Applying Deep Learning to Predicting Dementia and Mild Cognitive Impairment

Dementia has a large negative impact on the global healthcare and society. Diagnosis is rather challenging as there is no standardised test. The purpose of this paper is to conduct an analysis on ADNI data and determine its effectiveness for building classification models to differentiate the categories Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Dementia (DEM), based on tuning three Deep Learning models: two Multi-Layer Perceptron (MLP1 and MLP2) models and a Convolutional Bidirectional Long Short-Term Memory (ConvBLSTM) model. The results show that the MLP1 and MLP2 models accurately distinguish the DEM, MCI and CN classes, with accuracies as high as 0.86 (SD 0.01). The ConvBLSTM model was slightly less accurate but was explored in view of comparisons with the MLP models, and for future extensions of this work that will take advantage of time-related information. Although the performance of ConvBLSTM model was negatively impacted by a lack of visit code data, opportunities were identified for improvement, particularly in terms of pre-processing

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1

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Not AvailablePresent experiment was conducted to study the relative economics of crossbred (Landrace×Desi) pigs with thirty six crossbred barrows reared under 3 different floor space allowances (n=12 each) having group size of 4 pigs/pen. One group (TIS) was provided floor space as per Indian Standards (0.9, 1.35 and 1.8 m2/pig for weaner, grower and finisher stages, respectively) specifications, while other two groups with 33% (T2/3) and 50% (T1/2) reduced floor space allowances. Only covered floor area was provided for all the groups. Different parameters analyzed during the study involved growth, feed conversion efficiency, requirement of water and labour for floor washing, and some other economic variables. Pigs were reared up to 28 weeks of age. Relative economics of pig rearing for three floor space allocation groups was calculated using partial budget analysis. Major performance traits, i.e. average daily gain (ADG) and feed conversion efficiency (FCE) did not differ significantly among the groups. Although body weights of T2/3 and T1/2 groups were marginally higher than TIS group. In contrary to minor savings of labour, large quantity of water was saved in T1/2 and T2/3 groups (805.4 liters/pig and 400.1 liters/pig, respectively) than TIS group between weaner and finisher stages. Additionally, input costs of ` 145 and ` 96 per pig was saved by providing floor space as per T1/2 and T2/3 groups, respectively than TIS group. It can be concluded that economic gains were maximum in 50% floor space reduction group without adverse effect on performance traits of crossbred pigs.Not Availabl

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Not AvailableTo compare the effect of different floor space allowances on physiological status of pigs, 36 crossbred (Landrace x Desi) barrows were reared with 3 different floor space allowances [n = 4(group size) x 3(replications) = 12 each]. Group TIS (control) had floor space allowance (0.9, 1.35 and 1.8 m2/pig during weaner, grower and finisher stage) as per Indian Standards (IS: 3916-1966), while T2/3 and T1/2 treatment groups had 33% and 50% reduced floor space allocation with fixed small (n=4) group size throughout the experiment. Skin lesion score, blood parameters and back fat thickness (BFT) of pigs were estimated. Mean skin lesion score of head and ears (weaner, P<0.05) was lower in TIS group than other groups, and body regions (finisher, P<0.05) was lower in TIS than T1/2 group, whereas, lesion score for other body parts and growth stages did not differ among the groups. Plasma cortisol concentration was higher (P<0.05) in T1/2 group than other groups (grower) and TIS group (control). BFT of pigs did not differ statistically among the groups. It is concluded that suitable floor space allowance in Indian conditions should lie between T2/3 and T1/2 group for crossbred pigs.Not Availabl

Developing a reporting guideline for artificial intelligence-centred diagnostic test accuracy studies: the STARD-AI protocol

Introduction Standards for Reporting of Diagnostic Accuracy Study (STARD) was developed to improve the completeness and transparency of reporting in studies investigating diagnostic test accuracy. However, its current form, STARD 2015 does not address the issues and challenges raised by artificial intelligence (AI)-centred interventions. As such, we propose an AI-specific version of the STARD checklist (STARD-AI), which focuses on the reporting of AI diagnostic test accuracy studies. This paper describes the methods that will be used to develop STARD-AI. Methods and analysis The development of the STARD-AI checklist can be distilled into six stages. (1) A project organisation phase has been undertaken, during which a Project Team and a Steering Committee were established; (2) An item generation process has been completed following a literature review, a patient and public involvement and engagement exercise and an online scoping survey of international experts; (3) A three-round modified Delphi consensus methodology is underway, which will culminate in a teleconference consensus meeting of experts; (4) Thereafter, the Project Team will draft the initial STARD-AI checklist and the accompanying documents; (5) A piloting phase among expert users will be undertaken to identify items which are either unclear or missing. This process, consisting of surveys and semistructured interviews, will contribute towards the explanation and elaboration document and (6) On finalisation of the manuscripts, the group’s efforts turn towards an organised dissemination and implementation strategy to maximise end-user adoption. Ethics and dissemination Ethical approval has been granted by the Joint Research Compliance Office at Imperial College London (reference number: 19IC5679). A dissemination strategy will be aimed towards five groups of stakeholders: (1) academia, (2) policy, (3) guidelines and regulation, (4) industry and (5) public and non-specific stakeholders. We anticipate that dissemination will take place in Q3 of 2021

Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity

Gene therapies using integrating retrovirus vectors to modify hematopoietic stem and progenitor cells have shown great promise for the treatment of immune system and hematologic diseases. However, activation of proto-oncogenes via insertional mutagenesis has resulted in the development of leukemia. We have utilized cellular bar coding to investigate the impact of different vector designs on the clonal behavior of hematopoietic stem and progenitor cells (HSPCs) during in vivo expansion, as a quantitative surrogate assay for genotoxicity in a non-human primate model with high relevance for human biology. We transplanted two rhesus macaques with autologous CD34+ HSPCs transduced with three lentiviral vectors containing different promoters and/or enhancers of a predicted range of genotoxicities, each containing a high-diversity barcode library that uniquely tags each individual transduced HSPC. Analysis of clonal output from thousands of individual HSPCs transduced with these barcoded vectors revealed sustained clonal diversity, with no progressive dominance of clones containing any of the three vectors for up to almost 3 years post-transplantation. Our data support a low genotoxic risk for lentivirus vectors in HSPCs, even those containing strong promoters and/or enhancers. Additionally, this flexible system can be used for the testing of future vector designs. Keywords: lentivirus, genotoxicity, gene therapy, non-human primat