Ranking and filtering of neuropathology features in the machine learning evaluation of dementia studies.

Early diagnosis of dementia diseases, such as Alzheimer's disease, is difficult because of the time and resources needed to perform neuropsychological and pathological assessments. Given the increasing use of machine learning methods to evaluate neuropathology features in the brains of dementia patients, it is important to investigate how the selection of features may be impacted and which features are most important for the classification of dementia. We objectively assessed neuropathology features using machine learning techniques for filtering features in two independent ageing cohorts, the Cognitive Function and Aging Studies (CFAS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). The reliefF and least loss methods were most consistent with their rankings between ADNI and CFAS; however, reliefF was most biassed by feature-feature correlations. Braak stage was consistently the highest ranked feature and its ranking was not correlated with other features, highlighting its unique importance. Using a smaller set of highly ranked features, rather than all features, can achieve a similar or better dementia classification performance in CFAS (60%-70% accuracy with Naïve Bayes). This study showed that specific neuropathology features can be prioritised by feature filtering methods, but they are impacted by feature-feature correlations and their results can vary between cohort studies. By understanding these biases, we can reduce discrepancies in feature ranking and identify a minimal set of features needed for accurate classification of dementia.

Unsupervised machine learning to investigate trajectory patterns of COVID-19 symptoms and physical activity measured via the MyHeart Counts App and smart devices.

Previous studies have associated COVID-19 symptoms severity with levels of physical activity. We therefore investigated longitudinal trajectories of COVID-19 symptoms in a cohort of healthcare workers (HCWs) with non-hospitalised COVID-19 and their real-world physical activity. 121 HCWs with a history of COVID-19 infection who had symptoms monitored through at least two research clinic visits, and via smartphone were examined. HCWs with a compatible smartphone were provided with an Apple Watch Series 4 and were asked to install the MyHeart Counts Study App to collect COVID-19 symptom data and multiple physical activity parameters. Unsupervised classification analysis of symptoms identified two trajectory patterns of long and short symptom duration. The prevalence for longitudinal persistence of any COVID-19 symptom was 36% with fatigue and loss of smell being the two most prevalent individual symptom trajectories (24.8% and 21.5%, respectively). 8 physical activity features obtained via the MyHeart Counts App identified two groups of trajectories for high and low activity. Of these 8 parameters only 'distance moved walking or running' was associated with COVID-19 symptom trajectories. We report a high prevalence of long-term symptoms of COVID-19 in a non-hospitalised cohort of HCWs, a method to identify physical activity trends, and investigate their association. These data highlight the importance of tracking symptoms from onset to recovery even in non-hospitalised COVID-19 individuals. The increasing ease in collecting real-world physical activity data non-invasively from wearable devices provides opportunity to investigate the association of physical activity to symptoms of COVID-19 and other cardio-respiratory diseases.

Assessment of Alzheimer-related pathologies of dementia using machine learning feature selection.

Although a variety of brain lesions may contribute to the pathological assessment of dementia, the relationship of these lesions to dementia, how they interact and how to quantify them remains uncertain. Systematically assessing neuropathological measures by their degree of association with dementia may lead to better diagnostic systems and treatment targets. This study aims to apply machine learning approaches to feature selection in order to identify critical features of Alzheimer-related pathologies associated with dementia. We applied machine learning techniques for feature ranking and classification to objectively compare neuropathological features and their relationship to dementia status during life using a cohort (n=186) from the Cognitive Function and Ageing Study (CFAS). We first tested Alzheimer's Disease and tau markers and then other neuropathologies associated with dementia. Seven feature ranking methods using different information criteria consistently ranked 22 out of the 34 neuropathology features for importance to dementia classification. Although highly correlated, Braak neurofibrillary tangle stage, beta-amyloid and cerebral amyloid angiopathy features were ranked the highest. The best-performing dementia classifier using the top eight neuropathological features achieved 79% sensitivity, 69% specificity and 75% precision. However, when assessing all seven classifiers and the 22 ranked features, a substantial proportion (40.4%) of dementia cases was consistently misclassified. These results highlight the benefits of using machine learning to identify critical indices of plaque, tangle and cerebral amyloid angiopathy burdens that may be useful for classifying dementia.

Application of 10% povidone iodine reduces conjunctival bacterial contamination rate in patients undergoing cataract surgery.

PURPOSE: To determine the efficacy of 10% povidone iodine (PVI) drops given before cataract extraction in addition to routine irrigation of the conjunctival sac with 1% PVI. METHODS: This prospective, randomized, single-center study at the Department of Ophthalmology, Ludwig-Maximilians-University, Munich, includes 263 eyes of 242 patients undergoing cataract surgery. Patients were randomized to receive 3 drops of 10% PVI into the conjunctival sac (study group) or no PVI drops (control group). All patients underwent periorbital disinfection with 10% PVI followed by irrigation of the conjunctiva with 10 mL of 1% PVI. Specimens were obtained prior to the application of PVI, after antibiotic administration (T1), after irrigation with PVI but before surgery (T2), and at the conclusion of surgery (T3). RESULTS: After PVI disinfection, the number of positive cultures was significantly reduced in all groups (p<0.0001) from 69%-93% at T1 to 1%-16% at T3. In outpatients, the study group showed significantly fewer positive cultures at the conclusion of surgery compared to the control group (4% vs 16%; p=0.03). Also in inpatients significant fewer positive cultures were found in the study group compared to the control group at T2 (12% vs 28%; p=0.03) and at T3 (1% vs 10%; p=0.03). CONCLUSIONS: Three additional drops of 10% PVI prior to surgery provided additional benefit by reducing the conjunctival bacterial contamination rate even in the setting of preoperative irrigation of the conjunctiva with 1% PVI.

Characterization of CTNS mutations in Arab patients with cystinosis.

BACKGROUND: Cystinosis is an autosomal recessive disease characterized by impaired transport of free cystine out of lysosomes with resulting renal and ophthalmic manifestations. Mutations in CTNS, encoding cystinosin, are the only known cause of this autosomal recessive disorder with more than 85 different mutations described so far. PURPOSE: To identify CTNS mutations in Arab cystinosis patients. METHODS: In this study, we have analyzed the mutational spectrum of CTNS in a population of 21 patients from 13 families of Arab origin. The entire coding region and flanking intronic regions of CTNS were analyzed by direct sequencing. RESULTS: Eight mutations were identified, four of which are novel (c.530A>G, c.681G>A, 1013T>G, and c.1018_1041del). CONCLUSION: These alleles will provide the basis for routine molecular diagnosis of cystinosis in the region.

Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example.

The increased frequency of rare autosomal recessive conditions in genetically isolated populations is a well-established phenomenon. This genetic isolation is invoked as an explanation when one particular mutation is the sole or most frequent mutation observed in a given population and is referred to as the founder effect. This trend of allelic homogeneity is contrasted by an opposite trend when the consanguinity factor is in play. Independent of endogamy at the population level, a consanguineous union is sufficient to render homozygous a percentage of the genome that is directly correlated with the degree of consanguinity. Assuming the gene in question has a normal mutation rate, the resulting homozygosity will inevitably include different defective alleles of that gene. By reporting four novel alleles, we use Alström disease to exemplify the interesting observation of allelic heterogeneity for a very rare autosomal recessive disorder in a highly inbred population. While we frequently assume founder effect in inbred populations, this report should serve to remind us of the powerful effect of the consanguinity factor, a common confounding variable among some of those populations.

Limonoids as larvicidal components against mosquito larvae (Aedes aegypti Linn.).

The study focussed on four limonoids (calodendrolide, harrisonin, pedonin and pyroangolensolide) as larvicidal components against mosquito 2nd instar larvae of the species Aedes aegypti Linn. senso stricto. Since pyroangolensolide is close to calodendrolide in structure, it was synthesized through reduction of calodendrolide with chromium(II) chloride in acetone. Harrisonin and pedonin were extracted with cold methanol from the root bark of Harrisonia abyssinica while calodendrolide was extracted with the same solvent from the root bark of Calodendrum capense. The structure of pyroangolensolide was elucidated using physical and spectroscopic techniques. 25, 50, 75, and 100 microM of each compound were tested against the mosquito larvae. Calodendrolide was the most toxic since 100% mortality was registered at all concentrations, while pyroangolensolide showed 100% mortality up to 50 microM and for contents of 25 microM, a mortality of 70% was registered. As a result of this toxicity, lower concentrations (5, 10 and 15 microM) were tested for both calodendrolide and pyroangolensolide. Toxicity of harrisonin and pedonin was lower. The relative toxicity was in the order: calodendrolide > pyroangolensolide > harrisonin > pedonin with LC50 values of 13.2, 16.6, 28.1 and 59.2 microM, respectively.

Familial blepharophimosis-like syndrome with esotropia, uveal coloboma, and short stature.

BACKGROUND: Interstitial deletion of Hsa 3q involves FOXL2, the gene responsible for blepharophimosis-ptosis-telecanthus-epicanthus inversus (BPES). Thought to be due to a contiguous gene syndrome, the recognizable phenotype of 3q interstitial deletion includes BPES facies and has not been associated with other loci. OBJECTIVE: To describe a familial syndrome that resembles the interstitial deletion of 3q clinically, but does not map to the FOXL2 region. METHODS: Clinical evaluation of family members and linkage analysis. RESULTS: Three affected siblings with a phenotype resembling that seen in 3q interstitial deletion were studied in addition to their clinically unaffected parents. Linkage analysis excluded FOXL2 as underlying the distinct phenotype, observed with > 99% confidence. CONCLUSIONS: The relevant locus in the current family, although remote from FOXL2, is likely important to the FOXL2 functional pathway. The phenotype observed in 3q interstitial deletion may be due to severe disruption of FOXL2 rather than to a contiguous gene syndrome.

Dolasetron versus ondansetron for the treatment of postoperative nausea and vomiting.

The management of postoperative nausea and vomiting (PONV) remains a persistent problem. Despite the use of prophylactic antiemetics, breakthrough nausea and vomiting still frequently occur. There have been no published studies comparing dolasetron and ondansetron for the treatment of PONV. This was a prospective, randomized, double-blind, active-controlled study in adult outpatient surgery patients. We screened 559 consecutive adult surgery patients, with 92 patients randomized to either ondansetron or dolasetron. The objectives of the study were 1) to determine whether treatment of PONV with ondansetron 4 mg IV or dolasetron 12.5 mg IV would result in better outcomes in patients undergoing day surgery and 2) to compare the cost of drugs used for treating PONV. Thirty-three (70%) of 47 patients given ondansetron required rescue medication, compared with 18 (40%) of 45 patients given dolasetron (P < 0.004). Dolasetron was approximately 40% less expensive than ondansetron, and the costs of the study drug plus rescue antiemetics were 30% less in the dolasetron group than in the ondansetron group. Dolasetron provided greater efficacy for antiemetic treatment because of the need for less rescue therapy. Because of the decreased use of rescue antiemetics and acquisition cost at our hospital, costs in the dolasetron group were less than costs in the ondansetron group.