GAN-based multiple adjacent brain MRI slice reconstruction for unsupervised alzheimer’s disease diagnosis

Unsupervised learning can discover various unseen diseases, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's Disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with disease stages. Therefore, we propose a two-step method using Generative Adversarial Network-based multiple adjacent brain MRI slice reconstruction to detect AD at various stages: (Reconstruction) Wasserstein loss with Gradient Penalty + L1 loss---trained on 3 healthy slices to reconstruct the next 3 ones---reconstructs unseen healthy/AD cases; (Diagnosis) Average/Maximum loss (e.g., L2 loss) per scan discriminates them, comparing the reconstructed/ground truth images. The results show that we can reliably detect AD at a very early stage with Area Under the Curve (AUC) 0.780 while also detecting AD at a late stage much more accurately with AUC 0.917; since our method is fully unsupervised, it should also discover and alert any anomalies including rare disease.Comment: 10 pages, 4 figures, Accepted to Lecture Notes in Bioinformatics (LNBI) as a volume in the Springer serie

Why do we treat adolescent idiopathic scoliosis? What we want to obtain and to avoid for our patients. SOSORT 2005 Consensus paper

BACKGROUND: Medicine is a scientific art: once science is not clear, choices are made according to individual and collective beliefs that should be better understood. This is particularly true in a field like adolescent idiopathic scoliosis, where currently does not exist definitive scientific evidence on the efficacy either of conservative or of surgical treatments. AIM OF THE STUDY: To verify the philosophical choices on the final outcome of a group of people believing and engaged in a conservative treatment of idiopathic scoliosis. METHODS: We performed a multifaceted study that included a bibliometric analysis, a questionnaire, and a careful Consensus reaching procedure between experts in the conservative treatment of scoliosis (SOSORT members). RESULTS: The Consensus reaching procedure has shown to be useful: answers changed in a statistically significant way, and 9 new outcome criteria were included. The most important final outcomes were considered Aesthetics (100%), Quality of life and Disability (more than 90%), while more than 80% of preferences went to Back Pain, Psychological well-being, Progression in adulthood, Breathing function, Scoliosis Cobb degrees (radiographic lateral flexion), Needs of further treatments in adulthood. DISCUSSION: In the literature prevail outcome criteria driven by the contingent treatment needs or the possibility to have measurement systems (even if it seems that usual clinical and radiographic methods are given much more importance than more complex Disability or Quality of Life instruments). SOSORT members give importance to a wide range of outcome criteria, in which clinical and radiographic issues have the lowest importance. CONCLUSION: We treat our patients for what they need for their future (Breathing function, Needs of further treatments in adulthood, Progression in adulthood), and their present too (Aesthetics, Disability, Quality of life). Technical matters, such as rib hump or radiographic lateral alignment and rotation, but not lateral flexion, are secondary outcomes and only instrumental to previously reported primary outcomes. We advocate a multidimensional, comprehensive evaluation of scoliosis patients, to gather all necessary data for a complete therapeutic approach, that goes beyond x-rays to reach the person and the family

The relation between neuromechanical parameters and Ashworth score in stroke patients

Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin

Chlamydia trachomatis Incidence and Re-Infection among Young Women – Behavioural and Microbiological Characteristics

This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women.1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR.There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01).Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia

Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We # hypothesised that these ‘‘resistant smokers’’ may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the ‘‘resistant smokers’’ and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.3461024) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10(-6)) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases

Transmission in Heteronymous Spinal Pathways Is Modified after Stroke and Related to Motor Incoordination

Changes in reflex spinal pathways after stroke have been shown to affect motor activity in agonist and antagonist muscles acting at the same joint. However, only a few studies have evaluated the heteronymous reflex pathways modulating motoneuronal activity at different joints. This study investigates whether there are changes in the spinal facilitatory and inhibitory pathways linking knee to ankle extensors and if such changes may be related to motor deficits after stroke. The early facilitation and later inhibition of soleus H reflex evoked by the stimulation of femoral nerve at 2 times the motor threshold of the quadriceps were assessed in 15 healthy participants and on the paretic and the non-paretic sides of 15 stroke participants. The relationships between this reflex modulation and the levels of motor recovery, coordination and spasticity were then studied. Results show a significant (Mann-Whitney U; P<0.05) increase in both the peak amplitude (mean±SEM: 80±22% enhancement of the control H reflex) and duration (4.2±0.5 ms) of the facilitation on the paretic side of the stroke individuals compared to their non-paretic side (36±6% and 2.9±0.4 ms) and to the values of the control subjects (33±4% and 2.8±0.4 ms, respectively). Moreover, the later strong inhibition observed in all control subjects was decreased in the stroke subjects. Both the peak amplitude and the duration of the increased facilitation were inversely correlated (Spearman r = −0.65; P = 0.009 and r = −0.67; P = 0.007, respectively) with the level of coordination (LEMOCOT) of the paretic leg. Duration of this facilitation was also correlated (r = −0.58, P = 0.024) with the level of motor recovery (CMSA). These results confirm changes in transmission in heteronymous spinal pathways that are related to motor deficits after stroke

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale