONS: Our study suggests the possibility to use a score based on the pre-triage interview and the LUS findings to correctly manage the patients admitted to the ED, and the importance of an intermediate area to limit the spread of SARS-CoV-2 in the ED and, as a consequence, in the hospital.

Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group.

BACKGROUND AND AIMS: Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives. METHODS: 653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors. RESULTS: Subjects with Lp(a) > 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p < 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) > 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) > 30 mg/dl (46.25% vs 17.65%, p < 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101). CONCLUSIONS: Children/adolescents with FH and Lp(a) > 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.

Bayesian Analysis of ANOVA and Mixed Models on the Log-Transformed Response Variable.

The analysis of variance, and mixed models in general, are popular tools for analyzing experimental data in psychology. Bayesian inference for these models is gaining popularity as it allows to easily handle complex experimental designs and data dependence structures. When working on the log of the response variable, the use of standard priors for the variance parameters can create inferential problems and namely the non-existence of posterior moments of parameters and predictive distributions in the original scale of the data. The use of the generalized inverse Gaussian distributions with a careful choice of the hyper-parameters is proposed as a general purpose option for priors on variance parameters. Theoretical and simulations results motivate the proposal. A software package that implements the analysis is also discussed. As the log-transformation of the response variable is often applied when modelling response times, an empirical data analysis in this field is reported.

Does early cochlear implantation promote better reading comprehension skills?

OBJECTIVE: to investigate the effect of age at CI activation and to explore the role of other variables such as linguistic skills, stimulation modality and gender on reading comprehension. STUDY DESIGN: Prospective observational nonrandomized study. METHODS: 89 children with profound congenital sensorineural hearing loss were included in the study. The mean age at CI activation was 21 months (DS ± 11; range 7-50). The Italian reading standardized test, "Prove di lettura MT", was used to assess reading comprehension. The individual raw data MT score were converted into z scores (expected values: means = 0 and SD = 1). The positive values indicated better performance and negative values indicated worse performance. RESULTS: Early implanted children achieved significantly better reading comprehension skills, 55 out of 89 children are within 1 SD from the overall mean. 34 children (38.2%) attainted MT z-scores less than 1 SD below the mean. Children with unilateral CI performed somewhat worse if compared to bilateral CI and bimodal stimulation mode, although the differences were weakly significant from a statistical point of view. A strong and positive correlation (rho .69, p < .001) was found with the lexical and morphosyntactic comprehension (rho .70, p < .001). Not significantly different values were observed for gender and parental education level. CONCLUSION: Early cochlear implantation promoted better development of reading skills in children with cochlear implantation. LEVEL OF EVIDENCES: outcomes research.

Combining Landscape Genomics and Ecological Modelling to Investigate Local Adaptation of Indigenous Ugandan Cattle to East Coast Fever.

East Coast fever (ECF) is a fatal sickness affecting cattle populations of eastern, central, and southern Africa. The disease is transmitted by the tick Rhipicephalus appendiculatus, and caused by the protozoan Theileria parva parva, which invades host lymphocytes and promotes their clonal expansion. Importantly, indigenous cattle show tolerance to infection in ECF-endemically stable areas. Here, the putative genetic bases underlying ECF-tolerance were investigated using molecular data and epidemiological information from 823 indigenous cattle from Uganda. Vector distribution and host infection risk were estimated over the study area and subsequently tested as triggers of local adaptation by means of landscape genomics analysis. We identified 41 and seven candidate adaptive loci for tick resistance and infection tolerance, respectively. Among the genes associated with the candidate adaptive loci are PRKG1 and SLA2. PRKG1 was already described as associated with tick resistance in indigenous South African cattle, due to its role into inflammatory response. SLA2 is part of the regulatory pathways involved into lymphocytes' proliferation. Additionally, local ancestry analysis suggested the zebuine origin of the genomic region candidate for tick resistance.

Social conversational skills development in early implanted children.

OBJECTIVES/HYPOTHESIS: Social conversational skills are a salient aspect of early pragmatic development in young children. These skills include two different abilities, assertiveness and responsiveness. This study investigated the development of these abilities in early implanted children and their relationships with lexical development and some language-sensitive variables. STUDY DESIGN: Prospective, observational, nonrandomized study. METHODS: Participants included 28 children with congenital profound sensorineural hearing loss. The mean age at device activation was 13.3 months (standard deviation [SD] ±4.2). The Social-Conversational Skills Rating Scale was used to evaluate assertiveness and responsiveness. The MacArthur-Bates Communicative Development Inventory (Words and Sentences form) was used to analyze the lexical development. The device experience was 12 months for each child, and the mean age at testing was 25.9 months (SD ±4.6). RESULTS: Assertiveness and responsiveness scores were within the normal range of normal-hearing age-matched peers. Age at cochlear implant activation exerted a significant impact, with the highest scores associated to the youngest patients. The residual correlations between assertiveness and responsiveness with the lexical development were positive and strongly significant (r = 0.69 and 0.73, respectively). Preoperative hearing threshold demonstrated an associated significant coefficient on the assertiveness score. Age at diagnosis and maternal education level were not correlated with the social conversational skills. CONCLUSIONS: Early-implanted children developed social conversational skills that are similar to normal-hearing peers matched for age 1 year after device activation. Social conversational skills and lexical development were strongly correlated, but the present study design cannot specify the direction of this relationship. Children with better preoperative residual hearing exhibited better assertive ability. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2098-2105, 2016.

Narrative abilities in early implanted children.

OBJECTIVES/HYPOTHESIS: To investigate the effect of age at cochlear implant activation on oral narrative ability in children implanted before 2.5 years of age and to examine the role of other variables (gender, parental education level, stimulation modality) in narrative skills. STUDY DESIGN: retrospective nonrandomized group study METHODS: Thirty children (21 females; 9 males) with congenital, bilateral severe-to-profound sensorineural hearing loss were included in this study. The mean age at cochlear implant activation was 14.7 months (standard deviation [SD] ± 5.3). The Renfrew Bus Story was used to analyze oral narrative skills at mean chronological age of 63 months (SD ± 0.2). RESULTS: The total information on the Renfrew Bus Story raw score ranged from 8 to 40, with a mean of 22.7 (SD ± 8.6). Children produced on average 7.5 words in a sentence (SD ± 1.5). The mean score for complexity was 2.2 (SD ± 1.5). Regression analysis revealed a highly significant and negative linear effect of age at cochlear implant activation on all outcomes. The mother's education level had a positive strong effect on sentence length but a weak effect on total information and complexity. The paternal education score had a weak influence on the sentence length. Gender, age at diagnosis, and stimulation modality were not correlated with the narrative outcomes. CONCLUSIONS: Early implanted children can develop narrative skills close to normal hearing children. The sociocultural context, expressed by maternal and paternal educational level, are positively related to the development of oral narrative.

Pre-school children have better spoken language when early implanted.

OBJECTIVES: The objectives of this study were: (1) to investigate the effect of age at cochlear implantation (CI) on vocabulary development; (2) to evaluate the age effect at CI surgery on the syntactic development; and (3) to examine the role of gender, age at first diagnosis and maternal education level on spoken language development. MATERIAL AND METHODS: Retrospective study. Thirty children with congenital severe- to -profound sensorineural hearing loss (SNHL) were sampled. They were diagnosed and fitted with hearing aids through six months of age. They were implanted between 8 and 17 months of age. The MacArthur-Bates Communicative Development Inventory (MCDI) was administrated at the age of 36 months. The total productive vocabulary (word number raw score), the mean length of utterance (M3L) and the sentences complexity were analysed. RESULTS: The average word number raw score was 566.3 for the children implanted before 12 months of age versus 355 for those implanted later. The M3L was 8.3 for those implanted under 1 year versus 4.2 of those implanted later. The average sentences complexity was 82.3% for those receiving CI before 12 months, while it was 24.4% for those underwent at CI after 12 months. Regression analysis revealed a highly significant and negative linear effect of age at CI surgery on all outcomes. Females had better outcomes. Age at diagnosis was not correlated with the linguistic results. The mother's education level had a positive significant effect on sentences complexity. CONCLUSION: The CI in pre-school children with SNHL implanted under 1 year has a positive effect on spoken language. Females seem to have better linguistic results. Finally high maternal educational level appears to have some positive effect on language development.

Production of infant scale evaluation (PRISE) in Italian normal hearing children: a validation study.

OBJECTIVES: Parental questionnaires are important tools in the evaluation of auditory and language skills of very young children affected by sensorineural hearing loss. One of these instruments is the Production on Infant Scale Evaluation (PRISE). The purposes of this study were to adapt and validate the PRISE on Italian children with normal hearing; and to obtain normative data. METHODS: A back translation technique was used to adapt the Italian version of PRISE. The PRISE was submitted to parents of 234 normal children aged between 3 and 18 months of life. All of them passed local universal newborn hearing screenings and they presented no audiological risk factors. RESULTS: The PRISE internal reliability (Cronbach's alpha) was 0.87. Split-half reliability indexes were λ(4) = 0.89 and λ(6) = 0.89. Corrected item-total correlation coefficients were significant for all items. The correlation of PRISE with a modified Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS), collected for convergent validity measurement purposes, was good (r = 0.743). A positive correlation of PRISE scores with age was found, reflecting on the age-dependence of pre-verbal skills. CONCLUSION: These findings demonstrate high reliability and convergent validity of the Italian PRISE version. This questionnaire constitutes a robust tool for assessing early language development in infants and toddlers with normal hearing. It seems particularly sensitive to the normal language development in the first years of life, which can be very useful for early rehabilitation of hearing loss.

Biodiversity among Lactobacillus helveticus strains isolated from different natural whey starter cultures as revealed by classification trees.

Lactobacillus helveticus is a homofermentative thermophilic lactic acid bacterium used extensively for manufacturing Swiss type and aged Italian cheese. In this study, the phenotypic and genotypic diversity of strains isolated from different natural dairy starter cultures used for Grana Padano, Parmigiano Reggiano, and Provolone cheeses was investigated by a classification tree technique. A data set was used that consists of 119 L. helveticus strains, each of which was studied for its physiological characters, as well as surface protein profiles and hybridization with a species-specific DNA probe. The methodology employed in this work allowed the strains to be grouped into terminal nodes without difficult and subjective interpretation. In particular, good discrimination was obtained between L. helveticus strains isolated, respectively, from Grana Padano and from Provolone natural whey starter cultures. The method used in this work allowed identification of the main characteristics that permit discrimination of biotypes. In order to understand what kind of genes could code for phenotypes of technological relevance, evidence that specific DNA sequences are present only in particular biotypes may be of great interest.