Truncated Inference for Latent Variable Optimization Problems: Application to Robust Estimation and Learning

Optimization problems with an auxiliary latent variable structure in addition to the main model parameters occur frequently in computer vision and machine learning. The additional latent variables make the underlying optimization task expensive, either in terms of memory (by maintaining the latent variables), or in terms of runtime (repeated exact inference of latent variables). We aim to remove the need to maintain the latent variables and propose two formally justified methods, that dynamically adapt the required accuracy of latent variable inference. These methods have applications in large scale robust estimation and in learning energy-based models from labeled data.Comment: 16 page

Effect of controlled and uncontrolled cooling rate on motility parameters of cryopreserved ram spermatozoa

<p>Abstract</p> <p>Background</p> <p>Ram spermatozoa are sensitive to extreme changes in temperature during the freeze-thaw process. The degree of damage depends on a combined effect of various factors including freezing temperature. The aim of this study was to determine the effects of two cooling method (controlled-rate and uncontrolled-rate) on pre-freezing and post-thaw sperm motility parameters.</p> <p>Results</p> <p>Ejaculates were collected using the artificial vagina from four Chal rams and three replicates of the ejaculates were diluted with a Tris-based extender and packed in 0.25 ml straws. Then, sample processed according to the two methods. Method 1: straws cooled from 37 to 5°C, at a liner rate of -0.3°C/min in a controlled-rate cooling machine (custom-built) and equilibrated at 5°C for 80 min, then the straws were frozen at rate of -0.3°C/min from 5°C to -10°C and -25°C/min from -10°C to -150°C and plunged into liquid nitrogen for storage. Method 2: straws were transferred to refrigerator and maintained at 5°C for 3 h, then the straws were frozen in liquid nitrogen vapor, 4 cm above the liquid nitrogen for 15 min and plunged into liquid nitrogen. Computer-assisted sperm motility analysis was used to analyze sperm motion characteristics.</p> <p>Conclusions</p> <p>Controlled rate of freezing (Method 1) significantly improve the pre-freezing and post-thaw total and progressive motility compared to uncontrolled rate (Method 2). In specific kinetic parameters, Method 1 gives significantly higher value for VSL and VCL in comparison with Method 2. There are no significant differences between the two methods for VAP and LIN. In conclusion, controlled rate of cooling conferred better cryopreserving ability to ram spermatozoa compared to uncontrolled rate of cooling prior to programmable freezing.</p

Habitual Physical Activity in Mitochondrial Disease

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. = −0.49; 95% CI −0.33, −0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

Applicability of an abbreviated version of the Child-OIDP inventory among primary schoolchildren in Tanzania

Background: There is a need for studies evaluating oral health related quality of life (OHRQoL) of children in developing countries. Aim: to assess the psychometric properties, prevalence and perceived causes of the child version of oral impact on daily performance inventory (Child- OIDP) among school children in two socio-demographically different districts of Tanzania. Socio-behavioral and clinical correlates of children's OHRQoL were also investigated.Method: One thousand six hundred and one children ( mean age 13 yr, 60.5% girls) attending 16 ( urban and rural) primary schools in Kinondoni and Temeke districts completed a survey instrument in face to face interviews and participated in a full mouth clinical examination. The survey instrument was designed to measure a Kiswahili translated and culturally adapted Child-OIDP frequency score, global oral health indicators and socio-demographic factors. Results: The Kiswahili version of the Child- OIDP inventory preserved the overall concept of the original English version and revealed good reliability in terms of Cronbach's alpha coefficient of 0.77 ( Kinondoni: 0.62, Temeke: 0.76). Weighted Kappa scores from a test-retest were 1.0 and 0.8 in Kinondoni and Temeke, respectively. Validity was supported in that the OIDP scores varied systematically and in the expected direction with self-reported oral health measures and socio-behavioral indicators. Confirmatory factor analyses, CFA, confirmed three dimensions identified initially by Principle Component Analysis within the OIDP item pool. A total of 28.6% of the participants had at least one oral impact. The area specific rates for Kinondoni and Temeke were 18.5% and 45.5%. The most frequently reported impacts were problems eating and cleaning teeth, and the most frequently reported cause of impacts were toothache, ulcer in mouth and position of teeth. Conclusion: This study showed that the Kiswahili version of the Child- OIDP was applicable for use among schoolchildren in Tanzania

Lateralization in the Invertebrate Brain: Left-Right Asymmetry of Olfaction in Bumble Bee, Bombus terrestris

Brain and behavioural lateralization at the population level has been recently hypothesized to have evolved under social selective pressures as a strategy to optimize coordination among asymmetrical individuals. Evidence for this hypothesis have been collected in Hymenoptera: eusocial honey bees showed olfactory lateralization at the population level, whereas solitary mason bees only showed individual-level olfactory lateralization. Here we investigated lateralization of odour detection and learning in the bumble bee, Bombus terrestris L., an annual eusocial species of Hymenoptera. By training bumble bees on the proboscis extension reflex paradigm with only one antenna in use, we provided the very first evidence of asymmetrical performance favouring the right antenna in responding to learned odours in this species. Electroantennographic responses did not reveal significant antennal asymmetries in odour detection, whereas morphological counting of olfactory sensilla showed a predominance in the number of olfactory sensilla trichodea type A in the right antenna. The occurrence of a population level asymmetry in olfactory learning of bumble bee provides new information on the relationship between social behaviour and the evolution of population-level asymmetries in animals

Unstated factors in orthopaedic decision-making: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Total joint replacement (TJR) of the hip or knee for osteoarthritis is among the most common elective surgical procedures. There is some inequity in provision of TJR. How decisions are made about who will have surgery may contribute to disparities in provision. The model of shared decision-making between patients and clinicians is advocated as an ideal by national bodies and guidelines. However, we do not know what happens within orthopaedic practice and whether this reflects the shared model. Our study examined how decisions are made about TJR in orthopaedic consultations.</p> <p>Methods</p> <p>The study used a qualitative research design comprising semi-structured interviews and observations. Participants were recruited from three hospital sites and provided their time free of charge. Seven clinicians involved in decision-making about TJR were approached to take part in the study, and six agreed to do so. Seventy-seven patients due to see these clinicians about TJR were approached to take part and 26 agreed to do so. The patients' outpatient appointments ('consultations') were observed and audio-recorded. Subsequent interviews with patients and clinicians examined decisions that were made at the appointments. Data were analysed using thematic analysis.</p> <p>Results</p> <p>Clinical and lifestyle factors were central components of the decision-making process. In addition, the roles that patients assigned to clinicians were key, as were communication styles. Patients saw clinicians as occupying expert roles and they deferred to clinicians' expertise. There was evidence that patients modified their behaviour within consultations to complement that of clinicians. Clinicians acknowledged the complexity of decision-making and provided descriptions of their own decision-making and communication styles. Patients and clinicians were aware of the use of clinical and lifestyle factors in decision-making and agreed in their description of clinicians' styles. Decisions were usually reached during consultations, but patients and clinicians sometimes said that treatment decisions had been made beforehand. Some patients expressed surprise about the decisions made in their consultations, but this did not necessarily imply dissatisfaction.</p> <p>Conclusions</p> <p>The way in which roles and communication are played out in decision-making for TJR may affect the opportunity for shared decisions. This may contribute to variation in the provision of TJR. Making the importance of these factors explicit and highlighting the existence of patients' 'surprise' about consultation outcomes could empower patients within the decision-making process and enhance communication in orthopaedic consultations.</p

The Complex Genetic Architecture of the Metabolome

Discovering links between the genotype of an organism and its metabolite levels can increase our understanding of metabolism, its controls, and the indirect effects of metabolism on other quantitative traits. Recent technological advances in both DNA sequencing and metabolite profiling allow the use of broad-spectrum, untargeted metabolite profiling to generate phenotypic data for genome-wide association studies that investigate quantitative genetic control of metabolism within species. We conducted a genome-wide association study of natural variation in plant metabolism using the results of untargeted metabolite analyses performed on a collection of wild Arabidopsis thaliana accessions. Testing 327 metabolites against >200,000 single nucleotide polymorphisms identified numerous genotype–metabolite associations distributed non-randomly within the genome. These clusters of genotype–metabolite associations (hotspots) included regions of the A. thaliana genome previously identified as subject to recent strong positive selection (selective sweeps) and regions showing trans-linkage to these putative sweeps, suggesting that these selective forces have impacted genome-wide control of A. thaliana metabolism. Comparing the metabolic variation detected within this collection of wild accessions to a laboratory-derived population of recombinant inbred lines (derived from two of the accessions used in this study) showed that the higher level of genetic variation present within the wild accessions did not correspond to higher variance in metabolic phenotypes, suggesting that evolutionary constraints limit metabolic variation. While a major goal of genome-wide association studies is to develop catalogues of intraspecific variation, the results of multiple independent experiments performed for this study showed that the genotype–metabolite associations identified are sensitive to environmental fluctuations. Thus, studies of intraspecific variation conducted via genome-wide association will require analyses of genotype by environment interaction. Interestingly, the network structure of metabolite linkages was also sensitive to environmental differences, suggesting that key aspects of network architecture are malleable

Colocalization of 14-3-3 Proteins with SOD1 in Lewy Body-Like Hyaline Inclusions in Familial Amyotrophic Lateral Sclerosis Cases and the Animal Model

Background and Purpose: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice. Methods: We examined the postmortem brains and the spinal cords of three FALS cases (A4V SOD1 mutant). Transgenic mice expressing the G93A mutant human SOD1 (mutant SOD1-Tg mice), transgenic mice expressing the wild-type human SOD1 (wild-type SOD1-Tg mice), and non-Tg wild-type mice were also subjected to the immunohistochemical analysis. Results: In all the FALS patients, LBHIs were observed in the cytoplasm of the anterior horn cells, and these inclusions were immunopositive intensely for pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$. In the mutant SOD1-Tg mice, a high degree of immunoreactivity for misfolded SOD1 (C4F6) was observed in the cytoplasm, with an even greater degree of immunoreactivity present in the cytoplasmic aggregates of the anterior horn cells in the lumbar spinal cord. Furthermore, we have found increased 14-3-3$\beta$ and 14-3-3$\gamma$ immunoreactivities in the mutant SOD1-Tg mice. Double immunofluorescent staining showed that C4F6 and 14-3-3 proteins were partially co-localized in the spinal cord with FALS and the mutant SOD1-Tg mice. In comparison, the wild-type SOD1-Tg and non-Tg wild-type mice showed no or faint immunoreactivity for C4F6 and 14-3-3 proteins (pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$) in any neuronal compartments. Discussion: These results suggest that 14-3-3 proteins may be associated with the formation of SOD1-containing inclusions, in FALS patients and the mutant SOD1-Tg mice.Mathematic