Assistive technology and people: a position paper from the first global research,innovation and education on assistive technology (GREAT) summit

Abstract

Assistive technology (AT) is a powerful enabler of participation. The World Health Organization’s Global Collaboration on Assistive Technology (GATE) programme is actively working towards access to assistive technology for all. Developed through collaborative work as a part of the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit, this position paper provides a “state of the science” view of AT users, conceptualized as “People” within the set of GATE strategic “P”s. People are at the core of policy, products, personnel and provision. AT is an interface between the person and the life they would like to lead. People’s preferences, perspectives and goals are fundamental to defining and determining the success of AT. Maximizing the impact of AT in enabling participation requires an individualized and holistic understanding of the value and meaning of AT for the individual, taking a universal model perspective, focusing on the person, in context, and then considering the condition and/or the technology. This paper aims to situate and emphasize people at the centre of AT systems: we highlight personal meanings and perspectives on AT use and consider the role of advocacy, empowerment and co-design in developing and driving AT processes.     

Accidental pharmacological poisonings in young children: population-based study in three settings

Introduction: Pharmacological poisonings in young children are avoidable. Previous studies report calls to poisons centres, presentations to emergency departments (ED) or hospital admissions. There are limited data assessing concurrent management of poisonings across all three settings. We aimed to describe accidental pharmacological poisonings in young children across our Poisons Information Centre (PIC), EDs and hospitals.

Methods: A population-based study in New South Wales, Australia, of PIC calls, ED presentations and hospital admissions for accidental pharmacological poisoning in children aged <5 years, 2007–2013. We examined trends, medicines responsible and subsequent management. Medicines were coded using ICD10-AM diagnosis codes (T36-50).

Results: Over 2007–2013, pharmacological poisonings accounted for 67,816 PIC calls, 7739 ED presentations and 2082 admissions. Rates (per 10,000 children) of PIC calls declined from 220 to 178; ED presentations were stable (～22–24), with a decrease in emergency cases offset by an increase in semi- or non-urgent presentations; hospital admissions declined (8–5). Most PIC calls related to “non-opioid analgesics” (25%), and “topical agents” (18%). Nearly every day, one child aged <5 years was admitted to hospital for poisoning. “Benzodiazepines”, “other and unspecified antidepressants”, “uncategorised antihypertensives”, and “4-aminophenol derivatives” accounted for over one-third of all admissions. Most PIC calls (90%) were advised to stay home, 6% referred to hospital. One-quarter of ED presentations resulted in admission.

Conclusions: Poisonings reported to PIC and hospitals declined, however, non-urgent ED presentations increased. Strategies to reduce therapeutic errors and access to medicines, and education campaigns to improve Poisons Centre call rates to prevent unnecessary ED presentations are needed.     

Fragmentation of Therapeutic Human Immunoglobulin Preparations

Some commercial batches of human therapeutic immunoglobulins (Ig) have been found to show evidence of molecular fragmentation when examined by molecular sizing methodologies including sodium dodecyl sulphate polyacrylamide gel electrophoresis [SDS-PAGE] and size exclusion high performance liquid chromatography (SE-HPLC). These batches all demonstrated impaired immunobiological activity (efficacy) as assessed by Fc function measured using a rubella haemolytic assay and as such are likely to be subpotent for therapeutic use. Fragmented Igs were characterized by the presence of at least three protein bands and peaks additional to monomeric IgG. Incubation of Igs with blood enzymes (plasmin and kallikrein) reproduced the fragmentation patterns observed for intrinsically degraded batches, suggesting that fragmentation occurred by contamination with these proteases from the source material (human blood) during manufacture. Intravenous Igs (IVIG) were found to be more susceptible to proteolysis than intramuscular Igs, probably as a consequence of the post-fractionation processing that some IVIGs receive which may induce molecular alterations, allowing enzyme access and fragmentation. Two of the products examined were found to be relatively resistant to proteolysis and both were formulated by processes that limit enzyme activity. These processes were inclusion of an enzyme inhibitor, α₂-macroglobulin, and formulation at acidic pH. Enzyme carry-over into the final product is a likely cause of Ig fragmentation, and reduction in levels of such contamination should lead to improvements in product stability and efficacy.     

An in vitro assay for gonadotrophic hormone in the polychaete Nephtys hombergii Sav. (Nephtyidae)

A method for the culture of ovaries from the polychaete Nephtys hombergii in vitro is described together with an assay for gonadotrophic hormone. Data is also presented on the timing of the production of gonadotrophic hormone. Ovaries of Nephtys hombergii are cultured on membrane filters floating on a liquid medium to which cerebral extracts are added. The exclusion of cerebral extract or its replacement with ventral nerve cord extract, results in the degeneration of oocytes in the explanted ovaries. The results of serial dilution experiments are presented. Oocyte degeneration is prevented in culture medium with brain extract added down to a concentration of 1.25 brain equivalents/ml. A trophic effect is still observed at a dilution of about 0.5 brain equivalonts/ml. Gonadotrophic hormone is present in the brain in September. The concentration of hormone increases to a high level in November and decreases to a very low level as the time of spawning approaches in May.     

Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

Because amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer's disease. Using immunohistochemistry, immunoelectron microscopy, Western blot, and quantitative real-time-polymerase chain reaction (qRT-PCR) analysis we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blot analysis data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. A Disintegrin and Metalloproteinase domain 10 (ADAM10), nicastrin, and beta-secretase 2 (BACE2) were present in brain but were undetected in PBL. Presenilin 1 and beta-secretase 1 (BACE1) were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated in which Western and quantitative PCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers.     

Real-Time Genomic Epidemiological Evaluation of Human Campylobacter Isolates by Use of Whole-Genome Multilocus Sequence Typing

Sequence-based typing is essential for understanding the epidemiology of Campylobacter infections, a major worldwide cause of bacterial gastroenteritis. We demonstrate the practical and rapid exploitation of whole-genome sequencing to provide routine definitive characterization of Campylobacter jejuni and Campylobacter coli for clinical and public health purposes. Short-read data from 384 Campylobacter clinical isolates collected over 4 months in Oxford, United Kingdom, were assembled de novo. Contigs were deposited at the pubMLST.org/campylobacter website and automatically annotated for 1,667 loci. Typing and phylogenetic information was extracted and comparative analyses were performed for various subsets of loci, up to the level of the whole genome, using the Genome Comparator and Neighbor-net algorithms. The assembled sequences (for 379 isolates) were diverse and resembled collections from previous studies of human campylobacteriosis. Small subsets of very closely related isolates originated mainly from repeated sampling from the same patients and, in one case, likely laboratory contamination. Much of the within-patient variation occurred in phase-variable genes. Clinically and epidemiologically informative data can be extracted from whole-genome sequence data in real time with straightforward, publicly available tools. These analyses are highly scalable, are transparent, do not require closely related genome reference sequences, and provide improved resolution (i) among Campylobacter clonal complexes and (ii) between very closely related isolates. Additionally, these analyses rapidly differentiated unrelated isolates, allowing the detection of single-strain clusters. The approach is widely applicable to analyses of human bacterial pathogens in real time in clinical laboratories, with little specialist training required.     

Mass drug administration with azithromycin for trachoma elimination and the population structure of Streptococcus pneumoniae in the nasopharynx

ObjectiveMass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage of Streptococcus pneumoniae in the short term. We evaluated S. pneumoniae carried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure and resistance.MethodsWe analysed 514 pneumococcal whole genomes randomly selected from nasopharyngeal samples collected in two Gambian villages that received three annual rounds of MDA for trachoma elimination. The 514 samples represented 293 participants, of which 75% were children aged 0–9 years, isolated during three cross-sectional surveys (CSSs) conducted before the third round of MDA (CSS-1) and at 1 (CSS-2) and 6 (CSS-3) months after MDA. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multilocus sequence type were inferred from the genotype. Antimicrobial resistance determinants were identified from assemblies, including known macrolide resistance genes.ResultsTwenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs). Two BAPS clusters not observed in CSS-1 (n = 109) or CSS-2 (n = 69), increased in frequency in CSS-3 (n = 126); BAPS20 (8.73%, p 0.016) and BAPS22 (7.14%, p 0.032) but were not associated with antimicrobial resistance. Macrolide resistance within BAPS17 increased after treatment (CSS-1 n = 0/6, CSS-2/3 n = 5/5, p 0.002) and was carried on a mobile transposable element that also conferred resistance to tetracycline.DiscussionLimited changes in pneumococcal population structure were observed after the third round of MDA, suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.