Identifying Consensus and Open Questions around Assessing or Predicting the Quality and Success of Cartilage Repair: A Delphi Study

A range of surgical techniques have been developed for the repair or regeneration of lesioned cartilage in the human knee and a corresponding array of scoring systems have been created to assess their outcomes. The published literature displays a wide range of opinions regarding the factors that influence the success of surgical cartilage repair and which parameters are the most useful for measuring the quality of the repair at follow-up. Our objective was to provide some clarity to the field by collating items that were agreed upon by a panel of experts to be important in these areas. A modified, three-round Delphi consensus study was carried out consisting of one idea-generating focus-group and two subsequent, self-completed questionnaire rounds. In each round, items were assessed for their importance and level of consensus against pre-determined threshold levels. In total, 31 items reached consensus, including a hierarchy of tissues in the joint based on their importance in cartilage repair, markers of repair cartilage quality and the implications of environmental and patient-related factors. Items were stratified into those that can be employed for predicting the success of cartilage repair and those that could be used for assessing the structural quality of the resulting repair cartilage. Items that did not reach consensus represent areas where dissent remains and could, therefore, be used to guide future clinical and fundamental scientific research.</jats:p

An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans.

Chondrocyte-based cartilage repair strategies, such as articular chondrocyte implantation, are widely used, but few studies addressed the communication between native subchondral bone cells and the transplanted chondrocytes. An indirect co-culture model was developed, representing a chondrocyte/scaffold-construct repair of a cartilage defect adjoining bone, where the bone could have varying degrees of degeneration. Human BM-MSCs were isolated from two areas of subchondral bone in each of five osteochondral tissue specimens from five patients undergoing knee arthroplasty. These two areas underlaid the macroscopically and histologically best and worst cartilage, representing early and late-stage OA, respectively. BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte-agarose scaffolds were assessed by gene expression and biochemical analyses, and the abundance of selected proteins in conditioned media was assessed by ELISA. Co-culture with late-OA BM-MSCs resulted in a reduction in GAG deposition and a decreased expression of genes encoding matrix-specific proteins (COL2A1 and ACAN), compared to culturing with early OA BM-MSCs. The concentration of TGF-β1 was significantly higher in the early OA conditioned media. The results of this study have clinical implications for cartilage repair, suggesting that the health of the subchondral bone may influence the outcomes of chondrocyte-based repair strategies

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Physiological and Biomechanical Responses of Highly Trained Distance Runners to Lower-Body Positive Pressure Treadmill Running

Background: As a way to train at faster running speeds, add training volume, prevent injury, or rehabilitate after an injury, lower-body positive pressure treadmills (LBPPT) have become increasingly commonplace among athletes. However, there are conflicting evidence and a paucity of data describing the physiological and biomechanical responses to LBPPT running in highly trained or elite caliber runners at the running speeds they habitually train at, which are considerably faster than those of recreational runners. Furthermore, data is lacking regarding female runners’ responses to LBPPT running. Therefore, this study was designed to evaluate the physiological and biomechanical responses to LBPPT running in highly trained male and female distance runners. Methods: Fifteen highly trained distance runners (seven male; eight female) completed a single running test composed of 4 × 9-min interval series at fixed percentages of body weight ranging from 0 to 30% body weight support (BWS) in 10% increments on LBPPT. The first interval was always conducted at 0% BWS; thereafter, intervals at 10, 20, and 30% BWS were conducted in random order. Each interval consisted of three stages of 3 min each, at velocities of 14.5, 16.1, and 17.7 km·h−1 for men and 12.9, 14.5, and 16.1 km·h−1 for women. Expired gases, ventilation, breathing frequency, heart rate (HR), rating of perceived exertion (RPE), and stride characteristics were measured during each running speed and BWS. Results: Male and female runners had similar physiological and biomechanical responses to running on LBPPT. Increasing BWS increased stride length (p \u3c 0.02) and flight duration (p \u3c 0.01) and decreased stride rate (p \u3c 0.01) and contact time (p \u3c 0.01) in small-large magnitudes. There was a large attenuation of oxygen consumption (VO2) relative to BWS (p \u3c 0.001), while there were trivial-moderate reductions in respiratory exchange ratio, minute ventilation, and respiratory frequency (p \u3e 0.05), and small-large effects on HR and RPE (p \u3c 0.01). There were trivial-small differences in VE, respiratory frequency, HR, and RPE for a given VO2 across various BWS (p \u3e 0.05). Conclusions: The results indicate the male and female distance runners have similar physiological and biomechanical responses to LBPPT running. Overall, the biomechanical changes during LBPPT running all contributed to less metabolic cost and corresponding physiological changes. Keywords: AlterG, Lower-body positive pressure, Body weight support, Anti-gravity, Running, Stride characteristics, Physiological characteristics, Metabolic demand, Oxygen demand, Oxygen cos

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Control of neglected tropical diseases (NTDs) is suggested to be more cost-effective when drugs are co-administered through a single integrated delivery system rather than separate systems. An essential prerequisite for such efficiency gains is sufficient geographical overlap of the targeted diseases – lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminth infection and trachoma. Lack of data on geographical NTD distribution currently hampers the implementation of integrated control in many African countries. To generate the required data quickly and efficiently, integrated surveys of several NTDs simultaneously have been recommended. However, experience with integrated surveys is limited and requires additional research on cost and effectiveness to inform improvements in methodology and to guide scale-up. Here we analyse costs of the first integrated NTD survey round in Southern Sudan, generating average costs per implementation unit surveyed. Cost estimates are presented for use of the existing survey method and for modified versions. Key cost drivers were survey consumables and personnel, both of which are recurrent costs. These inputs could be reduced or put to more efficient use by modifying sampling for LF. To generate comparable cost estimates and identify key cost drivers in other settings we provide detailed cost data and guidance on how to replicate this work

The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Розрахунок та проектування окремого фундаменту будівлі на природній ґрунтовій основі. Методичні рекомендації до виконання практичних завдань та курсового проекту з дисципліни «Механіка ґрунтів, основи і фундаменти» сту- дентами напрямів підготовки 6.060101 Будівництво та 6.050301 Гірництво

Подано методичні рекомендації до виконання практичних завдань та кур- сового проекту з дисципліни «Механіка ґрунтів, основи і фундаменти» для сту- дентів напрямів підготовки 6.060101 Будівництво та 6.050301 Гірництво. Розглянуто порядок проектування фундаменту будівлі мілкого закладан- ня на природній ґрунтовій основі. Методичні рекомендації передбачають виконання курсового проекту «Розрахунок та проектування окремого фундаменту будівлі на природній ґрун- товій основі» як із викладачем, так і під час самостійної роботи. Можна використовувати також у підготовці курсового та дипломного про- ектування

Maternal allergic contact dermatitis causes increased asthma risk in offspring

<p>Abstract</p> <p>Background</p> <p>Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring.</p> <p>Methods</p> <p>BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice.</p> <p>Results</p> <p>Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease.</p> <p>Conclusion</p> <p>Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate) can result in the maternal transmission of asthma risk in mice.</p

Field assessment of dog as sentinel animal for plague in endemic foci of Madagascar

Funding Information: Sincere thanks to Mrs. L Angeltine Ralafiarisoa for technical assistance and the staff of the Plague Unit for their assistance during sample collections. This work was funded by an internal research grant (Ref: PA 14.25) from the Institut Pasteur de Madagascar. This research was also funded in part by the Wellcome Trust [095171/Z/10/Z]. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Social representations and the politics of participation

Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge