The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.     

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

Online learning and fusion of orientation appearance models for robust rigid object tracking

We introduce a robust framework for learning and fusing of orientation appearance models based on both texture and depth information for rigid object tracking. Our framework fuses data obtained from a standard visual camera and dense depth maps obtained by low-cost consumer depth cameras such as the Kinect. To combine these two completely different modalities, we propose to use features that do not depend on the data representation: angles. More specifically, our framework combines image gradient orientations as extracted from intensity images with the directions of surface normals computed from dense depth fields. We propose to capture the correlations between the obtained orientation appearance models using a fusion approach motivated by the original Active Appearance Models (AAMs). To incorporate these features in a learning framework, we use a robust kernel based on the Euler representation of angles which does not require off-line training, and can be efficiently implemented online. The robustness of learning from orientation appearance models is presented both theoretically and experimentally in this work. This kernel enables us to cope with gross measurement errors, missing data as well as other typical problems such as illumination changes and occlusions. By combining the proposed models with a particle filter, the proposed framework was used for performing 2D plus 3D rigid object tracking, achieving robust performance in very difficult tracking scenarios including extreme pose variations.     

A Review of Element-Based Galerkin Methods for Numerical Weather Prediction: Finite Elements,Spectral Elements,and Discontinuous Galerkin

Numerical weather prediction (NWP) is in a period of transition. As resolutions increase, global models are moving towards fully nonhydrostatic dynamical cores, with the local and global models using the same governing equations; therefore we have reached a point where it will be necessary to use a single model for both applications. The new dynamical cores at the heart of these unified models are designed to scale efficiently on clusters with hundreds of thousands or even millions of CPU cores and GPUs. Operational and research NWP codes currently use a wide range of numerical methods: finite differences, spectral transform, finite volumes and, increasingly, finite/spectral elements and discontinuous Galerkin, which constitute element-based Galerkin (EBG) methods. Due to their important role in this transition, will EBGs be the dominant power behind NWP in the next 10 years, or will they just be one of many methods to choose from? One decade after the review of numerical methods for atmospheric modeling by Steppeler et al. (Meteorol Atmos Phys 82:287–301, 2003), this review discusses EBG methods as a viable numerical approach for the next-generation NWP models. One well-known weakness of EBG methods is the generation of unphysical oscillations in advection-dominated flows; special attention is hence devoted to dissipation-based stabilization methods. Since EBGs are geometrically flexible and allow both conforming and non-conforming meshes, as well as grid adaptivity, this review is concluded with a short overview of how mesh generation and dynamic mesh refinement are becoming as important for atmospheric modeling as they have been for engineering applications for many years.     

An alternative specification of generalized linear mixed models

Consider stratified data in which Y_i1,…,Y_ini denote real-valued response variables corresponding to the observations from stratum i, i=1,…,m and suppose that Y_ij follows an exponential family distribution with canonical parameter of the form θ_ij=x_ijβ+γ_i. In analyzing data of this type, the stratum-specific parameters are often modeled as random effects; a commonly-used approach is to assume that γ₁,…,γ_m are independent, identically distributed random variables.The purpose of this paper is to consider an alternative approach to defining the random effects, in which the stratum means of the response variable are assumed to be independent and identically distributed, with a distribution not depending on β. It will be shown that inferences about β based on this formulation of the generalized linear mixed model have many desirable properties. For instance, inferences regarding β are less sensitive to the choice of random effects distribution, are less subject to bias from omitted stratum-level covariates and are less affected by separate between- and within-cluster covariate effects.     

National occupational research agenda (NORA) future directions in occupational musculoskeletal disorder health research

Musculoskeletal disorders are among the most costly health care problems facing society today. The scientific literature has indicated that psychosocial factors, individual factors, workplace physical requirements, and workplace organizational factors have been associated with risk. Since musculoskeletal risk is multi-dimensional, the magnitude of risk attributable to various factors can be of importance to scientists and policy makers in designing countermeasures to reduce injury incidence. Traditionally, the disciplines of biomechanics, physiology, and psychophysics have dominated the body of knowledge that has defined exposure limitations to work. However, recent research has explored the association of psychosocial and work organization factors with musculoskeletal problems. Advances have been made to better quantify the levels of occupational exposure by improved exposure metrics, quantification of three-dimensional loads experienced by certain joints (e.g. the spine), identification of tissue tolerance limits and tissue response to mechanical stresses, and the impact of psychosocial stresses. However, efforts to quantitatively link epidemiological, biomechanical loading, soft tissue tolerance, and psychosocial studies should be pursued to establish a better understanding of the pathways of injury and resultant preventive strategies. Although we are beginning to understand how the major risk factors influence the load-tolerance relationship of human tissue, how these risk factors interact is virtually unexplored. Since the impact of the interactions may be far greater than that of any individual factor, the impact of the interactions between risk factors must be delineated so that work-related risk can be better quantified. Efforts to quantitatively link epidemiological, biomechanical loading, soft tissue tolerance, and psychosocial studies should be pursued to establish a better understanding of the pathways of injury and resultant preventive strategies.     

The effect of phone design on upper extremity discomfort and muscle fatigue

OBJECTIVE: To compare a small cellular clamshell phone with a traditional office phone in the development of discomfort and muscle fatigue over time during phone use. BACKGROUND: Phone use involves low-level static exertions that may be influenced by phone design. Phone design and its interactions with anthropometry may change shoulder and hand postures assumed during use, which in turn may modify the length-strength relationship and moment arms of the muscles. METHOD: Ten adults participated in a study that simulated phone use using a small clamshell and a traditional office phone. Discomfort information and electromyographic (EMG) muscle activity were monitored on four upper extremity muscles. Discomfort and fatigue data (EMG median frequency shifts) were analyzed to assess differences between phones as well as differing effects attributable to anthropometry. RESULTS: Median frequency shifts supported discomfort claims and indicated muscle fatigue in the deltoid and thenar muscles. Biomechanical measures demonstrated that participants with short limb lengths developed more severe signs of thenar fatigue. Participants with longer arms developed greater discomfort in the neck, shoulder, and back. The deltoid confirmed this occurrence, showing signs of muscle fatigue. CONCLUSION: Phone design and anthropometry influenced the development of discomfort and fatigue during phone use. Phone design dictated grip style, resulting in differing discomfort and fatigue levels. Anthropometry influenced the severity of the discomfort and fatigue present in the shoulder and hand. APPLICATION: Use of small clamshell phones may contribute to a lack of rest and recovery from typical workday exposures. It should be explored from an ergonomic perspective.     

The influence of lift frequency, lift duration and work experience on discomfort reporting

Discomfort surveys are commonly used to assess risk in the workplace and prioritize jobs for interventions before an injury or illness occurs. However, discomfort is a subjective measure and the relationship of discomfort to work-related factors is poorly understood. The objective of this study was to understand how reports of discomfort relate to work-related risk factors for the low back. A total of 12 novice and 12 experienced manual materials handlers performed repetitive, asymmetric lifts at different load levels and at six different lift frequencies throughout an 8-h exposure period. Discomfort was recorded hourly throughout the day. Analyses were performed to determine which experimental factors influenced reporting of discomfort and if discomfort trends matched spine loading trends. Novice lifters reported significantly higher discomfort levels than experienced subjects. They also reported increases in discomfort as moment exposure increased and as the exposure time increased. Novices lifting at 8 Nm load moment level reported increased discomfort from 0.07 to 0.63 by the end of the day, at 36 Nm they reported an increase from 0.04 to 0.40 and at 85 Nm they reported an increase from 0.37 to 3.06. Experienced subjects, on the other hand, reported low levels of discomfort regardless of moment exposure, lift frequency or exposure duration. The reported discomforts were generally unrelated to the biomechanical loading on the spine. Discomfort reporting appears to be more a reflection of experience than of work risk factor exposure. Experienced subjects may have more efficient motor patterns, which reduce spinal load and thus discomfort. Novice subjects seemed to have a lower threshold of discomfort. Caution is needed when using discomfort reporting as a means to identify jobs in need of interventions, in that biomechanical loading may not be accurately represented. Discomfort should only be used as a supplement to objective measures, such as spinal loading, to assess the risk of low back disorders.     

Musculoskeletal disorder risk during automotive assembly: current vs. seated

Musculoskeletal disorder risk was assessed during automotive assembly processes. The risk associated with current assembly processes was compared to using a cantilever chair intervention. Spine loads and normalized shoulder muscle activity were evaluated during assembly in eight regions of the vehicle. Eight interior cabin regions of the vehicle were classified by reach distance, height from vehicle floor and front to back. The cantilever chair intervention tool was most effective in the far reach regions regardless of the height. In the front far reach regions both spine loads and normalized shoulder muscle activity levels were reduced. In the middle and close reach regions spine loads were reduced, however, shoulder muscle activity was not, thus an additional intervention would be necessary to reduce shoulder risk. In the back far reach region, spine loads were not significantly different between the current and cantilever chair conditions. Thus, the effectiveness of the cantilever chair was dependent on the region of the vehicle.