Human-centred explanations for artificial intelligence systems.

As Artificial Intelligence (AI) systems increase in capability, so there are growing concerns over the ways in which the recommendations they provide can affect people's everyday life and decisions. The field of Explainable AI (XAI) aims to address such concerns but there is often a neglect of the human in this process. We present a formal definition of human-centred XAI and illustrate the application of this formalism to the design of a user interface. The user interface supports users in indicating their preferences relevant to a situation and to compare their preferences with those of a computer recommendation system. A user trial is conducted to evaluate the resulting user interface. From the user trial, we believe that users are able to appreciate how their preferences can influence computer recommendations, and how these might contrast with the preferences used by the computer. We provide guidelines of implementing human-centred XAI.

This paper presents a formal description of explanatory discourse for Human-Centred Explainable Artificial Intelligence (XAI) and demonstrate the use of this formalism as the basis for designing user interface for a recommender system. The recommender system is evaluated through a user trial. The paper concludes with guidelines for developing Human-Centred XAI.

Involvement of the Spinal Cord in Primary Mitochondrial Disorders: A Neuroimaging Mimicker of Inflammation and Ischemia in Children.

BACKGROUND AND PURPOSE: Little is known about imaging features of spinal cord lesions in mitochondrial disorders. The aim of this research was to assess the frequency, imaging features, and pathogenic variants causing primary mitochondrial disease in children with spinal cord lesions. MATERIALS AND METHODS: This retrospective analysis included patients seen at Children's Hospital of Philadelphia between 2000 and 2019 who had a confirmed diagnosis of a primary (genetic-based) mitochondrial disease and available MR imaging of the spine. The MR imaging included at least both sagittal and axial fast spin-echo T2-weighted images. Spine images were independently reviewed by 2 neuroradiologists. Location and imaging features of spinal cord lesions were correlated and tested using the Fisher exact test. RESULTS: Of 119 children with primary mitochondrial disease in whom MR imaging was available, only 33 of 119 (28%) had available spine imaging for reanalysis. Nineteen of these 33 individuals (58%) had evidence of spinal cord lesions. Two main patterns of spinal cord lesions were identified: group A (12/19; 63%) had white ± gray matter involvement, and group B (7/19; 37%) had isolated gray matter involvement. Group A spinal cord lesions were similar to those seen in patients with neuromyelitis optica spectrum disorder, multiple sclerosis, anti-myelin oligodendrocyte glycoprotein-IgG antibody disease, and leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Group B patients had spinal cord findings similar to those that occur with ischemia and viral infections. Significant associations were seen between the pattern of lesions (group A versus group B) and the location of lesions in cervical versus thoracolumbar segments, respectively (P < .01). CONCLUSIONS: Spinal cord lesions are frequently observed in children with primary mitochondrial disease and may mimic more common causes such as demyelination and ischemia.

Erratum to: Finding people like me: contact among young adults who share an open-identity sperm donor.

[This corrects the article DOI: 10.1093/hropen/hoaa057.].

The Perirolandic Sign: A Unique Imaging Finding Observed in Association with Polymerase γ-Related Disorders.

Pathogenic variants in the polymerase γ gene (POLG) cause a diverse group of pathologies known as POLG-related disorders. In this report, we describe brain MR imaging findings and electroencephalogram correlates of 13 children with POLG-related disorders at diagnosis and follow-up. At diagnosis, all patients had seizures and 12 had abnormal MR imaging findings. The most common imaging findings were unilateral or bilateral perirolandic (54%) and unilateral or bilateral thalamic signal changes (77%). Association of epilepsia partialis continua with perirolandic and thalamic signal changes was present in 86% and 70% of the patients, respectively. The occipital lobe was affected in 2 patients. On follow-up, 92% of the patients had disease progression or fatal outcome. Rapid volume loss was seen in 77% of the patients. The occipital lobe (61%) and thalamus (61%) were the most affected brain regions. Perirolandic signal changes and seizures may represent a brain imaging biomarker of early-onset pediatric POLG-related disorders.

Finding people like me: contact among young adults who share an open-identity sperm donor.

STUDY QUESTION: What interests and experiences do donor-conceived adults have with respect to same-donor peers/siblings, when they share an open-identity sperm donor? SUMMARY ANSWER: Donor-conceived young adults report considerable interest in, and primarily positive experiences with, their same-donor peers, with some finding 'people like me'. WHAT IS KNOWN ALREADY: Through mutual-consent contact registries, director-to-consumer DNA testing and other means, donor-conceived people with anonymous (i.e. closed-identity) sperm donors are gaining identity-related information from, and establishing relationships with, people who share their donor. STUDY DESIGN SIZE DURATION: Semi-structured, in depth telephone and Skype interviews with 47 donor-conceived young adults were carried out over a 31-month period. Inclusion criteria were being one of the first adults for each donor to obtain their identity and being at least 1-year post donor-information release. PARTICIPANTS/MATERIALS SETTING METHODS: Participants (aged 19-29 years, 68.1% women) were born to female same-sex couple parents (46.8%), a single mother (29.8%) or heterosexual couple parents (23.4%); all parents had conceived through the same US open-identity sperm donation program. The dataset was analyzed thematically and included interviews from only one participant per family. Each participant had a different donor. MAIN RESULTS AND THE ROLE OF CHANCE: Interest in, and experiences with, same-donor peers suggested that they occupy a unique position in the lives of donor-conceived young adults who share their open-identity donor. Contact can provide identity-relevant information and support through the availability of relationships (whether actualized or potential), shared experiences, and easier relationships than with their donor. Most donor-conceived young adults felt positively about their contact experiences. Of those not yet linked, almost all expressed an interest to do so. Some had met the children raised by their donor. When asked, all expressed an interest in doing so. LIMITATIONS REASONS FOR CAUTION: Interviews were conducted with donor-conceived young adults who were uncommon in their generation in terms of: having an open-identity sperm donor; the majority knowing about their family's origins from childhood; and having parents that accessed at the time one of the only open-identity sperm donation programs. Further research is needed to assess applicability to all donor-conceived adults; findings may be more relevant to the growing number of people who have an open-identity donor and learned in childhood about their family's origins. WIDER IMPLICATIONS OF THE FINDINGS: Participants were among the first generation of donor-conceived adults with an open-identity sperm donor. Their experiences and perspectives can provide essential guidance to programs and others with similar origins. Early disclosure of family origins and identifying the donor did not diminish the young adults' interest in their same-donor peers. Positive experiences suggest that the benefits of contact include not only identity-relevant information (through shared traits and experiences), but also relationships with and support from people who understand the uncommon experience of being donor conceived. Implications include the need to educate families and intended parents about the potential benefits of knowing others who are donor conceived, and the risk of unexpected linking across families by donors, regardless of donor-conceived person or family interest. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Lesbian Health Fund of GLMA: Health Professionals Advancing LGBTQ Equality. The authors have no conflict of interest to declare.

Evaluation of Binax NOW RSV as an acute point-of-care screening test in a paediatric accident and emergency unit.

Point-of-care tests (POCTs) for respiratory syncytial virus infections are a useful adjunct to reduce the risk of healthcare-associated infections in paediatric wards. A new test based on immunochromatography, Binax NOW RSV, was introduced in the winter of 2002-03. It has user friendly features making it particularly suitable for non-laboratory personnel in a paediatric accident and emergency unit. A prospective study comparing the POCT with laboratory-based direct immunofluorescence (DIF) showed sensitivity of 87% specificity of 94%, positive predictive value of 89% and negative predictive value 92%. The simplicity of Binax NOW RSV should not detract from training staff and maintaining consistent vigilance on quality control.

Engineering of complex polyketide biosynthesis--insights from sequencing of the monensin biosynthetic gene cluster.

The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifunctional enzymes, the modular Type I polyketide synthases (PKSs). Most of our current knowledge of such systems stems from the study of a restricted number of macrolide-synthesising enzymes. The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic evidence for the mechanism of oxidative cyclisation through which polyethers such as monensin are formed from the uncyclised products of the PKS. Two intriguing genes associated with the monensin PKS cluster code for proteins, which show strong homology with enzymes that trigger double bond migrations in steroid biosynthesis by generation of an extended enolate of an unsaturated ketone residue. A similar mechanism operating at the stage of an enoyl ester intermediate during chain extension on a PKS could allow isomerisation of an E double bond to the Z isomer. This process, together with epoxidations and cyclisations, form the basis of a revised proposal for monensin formation. The monensin PKS has also provided fresh insight into general features of catalysis by modular PKSs, in particular into the mechanism of chain initiation.

Production of 6-deoxy-13-cyclopropyl-erythromycin B by Saccharopolyspora erythraea NRRL 18643.

Cyclopropane carboxylic acid was fed to Saccharopolyspora erythraea NRRL 18643 (6-deoxyerythromycin producer), resulting in the production of 6-deoxy-13-cyclopropyl-erythromycin B. These studies provide further evidence that deoxyerythronolide B synthase has a relaxed specificity for the starter unit.

The timing of congenital brachial plexus injury: a study of electromyography findings in the newborn piglet.

OBJECTIVE: Permanent congenital brachial plexus palsy is a recognized serious complication associated with shoulder dystocia. The timing and etiology of this injury remains controversial. Previous authorities have used adult-derived, non-brachial plexus data to extrapolate the anticipated timing for electromyographic denervation changes to date such injuries in the newborn. With use of a domestic swine model, this investigation tests the hypothesis that electromyographic evidence of brachial plexus denervation in the newborn is temporally different than that in the adult. STUDY DESIGN: Five healthy 2-day-old and two adult pigs underwent unilateral sharp transection of the brachial plexus. Daily electromyographic studies were performed in brachial plexus innervated muscle groups on the involved and contralateral (control) front limbs. Postmortem measurements of the transected nerve segments were obtained in one piglet and one adult animal. Representative hard copy recordings of individual electromyographic studies were collected. RESULTS: Immediately after surgical transection of the brachial plexus, no electromyographic evidence of denervation was observed. Uniformly in the newborn piglets, at 24 hours after transection, denervation in the form of fibrillation potentials, positive sharp waves, and complex repetitive discharges was seen. Serial testing demonstrated proximal to distal gradients of denervation over the next 24 to 48 hours. A delay in electromyographic evidence of denervation was observed in the two adult pigs until days 5 and 8, respectively. Control limb studies remained normal throughout the study period. Nerve length measurements for individual muscle groups were as follows for the adult and newborn pigs, respectively: deltoid 11.4 cm, 2.5 cm; cleidobrachialis 16.0 cm, 4.0 cm; triceps 15.5 cm, 4.5 cm; forelimb flexors 26.0 cm, 6.5 cm; and extensor carpi radialis 31.0 cm, 9.0 cm. CONCLUSION: Electromyographic evidence of brachial plexus denervation after surgical transection differs between the newborn and the adult pig. Consistent with wallerian degeneration, a correlation exists between length of the distal nerve segment and timing for electromyographic signs of denervation. These findings suggest it would be inappropriate to extrapolate the anticipated timing for electromyographic changes in the newborn on the basis of previously established adult non-brachial plexus data.

Novel erythromycins from a recombinant Saccharopolyspora erythraea strain NRRL 2338 pIG1. I. Fermentation, isolation and biological activity.

In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338. Both strains incorporated exogenously supplied fatty acids to produce novel, biologically active, C-13 substituted erythromycins.

A case-mix classification system for long-term care facilities.

The resident assessment and associated classification model inherent in any case-mix classification system are particularly germane to nursing. Resource Utilization Groups-Version III (RUG-III) illustrates how a case-mix classification system for long-term care nursing facilities is designed and constructed. Understanding the RUG-III classification system can assist nurses in evaluating other classification systems that may be adopted by Medicaid programs. Nurses provide a crucial perspective in forming and informing healthcare policy associated with nursing home payment and quality.

The hidden costs of accounts receivable.

To maintain and expand their missions, hospitals must make the best use of their assets. Knowing the true cost of accounts receivable is important for efficient operations. Knowing how to reduce this cost is critical for liquidity. This article offers a guide to ensuring these assets are used most productively.

Utilization care plans and effective patient data management.

This article introduces the concept of a utilization care plan (UCP) for supporting the communication of data required for effective utilization review and utilization management. Utilization review is a process of measurement that compares the performance of a ward, department, or entire facility against accepted criteria to identify resource use shortfalls. Utilization management is the deliberate action by third party payers to ensure that shortfalls in resource utilization are minimized. Critical to the success of utilization management is effective data communication; utilization review data must be accurate, complete, accessible, timely, and coordinated. Computer-based UCP systems can remind caregivers when and what services should be provided to patients and also monitor the portion of those services that should be administered during each phase of a patient's therapy. Deviations from the UCP system template constitute variances that can be documented and highlighted in a friendly automated system that ensures highly accurate and extremely timely concurrent utilization information. Some implications of using UCP systems for future research and practice are also discussed.

Pharmacokinetics of ciprofloxacin in subjects with varying degrees of renal function and undergoing hemodialysis or CAPD.

The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.

Comparative serum bactericidal activity of ceftizoxime/metronidazole, ceftizoxime, clindamycin, and imipenem against obligate anaerobic bacteria.

We compared the bactericidal activity of serum obtained from healthy volunteers after single intravenous infusions of the combination of ceftizoxime (1 g) plus metronidazole (1 g) and after infusions of ceftizoxime (2 g), clindamycin (900 mg), and imipenem (1 g) against six obligate anaerobes. All agents were bactericidal but only the combination regimen resulted in bactericidal titres greater than 1:2 at 12 h for all the Bacteroides fragilis group organisms. High titres against Fusobacterium necrophorum and anaerobic Gram-positive cocci were attained with ceftizoxime/metronidazole, ceftizoxime, and imipenem 12 h after the dose. Imipenem and the combination of ceftizoxime/metronidazole had the greatest area under the bactericidal curve (AUBC) against the Bacteroides species. Clindamycin had a significantly smaller AUBC than other regimens for all strains tested except B. thetaiotaomicron. Clinical trials are needed to assess the efficacy and cost-benefit ratio of a 12 h dosing regimen of ceftizoxime in combination with metronidazole for treating mixed aerobic/anaerobic infections.

Evaluation of impairment of the upper extremity.

Evaluation of impairment of the upper extremity is the product of a team effort by the physician, occupational therapist, physical therapist, and rehabilitation counselor. A careful recording of the anatomic impairment should be made because this is critical in determining the subsequent functional activities of the extremity. The measurement criteria for clinical and functional evaluation includes condition assessment instruments. Some assess the neurovascular system, others assess movements including the monitoring of articular motion and musculotendinous function. Sensibility assessment instruments measure sympathetic response and detect single joint stimulus, discrimination, quantification, and recognition abilities. A detailed description of each assessment is recorded and physical capacity evaluation is only one component of the entire vocational evaluation. This evaluation answers questions regarding the injured worker's ability to return to his previous job. The work simulator is a useful instrument that allows rehabilitation and testing of the injured upper extremity. Job site evaluation includes assessment criteria for work performance, work behavior, and work environment.