The Ethical Considerations of Artificial Intelligence in Clinical Decision Support

With the explosion in technological innovation facilitating the advent of artificially intelligent systems, specifically clinical decision support, a unique subset of ethical and sustainability concerns arises. Although this technology possesses remarkable potential to revolutionise the healthcare industry, it becomes apparent that an innovative ethical framework must be posited to facilitate integration into the mainstream. Due to the sensitive nature of healthcare, ethical oversights pertaining to incorporation of such technologies would lead to the detriment of its public perception, potentially stigmatising related systems for years to come. By delving into the literature surrounding the idiosyncratic ethical considerations of artificially intelligent clinical decision support in this paper, best practices which seek to mitigate the impact of these concerns emerge. The objective of this work is to assimilate these best practices, which are used in the synthesis of a six principle code of ethics which are as follows: protect healthcare professional authority, ensure technological non-maleficence, cultivate clinical decision support transparency, establish procedures for accountability determination, promote sustainability of artificially intelligence based clinical decision support and encourage equity in the training and deployment of clinical decision support. These principles are then applied to the real world of Watson for Oncology by IBM, to assess the adherence of the product to ethical and sustainability best practices

On the Feasibility of Carbon Nanotube Windings for Electrical Machines — Case Study for a Coreless Axial Flux Motor

The latest developments in carbon nanotube (CNT) wires and yarns attract great interest for potential application to electromagnetic devices, such as electrical machines and transformers. The CNT material properties are largely different from copper and aluminum in terms of electrical conductivity, mass density, and thermal transfer, creating a new design paradigm for which the traditional rules and device topologies no longer apply. This paper proposes a brushless permanent magnet multidisc axial flux construction with coreless stator and special windings and minimal rotor back iron, as a suitable topology for CNT winding application. Specific analytical closed-form sizing equations, as a function of winding electric conductivity, machine dimensions, and operating speed/frequency, are derived and employed in a systematic comparative study over a range of kW power ratings and speeds between 1,000 and 10,000 rpm. The numerical study is complemented by 3D and 2D electromagnetic FEA. The results show that the designs with CNT windings may have substantially higher specific power per mass, particularly at high rotational speeds and/or supply frequency, where the combined effect of DC and AC conduction losses in the windings is significant

Coreless Multidisc Axial Flux PM Machine with Carbon Nanotube Windings

Coreless axial flux permanent magnet (AFPM) machines are attracting increasing attention due to their compact structure and high torque density. The torque to weight ratio can be further enhanced by the use of alternate conductor materials, such as carbon nanotube (CNT), or aluminum windings in place of the copper material coils. This paper proposes a coreless AFPM synchronous motor with CNT windings. Analytical equations are developed to allow a systematic comparison of machine designs with different conductor materials. The performance of machine designs with different coil materials, namely, copper, aluminum, and CNT, is evaluated and compared. The calculations are also backed by 3-D finite-element analysis

Multiple myeloma: what a non-haematologist should know

Multiple myeloma (MM) is a type of haematological bone marrow malignancy. Cancer Research UK reports that MM is the 18th most common cancer in the UK, accounting for 2% of all new cancer cases, yet, non-haematologists often lack familiarity with the pathology and initial investigations. This paper aims to demonstrate the diagnostic features, relevant investigations and basic management plan for the non-specialist

A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the Striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PJPAP). Unlike other P. falciparum aminopeptidases, PJPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PJPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PJPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies. (C) 2016 Elsevier Inc. All rights reserved

CDKL5 kinase controls transcription‐coupled responses to DNA damage

Mutations in the gene encoding the CDKL5 kinase are among the most common genetic causes of childhood epilepsy and can also give rise to the severe neurodevelopmental condition CDD (CDKL5 deficiency disorder). Despite its importance for human health, the phosphorylation targets and cellular roles of CDKL5 are poorly understood, especially in the cell nucleus. Here, we report that CDKL5 is recruited to sites of DNA damage in actively transcribed regions of the nucleus. A quantitative phosphoproteomic screen for nuclear CDKL5 substrates reveals a network of transcriptional regulators including Elongin A (ELOA), phosphorylated on a specific CDKL5 consensus motif. Recruitment of CDKL5 and ELOA to damaged DNA, and subsequent phosphorylation of ELOA, requires both active transcription and the synthesis of poly(ADP‐ribose) (PAR), to which CDKL5 can bind. Critically, CDKL5 kinase activity is essential for the transcriptional silencing of genes induced by DNA double‐strand breaks. Thus, CDKL5 is a DNA damage‐sensing, PAR‐controlled transcriptional modulator, a finding with implications for understanding the molecular basis of CDKL5‐related diseases

Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000

BACKGROUND: Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors. METHODS: We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires. DISCUSSION: This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes