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Time constraints—having more to do than time to do it—can prevent us from doing everything we need and want to do. When lack of time constrains our behavior, the behavior linked to voluntary role identities (like being a member of a softball team or bowling league) may be the first to be cut. Although, as many of these role identities are socially desirable, survey respondents may still claim to have performed them. Thus, this study examines role behavior and its measurement in the face of time constraints. The athlete identity is examined as a potential casualty of the time crunch, used because it is a common, typically voluntary identity that has a relatively standard set of role behaviors (e.g., participating in sporting events, like games or matches, as an athlete). Situational constraints, namely, a lack of time, are brought into a model based on the structure posited in identity theory (Stryker [1980] 2003) to help explain variation between self-reported and actual role behavior. Thus, the c...

Alveolar epithelial regeneration is essential for resolution of the acute respiratory distress syndrome (ARDS). Although neutrophils have traditionally been considered mediators of epithelial damage, recent studies suggest they promote type II pneumocyte (AT2) proliferation, which is essential for regenerating alveolar epithelium. These studies did not, however, evaluate this relationship in an in vivo model of alveolar epithelial repair following injury. To determine whether neutrophils influence alveolar epithelial repair in vivo, we developed a unilateral acid injury model that creates a severe yet survivable injury with features similar to ARDS. Mice that received injections of the neutrophil-depleting Ly6G antibody had impaired AT2 proliferation 24 and 72 h after acid instillation, which was associated with decreased reepithelialization and increased alveolar protein concentration 72 h after injury. As neutrophil depletion itself may alter the cytokine response, we questioned the contribution of neutrophils to alveolar epithelial repair in neutropenic granulocyte-colony stimulating factor (G-CSF)−/− mice. We found that the loss of G-CSF recapitulated the neutrophil response of Ly6G-treated mice and was associated with defective alveolar epithelial repair, similar to neutrophil-depleted mice, and was reversed by administration of exogenous G-CSF. To approach the mechanisms, we employed an unbiased protein analysis of bronchoalveolar lavage fluid from neutrophil-depleted and neutrophil-replete mice 12 h after inducing lung injury. Pathway analysis identified significant differences in multiple signaling pathways that may explain the differences in epithelial repair. These data emphasize an important link between the innate immune response and tissue repair in which neutrophils promote alveolar epithelial regeneration.

Explanations of error in survey self-reports have focused on social desirability: that respondents answer questions about normative behavior to appear prosocial to interviewers. However, this paradigm fails to explain why bias occurs even in self-administered modes like mail and web surveys. We offer an alternative explanation rooted in identity theory that focuses on measurement directiveness as a cause of bias. After completing questions about physical exercise on a web survey, respondents completed a text message–based reporting procedure, sending updates on their major activities for five days. Random assignment was then made to one of two conditions: instructions mentioned the focus of the study, physical exercise, or not. Survey responses, text updates, and records from recreation facilities were compared. Direct measures generated bias—overreporting in survey measures and reactivity in the directive text condition—but the nondirective text condition generated unbiased measures. Findings are discussed in terms of identity.

Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans.

4618 Background: APACT was a phase III trial of adjuvant nab-paclitaxel + gemcitabine ( nab-P + Gem) vs Gem alone in patients with resected pancreatic cancer (PC) and the first adjuvant PC trial to use independently assessed DFS as the primary endpoint (DFS by investigator review was a prespecified sensitivity analysis). We examined concordance between independent and investigator DFS review. Methods: For the independent assessment, reviewers determined recurrence by computed tomography or magnetic resonance imaging but were blinded to treatment and clinical data. Investigator-assessed DFS was based on all available data. Concordance was summarized by κ statistics. Patients who did not have recurrence or were alive were censored at the last tumor assessment date with disease-free status or the randomization date if the last tumor assessment with disease-free status was missing. Patients who received new anticancer therapy or cancer-related surgery prior to recurrence or death were censored at the date of last tumor assessment with disease-free status prior to the start of new anticancer therapy or cancer-related surgery or the randomization date if the last tumor assessment date with disease-free status prior to the start of subsequent new anticancer therapy or cancer-related surgery was missing. All censoring rules were the same for analysis of DFS by independent and investigator review. Results: Median DFS by independent review was 19.4 ( nab-P + Gem) vs 18.8 (Gem) months (hazard ratio [HR] 0.88; 95% CI, 0.73 - 1.06; P = 0.18); median investigator-assessed DFS was 16.6 ( nab-P + Gem) vs 13.7 (Gem) months (HR 0.82; 95% CI, 0.69 - 0.97; nominal P = 0.017). Moderate concordance was found between independent- and investigator-assessed DFS (Table); similar results were observed in the nab-P + Gem (concordance, 78%; κ coefficient, 0.56) and Gem alone (concordance, 76%; κ coefficient, 0.53) arms. Conclusions: The results reflect the complexities of defining the recurrence timepoint accurately and suggest that radiological review in the absence of clinical context is suboptimal for recurrence detection in resected PC. These findings may inform future clinical trial design. Registration: EudraCT (2013-003398-91); ClinicalTrials.gov (NCT01964430). Clinical trial information: NCT01964430 . [Table: see text]

Every author has erroneously been assigned to the affiliation “62”. The affiliation 62 belongs to the author Graham Casey. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10− 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10− 4, replication P = 6.7 × 10− 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci. © 2019, The Author(s).

Covalent conjugation of chemical moieties to antibodies has numerous applications, including antibody-drug conjugates, antibody conjugation for diagnostics, and more. Most nonspecific chemical conjugation methods ligate onto any of a number of sites on the antibody, leading to multiple conjugated species, many of which perturb antibody function. To solve these problems, we used CRISPR/Cas9-edited hybridomas to introduce a Sortase tag (LPXTG) and a Flag tag at the 3' end of the CH3 heavy chain region of a mouse monoclonal antibody. The Flag tag allows easy purification of the antibody, while the LPXTG is then acted on by the bacterial transpeptidase Sortase to site-specifically add on any of a number of chemical moieties that possess a triglycine repeat. This technique thus allows rapid production of an antibody onto which a wide array of chemical moieties can be site-specifically conjugated.

Systemic administration of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) leads predominantly to hepatic uptake and expression. Here, we conjugated nucleoside-modified mRNA-LNPs with antibodies (Abs) specific to vascular cell adhesion molecule, PECAM-1. Systemic (intravenous) administration of Ab/LNP-mRNAs resulted in profound inhibition of hepatic uptake concomitantly with ~200-fold and 25-fold elevation of mRNA delivery and protein expression in the lungs compared to non-targeted counterparts. Unlike hepatic delivery of LNP-mRNA, Ab/LNP-mRNA is independent of apolipoprotein E. Vascular re-targeting of mRNA represents a promising, powerful, and unique approach for novel experimental and clinical interventions in organs of interest other than liver.

Participation in sports offers both short-term and long-term physical and psychosocial benefits for children and adolescents. However, an overemphasis on competitive success in youth sports may limit the benefits of participation, and could increase the risk of injury, burnout, and disengagement from physical activity. The National Basketball Association and USA Basketball recently assembled a group of leading experts to share their applied research and practices to address these issues. This review includes the group’s analysis of the existing body of research regarding youth sports participation and the related health, performance, and psychosocial outcomes. Based upon this, age-specific recommendations for basketball participation are provided that aim to promote a healthy and positive experience for youth basketball players.

The nature of religious change and the future of religion have been central questions of social science since its inception. But empirical research on this question has been quite American-centric, encouraged by the conventional wisdom that the United States is an outlier of religiosity in the developed world, and, more pragmatically, by the availability of survey data. The dramatic growth in the number and reach of cross-national surveys over the past two decades has offered a corrective. These data have allowed research on religious trends in the United States, Canada, and Europe, putting American trends into comparative relief. This research synthesis reviews the past quarter century of cross-national comparative survey research on religious behavior, focusing on religious service attendance as a commonly measured behavior that is arguably more equivalent across societies and cultures than other measures of religiosity. The lack of evidence for religious revival is highlighted, noting instead declining rates of attendance in the United States and Canada, and either declining rates or low "bottomed-out" stability in Western Europe, most of Eastern Europe, and Australia and New Zealand. Finally, countries in Latin America, Africa, and Asia are discussed to the extent that research allows, before a call for future research-in these places in particular-is made in order to correct for the Western and Christian focus of much of the research on cross-national religious trends.

American football remains one of the most popular sports for young athletes. The injuries sustained during football, especially those to the head and neck, have been a topic of intense interest recently in both the public media and medical literature. The recognition of these injuries and the potential for long-term sequelae have led some physicians to call for a reduction in the number of contact practices, a postponement of tackling until a certain age, and even a ban on high school football. This statement reviews the literature regarding injuries in football, particularly those of the head and neck, the relationship between tackling and football-related injuries, and the potential effects of limiting or delaying tackling on injury risk.

Optogenetics allows rapid, temporally specific control of neuronal activity via targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose significant physical constraints on natural behaviors. In this report we bypass these limitations using novel technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliques that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain.

That rates of normative behaviors produced by sample surveys are higher than actual behavior warrants is well evidenced in the research literature. Less well understood is the source of this error. Twenty-five cognitive interviews were conducted to probe responses to a set of common, conventional survey questions about one such normative behavior: religious service attendance. Answers to the survey questions and cognitive probes are compared both quantitatively and qualitatively. Half of the respondents amended their answer during cognitive probing, all amendments indicating a lower rate of attendance than originally reported, yielding a statistically significant reduction in reported attendance. Narrative responses shed light onto the source of bias, as respondents pragmatically interpreted the survey question to allow themselves to include other types of religious behavior, to report on a more religious past, and discount current constraints on their religious behavior, in order to report aspirational or normative religious identities.

Educating home health nurses presents significant challenges for nurse educators because of the vast geographical areas served and the types of patient cared for. The integration of technology into the home health care arena offers new and innovative opportunities to address the ongoing educational needs of nurses as required by accrediting bodies. This exploratory study evaluated a Web-based educational module on home inotrope therapy in regard to nurses' perceived knowledge and confidence.

Targeted drug delivery aims to improve therapeutic effects and enable mechanisms that are not feasible for untargeted agents (e.g., due to impermeable biological barriers). To achieve targeting, a drug or its carrier should possess properties providing specific accumulation from circulation at the desired site. There are several examples of systems-inspired approaches that have been applied to achieve this goal. First, proteomics analysis of plasma membrane fraction of the vascular endothelium has identified a series of target molecules and their ligands (e.g., antibodies) that deliver conjugated cargoes to well-defined vascular cells and subcellular compartments. Second, selection of ligands binding to cells of interest using phage display libraries in vitro and in vivo has provided peptides and polypeptides that bind to normal and pathologically altered cells. Finally, large-scale high-throughput combinatorial synthesis and selection of lipid- and polymer-based nanocarriers varying their chemical components has yielded a series of carriers accumulating in diverse organs and delivering RNA interference agents to diverse cells. Together, these approaches offer a basis for systems-based design and selection of targets, targeting molecules, and targeting vehicles. Current studies focus on expanding the arsenal of these and alternative targeting strategies, devising drug delivery systems capitalizing on these strategies and evaluation of their benefit/risk ratio in adequate animal models of human diseases. These efforts, combined with better understanding of mechanisms and unintended consequences of these targeted interventions, need to be ultimately translated into industrial development and the clinical domain.

This article investigates the effect of the Boston Marathon Bombing on city residents— how the tragic incident changed, or did not change, how Bostonians live in and feel about their community and neighborhoods. Unlike prior research that began weeks or months after a terrorist attack and used retrospective reports, this study spans the focal event. An address-based sample of residents from three neighborhoods, distinct in racial and economic makeup was surveyed by mail using a three-contact protocol. About two-thirds of respondents answered a survey of neighborhood sentiments, and health and well-being in the days before the bombing (N = 581) and slightly over a third answered the survey after the bombing (N = 313). Assessments of safety, city and neighborhood satisfaction and solidarity, mental health, and other key measures vary greatly between the three neighborhoods, which are diverse in racial and economic composition, but also vary in proximity to the bomb site. Net of neighborhood differences, the bombing had a strong negative effect on neighborhood cohesion and reduced use of public transit. Strong interactions are also found between timing of survey completion (pre and post bombing) and neighborhood for assessments of neighborhood solidarity.

Attachment of nanoparticles (NPs) to the surface of carrier red blood cells (RBCs) profoundly alters their interactions with the host organism, decelerating NP clearance from the bloodstream while enabling NP transfer from the RBC surface to the vascular cells. These changes in pharmacokinetics of NPs imposed by carrier RBCs are favorable for many drug delivery purposes. On the other hand, understanding effects of NPs on the carrier RBCs is vital for successful translation of this novel drug delivery paradigm. Here, using two types of distinct nanoparticles (polystyrene (PSNP) and lysozyme-dextran nanogels (LDNG)) we assessed potential adverse and sensitizing effects of surface adsorption of NPs on mouse and human RBCs. At similar NP loadings (approx. 50 particles per RBC), adsorption of PSNPs, but not LDNGs, induces RBCs agglutination and sensitizes RBCs to damage by osmotic, mechanical and oxidative stress. PSNPs, but not LDNGs, increase RBC stiffening and surface exposure of phosphatidylserine, both known to accelerate RBC clearance in vivo. Therefore, NP properties and loading amounts have a profound impact on RBCs. Furthermore, LDNGs appear conducive to nanoparticle drug delivery using carrier RBCs.

Die sekundare klinische Zustandsverschlechterung eines Neugeborenen in der fruhen Postnatalzeit kann mannigfaltige Ursachen haben, u. a. Sepsis, Herzfehler und Stoffwechselerkrankungen. Die klinische Symptomatik ist unspezifisch und haufig fulminant. Vor allem aber kann sie einen lebensbedrohlichen Notfall darstellen, dessen fruhzeitige Erkennung von elementarer Bedeutung ist. Diagnostik und Therapie mussen parallel ohne Zeitverzug erfolgen. Um dies zu gewahrleisten, sind regelmasige Schulungen aller an der Versorgung von Neugeborenen beteiligten Berufsgruppen unabdingbar.

To evaluate the economic impact of chronic kidney disease (CKD) on US health plans.A retrospective analysis identified patients with a renin-angiotensin-aldosterone system inhibitor (RAASi) prescription from an electronic medical record (EMR) database (Humedica); those with =90 days in =1 CKD stage were selected based on estimated glomerular filtration rate or diagnosis code, and a cohort on RAASi medications without CKD was selected. Costs for specific services obtained from OptumInsight were applied to services in EMR data of patients aged65 years (commercial) and =65 years (Medicare). Dialysis costs were excluded.The study included 106,050 patients with CKD and 56,761 no-CKD controls (90,302 commercial and 72,509 Medicare overall). Mean annualized all-cause costs increased exponentially with advancing stage, from $7537 (no CKD) to $76,969 (CKD stages 4-5) in the commercial group, and $8091 (no CKD) to $46,178 (CKD stages 4-5) in the Medicare group (P.001; all comparisons with preceding disease stage). Mean costs for end-stage renal disease (ESRD) patients were $121,948 and $87,339 in the commercial and Medicare groups, respectively. Inpatient costs were the largest contributor to total costs, and their relative contribution increased with advancing CKD.Cost to US health plans increases exponentially with each CKD stage progression. ESRD costs are even higher. Because readmissions lead to higher costs, efforts to reduce readmissions would result in cost reductions. Furthermore, healthcare reengineering paradigms that manage increasing comorbidities with advancing CKD, including heart failure, diabetes, and hyperkalemia, should offer additional potential for cost reductions.

Preclinical pediatric emergencies are rare events and are therefore often associated with stress and uncertainty for emergency medical service personnel. To ensure adequate treatment of pediatric patients a variety of different cognitive aids exist (e.g. books, apps, rulers, weight-adapted bag systems). Especially the size specifications of the medical equipment and the dosage of emergency medication are individually very different in children and are dependent on parameters, such as body height and weight. Therefore, cognitive aids often enable length measurement whereby it is possible to draw conclusions on body weight for calculating the child's medication dosage. These aids may help to avoid the wrong medication dose or the wrong therapy of children but uncritical and untrained usage of these aids carries a potential risk of mistakes. This recommendation gives an overview of the general requirements and different problems of cognitive aids and should help improve the general framework and the rational basis for the use and further development of cognitive aids in emergency medicine.

Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many antipain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally innervated territories in mice. In addition, we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, and because we have recently defined TRPV4’s role in response to airborne irritants and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion is supported by studies with Trpv4−/− mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca2+. Using TRPA1-blocker and Trpa1−/− mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation of trigeminally innervated surface epithelia.

The ability to sense and respond to thermal stimuli at varied environmental temperatures is essential for survival in seasonal areas. In this study, we show that mice respond similarly to ramping changes in temperature from a wide range of baseline temperatures. Further investigation suggests that this ability to adapt to different ambient environments is based on rapid adjustments made to a dynamic temperature set point. The adjustment of this set point requires transient receptor potential cation channel, subfamily member 8 (TRPM8), but not transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and is regulated by phospholipase C (PLC) activity. Overall, our findings suggest that temperature response thresholds in mice are dynamic, and that this ability to adapt to environmental temperature seems to mirror the in vitro findings that PLC-mediated hydrolysis of phosphoinositol 4,5-bisphosphate modulates TRPM8 activity and thereby regulates the response thresholds to cold stimuli.

Adaptation to environmental temperature is essential for survival in seasonal areas. The mechanisms of adaptation have been studied in vitro, but it has not been quantified in vivo.The extended Cold Plantar Assay (eCPA) cools the entire testing environment. Once the desired environmental temperature has been reached, a separate focal cold stimulus is applied to the hindpaw and the latency to withdrawal is recorded as a proxy for cold sensitivity.Using this technique, we can test the cold responsiveness of freely behaving mice at ambient temperatures ranging from 5°C to 30°C. The responses are consistent and unambiguous, and the environmental temperatures generated are reproducible. We are also able to measure cold responsiveness as animals are in the process of adapting to cold environments.Existing methods, such as the dynamic cold plate and the 2-plate preference assay test how mice respond to cold environments, but cannot assess how the thresholds for response are changed by acclimation in cold environments. Additionally, the eCPA requires very little specialized equipment, can test many mice at the same time on one apparatus, and has an objective readout.The extended Cold Plantar assay is a significant methodological improvement, allowing the assessment of cold responsiveness in freely behaving mice at a wide range of environmental temperature conditions and during cold adaptation.

The number of anterior cruciate ligament (ACL) injuries reported in athletes younger than 18 years has increased over the past 2 decades. Reasons for the increasing ACL injury rate include the growing number of children and adolescents participating in organized sports, intensive sports training at an earlier age, and greater rate of diagnosis because of increased awareness and greater use of advanced medical imaging. ACL injury rates are low in young children and increase sharply during puberty, especially for girls, who have higher rates of noncontact ACL injuries than boys do in similar sports. Intrinsic risk factors for ACL injury include higher BMI, subtalar joint overpronation, generalized ligamentous laxity, and decreased neuromuscular control of knee motion. ACL injuries often require surgery and/or many months of rehabilitation and substantial time lost from school and sports participation. Unfortunately, regardless of treatment, athletes with ACL injuries are up to 10 times more likely to develop degenerative arthritis of the knee. Safe and effective surgical techniques for children and adolescents continue to evolve. Neuromuscular training can reduce risk of ACL injury in adolescent girls. This report outlines the current state of knowledge on epidemiology, diagnosis, treatment, and prevention of ACL injuries in children and adolescents.

Background Youth sport participation offers many benefits including the development of self-esteem, peer socialisation and general fitness. However, an emphasis on competitive success, often driven by goals of elite-level travel team selection, collegiate scholarships, Olympic and National team membership and even professional contracts, has seemingly become widespread. This has resulted in an increased pressure to begin high-intensity training at young ages. Such an excessive focus on early intensive training and competition at young ages rather than skill development can lead to overuse injury and burnout. ### Purpose To provide a systematic, evidenced-based review that will (1) assist clinicians in recognising young athletes at risk for overuse injuries and burnout; (2)delineate the risk factors and injuries that are unique to the skeletally immature young athlete; (3) describe specific high-risk overuse injuries that present management challenges and/or can lead to long-term health consequences; (4) summarise the risk factors and symptoms associated with burnout in young athletes; (5)provide recommendations on overuse injury prevention. ### Methodology Medical Subject Headings (MeSHs) and text words were searched on 26 March 2012 from MEDLINE, CINAHL and PsycINFO. The search yielded 953 unique articles. Additional articles were found using cross-referencing. The process was repeated on 10 July 2013 to review any new articles since the original search. Screening by the authors yielded a total of 208 relevant sources that were used for this article. Recommendations were classified using the Strength of Recommendation Taxonomy (SORT) grading system. ### Definition of overuse injury Overuse injuries occur due to repetitive submaximal loading of the musculoskeletal system when rest is not adequate to allow for structural adaptation to take place. Injury can involve the muscle-tendon unit, bone, bursa, neurovascular structures and the physis. Overuse injuries unique to young athletes include apophyseal injuries and physeal stress injuries. ### Epidemiology It is estimated that 27 million US youth between 6 and 18 years of age participate in …

Es werden standardisierte Prozeduren (SOPs) in der Schlafmedizin beschrieben und damit eine Fortsetzung der bisher publizierten europaischen Leitlinien zur Akkreditierung von Schlafmedizinischen Zentren (SMZ) und zur Zertifizierung von Fachleuten in der Schlafmedizin erstellt. Das Ziel ist es, hiermit Qualitatsstandards in der europaischen Schlafmedizin zu definieren. Diese Publikation ist Teil eines breiteren Aktionsplans der European Sleep Research Society (ESRS). Ein aktualisierter Teil weist auf die Kosteneffektivitat der Schlafmedizin und ihre Bedeutung fur die Ressourcenallokation in der offentlichen Gesundheitsversorgung hin. Der daran anschliesende Teil des Artikels stellt die deutsche Ubersetzung der europaischen Leitlinie dar: Fischer J, Dogas Z, Bassetti CL et al. (2012) Standard procedures for adults in accredited sleep medicine centres in Europe. J Sleep Res 21:357–368. Die hier vorgestellten standardisierten Prozeduren in akkreditierten SMZ berucksichtigen das diagnostische und therapeutische Vorgehen bei Patienten mit Schlafstorungen und basieren auf dem Prinzip der evidenzbasierten Medizin (EbM). Erganzend wurden einige der SOPs im Rahmen eines formalen Konsensusprozesses von schlafmedizinischen Fachleuten der europaischen Nationalen Gesellschaften fur Schlafmedizin (ANSS) beschlossen. Fur den hier dargestellten zeitlichen und personellen Arbeitsaufwand der Fachleute im SMZ wurde ebenfalls Konsens erzielt. Die endgultigen Empfehlungen sind als „Standardpraxis“, „Prozedur die sinnvoll sein kann“, „Prozedur die nicht sinnvoll ist“ oder „Prozedur mit nicht ausreichender Information“ bezeichnet. Die hier behandelten SOPs schliesen sowohl subjektive als auch objektive Messungen und auch Empfehlungen fur Nachuntersuchungen und zur Patientensicherheit in der Schlafmedizin ein. Es besteht das umfassende Ziel, mit diesen Standardprozeduren die Excellence in der Praxis und die Qualitatssicherung in der Schlafmedizin in Europa weiter zu entwickeln.

Short Message Service (SMS) text messaging is a ubiquitous technology available on the vast majority of cellphones in use in 2013. It provides a common technological denominator between mobile devices of nearly every make and model, supplying researchers an avenue to collect data without the expense and difficulty of designing specific applications for every cellphone or device on the market. SMS/text messaging was used as a method of data collection using a sample of students from a large, Midwestern university. The procedure adapted conventional time use measurement procedures to fit the device, the sample, and the behavior of interest. After answering questions on a brief Web survey, respondents were asked to text researchers for five days, updating major changes in their activities. Following data collection, data from the text condition was compared to that from a conventional (Web) survey and data from a reverse record check from campus recreation facilities to validate reports of the behavior of interest – physical exercise and activity. Findings suggest that respondents provided consistently high quality data on self-reports of the behaviors of interest. Moreover, paradata measures of text data quality (e.g., number of text messages sent, number of days with messages) predict data quality on the behavior of interest.

Survey findings suggest that predominantly Muslim countries are among the most religious in the world and validate commonly held, but overly simplistic, perceptions of Muslims as extremely and uniformly religious. Existing research has demonstrated that survey estimates can give a distorted view of the reality of levels of religious practice; however, it has thus far focused exclusively on traditionally Christian, advanced Western democracies. To address this oversight, the veracity of self-reported religious practice in the Muslim world is tested using Pakistan, the Palestinian territories, and Turkey as cases for study. Comparing estimates of prayer from conventional surveys with those from time diaries, marginal rates of overreporting are estimated for each country by sex. The time-use measure of prayer is then imputed for the conventional survey data set to estimate overreporting at the respondent level and to predict overreporting using a measure of religious identity importance. Findings suggest that overreporting of prayer occurs in each country considered, although more consistently for women than for men. Moreover, religious identity importance is strongly correlated with overreporting of prayer, suggesting that a similar mechanism may promote the measurement error for overreported prayer in the Muslim world and overreported church attendance in the West.

Like that of other normative behaviors, much of the research on physical exercise is based on self-reports that are prone to overreporting. While research has focused on identifying the presence and degree of overreporting, this paper fills an important gap by investigating its causes. The explanation based in impression management will be challenged, using an explanation based in identity theory as an arguably better fitting alternative. Respondents were randomly assigned to one of two conditions: (1) a web instrument using direct survey questions, or (2) a chronological reporting procedure using text messaging. Comparisons to validation data from a reverse record check indicate significantly greater rates of overreporting in the web condition than in the text condition. Results suggest that measurement bias is associated with the importance of the respondents’ exercise identity, prompted by the directness of the conventional survey question. Findings call into question the benefit of self-administration for bias reduction in measurement of normative behaviors.

[1] A methodology to attain daily variability of turbidity in the Dead Sea by means of remote sensing was developed. 250 m/pixel moderate resolution imaging spectroradiometer (MODIS) surface reflectance data were used to characterize the seasonal cycle of turbidity and plume spreading generated by flood events in the lake. Fifteen minutes interval images from meteosat second generation 1.6 km/pixel high-resolution visible (HRV) channel were used to monitor daily variations of turbidity. The HRV reflectance was normalized throughout the day to correct for the changing geometry and then calibrated against available MODIS surface reflectance. Finally, hourly averaged reflectance maps are presented for summer and winter. The results show that turbidity is concentrated along the silty shores of the lake and the southern embayments, with a gradual decrease of turbidity values from the shoreline toward the center of the lake. This pattern is most pronounced following the nighttime hours of intense winds. A few hours after winds calm the concentric turbidity pattern fades. In situ and remote sensing observations show a clear relation between wind intensity, wave amplitude and water turbidity. In summer and winter similar concentric turbidity patterns are observed but with a much narrower structure in winter. A simple Lagrangain trajectory model suggests that the combined effects of horizontal transport and vertical mixing of suspended particles leads to more effective mixing in winter. The dynamics of suspended matter contributions from winter desert floods are also presented in terms of hourly turbidity maps showing the spreading of the plumes and their decay.

Heart failure remains a frequent cause of death and is the leading reason for hospitalization in Germany although therapeutic options have significantly increased over the past years particularly in heart failure with reduced ejection fraction. Clinical symptoms are usually preceded by cardiac remodeling, which was originally defined only by left ventricular dilatation and depressed function but is also associated with typical cellular and molecular processes. Healing after acute myocardial infarction is characterized by inflammation, cellular migration and scar formation. Cardiac remodeling is accompanied by adaptive changes of the peripheral cardiovascular system. Since prevention is the primary goal, rapid diagnosis and treatment of myocardial infarction are mandatory. Early reperfusion therapy limits infarct size and enables the best possible preservation of left ventricular function. Standard pharmacotherapy includes angiotensin-converting enzyme inhibitors, angiotensin-1-receptor blockers and beta blockers. In addition, mineralocorticoid receptor antagonists have proven beneficial. Compounds specifically targeting infarct healing processes are currently under development.

The available data on the effectiveness of therapeutic hypothermia in different patient groups are heterogeneous. Although the benefits have been proven for some collectives, recommendations for the use of hypothermia treatment in other groups are based on less robust data and conclusions by analogy. This article gives a review of the current evidence of temperature management in all age groups and based on this state of knowledge, recommends active temperature management with the primary aim of strict normothermia (36-36.5 °C) for 72 hours after cardiopulmonary arrest or severe traumatic brain injury for children beyond the neonatal period.

Background No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors. Methods We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods. Findings 223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75–79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2–9·7) followed by physical inactivity (5·5%, 2·1–8·5), history of diabetes (2·8%, 2·1–4·0), and low to average BMI (2·0%, 1·4–2·7), whereas low alcohol consumption (0·01–2·5 g per day) and high BMI had a protective effect. Interpretation Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle. Funding European Community's Seventh Framework Programme. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license

Among many parents and coaches, it is believed that early single sport specialisation is essential for future competitive sport success and, further, that a high level of achievement in youth sports predicts future success. Owing to these misconceptions, youth sport has become focused on results at young ages rather than the overall development process, including physical and psychosocial health and well-being. The emphasis on competitive success in youth sports has been driven by a variety of factors including efforts to make elite travel or club teams, attend exclusive camps or showcase events, secure high school roster spots, garner collegiate scholarships and achieve professional careers. In addition, in the USA, the college recruiting process itself is a significant issue, with those as young as the eighth grade committing to a college programme.1 All of this has led to pressure to begin high-intensity training and single sport specialisation in childhood. As a consequence, many parents and young athletes are concerned that not specialising early will place them at a disadvantage in achieving their sport-related goals. In the sport of basketball, a recent National Collegiate Athletic Association (NCAA) survey found that ∼49% of men and 55% of women at the Division 1 level …

Inflamed organs display marked spatial heterogeneity of inflammation, with patches of inflamed tissue adjacent to healthy tissue. To investigate how nanocarriers (NCs) distribute between such patches, we created a mouse model that recapitulates the spatial heterogeneity of the inflammatory lung disease ARDS. NCs targeting the epitope PECAM strongly accumulated in the lungs, but were shunted away from inflamed lung regions due to hypoxic vasoconstriction (HVC). In contrast, ICAM-targeted NCs, which had lower whole-lung uptake than PECAM/NCs in inflamed lungs, displayed markedly higher NC levels in inflamed regions than PECAM/NCs, due to increased regional ICAM. Regional HVC, epitope expression, and capillary leak were sufficient to predict intra-organ of distribution of NCs, antibodies, and drugs. Importantly, these effects were not observable with traditional spatially-uniform models of ARDS, nor when examining only whole-organ uptake. This study underscores how examining NCs' intra-organ distribution in spatially heterogeneous animal models can guide rational NC design.

Sports specialization is becoming the norm in youth sports for a variety of reasons. When sports specialization occurs too early, detrimental effects may occur, both physically and psychologically. If the timing is correct and sports specialization is performed under the correct conditions, the athlete may be successful in reaching specific goals. Young athletes who train intensively, whether specialized or not, can also be at risk of adverse effects on the mind and body. The purpose of this clinical report is to assist pediatricians in counseling their young athlete patients and their parents regarding sports specialization and intensive training. This report supports the American Academy of Pediatrics clinical report “Overuse Injuries, Overtraining, and Burnout in Child and Adolescent Athletes.”

After assessment of thermal sensitivity during development of a novel cold pain assay, one subject developed postinflammatory hyperpigmentation. Resultant epidermal darkening gradually faded without clinical intervention., Changes in cold temperature sensitivity are often associated with chronic pain conditions. Progress in understanding the neurobiological mechanism underlying these changes and resulting development of effective therapies has been slowed by the accessibility and affordability of devices used to measure thermal sensitivity in humans. To address this gap, we developed an inexpensive method to measure cold pain thresholds in healthy adult volunteers using dry ice and a thermode. However, early in preliminary testing, a subject presented with epidermal postinflammatory hyperpigmentation that lasted for >200 days. Although this response was unique among the small number of subjects in development of the assay, it raised questions as to the safety of the assay design.

The atom probe field ion microscope has been used to study the redistribution of carbon in iron-nickel-carbon martensites aged in the temperature range 22 to 250 °C. The Ms temperature of the alloy used was -50 °C. During all stages of aging a considerable amount of redistribution of carbon was detected in the form of carbon segregation to twin boundaries and other lattice defects and in the formation of small clusters and carbides. Small carbon-rich areas were detected at 40 °C, and disc-shaped carbide particles were found after 24 hours at 100 °C. Thin cementite lamellae were observed after one hour at 250 °C. It is evident that a close similarity exists between the sequence of reactions o°Curring during the tempering process and the sequence of precipitation reactions observed in age-hardening alloys. The main additional complications that arise in the case of martensites are due to the high densities of lattice defects that are present and to the strong interaction between carbon atoMs and such defects.

Identity theory invokes two distinct but related concepts, identity salience and prominence, to explain how the organization of identities that make up the self impacts the probability that a given identity is situationally enacted. However, much extant research has failed to clearly distinguish between salience and prominence, and their empirical relationship has not been adequately investigated, impeding a solid understanding of the significance and role of each in a general theory of the self. This study examines their causal ordering using three waves of panel data from 48 universities focusing on respondents’ identities as science students. Analyses strongly support a causal ordering from prominence to salience. We provide theoretical and empirical grounds to justify this ordering while acknowledging potential variation in its strength across identities. Finally, we offer recommendations about the use of prominence and salience when measures of one or both are available or when analyses use cross-sectional data.

More young children are participating in endurance running events such as full and half marathons, and the safety of these events for children has been heavily debated. There is a paucity of evidence on either side of the debate. However, overuse injuries, stress fractures, as well as the potential for psychologic burnout are legitimate concerns. Parents who are seeking advice from pediatricians about child participation in these endurance events should be made aware of these risks. Young children may participate in endurance running events under close supervision from health professionals, coaches, and parents, with full medical evaluation before initiation of training, throughout training, as well as 6 to 12 months post-race. Special attention should be made to the psychologic well-being of the child, with the participation in running being child-driven, not parent- or coach-driven, and emphasis on enjoyment and fitness, not competition. [ Pediatr Ann . 2016;45(3):e83–e86.]

This paper proposes an explanation of the overreporting of voting participation based in Stryker's identity theory (1980) , integrating the social pressure approach of Bernstein, Chadha, and Montjoy (2001) . A set of logistic regression models is estimated to predict the propensity to overreport using indicators of extensive and intensive commitments to a political identity. Models are tested using vote verification data from five years of the American National Election Studies (1978, 1980, 1984, 1988, and 1990). Identity commitments are strongly predictive of overreporting and conventional understandings of social desirability fail to predict overreporting. Findings suggest that a conceptualization of self-reported voting as a measure of identity may provide a better explanation for why respondents overreport their voting in terms of extensive and intensive commitments to a political identity.