Machine-learning algorithm in acute stroke: real-world experience.

AIM: To assess the clinical performance of a commercially available machine learning (ML) algorithm in acute stroke. MATERIALS AND METHODS: CT and CT angiography (CTA) studies of 104 consecutive patients (43 females, age range 19-93, median age 62) performed for suspected acute stroke at a single tertiary institution with real-time ML software analysis (RAPID™ ASPECTS and CTA) were included. Studies were retrospectively reviewed independently by two neuroradiologists in a blinded manner. RESULTS: The cohort included 24 acute infarcts and 16 large vessel occlusions (LVO). RAPID™ ASPECTS interpretation demonstrated high sensitivity (87.5%) and NPV (87.5%) but very poor specificity (30.9%) and PPV (30.9%) for detection of acute ischaemic parenchymal changes. There was a high percentage of false positives (51.1%). In cases of proven LVO, RAPID™ ASPECTS showed good correlation with neuroradiologists' blinded independent interpretation, Pearson correlation coefficient = 0.96 (both readers), 0.63 (RAPID™ vs reader 1), 0.69 (RAPID™ vs reader 2). RAPID™ CTA interpretation demonstrated high sensitivity (92.3%), specificity (85.3%), and negative predictive (NPV) (98.5%) with moderate positive predictive value (PPV) (52.2%) for detection of LVO (N=13). False positives accounted for 12.5% of cases, of which 27.3% were attributed to arterial stenosis. CONCLUSION: RAPID™ CTA was robust and reliable in detection of LVO. Although demonstrating high sensitivity and NPV, RAPID™ ASPECTS interpretation was associated with a high number of false positives, which decreased clinicians' confidence in the algorithm. However, in cases of proven LVO, RAPID™ ASPECTS performed well and had good correlation with neuroradiologists' blinded interpretation.

Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis.

Myelin is a specialized membrane that wraps around nerve fibers and is essential for normal axonal conduction in neurons. In the central nervous system, oligodendrocytes are responsible for myelin formation. Recent studies have reported pathological abnormalities in oligodendrocytes in human patients with amyotrophic lateral sclerosis (ALS) and a mouse model of ALS expressing the G93A mutation of the human superoxide dismutase 1 (mtSOD1). However, it is unclear whether oligodendrocyte pathology in ALS represents the primary dysfunction induced by mtSOD1 and how mtSOD1 contributes to oligodendrocyte degeneration and ALS pathogenesis. We analyzed GAL4-VP16-UAS transgenic zebrafish selectively expressing mtSOD1 in mature oligodendrocytes. We observed that mtSOD1 directly induced oligodendrocyte degeneration by disrupting the myelin sheath and downregulating monocarboxylate transporter 1 (MCT1), thereby causing spinal motor neuron degeneration. Pathological changes observed in this transgenic zebrafish were similar to the pathology observed in the SOD1G93A mouse model of ALS, which is characterized by expression of mtSOD1 in all cells. In addition, oligodendrocyte dysfunction induced by mtSOD1 was associated with anxiety-related behavioral abnormalities, learning impairments, and motor defects in the early symptomatic stage. We also found that treatment with potassium channel inhibitors rescued behavioral abnormalities without rescuing MCT1 expression, suggesting that myelin disruption induces behavioral abnormalities independently of MCT1. These results indicate that mtSOD1-induced dysfunction of mature oligodendrocytes is sufficient to induce motor neuron degeneration, thus informing future therapeutic strategies targeted at oligodendrocytes in ALS.

Healthcare utilisation patterns for respiratory and gastrointestinal syndromes and meningitis in Msunduzi municipality, Pietermaritzburg, KwaZulu-Natal Province, South Africa, 2013.

BACKGROUND: Public health facilities are used by the majority of South Africans, and healthcare utilisation surveys have been a useful tool to estimate the burden of disease in a given area. OBJECTIVES: To describe care-seeking behaviour in a periurban site with a high prevalence of HIV infection, as well as barriers to seeking appropriate healthcare. METHODS: We conducted a cross-sectional household survey in 22 wards of the Msunduzi municipality in KwaZulu-Natal Province, South Africa, from October to December 2013 using a simple random sample of households selected from a 2011 census enumeration. A primary caregiver/adult decision-maker was interviewed regarding demographic data as well as health status and recent self-reported episodes of selected illnesses and healthcare utilisation. RESULTS: Of the 2 238 eligible premises visited, 1 936 households (87%) with a total of 9 733 members were enrolled in the study. Of these, 635 (7%) reported one or more episodes of infectious illness during the study period. Public health clinics were most frequently consulted for all illnesses (361/635, 57%). Private healthcare (general practitioner, private clinic, private hospital) was sought by 90/635 of individuals (14%), only 13/635 (2%) reported seeking care from traditional healers, religious leaders or volunteers, and 71/635 (11%) did not seek any medical care for acute illnesses. Individuals in the lowest income group were more likely to seek care at public health facilities than those in the highest income group (70% v. 32%). CONCLUSIONS: Public health facility-based surveillance may be representative of disease patterns in this community, although surveillance at household level shows that high-income individuals may be excluded because they were more likely to use private healthcare, and the proportion of individuals who died at home would have been missed by facility-based surveillance. Data obtained in such surveys may be useful for public health planning.

Identification of a new HLA-A*11 allele, A*11:251N.

The new allele, A*11:251N, differs from A*11:01:01 by insertion of two nucleotides at position 204-205.

Identification of the novel HLA-B*15:18:01:04 in a Korean individual.

HLA-B*15:18:01:04 differs from HLA-B*15:18:01:02 by single nucleotide substitution at position 2176 (G > A).

A standardised pathway for the surveillance of stable vestibular schwannoma.

Introduction Conservative management of patients with a stable vestibular schwannoma (VS) places a significant burden on National Health Service (NHS) resources and yet patients' surveillance management is often inconsistent. Our unit has developed a standardised pathway to guide surveillance imaging of patients with stable VS. In this article, we provide the basis for our imaging protocol by reviewing the measurement, natural history and growth patterns of VS, and we present a cost analysis of implementing the pathway both regionally and nationally. Methods Patients with an extrameatal VS measuring ≤20mm in maximal diameter receive magnetic resonance imaging (MRI) six months after their index imaging, followed by three annual MRI scans, two two-year interval MRI scans, a single three-year interval MRI scan and then five-yearly MRI scans to be continued lifelong. Patients with purely intrameatal tumours follow the same protocol but the initial six-month imaging is omitted. A cost analysis of the new pathway was modelled on our unit's retrospective data for 2015 and extrapolated to reflect the cost of VS surveillance nationally. Results Based on an estimation that imaging surveillance would last approximately 25 years (+/- 10 years), the cost of implementing our regional surveillance programme would be £151,011 per year (for 99 new referrals per year) and it would cost the NHS £1,982,968 per year if implemented nationally. Conclusions A standardised surveillance pathway promotes safe practice in the conservative management of VS. The estimated cost of a national surveillance programme compares favourably with other tumour surveillance initiatives, and would enable the NHS to provide a safe and economical service to patients with VS.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

Three novel HLA alleles discovered in Koreans, HLA-A*26:118, DQB1*02:65 and DPB1*05:01:07.

Three novel HLA alleles, HLA-A*26:118, DQB1*02:65 and DPB1*05:01:07, were identified and confirmed by monoallelic sequencing.

Identification of the novel HLA-C*03 allele, HLA-C*03:03:35.

The new allele HLA-C*03:03:35 showed one nucleotide difference with C*03:03:01:01 at position 408 (G>T).

A new HLA-DQB1*04 allele, HLA-DQB1*04:01:05, identified in a Korean individual.

HLA-DQB1*04:01:05 differs from DQB1*04:01:01 by a single nucleotide substitution at codon 30 (TAC>TAT).

Four novel alleles in Korean individuals, HLA-B*40:323, DRB1*14:177, DQB1*03:200, and DQB1*06:205.

Four novel HLA alleles identified in Korean individuals and confirmed by monoallelic sequencing.

Evaluation of abundance of artificial radionuclides in food products in South Korea and sources.

Food samples are collected nationwide from January 2016 to February 2017 and their contents of artificial radionuclides are measured to address the growing concerns regarding the radioactive contamination of food products in Korea. Specifically, 900 food samples are collected for this study and their contents of representative artificial radionuclides 134Cs, 137Cs, 239,240Pu, and 90Sr are analyzed. The analysis shows that the activity concentrations of 137Cs in fish range from minimum detectable activity (MDA) to 340 mBq/kg of fresh weight. The concentration factor (CF) determined for 137Cs as a measure of its bioavailability is calculated to be ca. 74 and found to be very similar to that (100) recommended by the International Atomic Energy Agency. With an MDA of <0.221 mBq/kg, the results reveal that 239,240Pu values in fish are below the MDA. The activity concentrations of 137Cs and 90Sr are lower than the MDA in both shellfish and seaweed, while the activity concentrations of 239,240Pu in shellfish range from 0.26 to 2.18 mBq/kg, and for seaweed samples range from 2.07 to 3.38 mBq/kg. The atom ratios of 240Pu/239Pu in shellfish caught at the Korean coast vary from 0.209 to 0.237, with a mean of 0.227. The higher 240Pu/239Pu atom ratio determined in shellfish is thought to be caused by the plutonium transported from the Pacific Proving Grounds rather than other sources such as the Fukushima nuclear power plant accident. The activity concentrations of 137Cs in mushrooms are found to vary from 1.0 to 21.4 Bq/kg, with the highest concentrations observed in the Oak (shiitake) and Sarcodon asparatus. 134Cs is detected in three mushroom specimens collected from Jeju Island and about 3-3.6% of 137Cs present in the wild mushrooms native to the Jeju Island are introduced as a result of the Fukushima nuclear plant accident. The annual effective doses of 137Cs received through consumption of mushrooms and fish are 2.0 × 10-4 mSv yr-1 and 3.9 × 10-5 mSv yr-1, and those values are negligible compared to the annual effective doses limit of 1 mSv yr-1.

HLA-B*40:302, a novel allele identified by sequence-based typing in a Korean individual.

B*40:302 differs from B*40:02:01:01 by a single nonsynonymous nucleotide substitution at codon 81 (CCG→CTG).

HLA-DPB1*518:01, a new allele identified by sequence-based typing in a Korean individual.

The new allele DPB1*518:01 showed one nucleotide difference with DPB1*13:01:01 at codon 124 (CCT/ACT).

HLA-DPB1*519:01, a new allele identified by sequence-based typing in a Korean individual.

The new allele DPB1*519:01 showed one nucleotide difference with DPB1*13:01:01 at codon 234 (GTG/ATG).

Identification of a novel allele, HLA-A*02:01:131, by full-length genomic sequencing.

The HLA-A*02:01:131 allele differs by a single nucleotide at codon 236 compared with HLA-A*02:01:01:01.

Identification of a novel allele, HLA-C*01:135, by full-length genomic sequencing.

The HLA-C*01:135 allele differs by a single nucleotide at codon 265 compared with HLA-C*01:02:01:01.

A novel allele, HLA-C*14:02:01:03, identified by full-length genomic sequencing.

The HLA-C*14:02:01:03 differs by a single nucleotide at intron 5 (2157 C>T) compared with C*14:02:01:01.