Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study.

BACKGROUND: In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, we aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). METHODS: We used updated excess mortality and fertility data to model increases in minimum estimates of COVID-19-associated orphanhood and caregiver deaths from our original study period of March 1, 2020-April 30, 2021, to include the new period of May 1-Oct 31, 2021, for 21 countries. Orphanhood was defined as the death of one or both parents; primary caregiver loss included parental death or the death of one or both custodial grandparents; and secondary caregiver loss included co-residing grandparents or kin. We used logistic regression and further incorporated a fixed effect for western European countries into our previous model to avoid over-predicting caregiver loss in that region. For the entire 20-month period, we grouped children by age (0-4 years, 5-9 years, and 10-17 years) and maternal or paternal orphanhood, using fertility contributions, and we modelled global and regional extrapolations of numbers of orphans. 95% credible intervals (CrIs) are given for all estimates. FINDINGS: The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7-90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100-2 987 000) to 5 200 300 (3 619 400-5 731 400). Between March 1, 2020, and Oct 31, 2021, 491 300 (95% CrI 485 100-497 900) children aged 0-4 years, 736 800 (726 900-746 500) children aged 5-9 years, and 2 146 700 (2 120 900-2 174 200) children aged 10-17 years are estimated to have experienced COVID-19-associated orphanhood. Globally, 76·5% (95% CrI 76·3-76·7) of children were paternal orphans, whereas 23·5% (23·3-23·7) were maternal orphans. In each age group and region, the prevalence of paternal orphanhood exceeded that of maternal orphanhood. INTERPRETATION: Our findings show that numbers of children affected by COVID-19-associated orphanhood and caregiver death almost doubled in 6 months compared with the amount after the first 14 months of the pandemic. Over the entire 20-month period, 5·0 million COVID-19 deaths meant that 5·2 million children lost a parent or caregiver. Our data on children's ages and circumstances should support pandemic response planning for children globally. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, and Medical Research Council), Oak Foundation, UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study.

BACKGROUND: The COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation. METHODS: We used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60-84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection-fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers. FINDINGS: Globally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000-1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000-1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15-50 years. Between two and five times more children had deceased fathers than deceased mothers. INTERPRETATION: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

Novel percutaneous dual-lumen cannula-based right ventricular assist device provides effective support for refractory right ventricular failure after left ventricular assist device implantation.

OBJECTIVES: Right heart failure after left ventricular assist device (LVAD) implantation is associated with significant morbidity and mortality. A new generation of percutaneous right ventricular assist devices (RVADs) may mitigate the need for invasive surgical RVAD implantation. The purpose of this study was to evaluate the safety and efficacy of the Protek Duo (TandemLife, Pittsburgh, PA, USA) RVAD in patients who developed severe acute right heart failure in the intensive care unit after LVAD implantation. METHODS: This was a retrospective cohort study of 27 patients who received a Protek Duo after LVAD implantation from January 2016 to March 2019 at our centre. The primary outcome of interest was survival to hospital discharge. Secondary outcomes included procedural success, device-related complications and conversion to a surgical RVAD. RESULTS: The median age of patients was 63 years (interquartile range 58-71), 78% were men and 78% were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2. Patients were on a median of 2 inotropes and 2 pressors prior to Protek Duo insertion. The device successfully implanted on the first attempt in all patients a median of 1 day (interquartile range 1-2) after LVAD implantation and the median duration of support was 11 days (interquartile range 7-16). Device weaning occurred in 86% of patients, with 15% in-hospital mortality. Major complications related to the device included new moderate-to-severe tricuspid regurgitation (36%), haemolysis (14%) and cannula migration (7%). Three patients (11%) required conversion to surgical RVAD. Overall survival to 1 year was 81%. CONCLUSIONS: The use of the Protek Duo as a percutaneous RVAD is a safe and feasible treatment for patients who develop acute right heart failure after LVAD implantation.

An Innovative Speech-Based User Interface for Smarthomes and IoT Solutions to Help People with Speech and Motor Disabilities.

A better use of the increasing functional capabilities of home automation systems and Internet of Things (IoT) devices to support the needs of users with disability, is the subject of a research project currently conducted by Area Ausili (Assistive Technology Area), a department of Polo Tecnologico Regionale Corte Roncati of the Local Health Trust of Bologna (Italy), in collaboration with AIAS Ausilioteca Assistive Technology (AT) Team. The main aim of the project is to develop experimental low cost systems for environmental control through simplified and accessible user interfaces. Many of the activities are focused on automatic speech recognition and are developed in the framework of the CloudCAST project. In this paper we report on the first technical achievements of the project and discuss future possible developments and applications within and outside CloudCAST.

Restoring Speech Following Total Removal of the Larynx.

By speech articulator movement and training a transformation to audio we can restore the power of speech to someone who has lost their larynx. We sense changes in magnetic field caused by movements of small magnets attached to the lips and tongue. The sensor transformation uses recurrent neural networks.

Cloud-Based Speech Technology for Assistive Technology Applications (CloudCAST).

The CloudCAST platform provides a series of speech recognition services that can be integrated into assistive technology applications. The platform and the services provided by the public API are described. Several exemplar applications have been developed to demonstrate the platform to potential developers and users.

Restoring speech following total removal of the larynx by a learned transformation from sensor data to acoustics.

Total removal of the larynx may be required to treat laryngeal cancer: speech is lost. This article shows that it may be possible to restore speech by sensing movement of the remaining speech articulators and use machine learning algorithms to derive a transformation to convert this sensor data into an acoustic signal. The resulting "silent speech," which may be delivered in real time, is intelligible and sounds natural. The identity of the speaker is recognisable. The sensing technique involves attaching small, unobtrusive magnets to the lips and tongue and monitoring changes in the magnetic field induced by their movement.

Colour Coding of Maps for Colour Deficient Observers.

We evaluate the colour coding of a web map traffic information service based on profiles simulating colour vision deficiencies. Based on these simulations and principles for universal design, we propose adjustments of the existing colours creating more readable maps for the colour vision deficient observers.

Characterizing coated paper surface for modeling apparent dot area of halftone prints.

A new model is proposed for predicting the apparent dot area of simulated halftone prints on coated paper surface without requiring printing. It is based on Hotelling's multivariate T(2) statistic which is shown to provide a measure of lateral light scattering. The T(2) statistic is computed from colorimetric coordinates obtained from of a knife shadow image response on the paper surface. The proposed method offers superior prediction of halftone dot area compared to current light scattering models. A method for characterising peaks on the coated paper surface is introduced in this work. The effect of the paper coating layer thickness and the surface peak height on lateral light scattering and printed dot size are shown.

Consistency and standardization of color in medical imaging: a consensus report.

This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8-9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group.

Efficient production of fermentable sugars from oil palm empty fruit bunch by combined use of acid and whole cell culture-catalyzed hydrolyses.

Empty fruit bunch (EFB) of oil palm trees was converted to fermentable sugars by the combined use of dilute acids and whole fungal cell culture-catalyzed hydrolyses. EFB (5%, w/v) was hydrolyzed in the presence of 0.5% H2 SO4 and 0.2% H3 PO4 at 160 °C for 10 Min. The solid fraction was separated from the acid hydrolysate by filtration and subjected to enzymatic hydrolysis at 50 °C using the whole cell culture of Trichoderma reesei RUT-C30 (2%, w/v), which was prepared by cultivation at 30 °C for 7 days to reach its maximal cellulase activity. The combined hydrolyses of EFB gave a total sugar yield of 82.0%. When used as carbon sources for cultivating Escherichia coli in M9 medium at 37 °C, the combined EFB hydrolysates were shown to be more favorable or at least as good as pure glucose for cell growth in terms of the higher (1.1 times) optical density of E. coli cells. The by-products generated during the acid-catalyzed hydrolysis did not seem to obviously affect cell growth. The combined use of acid and whole cell culture hydrolyses might be a commercially promising method for pretreatment of lignocellulose to get fermentable sugars.

Characterisation of the n-colour printing process using the spot colour overprint model.

This paper is aimed at reproducing the solid spot colours using the n-colour separation. A simplified numerical method, called as the spot colour overprint (SCOP) model, was used for characterising the n-colour printing process. This model was originally developed for estimating the spot colour overprints. It was extended to be used as a generic forward characterisation model for the n-colour printing process. The inverse printer model based on the look-up table was implemented to obtain the colour separation for n-colour printing process. Finally the real-world spot colours were reproduced using 7-colour separation on lithographic offset printing process. The colours printed with 7 inks were compared against the original spot colours to evaluate the accuracy. The results show good accuracy with the mean CIEDE2000 value between the target colours and the printed colours of 2.06. The proposed method can be used successfully to reproduce the spot colours, which can potentially save significant time and cost in the printing and packaging industry.

Expression-based segmentation of the Drosophila genome.

BACKGROUND: It is generally accepted that gene order in eukaryotes is nonrandom, with adjacent genes often sharing expression patterns across tissues, and that this organization may be important for gene regulation. Here we describe a novel method, based on an explicit probability model instead of correlation analysis, for identifying coordinately expressed gene clusters ('coexpression segments'), apply it to Drosophila melanogaster, and look for epigenetic associations using publicly available data. RESULTS: We find that two-thirds of Drosophila genes fall into multigenic coexpression segments, and that such segments are of two main types, housekeeping and tissue-restricted. Consistent with correlation-based studies, we find that adjacent genes within the same segment tend to be physically closer to each other than to the adjacent genes in different segments, and that tissue-restricted segments are enriched for testis-expressed genes. Our segmentation pattern correlates with Hi-C based physical interaction domains, but segments are generally much smaller than domains. Intersegment regions (including those which do not correspond to physical domain boundaries) are enriched for insulator binding sites. CONCLUSIONS: We describe a novel approach for identifying coexpression clusters that does not require arbitrary cutoff values or heuristics, and find that coexpression of adjacent genes is widespread in the Drosophila genome. Coexpression segments appear to reflect a level of regulatory organization related to, but below that of physical interaction domains, and depending in part on insulator binding.

Consed: a graphical editor for next-generation sequencing.

SUMMARY: The rapid growth of DNA sequencing throughput in recent years implies that graphical interfaces for viewing and correcting errors must now handle large numbers of reads, efficiently pinpoint regions of interest and automate as many tasks as possible. We have adapted consed to reflect this. To allow full-feature editing of large datasets while keeping memory requirements low, we developed a viewer, bamScape, that reads billion-read BAM files, identifies and displays problem areas for user review and launches the consed graphical editor on user-selected regions, allowing, in addition to longstanding consed capabilities such as assembly editing, a variety of new features including direct editing of the reference sequence, variant and error detection, display of annotation tracks and the ability to simultaneously process a group of reads. Many batch processing capabilities have been added. AVAILABILITY: The consed package is free to academic, government and non-profit users, and licensed to others for a fee by the University of Washington. The current version (26.0) is available for linux, macosx and solaris systems or as C++ source code. It includes a user's manual (with exercises) and example datasets. http://www.phrap.org/consed/consed.html CONTACT: dgordon@uw.edu .

Comment on "Evidence of abundant purifying selection in humans for recently acquired regulatory functions".

Ward and Kellis (Reports, 28 September 2012, p. 1675; published online 5 September 2012) found altered patterns of human polymorphism in biochemically active but non-mammalian-conserved genomic regions relative to control regions and interpreted this as due to lineage-specific purifying selection. We find on closer inspection of their data that the polymorphism trends are primarily attributable to mutational variation and technical artifacts rather than selection.

A voice-input voice-output communication aid for people with severe speech impairment.

A new form of augmentative and alternative communication (AAC) device for people with severe speech impairment-the voice-input voice-output communication aid (VIVOCA)-is described. The VIVOCA recognizes the disordered speech of the user and builds messages, which are converted into synthetic speech. System development was carried out employing user-centered design and development methods, which identified and refined key requirements for the device. A novel methodology for building small vocabulary, speaker-dependent automatic speech recognizers with reduced amounts of training data, was applied. Experiments showed that this method is successful in generating good recognition performance (mean accuracy 96%) on highly disordered speech, even when recognition perplexity is increased. The selected message-building technique traded off various factors including speed of message construction and range of available message outputs. The VIVOCA was evaluated in a field trial by individuals with moderate to severe dysarthria and confirmed that they can make use of the device to produce intelligible speech output from disordered speech input. The trial highlighted some issues which limit the performance and usability of the device when applied in real usage situations, with mean recognition accuracy of 67% in these circumstances. These limitations will be addressed in future work.

Reconstructing the voice of an individual following laryngectomy.

This case study describes the generation of a synthetic voice resembling that of an individual before she underwent a laryngectomy. Recordings of this person (6-7 min) speaking prior to the operation were used to create the voice. Synthesis was based on statistical speech models and this method allows models pre-trained on many speakers to be adapted to resemble an individual voice. The results of a listening test in which participants were asked to judge the similarity of the synthetic voice to the pre-operation (target) voice are reported. Members of the patient's family were asked to make a similar judgment. These experiments show that, for most listeners, the voice is quite convincing despite the low quality and small quantity of adaptation data.

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

Genomic signatures of germline gene expression.

Transcribed regions in the human genome differ from adjacent intergenic regions in transposable element density, crossover rates, and asymmetric substitution and sequence composition patterns. We tested whether these differences reflect selection or are instead a byproduct of germline transcription, using publicly available gene expression data from a variety of germline and somatic tissues. Crossover rate shows a strong negative correlation with gene expression in meiotic tissues, suggesting that crossover is inhibited by transcription. Strand-biased composition (G+T content) and A → G versus T → C substitution asymmetry are both positively correlated with germline gene expression. We find no evidence for a strand bias in allele frequency data, implying that the substitution asymmetry reflects a mutation rather than a fixation bias. The density of transposable elements is positively correlated with germline expression, suggesting that such elements preferentially insert into regions that are actively transcribed. For each of the features examined, our analyses favor a nonselective explanation for the observed trends and point to the role of germline gene expression in shaping the mammalian genome.