Genomic characterization of murine monocytes reveals C/EBPβ transcription factor dependence of Ly6C(-) cells

Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C(+) monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C(-) monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment. Single cell RNA-seq and transplantation experiments confirmed homeostatic default differentiation of Ly6C(+) into Ly6C(-) monocytes. The main two subsets were homogeneous, but linked by a more heterogeneous differentiation intermediate. We show that monocyte differentiation occurred through de novo enhancer establishment and activation of pre-established (poised) enhancers. Generation of Ly6C(-) monocytes involved induction of the transcription factor C/EBP{beta} and C/EBP{beta}-deficient mice lacked Ly6C(-) monocytes. Mechanistically, C/EBP{beta} bound the Nr4a1 promoter and controlled expression of this established monocyte survival factor

Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin

Consequences of Intraspecific Variation in Seed Dispersal for Plant Demography, Communities, Evolution and Global Change

As the single opportunity for plants to move, seed dispersal has an important impact on plant fitness, species distributions and patterns of biodiversity. However, models that predict dynamics such as risk of extinction, range shifts and biodiversity loss tend to rely on the mean value of parameters and rarely incorporate realistic dispersal mechanisms. By focusing on the mean population value, variation among individuals or variability caused by complex spatial and temporal dynamics is ignored. This calls for increased efforts to understand individual variation in dispersal and integrate it more explicitly into population and community models involving dispersal. However, the sources, magnitude and outcomes of intraspecific variation in dispersal are poorly characterized, limiting our understanding of the role of dispersal in mediating the dynamics of communities and their response to global change. In this manuscript, we synthesize recent research that examines the sources of individual variation in dispersal and emphasize its implications for plant fitness, populations and communities. We argue that this intraspecific variation in seed dispersal does not simply add noise to systems, but, in fact, alters dispersal processes and patterns with consequences for demography, communities, evolution and response to anthropogenic changes. We conclude with recommendations for moving this field of research forward

Consequences of Intraspecific Variation in Seed Dispersal for Plant Demography, Communities, Evolution and Global Change

As the single opportunity for plants to move, seed dispersal has an important impact on plant fitness, species distributions and patterns of biodiversity. However, models that predict dynamics such as risk of extinction, range shifts and biodiversity loss tend to rely on the mean value of parameters and rarely incorporate realistic dispersal mechanisms. By focusing on the mean population value, variation among individuals or variability caused by complex spatial and temporal dynamics is ignored. This calls for increased efforts to understand individual variation in dispersal and integrate it more explicitly into population and community models involving dispersal. However, the sources, magnitude and outcomes of intraspecific variation in dispersal are poorly characterized, limiting our understanding of the role of dispersal in mediating the dynamics of communities and their response to global change. In this manuscript, we synthesize recent research that examines the sources of individual variation in dispersal and emphasize its implications for plant fitness, populations and communities. We argue that this intraspecific variation in seed dispersal does not simply add noise to systems, but, in fact, alters dispersal processes and patterns with consequences for demography, communities, evolution and response to anthropogenic changes. We conclude with recommendations for moving this field of research forward

Non-reductivism and the Metaphilosophy of Mind

This paper discusses the metaphilosophical assumptions that have dominated analytic philosophy of mind, and how they gave rise to the central question that the best-known forms of non-reductivism available have sought to answer, namely: how can mind fit within nature? Its goal is to make room for forms of non-reductivism that have challenged the fruitfulness of this question, and which have taken a different approach to the so-called “placement” problem. Rather than trying to solve the placement problem, the forms of non-reductivism discussed in this paper have put pressure on the metaphilosophical assumptions that have given rise to the question of the place of mind in nature in the first instance

Deep neural architectures for prediction in healthcare

This paper presents a novel class of systems assisting diagnosis and personalised assessment of diseases in healthcare. The targeted systems are end-to-end deep neural architectures that are designed (trained and tested) and subsequently used as whole systems, accepting raw input data and producing the desired outputs. Such architectures are state-of-the-art in image analysis and computer vision, speech recognition and language processing. Their application in healthcare for prediction and diagnosis purposes can produce high accuracy results and can be combined with medical knowledge to improve effectiveness, adaptation and transparency of decision making. The paper focuses on neurodegenerative diseases, particularly Parkinson’s, as the development model, by creating a new database and using it for training, evaluating and validating the proposed systems. Experimental results are presented which illustrate the ability of the systems to detect and predict Parkinson’s based on medical imaging information

Dietary intake and stress fractures among elite male combat recruits

<p>Abstract</p> <p>Background</p> <p>Appropriate and sufficient dietary intake is one of the main requirements for maintaining fitness and health. Inadequate energy intake may have a negative impact on physical performance which may result in injuries among physically active populations. The purpose of this research was to evaluate a possible relationship between dietary intake and stress fracture occurrence among combat recruits during basic training (BT).</p> <p>Methods</p> <p>Data was collected from 74 combat recruits (18.2 ± 0.6 yrs) in the Israeli Defense Forces. Data analyses included changes in anthropometric measures, dietary intake, blood iron and calcium levels. Measurements were taken on entry to 4-month BT and at the end of BT. The occurrence of stress reaction injury was followed prospectively during the entire 6-month training period.</p> <p>Results</p> <p>Twelve recruits were diagnosed with stress fracture in the tibia or femur (SF group). Sixty two recruits completed BT without stress fractures (NSF). Calcium and vitamin D intakes reported on induction day were lower in the SF group compared to the NSF group-38.9% for calcium (589 ± 92 and 964 ± 373 mg·d^-1, respectively, <it>p </it>< 0.001), and-25.1% for vitamin D (117.9 ± 34.3 and 157.4 ± 93.3 IU·d^-1, respectively, <it>p </it>< 0.001). During BT calcium and vitamin D intake continued to be at the same low values for the SF group but decreased for the NSF group and no significant differences were found between these two groups.</p> <p>Conclusions</p> <p>The development of stress fractures in young recruits during combat BT was associated with dietary deficiency before induction and during BT of mainly vitamin D and calcium. For the purpose of intervention, the fact that the main deficiency is before induction will need special consideration.</p

Assessment of fall-related self-efficacy and activity avoidance in people with Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Fear of falling (FOF) is common in Parkinson's disease (PD), and it is considered a vital aspect of comprehensive balance assessment in PD. FOF can be conceptualized differently. The Falls-Efficacy Scale (FES) assesses fall-related self-efficacy, whereas the Survey of Activities and Fear of Falling in the Elderly (SAFFE) assesses activity avoidance due to the risk of falling. This study aimed at investigating the validity and reliability of FES and SAFFE in people with PD.</p> <p>Methods</p> <p>Seventy-nine people with PD (mean age; 64 years, SD 7.2) completed the Swedish version of FES(S), SAFFE and the physical functioning (PF) scale of the 36-Item Short-Form Health Survey (SF-36). FES(S) and SAFFE were administered twice, with an 8.8 (SD 2.3) days interval. Assumptions for summing item scores into total scores were examined and score reliability (Cronbach's alpha and test-retest reliability) were calculated. Construct validity was assessed by examining the pattern of Spearman correlations (r_s) between the FES(S)/SAFFE and other variables, and by examining differences in FES(S)/SAFFE scores between fallers and non-fallers, genders, and between those reporting FOF and unsteadiness while turning.</p> <p>Results</p> <p>For both scales, item mean scores (and standard deviations) were roughly similar and corrected item-total correlations exceeded 0.4. Reliabilities were ≥0.87. FES(S)-scores correlated strongest (r_s, -0.74, p < 0.001) with SAFFE-scores, whereas SAFFE-scores correlated strongest with PF-scores (r_s, -0.76, p < 0.001). Both scales correlated weakest with age (r_s≤ 0.08). Experiencing falls, unsteadiness while turning, and FOF was associated with lower fall-related self-efficacy and higher activity avoidance.</p> <p>Conclusions</p> <p>This study provides initial support for the score reliability and validity of the FES(S) and SAFFE in people with PD.</p

Epistemic injustice: A role for recognition?

© The Author(s) 2017. My aim in this article is to propose that an insightful way of articulating the feminist concept of epistemic injustice can be provided by paying significant attention to recognition theory. The article intends to provide an account for diagnosing epistemic injustice as a social pathology and also attempts to paint a picture of some social cure of structural forms of epistemic injustice. While there are many virtues to the literature on epistemic injustice, epistemic exclusion and silencing, current discourse on diagnosing as well as explicating and overcoming these social pathologies can be improved and enriched by bringing recognition theory into the conversation: under recognition theory, social normative standards are constructed out of the moral grammar of recognition attributions. I shall argue that the failure to properly recognize and afford somebody or a social group the epistemic respect they merit is an act of injustice in the sense of depriving individuals of a progressive social environment in which the epistemic respect afforded to them plays a significant role in enabling and fostering their self-confidence as rational enquirers. Testimonial injustice is particularly harrowing, because it robs a group or an individual of the status of a rational enquirer, thereby creating an asymmetrical cognitive environment in which that group or individual is not deemed one’s conversational peer. Hermeneutical injustice is particularly harrowing, because asymmetrical cognitive environments further entrench the normative power of ideology