Ethical Considerations and Fairness in the Use of Artificial Intelligence for Neuroradiology.

In this review, concepts of algorithmic bias and fairness are defined qualitatively and mathematically. Illustrative examples are given of what can go wrong when unintended bias or unfairness in algorithmic development occurs. The importance of explainability, accountability, and transparency with respect to artificial intelligence algorithm development and clinical deployment is discussed. These are grounded in the concept of "primum no nocere" (first, do no harm). Steps to mitigate unfairness and bias in task definition, data collection, model definition, training, testing, deployment, and feedback are provided. Discussions on the implementation of fairness criteria that maximize benefit and minimize unfairness and harm to neuroradiology patients will be provided, including suggestions for neuroradiologists to consider as artificial intelligence algorithms gain acceptance into neuroradiology practice and become incorporated into routine clinical workflow.

Medial temporal lobe functional connectivity predicts stimulation-induced theta power.

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended to decrease power in the high-frequency broadband (HFB; 50-200 Hz) range, and these modulations were correlated with HFB-based networks in a subset of subjects. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, capturing evoked activity across brain regions and frequency bands.

Widespread theta synchrony and high-frequency desynchronization underlies enhanced cognition.

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region's gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.

The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells.

BACKGROUND AND OBJECTIVE: Angiogenesis plays a crucial role in early wound healing and tissue regeneration. Although enamel matrix derivative (EMD) has demonstrated the potential to stimulate periodontal regeneration, the biological effects of EMD on angiogenesis and underlying mechanisms have not been fully elucidated. The aim of the present study was to examine the angiogenic effects of EMD in vitro. MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVECs) were used to assess the effect of EMD on proliferation, survival, adhesion and migration. The effect of EMD on HUVEC angiogenesis was assessed by a three-dimensional sprouting assay. In order to understand the signalling mechanism of altered cell proliferation of HUVECs caused by EMD, the phosphorylation status of ERK1/2 and of the serine/threonine protein kinase Akt was analysed by western blot using phospho-specific antibodies. RESULTS: The proliferation of HUVECs was stimulated by 50 µg/mL EMD, whereas higher concentrations (≥100 µg/mL) resulted in an increased apoptotic rate. The mitogenic response to EMD was associated with the activation of ERK1/2. Enamel matrix derivative did not affect cell adhesion, but all concentrations of EMD tested (0.1-250 µg/mL) promoted migration of HUVECs. Furthermore, EMD induced capillary-like sprout formation from HUVEC spheroids in a dose-dependent manner. CONCLUSION: Our data indicate that EMD acts as a proangiogenic factor in vitro and, as such, might contribute to periodontal tissue regeneration by stimulation of vessel formation during wound healing.

Development of Weather-Based Predictive Models for Fusarium Head Blight and Deoxynivalenol Accumulation for Spring Malting Barley.

The associations between Fusarium head blight (FHB), caused by Gibberella zeae, and deoxynivalenol (DON) accumulation in spring malting barley (Hordeum vulgare) and hourly weather conditions predictive of DON accumulation were examined using data from six growing seasons in the U.S. Northern Great Plains. Three commonly grown cultivars were planted throughout the region, and FHB disease and DON concentration were recorded. Nine predictor variables were calculated using hourly temperature and relative humidity during the 10 days preceding full head spike emergence. Simple logistic regression models were developed using these predictor variables based on a binary threshold for DON of 0.5 mg/kg. Four of the nine models had sensitivity greater than 80%, and specificity of these models ranged from 67 to 84% (n = 150). The most useful predictor was the joint effect of average hourly temperature and a weighted duration of uninterrupted hours (h) with relative humidity greater than or equal to 90%. The results of this study confirm that FHB incidence is significantly associated with DON accumulation in the grain and that weather conditions prior to full head emergence could be used to accurately predict the risk of economically significant DON accumulation for spring malting barley.

The del/del genotype of the nuclear factor-kappaB -94ATTG polymorphism and its relation to aggressive periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is influenced by specific host-dependent immune responses. Periodontopathogens induce innate immune responses, amongst others, via toll-like receptor 2 (TLR2), resulting in activation of the nuclear transcription factor nuclear factor-kappaB (NF-kappaB). The aim of this case-control study was to evaluate links between genetic variants of these genes and chronic/aggressive periodontitis in a multivariate model. MATERIAL AND METHODS: A total of 141 patients with periodontitis (63 with chronic periodontitis and 78 with aggressive periodontitis) and 81 controls without periodontitis were included in the study. Polymorphisms in TLR2 (Arg677Trp, Arg753Gln) and in NF-kappaB (-94ins/delATTG) were determined by restriction fragment length polymorphism and fragment length analyses, respectively. Subgingival bacterial colonization was evaluated using a PCR/DNA probe test (micro-Ident). RESULTS: Although there was no association of the TLR2 polymorphism Arg753Gln with periodontitis, heterozygous carriers (Arg/Gln) were at a higher risk for colonization with bacteria of the 'red complex' (corrected p-value = 0.042). The del/del genotype of the NF-kappaB polymorphism was associated with aggressive periodontitis considering age, gender, smoking and approximal plaque index as potential confounders (odds ratio = 2.81, p = 0.035, 95% confidence interval: 1.08-7.33). del/del carriers had a higher risk for subgingival colonization with Aggregatibacter actinomycetemcomitans (odds ratio = 2.36, p = 0.030, 95% confidence interval: 1.09-5.1; adjusted for age, gender, smoking and pocket depth(bacteria)). CONCLUSIONS: The del/del genotype of NF-kappaB was shown to be associated with the occurrence of aggressive periodontitis.

Genotypic interaction and gender specificity of common genetic variants in the p53/mdm2 network in Crohn's disease.

BACKGROUND/AIMS: Defective p53-mediated apoptosis and cell cycle control have been implicated in the immunopathogenesis of Crohn's disease (CD). Since common functional variants of p53 (SNP72 G/C) and its key negative regulator mdm2 (SNP309 T/G) have been reported to affect cellular apoptotic and cell cycle arrest capacities, we assessed the effects of these variants on CD susceptibility and their relationship to NOD2/CARD15 as a well-established genetic CD risk factor. METHODS: The variants SNP72 G/C and SNP309 T/G were genotyped in 149 European CD patients and 478 healthy controls. Subgroup analysis was performed in relation to NOD2/CARD15 status and to demographic/clinical characteristics. RESULTS: The p53 SNP72 CC genotype tended to be less frequent in CD. This reached statistical significance only in the male cohort (0 vs. 7.3%; p = 0.037). Genotype and allele frequencies of both single-nucleotide polymorphisms (SNPs) were otherwise not significantly different. In the combined genotypic analysis, the genotype p53 SNP72 CC was significantly underrepresented in mdm2 SNP309 TT homozygotes (0 vs. 9.7%; p = 0.034). No association was observed between NOD2/CARD15 and the respective SNPs. CONCLUSION: We report on a gender-specific protective effect of the low-apoptotic SNP72 CC genotype, and a gender-unrestricted genotypic interaction between SNP309 TT and SNP72 CC, which, for the first time, links sequence variation of the p53/mdm2 network to CD, independent of NOD2/CARD15.

Mass effect in the thoracic spine from remnant bone wax: an MR imaging pitfall.

Bone wax used in neurosurgical procedures is a rare cause of complications after surgery. We present a patient who developed paraplegia following thoracic spine surgery. A subsequent MR imaging study demonstrated a signal void that resembled postoperative air but appeared to cause cord compression and proved after a second surgery to represent bone wax. Recognizing the MR imaging and CT characteristics of bone wax is important to prevent mistaking it for residual air in postoperative imaging.

[Are there gender-related differences in the therapeutic management of patients suffering from inflammatory bowel disease? Subgroup analysis of a prospective multicentre online-based trial]. / Gibt es geschlechtsspezifische Behandlungsunterschiede bei Patienten mit chronisch entzündlichen Darmerkrankungen? Eine Subgruppenanalyse einer prospektiven, multizentrischen, online-basierten Studie.

INTRODUCTION: The most frequently prescribed medications for patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region of Germany are aminosalicylates and corticosteroids irrespective of the disease activity. In contrast, immunomodulators only play a marginal role. As anti-TNF therapy is very costly, it is prescribed in outpatient services of hospitals rather than in gastroenterological practices. AIM: The aim of this study was to evaluate possible gender-related differences in the therapeutic management of IBD patients treated in the Rhein-Main region of Germany. METHODS: Data records about past medical history, disease status, laboratory values and medical treatment of outpatients of 10 gastroenterological practices and 3 hospitals were collected from November 1st 2005 to July 31st 2007 and analysed with regard to gender-related differences in therapy and disease management. RESULTS: Overall, no statistically significant difference in gender-specific medical treatment could be observed in the study cohort. However, detailed analyses revealed, that 1. women suffering from IBD, who are treated in outpatient services of hospitals, are more often under immunosuppressants, irrespective of disease activity, 2. in gastroenterological practices less than 3 % of patients are prescribed any immunosuppressive therapy (vs. 17 % [men] und 42 % [women] in hospital outpatient services), and 3. anti-TNF therapy is applied more frequently in men as compared to women in hospital outpatient services in both remission and active disease. CONCLUSION: This study discloses the gender-specific differences in the therapeutic management of IBD patients in a congested urban area in Germany. Further studies are required to confirm the tendencies detected.

Fusarium head blight severity and deoxynivalenol concentration in wheat in response to Gibberella zeae inoculum concentration.

The relationship between inoculum dose and resulting disease levels and deoxynivalenol (DON) accumulation in the Fusarium head blight (FHB) of wheat pathosystem was examined under controlled conditions. Greenhouse-grown spring wheat plants were inoculated at flowering with suspensions that varied in Gibberella zeae macroconidia concentration. The spikes were bagged for 72 h to promote infection and plants were then kept under ambient greenhouse conditions and disease allowed to develop. Spikes were rated at 15 days after inoculation for disease incidence and severity, removed from the greenhouse, and dried. DON concentration was determined in grain-only and whole-spike samples for each inoculation treatment. Regression analysis was used to evaluate the mathematical relationship between inoculum dose and the (i) disease metrics or (ii) DON concentration. Both disease incidence and severity were found to increase sharply in relation to inoculum concentration until an asymptote was reached. In both instances, a negative exponential function was found to best explain this relationship. By contrast, DON concentration in both grain-only and whole-spike tissues increased with additional inoculum. These relationships were best explained with linear functions for both sample types, although DON accumulation increased at a greater rate in whole-spike tissue. The functions were evaluated further using data collected from unrelated field studies and, although not particularly consistent, provided reasonably accurate predictions in growing seasons when the environment was only moderately favorable for FHB.

Family-based mapping of quantitative trait loci in plant breeding populations with resistance to Fusarium head blight in wheat as an illustration.

Traditional quantitative trait loci (QTL) mapping approaches are typically based on early or advanced generation analysis of bi-parental populations. A limitation associated with this methodology is the fact that mapping populations rarely give rise to new cultivars. Additionally, markers linked to the QTL of interest are often not immediately available for use in breeding and they may not be useful within diverse genetic backgrounds. Use of breeding populations for simultaneous QTL mapping, marker validation, marker assisted selection (MAS), and cultivar release has recently caught the attention of plant breeders to circumvent the weaknesses of conventional QTL mapping. The first objective of this study was to test the feasibility of using family-pedigree based QTL mapping techniques generally used with humans and animals within plant breeding populations (PBPs). The second objective was to evaluate two methods (linkage and association) to detect marker-QTL associations. The techniques described in this study were applied to map the well characterized QTL, Fhb1 for Fusarium head blight resistance in wheat (Triticum aestivum L.). The experimental populations consisted of 82 families and 793 individuals. The QTL was mapped using both linkage (variance component and pedigree-wide regression) and association (using quantitative transmission disequilibrium test, QTDT) approaches developed for extended family-pedigrees. Each approach successfully identified the known QTL location with a high probability value. Markers linked to the QTL explained 40-50% of the phenotypic variation. These results show the usefulness of a human genetics approach to detect QTL in PBPs and subsequent use in MAS.

[Pathophysiological-based diagnosis and therapy of iron-deficient anaemia in inflammatory bowel disease]. / Pathophysiologisch-orientierte Diagnostik und Therapie der Eisenmangelanämie bei chronisch entzündlichen Darmerkrankungen.

Anaemia is the most frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A disabling complication of IBD, anaemia worsens the patient's general condition and quality of life, and increases hospitalization rates. The main types of anemia in IBD are iron deficiency anemia and anemia of chronic disease. The combination of the serum transferrin receptor with ferritin concentrations and inflammatory markers allows a reliable assessment of the iron status. Iron deficiency is usually treated with oral iron supplements. However, it is less effective in IBD and may lead to an increased inflammatory activity through the generation of reactive oxygen species. A systematic review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on the evidence from recent studies will be the focus of this article.

Developmental etiology for neuroanatomical and cognitive deficits in mice overexpressing Galphas, a G-protein subunit genetically linked to schizophrenia.

Schizophrenia is a widespread psychiatric disorder, affecting 1% of people. Despite this high prevalence, schizophrenia is not well treated because of its enigmatic developmental origin. We explore here the developmental etiology of endophenotypes associated with schizophrenia using a regulated transgenic approach in mice. Recently, a polymorphism that increases mRNA levels of the G-protein subunit Galphas was genetically linked to schizophrenia. Here we show that regulated overexpression of Galphas mRNA in forebrain neurons of mice is sufficient to cause a number of schizophrenia-related phenotypes, as measured in adult mice, including sensorimotor gating deficits (prepulse inhibition of acoustic startle, PPI) that are reversed by haloperidol or the phosphodiesterase inhibitor rolipram, psychomotor agitation (hyperlocomotion), hippocampus-dependent learning and memory retrieval impairments (hidden water maze, contextual fear conditioning), and enlarged ventricles. Interestingly, overexpression of Galphas during development plays a significant role in some (PPI, spatial learning and memory and neuroanatomical deficits) but not all of these adulthood phenotypes. Pharmacological and biochemical studies suggest the Galphas-induced behavioral deficits correlate with compensatory decreases in hippocampal and cortical cyclic AMP (cAMP) levels. These decreases in cAMP may lead to reduced activation of the guanine exchange factor Epac (also known as RapGEF 3/4) as stimulation of Epac with the select agonist 8-pCPT-2'-O-Me-cAMP increases PPI and improves memory in C57BL/6J mice. Thus, we suggest that the developmental impact of a given biochemical insult, such as increased Galphas expression, is phenotype specific and that Epac may prove to be a novel therapeutic target for the treatment of both developmentally regulated and non-developmentally regulated symptoms associated with schizophrenia.

[Nutritional factors and nutritional therapy for irritable bowel syndrome--what is worthwhile?]. / Ernährungsfaktoren und Ernährungstherapie beim Reizdarmsyndrom - was ist valide?

The prevalence of irritable bowel syndrome (IBS) has increased over the last 50 years in countries where a Western-style diet has been prominent or introduced and 20 - 65 % of patients with irritable bowel syndrome (IBS) attribute their symptoms to something in food that activates an abnormal response. However, data from dietary elimination and re-challenge studies are inconclusive. Although investigations have shown that bran may be helpful in some patients, a complete review of the literature does not reveal conclusive evidence that a high fibre diet therapy is effective in IBS. From the limited reports on probiotics, there appears to be a trend to decreasing symptoms. Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dietary experts may have a positive role in managing such patients. It is clear that much more prospective research is needed to study both dietary factors and probiotics in these areas.

Distribution and Recovery of Tilletia indica Teliospores from Regulated Wheat Fields in Texas.

Eight wheat fields from the Karnal bunt-regulated regions within Texas were grid sampled to gain a better understanding of the ecology and epidemiology of teliospores produced by the causal agent, Tilletia indica. Teliospores from 25-g aliquots of soil from each grid point were extracted using a size-selective sieving sucrose-centrifugation procedure. Teliospores were recovered from all eight fields and, in some cases, from every grid point within a field. Total teliospore numbers ranged from 0 to 1,305 per 25 g of soil. Over 70% of the total grid sampled points contained one or more teliospores. The relation between soil chemical and physical characteristics and teliospore numbers from each field was evaluated. In general, no consistent, significant trend could be made between soil factors and teliospore numbers. Geostatistics were used to analyze data from grid points and create contour maps. Teliospore distribution was aggregated in four of the fields, random in three of the fields, and discontinuous (neither random nor aggregated) in a single field. This is the first report of widespread distribution and high teliospore numbers from wheat field soils in the United States.

[Bacterial overgrowth syndrome]. / Bakterielle Fehlbesiedlung des Dünndarms.

Small bowel bacterial overgrowth is a syndrome caused by an abnormal number of bacteria in the upper part of the small bowel and associated with a complex array of clinical symptoms, i. e., chronic diarrhoea, steatorrhoea, macrocytic anaemia, weight loss, and less commonly, protein-losing enteropathy. The most common underlying factors are small intestinal stagnation or dysmotility, intestinal obstruction, blind or afferent loops, and decreased gastric secretion. The treatment usually consists in the eradication of bacterial overgrowth with repeated courses of antimicrobials, correction of associated nutritional deficiencies and, when possible, correction of the underlying predisposing conditions.

Epidemiology of Tilletia indica Teliospores in Regulated Wheat Fields in Texas.

To examine the epidemiology of Tilletia indica teliospores in naturally infested soils from wheat fields in both Karnal bunt-regulated regions in Texas, soil was grid sampled from fields that were bunted-kernel positive for Karnal bunt in 1997, 2001, both years, or never. Aliquots of soil from each point were pooled, and teliospores were extracted using a size-selective sieving-sucrose centrifugation method. Teliospores were enumerated microscopically, and low quantities (< 8 per 25 g of soil) were identified in 14 of 15 fields sampled from the regulated regions of Texas, including fields that have never tested positive for bunted kernels, indicating a widespread distribution. No teliospores were isolated from the single field examined outside of the regulated regions. The percent clay was significantly, negatively correlated with the baseline teliospore number and the estimated (extrapolated) number of teliospores per sample, indicating a potential impact of soil composition on teliospore survival. The latter factor was also significantly, positively correlated to the number of times a field had tested positive.

The Generation and Quantification of Resistance to Dimethomorph in Phytophthora infestans.

The generation of dimethomorph resistance in Phytophthora infestans was attempted using ethidium bromide/UV light mutagenesis and repeated culturing on dimethomorph-amended medium. Ethidium bromide/UV mutagenesis created two isolates of P. infestans with resistance factors for dimethomorph >20, i.e., the ratio of the 50% effective concentration (EC50) of the mutant to that of the wild-type. With repeated culturing on dimethomorph-amended medium, the rate of growth (mm diameter/day) increased until the tenth subculture for most P. infestans isolates. Resistance factors generated from repeated culturing were <8 for all isolates. For most isolates, the generation of dimethomorph resistance resulted in reduced growth rates on nonamended medium, regardless of the level of resistance or induction treatment. Additionally, the frequency of infection of leaf disks and whole tubers was significantly reduced in >20% of the isolates repeatedly subcultured on dimethomorph-amended medium. Regardless of the induction treatment, reduced fitness was common for all P. infestans isolates, indicating a potential biological cost associated with dimethomorph resistance. Based on these results, the development of field resistance to dimethomorph in P. infestans is unlikely with the currently employed resistance management strategies.