Language and speech perception of young children with bimodal fitting or bilateral cochlear implants

Abstract

Objectives

This paper compares language development and speech perception of children with bimodal fitting (a cochlear implant in one ear and a hearing aid in the opposite ear) or bilateral cochlear implantation.

Methods

Participants were children enrolled in the Longitudinal Outcomes of Children with Hearing Impairment study. Language development was assessed at 3 years of age using standardized tests. Speech perception was evaluated at 5 years of age. Speech was presented from a frontal loudspeaker, and babble noise was presented either from the front or from both sides.

Results

On average, there was no significant difference in language outcomes between 44 children with bimodal fitting and 49 children with bilateral cochlear implants; after controlling for a range of demographic variables. Earlier age at cochlear implant activation was associated with better outcomes. Speech perception in noise was not significantly different between children with bimodal fitting and those with bilateral cochlear implants. Compared to normal-hearing children, children with cochlear implants required a better signal-to-noise ratio to perform at the same level, but demonstrated spatial release from masking of a similar magnitude.

Conclusions

This population-based study found that language scores for children with bilateral implants were higher than those with bimodal fitting or those with unilateral implants, but neither reached significance level.     

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective

Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach.

Methods

This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m²) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators.

Results

Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1-3 disease (44.8%) recurred (average follow-up 28.1 months, range 8-60 months).

Conclusion

This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.     

An investigation into the subambient behavior of aqueous mannitol solutions using differential scanning calorimetry,cold stage microscopy,and X-ray diffractometry

The subambient behavior of aqueous mannitol solutions is of considerable relevance to the preparation of freeze dried formulations. In this investigation the properties of 3% w/v mannitol solutions were investigated using differential scanning calorimetry (DSC), cold stage microscopy (CSM), and X-ray diffraction (XRD) to identify the thermal transitions and structural transformations undergone by this system. It was found that on cooling from ambient the system formed ice at circa -20 degrees C while a further exotherm was seen at approximately -30 degrees C. Upon reheating an endotherm was seen at circa -30 degrees C followed immediately by an exotherm at circa -25 degrees C. Temperature cycling indicated that the thermal transitions observed upon reheating were not reversible. Modulated temperature DSC (MTDSC) indicated that the transitions observed upon reheating corresponded to a glass transition immediately followed by recrystallization, XRD data showed that recrystallization was into the beta form. Annealing at -35 degrees C for 40 min prior to cooling and reheating resulted in a maximum enthalpy being observed for the reheating exotherm. It is concluded that on cooling 3% w/v aqueous mannitol solutions an amorphous phase is formed that subsequently recrystallises into the beta form. The study has also shown that DSC, CSM, and XRD are useful complementary techniques for the study of frozen systems.     

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease

Background:

Prostate cancer (PrCa) is one of the most common diseases to affect men worldwide and among the leading causes of cancer-related death. The purpose of this study was to use second-generation sequencing technology to assess the frequency of deleterious mutations in 22 tumour suppressor genes in familial PrCa and estimate the relative risk of PrCa if these genes are mutated.

Methods:

Germline DNA samples from 191 men with 3 or more cases of PrCa in their family were sequenced for 22 tumour suppressor genes using Agilent target enrichment and Illumina technology. Analysis for genetic variation was carried out by using a pipeline consisting of BWA, Genome Analysis Toolkit (GATK) and ANNOVAR. Clinical features were correlated with mutation status using standard statistical tests. Modified segregation analysis was used to determine the relative risk of PrCa conferred by the putative loss-of-function (LoF) mutations identified.

Results:

We discovered 14 putative LoF mutations in 191 samples (7.3%) and these mutations were more frequently associated with nodal involvement, metastasis or T4 tumour stage (P=0.00164). Segregation analysis of probands with European ancestry estimated that LoF mutations in any of the studied genes confer a relative risk of PrCa of 1.94 (95% CI: 1.56–2.42).

Conclusions:

These findings show that LoF mutations in DNA repair pathway genes predispose to familial PrCa and advanced disease and therefore warrants further investigation. The clinical utility of these findings will become increasingly important as targeted screening and therapies become more widespread.     

Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome

We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.     

Hospital-acquired pneumonia in Japan may have a better mortality profile than HAP in the United States: a retrospective study

The characteristics of hospital-acquired pneumonia (HAP) are not well documented. In the present study we investigated the severity and mortality, microbiological profile, and the value of Gram staining in culture-confirmed HAP in a Japanese hospital by retrospective review conducted at a Japanese university hospital. Only culture-confirmed cases with good specimen quality were included in the analysis. The clinical characteristics of HAP, as well as the causative organisms, were investigated. Furthermore, the prognostic ability of existing prediction rules were evaluated for prediction of overall mortality. Forty-two cases were enrolled in this analysis. The majority of patients were admitted to the ICU (61.9 %), and 40.5 % had ventilator-associated pneumonia (VAP). The 30-day mortality was 23.8 %, which is less than that reported in the United States. Factors commonly known to be associated with worse outcome in the USA did not appear to influence the mortality from HAP in Japan. The most frequent causative organisms were methicillin-resistant Staphylococcus aureus (MRSA), followed by Pseudomonas spp. Sensitivity and negative predictive value of Gram staining were 89.4 and 85.7 %, respectively. SMART-COP predicted 30-day mortality with an area under the ROC curve (AUC) >0.7. The characteristics of HAP in Japan differ from HAP reported in the USA. In addition to lower mortality, we found both fewer ICU cases and VAP. Gram staining of good-quality specimens demonstrated promising sensitivity to predict the causative organisms. SMART-COP predicted mortality with appropriate ROC curve (AUC).     

Downregulation of TOMM40 expression in the blood of Alzheimer disease subjects compared with matched controls

Translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene has been reported in several GWAS to be associated with Alzheimer disease (AD). Gene expression studies thus far only showed TOMM40 differential expression in one study on brain cortex and not in peripheral blood. We studied the gene expression profiles of AD blood versus controls in an Asian population in Singapore. In this first analysis we focused on genes that have been previously reported on GWAS. We found TOMM40 to be significantly down-regulated in blood samples of AD in one discovery and two validation sets, totalling 45 subjects (mean age 76.90, SD 6.46) and 45 controls (mean age 76.23, SD 5.09), matched for ethnicity and gender. The function of TOMM40 is not yet fully characterized but is believed to be involved in import and trafficking of protein into mitochondria. Therefore TOMM40 downregulation, found in the brain in severe AD and in our blood profile, may be a potential marker for AD, disease severity or progression and merit further investigation.