Characterisation of RAET1E/ULBP4 exon 4 and 3' untranslated region genetic architecture reveals further diversity and allelic polymorphism.

NKG2D is a natural killer cell activating receptor recognising ligands on infected or tumorigenic cells, leading to their cytolysis. There are eight known genes encoding NKG2D ligands: MICA, MICB and ULBP1-6. MICA and MICB are highly polymorphic and well characterised, whilst ULBP ligands are less polymorphic and the functional implication of their diversity is not well understood. Using International HLA and Immunogenetics Workshop (IHIW) cell line DNA, we previously characterised alleles of the RAET1E gene (encoding ULBP4 proteins), including the 5' UTR promoter region and exons 1-3. We found 11 promoter haplotypes associating with alleles based on exons 1-3, revealing 19 alleles overall. The current study extends this analysis using 87 individual DNA samples from IHIW cell lines or cord blood to include RAET1E exon 4 and the 3' UTR, as polymorphism in these regions have not been previously investigated. We found two novel exon 4 polymorphisms encoding amino acid substitutions altering the transmembrane domain. An amino acid substitution at residue 233 was unique to the RAET1E*008 allele whereas the substitution at residue 237 was shared between groups of alleles. Additionally, four haplotypes were found based on 3' UTR sequences, which were unique to certain alleles or shared with allele groups based on exons 1-4 polymorphisms. Furthermore, putative microRNAs were identified that may interact with these polymorphic sites, repressing transcription and potentially affecting expression levels.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

OBJECTIVES: NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. METHODS: We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. RESULTS: In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CONCLUSION: CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

Addressing disparities in speech-language pathology and laryngology services with telehealth.

The COVID-19 pandemic disproportionately affected the health and well-being of marginalized communities, and it brought greater awareness to disparities in health care access and utilization. Addressing these disparities is difficult because of their multidimensional nature. Predisposing factors (demographic information, social structure, and beliefs), enabling factors (family and community) and illness levels (perceived and evaluated illness) are thought to jointly contribute to such disparities. Research has demonstrated that disparities in access and utilization of speech-language pathology and laryngology services are the result of racial and ethnic differences, geographic factors, sex, gender, educational background, income level and insurance status. For example, persons from diverse racial and ethnic backgrounds have been found to be less likely to attend or adhere to voice rehabilitation, and they are more likely to delay health care due to language barriers, longer wait times, a lack of transportation and difficulties contacting their physician. The purpose of this paper is to summarize existing research on telehealth, discuss how telehealth offers the potential to eliminate some disparities in the access and utilization of voice care, review its limitations, and encourage continued research in this area. A clinical perspective from a large volume laryngology clinic in a major city in northeastern United States highlights the use of telehealth in the provision of voice care by a laryngologist and speech-language pathologist during and after the COVID19 pandemic.

Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.

An acoustic study of Cantonese alaryngeal speech in different speaking conditions.

Esophageal (ES) speech, tracheoesophageal (TE) speech, and the electrolarynx (EL) are common methods of communication following the removal of the larynx. Our recent study demonstrated that intelligibility may increase for Cantonese alaryngeal speakers using clear speech (CS) compared to their everyday "habitual speech" (HS), but the reasoning is still unclear [Hui, Cox, Huang, Chen, and Ng (2022). Folia Phoniatr. Logop. 74, 103-111]. The purpose of this study was to assess the acoustic characteristics of vowels and tones produced by Cantonese alaryngeal speakers using HS and CS. Thirty-one alaryngeal speakers (9 EL, 10 ES, and 12 TE speakers) read The North Wind and the Sun passage in HS and CS. Vowel formants, vowel space area (VSA), speaking rate, pitch, and intensity were examined, and their relationship to intelligibility were evaluated. Statistical models suggest that larger VSAs significantly improved intelligibility, but slower speaking rate did not. Vowel and tonal contrasts did not differ between HS and CS for all three groups, but the amount of information encoded in fundamental frequency and intensity differences between high and low tones positively correlated with intelligibility for TE and ES groups, respectively. Continued research is needed to understand the effects of different speaking conditions toward improving acoustic and perceptual characteristics of Cantonese alaryngeal speech.

Are Mobile Applications in Laryngology Designed for All Patients?

OBJECTIVES: Mobile applications (apps) are multiplying in laryngology, with little standardization of content, functionality, or accessibility. The purpose of this study is to evaluate the quality, functionality, health literacy, readability, accessibility, and inclusivity of laryngology mobile applications. METHODS: Of the 3230 apps identified from the Apple and Google Play stores, 28 patient-facing apps met inclusion criteria. Apps were evaluated using validated scales assessing quality and functionality: the Mobile App Rating Scale (MARS) and the Institute for Healthcare Informatics App Functionality Scale. The Clear Communication Index (CDC) Institute of Medicine Strategies for Creating Health Literate Mobile Applications, and Patient Education Materials Assessment Tool (PEMAT) were used to evaluate apps health literacy level. Readability was assessed using established readability formulas. Apps were evaluated for language, accessibility features, and representation of a diverse population. RESULTS: Twenty-six apps (92%) had adequate quality (MARS score > 3). The mean PEMAT score was 89% for actionability and 86% for understandability. On average, apps utilized 25/33 health literate strategies. Twenty-two apps (79%) did not pass the CDC index threshold of 90% for health literacy. Twenty-four app descriptions (86%) were above an 8th grade reading level. Only 4 apps (14%) showed diverse representation, 3 (11%) had non-English language functions, and 2 (7%) offered subtitles. Inter-rater reliability for MARS was adequate (CA-ICC = 0.715). CONCLUSION: While most apps scored well in quality and functionality, many laryngology apps did not meet standards for health literacy. Most apps were written at a reading level above the national average, lacked accessibility features, and did not represent diverse populations. Laryngoscope, 133:1540-1549, 2023.

A Review of Voice Disorders in School-Aged Children.

OBJECTIVES: The purpose of this study was to review literature concerning voice disorders in school-aged children. STUDY DESIGN: Integrative review. MATERIALS AND METHODS: A database search was conducted using PubMed, Web of Science, Academic Search Complete, CINAHL Complete, and Medline. All records included in this review were peer-reviewed journal articles that discussed voice disorders in children, conducted in the United States or Canada, written in English, and published between 2009 and 2019. RESULTS: Database searching identified 1,771 records and 551 duplicates were removed. A total of 1,220 records were screened and 949 records were excluded. Two hundred and seventy-one full-text records were screened and 12 records met inclusion criteria. Vocal fold nodules were the most commonly reported vocal fold pathology. The Consensus Auditory Perceptual Evaluation of Voice and endoscopy were the most commonly reported assessments. However, variations in practice patterns and access to voice services may exist. CONCLUSIONS: The findings highlight that school-aged children may face barriers in accessing voice services. As a result, continued analyses of the potential barriers that hinder identification and treatment of voice disorders in this population appear warranted.

BIOME-Preserve: A novel storage and transport medium for preserving anaerobic microbiota samples for culture recovery.

Sequencing-based protocols for studying the human microbiome have unearthed a wealth of information about the relationship between the microbiome and human health. But these microbes cannot be leveraged as therapeutic targets without culture-based studies to phenotype species of interest and to establish culture collections for use in animal models. Traditional sample collection protocols are focused on preserving nucleic acids and metabolites and are largely inappropriate for preserving sensitive anaerobic bacteria for later culture recovery. Here we introduce a novel microbiome preservation kit (BIOME-Preserve) that facilitates recovery of anaerobic bacteria from human stool. Using a combination of culture recovery and shallow whole-genome shotgun sequencing, we characterized the anaerobes cultured from fresh human stool and from human stool held at room temperature in BIOME-Preserve for up to 120 hours. We recovered several species of interest to microbiome researchers, including Bifidobacterium spp., Bacteroides spp., Blautia spp., Eubacterium halii (now Anaerobutyricum hallii), Akkermansia muciniphila, and Faecalibacterium prausnitzii. We also demonstrated that freezing at -80°C did not adversely affect our ability to culture organisms from BIOME-Preserve, suggesting that it is appropriate both as a transport medium and as a medium for longer-term ultra-cold storage. Together, our results suggest BIOME-Preserve is practical for the collection, transport, and culture of anaerobic bacteria from human samples and can help enable researchers to better understand the link between the microbiome and human health and how to leverage that link through novel microbiome-based therapeutics.

The Effect of Clear Speech on Cantonese Alaryngeal Speakers' Intelligibility.

BACKGROUND/AIM: The purpose of this study was to provide preliminary data concerning the effect of clear speech (CS) on Cantonese alaryngeal speakers' intelligibility. METHODS: Voice recordings of 11 sentences randomly selected from the Cantonese Sentence Intelligibility Test (CSIT) were obtained from 31 alaryngeal speakers (9 electrolarynx [EL] users, 10 esophageal speakers and 12 tracheoesophageal [TE] speakers) in habitual speech (HS) and CS. Two naïve listeners orthographically transcribed a total of 1,364 sentences. RESULTS: Significant effects of speaking condition on speaking rate and CSIT scores were observed, but no significant effect of alaryngeal communication methods was noted. CS was significantly slower than HS by 0.78 syllables/s. Esophageal speakers demonstrated the slowest speech rate when using CS, while EL users demonstrated the largest decrease in speaking rate when using CS compared to HS. TE speakers had the highest CSIT scores in HS (listener 1 = 81.4%; listener 2 = 81.3%), and esophageal speakers had the highest CSIT scores in CS (listener 1 = 87.5%; listener 2 = 89.7%). EL users experienced the largest increase in intelligibility while using CS compared to HS (9.1%) followed by esophageal speakers (8.9%) and TE speakers (1.4%). CONCLUSION: Preliminary data indicate that CS may significantly affect Cantonese alaryngeal speakers' speaking rate and intelligibility. However, intelligibility appeared to vary considerably across speakers. Further research involving larger, heterogeneous groups of speakers and listeners alongside longer and more refined CS training protocols should be conducted to confirm that CS can improve Cantonese alaryngeal speakers' intelligibility.

Racial and Ethnic Disparities in Laryngeal Cancer Care.

There is a long history of racial and ethnic disparities in healthcare and they continue to persist in contemporary society. These disparities have the potential to negatively affect morbidity and mortality in racial and ethnic minorities diagnosed with laryngeal cancer. Diagnosis, medical treatment, and rehabilitation for laryngeal cancer have improved considerably, leading to improvements in overall survival rates and physical, social, and psychological functioning. Yet members of minority and underrepresented groups are at an increased risk for experiencing reduced access to quality care and delays between diagnosis and treatment, and as a result have lower survival rates. Increasing health providers' awareness of racial and ethnic disparities in laryngeal cancer is necessary to facilitate changes in patient and provider education, clinical practice, and health policies. The purpose of this review is to summarize current literature on disparities in laryngeal cancer diagnosis, treatment, and rehabilitation among Black and Hispanic patients. We present recent data from the Surveillance, Epidemiology, and End Results database to examine trends in laryngeal cancer and patient, provider, and health systems factors that may perpetuate these disparities. In addition, we offer interventions to address racism and other racial and ethnic biases in laryngeal cancer care and describe research and legislative actions that are needed to reduce disparities in this area.

Cord blood and amniotic membrane extract eye drop preparations display immune-suppressive and regenerative properties.

Diseases and injuries that compromise the ocular surface cause considerable patient distress and have long term consequences for their quality of life. Treatment modalities that can address the delicate balance of tissue regeneration, inflammation and maintenance of corneal transparency are therefore needed. We have recently formulated two novel eye drops from placental tissues: cord blood platelet lysate (CBED) and amniotic membrane extract eye drops (AMED), which can be used to treat severe ocular disorders. Here we characterise these two preparations by measuring: (a) growth factors (GF) and cytokines composition, (b) promotion of human corneal epithelial cell (HCEC) growth and (c) effects on immune cells in a lymphocyte culture assay. Finally, their bioavailability was assayed in an ex vivo porcine corneal model. We show that both preparations contain GF and cytokines that were able to promote the in vitro growth of HCEC and support repair in an in vitro scratch test. When assessed in a lymphocyte culture, both favoured immune suppression reducing the cellular expression of NKG2D and CD107a as well as the production of interferon gamma (IFN-γ) in natural killer, NKT and T cells. Regarding bioavailability, CBED active molecules were found mainly in the pre-corneal fraction with some penetration into the corneal fraction, in an ex vivo model. In summary, both placental-derived allogeneic preparations, CBED and AMED, display regenerative and immunomodulatory capabilities. These results will help define mechanisms of action and the best indications and doses of each product for use in a particular patient and support the development of off-the-shelf therapies for ocular surface pathologies in which wound healing defects and inflammatory events are contributing factors.

The Accuracy of Smartphone Sound Level Meter Applications (SLMAs) in Measuring Sound Levels in Clinical Rooms.

BACKGROUND: The accuracy of smartphone sound level meter applications (SLMAs) has been investigated with varied results, based on differences in platform, device, app, available features, test stimuli, and methodology. PURPOSE: This article determines the accuracy of smartphone SLMAs with and without calibration of external and internal microphones for measuring sound levels in clinical rooms. RESEARCH DESIGN: Quasi-experimental research design comparing the accuracy of two smartphone SLMAs with and without calibration of external and internal microphones. DATA COLLECTION AND ANALYSIS: Two iOS-based smartphone SLMAs (NIOSH SLM and SPL Meter) on an iPhone 6S were used with and without calibrated external and internal microphones. Measures included: (1) white noise (WN) stimuli from 20 to 100 dB sound pressure level in a sound-treated test booth and (2) sound levels in quiet in four nonsound-treated clinical rooms and in simulated background sound conditions using music at 45, 55, and 80 dBA. Chi-square analysis was used to determine a significant difference (p ≤ 0.05) in sound measures between the SLMAs and a Type 1 SLM. RESULTS: Measures of WN signals and room sound level measures in quiet and simulated background sound conditions were significantly more accurate at levels ≥ 40 dBA using the SLMAs with calibrated external and internal microphones. However, SLMA measures with and without calibration of external and internal microphones overestimated sound levels < 40 dBA. CONCLUSION: The SLMAs studied with calibrated external or internal microphones are able to verify the room environment for audiologic screening at 1,000, 2,000, and 4,000 Hz at 20 dB hearing level (American Academy of Audiology and American Speech-Language-Hearing Association) using supra-aural earphones (American National Standards Institute S3.1-1999 [R2018]). However, the tested SLMAs overestimated low-level sound < 40 dBA, even when the external or internal microphones were calibrated. Clinicians are advised to calibrate the microphones prior to using measurement systems involving smartphones and SLMAs to measure room sound levels and to monitor background noise levels throughout the provision of clinical services.

Visualization Environment for Federated Knowledge Graphs: Development of an Interactive Biomedical Query Language and Web Application Interface.

BACKGROUND: Efforts are underway to semantically integrate large biomedical knowledge graphs using common upper-level ontologies to federate graph-oriented application programming interfaces (APIs) to the data. However, federation poses several challenges, including query routing to appropriate knowledge sources, generation and evaluation of answer subsets, semantic merger of those answer subsets, and visualization and exploration of results. OBJECTIVE: We aimed to develop an interactive environment for query, visualization, and deep exploration of federated knowledge graphs. METHODS: We developed a biomedical query language and web application interphase-termed as Translator Query Language (TranQL)-to query semantically federated knowledge graphs and explore query results. TranQL uses the Biolink data model as an upper-level biomedical ontology and an API standard that has been adopted by the Biomedical Data Translator Consortium to specify a protocol for expressing a query as a graph of Biolink data elements compiled from statements in the TranQL query language. Queries are mapped to federated knowledge sources, and answers are merged into a knowledge graph, with mappings between the knowledge graph and specific elements of the query. The TranQL interactive web application includes a user interface to support user exploration of the federated knowledge graph. RESULTS: We developed 2 real-world use cases to validate TranQL and address biomedical questions of relevance to translational science. The use cases posed questions that traversed 2 federated Translator API endpoints: Integrated Clinical and Environmental Exposures Service (ICEES) and Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP). ICEES provides open access to observational clinical and environmental data, and ROBOKOP provides access to linked biomedical entities, such as "gene," "chemical substance," and "disease," that are derived largely from curated public data sources. We successfully posed queries to TranQL that traversed these endpoints and retrieved answers that we visualized and evaluated. CONCLUSIONS: TranQL can be used to ask questions of relevance to translational science, rapidly obtain answers that require assertions from a federation of knowledge sources, and provide valuable insights for translational research and clinical practice.

A semantic similarity based methodology for predicting protein-protein interactions: Evaluation with P53-interacting kinases.

Biomedical literature contains unstructured, rich information regarding proteins, ligands, diseases as well as biological pathways in which they are involved. Systematically analyzing such textual corpus has the potential for biomedical discovery of new protein-protein interactions and hidden drug indications. For this purpose, we have investigated a methodology that is based on a well-established text mining tool, Word2Vec, for the analysis of PubMed full text articles to derive word embeddings, and the use of a simple semantic similarity comparison either by itself or in conjunction with k-Nearest Neighbor (kNN) technique for the prediction of new relationships. To test this methodology, three lines of retrospective analyses of a dataset with known P53-interacting proteins have been conducted. First, we demonstrated that Word2Vec semantic similarity can infer functional relatedness among all kinases known to interact with P53. Second, in a series of time-split experiments, we demonstrated that both a simple similarity comparison and kNN models built with papers published up to a certain year were able to discover P53 interactors described in later publications. Third, in a different scenario of time-split experiments, we examined the predictions of P53-interacting proteins based on the kNN models built on data prior to a certain split year for different time ranges past that year, and found that the cumulative number of correct predictions was indeed increasing with time. We conclude that text mining of research papers in the PubMed literature based on Word2Vec analysis followed by a simple similarity comparison or kNN modeling affords excellent predictions of protein-protein interactions between P53 and kinases, and should have wide applications in translational biomedical studies such as repurposing of existing drugs, drug-drug interaction, and elucidation of mechanisms of action for drugs.

Variability of Electrolaryngeal Speech Intelligibility in Multitalker Babble.

Purpose The purpose of this study was to report the variability of electrolarynx (EL) users' speech intelligibility in quiet and in multitalker babble. Method Ten EL users (five Servox® Digital, five TruTone™) who were at least 2 years postlaryngectomy provided recordings of five sentences from the 1965 Revised List of Phonetically Balanced Sentences. Recordings were judged by two groups of naïve listeners in quiet and in the presence of multitalker babble. Fifteen listeners orthographically transcribed a total of 750 sentences containing 3,750 key words in quiet, and another 15 listeners orthographically transcribed the same sentences mixed with multitalker babble. Results Significant differences in speech intelligibility were observed between listening conditions; 17.9% more key words were correctly identified in quiet compared to multitalker babble. Significant differences in fundamental frequency (F0) standard deviation and range but not speech intelligibility were observed between EL device types. A positive correlation of moderate significance was observed between F0 standard deviation and intelligibility for TruTone users in multitalker babble. Conclusions Findings suggest that listeners are able to identify a significantly higher percentage of EL users' speech in quiet compared to multitalker babble, but a large variability in EL users' speech intelligibility exists. Continued investigation involving a larger number of EL users is necessary to confirm this study's findings. Future research should explore the relationships among F0 measures, speaker characteristics (e.g., rate of speech, articulatory precision), and speech intelligibility, in addition to improving alaryngeal rehabilitation training protocols for EL users.

Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais.

BACKGROUND: Major histocompatibility complex class I chain-related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. METHODS: MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. RESULTS: MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18-8.84] and 1.99 [1.07-2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21-.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22-.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14-.60). CONCLUSIONS: Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.

Translator Exposure APIs: Open Access to Data on Airborne Pollutant Exposures, Roadway Exposures, and Socio-Environmental Exposures and Use Case Application.

Environmental exposures have profound effects on health and disease. While public repositories exist for a variety of exposures data, these are generally difficult to access, navigate, and interpret. We describe the research, development, and application of three open application programming interfaces (APIs) that support access to usable, nationwide, exposures data from three public repositories: airborne pollutant estimates from the US Environmental Protection Agency; roadway data from the US Department of Transportation; and socio-environmental exposures from the US Census Bureau's American Community Survey. Three open APIs were successfully developed, deployed, and tested using random latitude/longitude values and time periods as input parameters. After confirming the accuracy of the data, we used the APIs to extract exposures data on 2550 participants from a cohort within the Environmental Polymorphisms Registry (EPR) at the National Institute of Environmental Health Sciences, and we successfully linked the exposure estimates with participant-level data derived from the EPR. We then conducted an exploratory, proof-of-concept analysis of the integrated data for a subset of participants with self-reported asthma and largely replicated our prior findings on the impact of select exposures and demographic factors on asthma exacerbations. Together, the three open exposures APIs provide a valuable resource, with application across environmental and public health fields.

Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.

BACKGROUND: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years. OBJECTIVE: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age. PARTICIPANTS: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age. INTERVENTION: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device. PRIMARY OUTCOME: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability. RESULTS: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003). CONCLUSION: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement. TRIAL REGISTRATION NUMBER: ISRCTN80286058.

Cord Blood Platelet Rich Plasma Derivatives for Clinical Applications in Non-transfusion Medicine.

Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively.

FHIR PIT: an open software application for spatiotemporal integration of clinical data and environmental exposures data.

BACKGROUND: Informatics tools to support the integration and subsequent interrogation of spatiotemporal data such as clinical data and environmental exposures data are lacking. Such tools are needed to support research in environmental health and any biomedical field that is challenged by the need for integrated spatiotemporal data to examine individual-level determinants of health and disease. RESULTS: We have developed an open-source software application-FHIR PIT (Health Level 7 Fast Healthcare Interoperability Resources Patient data Integration Tool)-to enable studies on the impact of individual-level environmental exposures on health and disease. FHIR PIT was motivated by the need to integrate patient data derived from our institution's clinical warehouse with a variety of public data sources on environmental exposures and then openly expose the data via ICEES (Integrated Clinical and Environmental Exposures Service). FHIR PIT consists of transformation steps or building blocks that can be chained together to form a transformation and integration workflow. Several transformation steps are generic and thus can be reused. As such, new types of data can be incorporated into the modular FHIR PIT pipeline by simply reusing generic steps or adding new ones. We validated FHIR PIT in the context of a driving use case designed to investigate the impact of airborne pollutant exposures on asthma. Specifically, we replicated published findings demonstrating racial disparities in the impact of airborne pollutants on asthma exacerbations. CONCLUSIONS: While FHIR PIT was developed to support our driving use case on asthma, the software can be used to integrate any type and number of spatiotemporal data sources at a level of granularity that enables individual-level study. We expect FHIR PIT to facilitate research in environmental health and numerous other biomedical disciplines.