Université du Québec

This work investigates the anti-ice performance of various superhydrophobic surfaces under different conditions. The adhesion strength of glaze ice (similar to that deposited during "freezing rain") is used as a measure of ice-releasing properties. The results show that the ice-repellent properties of the materials deteriorate during icing/deicing cycles, as surface asperities appear to be gradually damaged. It is also shown that the anti-icing efficiency of superhydrophobic surfaces is significantly lower in a humid atmosphere, as water condensation both on top of and between surface asperities takes place, leading to significantly larger values of ice adhesion strength. This work thus shows that superhydrophobic surfaces are not always ice-repellent and their use as anti-ice materials may therefore be limited.

With the goal of developing more accurate, efficient, non-invasive and fast diagnostic tools, the use of near-infrared (NIR) light in the range of the second and third biological windows (NIR-II: 1000-1350 nm, NIR-III: 1550-1870 nm) is growing remarkably as it provides the advantages of deeper penetration depth into biological tissues, better image contrast, reduced phototoxicity and photobleaching. Consequently, NIR-based bioimaging has become a quickly emerging field and manifold new NIR-emitting bioprobes have been reported. Classes of materials suggested as potential probes for NIR-to-NIR bioimaging (using NIR light for the excitation and emission) are quite diverse. These include rare-earth based nanoparticles, Group-IV nanostructures (single-walled carbon nanotubes, carbon nanoparticles and more recently Si- or Ge-based nanostructures) as well as Ag, In and Pb chalcogenide quantum dots. This review summarizes and discusses current trends, material merits, and latest developments in NIR-to-NIR bioimaging taking advantage of the region above 1000 nm (i.e. the second and third biological windows). Further consideration will be given to upcoming probe materials emitting in the NIR-I region (700-950 nm), thus do not possess emissions in these two windows, but have high expectations. Overall, the focus is placed on recent discussions concerning the optimal choice of excitation and emission wavelengths for deep-tissue high-resolution optical bioimaging and on fluorescent bioprobes that have successfully been implemented in in vitro and in vivo applications.

Rating-based collaborative filtering is the process of predicting how a user would rate a given item from other user ratings. We propose three related slope one schemes with predictors of the form f (x) = x + b, which precompute the average difference between the ratings of one item and another for users who rated both. Slope one algorithms are easy to implement, efficient to query, reasonably accurate, and they support both online queries and dynamic updates, which makes them good candidates for real-world systems. The basic slope one scheme is suggested as a new reference scheme for collaborative filtering. By factoring in items that a user liked separately from items that a user disliked, we achieve results competitive with slower memory-based schemes over the standard benchmark EachMovie and Movielens data sets while better fulfilling the desiderata of CF applications.

As the demand for wind energy continues to grow at exponential rates, reducing operation and maintenance (OM) costs and improving reliability have become top priorities in wind turbine (WT) maintenance strategies. In addition to the development of more highly evolved WT designs intended to improve availability, the application of reliable and cost-effective condition-monitoring (CM) techniques offers an efficient approach to achieve this goal. This paper provides a general review and classification of wind turbine condition monitoring (WTCM) methods and techniques with a focus on trends and future challenges. After highlighting the relevant CM, diagnosis, and maintenance analysis, this work outlines the relationship between these concepts and related theories, and examines new trends and future challenges in the WTCM industry. Interesting insights from this research are used to point out strengths and weaknesses in today’s WTCM industry and define research priorities needed for the industry to meet the challenges in wind industry technological evolution and market growth.

Qualitative research in general and the grounded theory approach in particular, have become increasingly prominent in medical education research in recent years. In this Guide, we first provide a historical perspective on the origin and evolution of grounded theory. We then outline the principles underlying the grounded theory approach and the procedures for doing a grounded theory study, illustrating these elements with real examples. Next, we address key critiques of grounded theory, which continue to shape how the method is perceived and used. Finally, pitfalls and controversies in grounded theory research are examined to provide a balanced view of both the potential and the challenges of this approach. This Guide aims to assist researchers new to grounded theory to approach their studies in a disciplined and rigorous fashion, to challenge experienced researchers to reflect on their assumptions, and to arm readers of medical education research with an approach to critically appraising the quality of grounded theory studies.

Dissolved organic carbon (DOC) is a key parameter in lakes that can affect numerous features, including microbial metabolism, light climate, acidity, and primary production. In an attempt to understand the factors that regulate DOC in lakes, we assembled a large database (7,514 lakes from 6 continents) of DOC concentrations and other parameters that characterize the conditions in the lakes, the catchment, the soil, and the climate. DOC concentrations were in the range 0.1–332 mg L −1 , and the median was 5.71 mg L −1 . A partial least squares regression explained 48% of the variability in lake DOC and showed that altitude, mean annual runoff, and precipitation were negatively correlated with lake DOC, while conductivity, soil carbon density, and soil C:N ratio were positively related with lake DOC. A multiple linear regression using altitude, mean annual runoff, and soil carbon density as predictors explained 40% of the variability in lake DOC. While lake area and drainage ratio (catchment : lake area) were not correlated to lake DOC in the global data set, these two factors explained significant variation of the residuals of the multiple linear regression model in several regional subsets of data. These results suggest a hierarchical regulation of DOC in lakes, where climatic and topographic characteristics set the possible range of DOC concentrations of a certain region, and catchment and lake properties then regulate the DOC concentration in each individual lake.

The purpose of this study was to propose and test a motivational model of high school dropout. The model posits that teachers, parents, and the school administration's behaviors towards students influence students' perceptions of competence and autonomy. The less autonomy supportive the social agents' behaviors are, the less positive the students' perceptions of competence and autonomy. In turn, the less positive students' perceptions are, the lower their level of self-determined school motivation are. Finally, low levels of self-determined motivation lead students to develop intentions to drop out of high school, which are later implemented, leading to actual dropout behavior. This model was tested with high school students (N = 4,537) by means of a prospective design. Results from analyses of variance and a structural equation modeling analysis (with LISREL) were found to support the model for all participants and for each gender separately.

Two different models for analyzing extreme hydrologic events, based on, respectively, partial duration series (PDS) and annual maximum series (AMS), are compared. The PDS model assumes a generalized Pareto distribution for modeling threshold exceedances corresponding to a generalized extreme value distribution for annual maxima. The performance of the two models in terms of the uncertainty of the T ‐year event estimator is evaluated in the cases of estimation with, respectively, the maximum likelihood (ML) method, the method of moments (MOM), and the method of probability weighted moments (PWM). In the case of ML estimation, the PDS model provides the most efficient T ‐year event estimator. In the cases of MOM and PWM estimation, the PDS model is generally preferable for negative shape parameters, whereas the AMS model yields the most efficient estimator for positive shape parameters. A comparison of the considered methods reveals that in general, one should use the PDS model with MOM estimation for negative shape parameters, the PDS model with exponentially distributed exceedances if the shape parameter is close to zero, the AMS model with MOM estimation for moderately positive shape parameters, and the PDS model with ML estimation for large positive shape parameters. Since heavy‐tailed distributions, corresponding to negative shape parameters, are far the most common in hydrology, the PDS model generally is to be preferred for at‐site quantile estimation.

Mammalian mitochondrial DNA (mtDNA) is a small, maternally inherited genome that codes for 13 essential proteins in the respiratory chain. Mature oocytes contain more than 150 000 copies of mtDNA, at least an order of magnitude greater than the number in most somatic cells, but sperm contain only approximately 100 copies. Mitochondrial oxidative phosphorylation has been suggested to be an important determinant of oocyte quality and sperm motility; however, the functional significance of the high mtDNA copy number in oocytes, and of the low copy number in sperm, remains unclear. To investigate the effects of mtDNA copy number on fertility, we genetically manipulated mtDNA copy number in the mouse by deleting one copy of Tfam, an essential component of the mitochondrial nucleoid, at different stages of germline development. We show that males can tolerate at least a threefold reduction in mtDNA copy number in their sperm without impaired fertility, and in fact, they preferentially transmit a deleted Tfam allele. Surprisingly, oocytes with as few as 4000 copies of mtDNA can be fertilized and progress normally through preimplantation development to the blastocyst stage. The mature oocyte, however, has a critical postimplantation developmental threshold of 40 000-50 000 copies of mtDNA in the mature oocyte. These observations suggest that the high mtDNA copy number in the mature oocyte is a genetic device designed to distribute mitochondria and mtDNAs to the cells of the early postimplantation embryo before mitochondrial biogenesis and mtDNA replication resumes, whereas down-regulation of mtDNA copy number is important for normal sperm function.

BACKGROUND: Skin-to-skin care (SSC), often referred to as 'kangaroo care' (KC) due to its similarity with marsupial behaviour of ventral maternal-infant contact, is one non-pharmacological intervention for pain control in infants. OBJECTIVES: The primary objectives were to determine the effect of SSC alone on pain from medical or nursing procedures in neonates compared to no intervention, sucrose or other analgesics, or additions to simple SSC such as rocking; and to determine the effects of the amount of SSC (duration in minutes), method of administration (e.g. who provided the SSC) of SSC in reducing pain from medical or nursing procedures in neonatesThe secondary objectives were to determine the safety of SSC care for relieving procedural pain in infants; and to compare the SSC effect in different postmenstrual age subgroups of infants. SEARCH METHODS: For this update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE via PubMed (1966 to 25 February 2016); Embase (1980 to 25 February 2016); and CINAHL (1982 to 25 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: Studies with randomisation or quasi-randomisation, double- or single-blinded, involving term infants (≥ 37 completed weeks' postmenstrual age (PMA) to a maximum of 44 weeks' PMA and preterm infants (< 37 completed weeks PMA) receiving SSC for painful procedures conducted by healthcare professionals. DATA COLLECTION AND ANALYSIS: The main outcome measures were physiological or behavioural pain indicators and composite pain scores. A mean difference (MD) with 95% confidence interval (CI) using a fixed-effect model was reported for continuous outcome measures. We included variations on type of tissue-damaging procedure, provider of care, and duration of SSC. MAIN RESULTS: Twenty-five studies (n = 2001 infants) were included. Nineteen studies (n = 1065) used heel lance as the painful procedure, one study combined venepuncture and heel stick (n = 50), three used intramuscular injection (n = 776), one used 'vaccination' (n = 60), and one used tape removal (n = 50). The studies were generally strong and had low or uncertain risk of bias. Blinding of the intervention was not possible, making them subject to high risk, depending on the method of scoring outcomes.Seventeen studies (n = 810) compared SSC to a no-treatment control. Although 15 studies measured heart rate during painful procedures, data from only five studies (n = 161) could be combined for a mean difference (MD) of -10.78 beats per minute (95% CI -13.63 to -7.93) favouring SSC. Meta-analysis of four studies (n = 120) showed no difference in heart rate following the painful procedure (MD 0.08, 95% CI -4.39 to 4.55). Two studies (n = 38) reported heart rate variability with no significant differences. Two studies (n = 101) in a meta-analysis on oxygen saturation at 30 and 60 seconds following the painful procedure did not show a difference. Duration of crying meta-analysis was performed on four studies (n = 133): two (n = 33) investigated response to heel lance (MD = -34.16, 95% CI -42.86 to -25.45), and two (n = 100) following IM injection (MD = -8.83, 95% CI -14.63 to -3.02), favouring SSC. Five studies, one consisting of two substudies (n = 267), used the Premature Infant Pain Profile (PIPP) as a primary outcome, which favoured SCC at 30 seconds (MD -3.21, 95% CI -3.94 to -2.47), at 60 seconds (3 studies; n = 156) (MD -1.64, 95% CI -2.86 to -0.43), and at 90 seconds (n = 156) (MD -1.28, 95% CI -2.53 to -0.04); but at 120 seconds there was no difference (n = 156) (MD 0.07, 95% CI -1.11 to 1.25). No studies on return of heart rate to baseline level, cortisol levels, and facial actions could be combined for meta-analysis findings.Eight studies compared SSC to another intervention with or without a no-treatment control. Two cross-over studies (n = 80) compared mother versus other provider (father, another female) on PIPP scores at 30, 60, 90, and 120 seconds with no significant difference. When SSC was compared to other interventions, there were not enough similar studies to pool results in an analysis. One study compared SSC (n = 640) with and without dextrose and found that the combination was most effective and that SSC alone was more effective than dextrose alone. Similarly, in another study SSC was more effective than oral glucose for heart rate (n = 95). SSC either in combination with breastfeeding or alone was favoured over a no-treatment control, but not different to breastfeeding. One study compared SSC alone and in combination with both sucrose and breastfeeding on heart rate (HR), NIPS scores, and crying time (n = 127). The combinations were more effective than SSC alone for NIPS and crying. Expressed breast milk was compared to SSC in one study (n = 50) and found both equally effective on PIPP scores. There were not enough participants with similar outcomes and painful procedures to compare age groups or duration of SSC. No adverse events were reported in any of the studies. AUTHORS' CONCLUSIONS: SSC appears to be effective as measured by composite pain indicators with both physiological and behavioural indicators and, independently, using heart rate and crying time; and safe for a single painful procedure. Purely behavioural indicators tended to favour SSC but with facial actions there is greater possibility of observers not being blinded. Physiological indicators were mixed although the common measure of heart rate favoured SSC. Two studies compared mother-providers to others, with non-significant results. There was more heterogeneity in the studies with behavioural or composite outcomes. There is a need for replication studies that use similar, clearly defined outcomes. Studies examining optimal duration of SSC, gestational age groups, repeated use, and long-term effects of SSC are needed. Of interest would be to study synergistic effects of SSC with other interventions.

BACKGROUND: Since mobility and social participation are key determinants of health and quality of life, it is important to identify factors associated with them. Although several investigations have been conducted on the neighborhood environment, mobility and social participation, there is no clear integration of the results. This study aimed to provide a comprehensive understanding regarding how the neighborhood environment is associated with mobility and social participation in older adults. METHODS: A rigorous methodological scoping study framework was used to search nine databases from different fields with fifty-one keywords. Data were exhaustively analyzed, organized and synthesized according to the International Classification of Functioning, Disability and Health (ICF) by two research assistants following PRISMA guidelines, and results were validated with knowledge users. RESULTS: The majority of the 50 selected articles report results of cross-sectional studies (29; 58%), mainly conducted in the US (24; 48%) or Canada (15; 30%). Studies mostly focused on neighborhood environment associations with mobility (39; 78%), social participation (19; 38%), and occasionally both (11; 22%). Neighborhood attributes considered were mainly 'Pro ducts and technology' (43; 86) and 'Services, systems and policies' (37; 74%), but also 'Natural and human-made changes' (27; 54%) and 'Support and relationships' (21; 42%). Mobility and social participation were both positively associated with Proximity to resources and recreational facilities, Social support, Having a car or driver's license, Public transportation and Neighborhood security, and negatively associated with Poor user-friendliness of the walking environment and Neighborhood insecurity. Attributes of the neighborhood environment not covered by previous research on mobility and social participation mainly concerned 'Attitudes', and 'Services, systems and policies'. CONCLUSION: Results from this comprehensive synthesis of empirical studies on associations of the neighborhood environment with mobility and social participation will ultimately support best practices, decisions and the development of innovative inclusive public health interventions including clear guidelines for the creation of age-supportive environments. To foster mobility and social participation, these interventions must consider Proximity to resources and to recreational facilities, Social support, Transportation, Neighborhood security and User-friendliness of the walking environment. Future studies should include both mobility and social participation, and investigate how they are associated with 'Attitudes', and 'Services, systems and policies' in older adults, including disadvantaged older adults.

The purpose of this study was to establish that anterior hip impingement, secondary to an anterior femoral offset deficiency from a pistol-grip deformity, was a common etiology of hip disorders. This impingement results in a spectrum of injury ranging from anterior hip pain, labral tears, damage to the acetabular articular cartilage and idiopathic arthritis. This was accomplished through three separate but closely related studies: (1) an arthroscopic labral tear study of 38 patients who had hip arthroscopy for a labral tear (2) a hip cheilectomy study of 10 patients who had a cheilectomy for anterior femoroacetabular impingement and (3) an idiopathic arthritis study of 200 consecutive patients having THA. In all three studies, a common etiology was identified. Repetitive anterior femoroacetabular impingement resulted in anterior groin pain, labral tears, chondral damage and eventually arthritis. This impingement was caused by a pistol-grip deformity of the proximal femur in 97% of the cases in the arthroscopic labral study and 100% of the cases in the idiopathic arthritis study. The identification of anterior hip impingement as a cause of labral tears and idiopathic arthritis may allow surgeons to correct it early in its natural history and delay or prevent end-stage arthritis.

The research access/impact problem arises because journal articles are not accessible to all of their would-be users; hence, they are losing potential research impact. The solution is to make all articles Open Access (OA; i.e., accessible online, free for all). OA articles have significantly higher citation impact than non-OA articles. There are two roads to OA: the “golden” road (publish your article in an OA journal) and the “green” road (publish your article in a non-OA journal but also self-archive it in an OA archive). Only 5% of journals are gold, but over 90% are already green (i.e., they have given their authors the green light to self-archive); yet only about 10–20% of articles have been self-archived. To reach 100% OA, self-archiving needs to be mandated by researchers' employers and funders, as the United Kingdom and the United States have recently recommended, and universities need to implement that mandate.

Trends in parental time invested in children since the 1960s are examined in 16 industrialized countries using time‐use survey data. Despite the time pressures that confront today's families, parents appear to be devoting more time to children than they did 40 years ago. Results also suggest that mothers continue to devote more time to childcare than fathers, but the gender gap has been reduced. The consistency of these results across countries suggests a global trend toward an increase in parental time investment in children. Multivariate analysis of trends in parental time by type of activity was undertaken for Canada. It revealed a significant increase in parental time even after controlling for changes in the demographic composition of the population during the past few decades.

In this work, we measured the adhesion strength of artificially created glaze ice (similar to accreted in nature) on rough fluoropolymer-based hydrophobic surfaces with different contact angle (CA) and wetting hysteresis. The previously reported direct correlation between ice repellency and CA on superhydrophobic surfaces is shown to be only valid for surfaces with low wetting hysteresis. Another correlation was found between wetting hysteresis and ice adhesion strength on rough surfaces with similar chemistry.

The rapidly diversified market demands have presented a huge challenge to the conventional mobile broadband network architecture. On one hand, the limited machine room space and insufficient power supply make it impossible to accommodate exponentially growing amount of network equipment of operators. On the other hand, net heterogeneity caused by different specifications of wireless access equipment causes costly trouble related to management and optimization. This article, correspondingly, proposes a holistic solution involving different technologies, i.e. network function virtualization (NFV), software defined radio (SDR), and software defined network (SDN). In particular, we investigate both existing standards and possible extensions for 4G/5G mobile networks, followed by a few open issues for future research.

Clinical practice guidelines are published and promoted, often by professional societies, because they provide a current and transparently analyzed review of relevant research and are written with the aim to guide clinical practice. The 2018 Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) (PADIS) guidelines (1) first 1) builds on this mission by updating the 2013 PAD guidelines (2); 2) by adding two inextricably related clinical care topics (immobility and sleep); 3) by including patients as collaborators and coauthors; and 4) by inviting panelists from high-income countries as an early step toward incorporating more diverse practices and expertise from the global critical care community. Readers will find rationales for 37 recommendations (derived from actionable Patient Intervention Comparison Outcome questions), two good practice statements, and 32 statements (derived from nonactionable, descriptive questions for which the Grading of Recommendations Assessment, Development and Evaluation methodology was not used) across the five guideline sections. Only two of the 37 recommendations are strong; most are conditional. Compared with a strong recommendation (most desirable to clinicians), conditional recommendations apply to most, but not all critically ill adults, and are made when evidence is conflicting, low quality, insufficient and/or applicable to just one patient subgroup, and/or when potential benefits require weighing almost equal risks. The supplemental digital figures and tables linked to the full guideline provide background on how the questions were established, profiles of the evidence, the “evidence to decision” tables used to develop recommendations, and voting results. We also describe the evidence gaps that prevented us from fully addressing all clinical priority questions. The five sections of this guideline are interrelated, and thus, the guideline should be considered in its entirety rather than as discrete or distinct recommendations. A separate PADIS guideline implementation and integration article (3) and a detailed description of the methodologic innovations that characterize these guidelines (4) have been published separately. This executive summary highlights the 18 recommendations the section leaders and guideline chair/vice-chair felt would be of greatest interest to ICU clinicians. All PADIS recommendations (including those highlighted in this executive summary) are found in Table 1. All descriptive questions and ungraded statements are found in Table 2.TABLE 1.: Summary of Actionable Patient Intervention Comparison Outcome Questions and RecommendationsTABLE 2.: Summary of Descriptive Questions and Ungraded StatementsRECOMMENDATIONS Pain Pain management is complex and has many origins. A consistent approach to pain assessment and management is paramount, particularly given the unique features inherent to critically ill adults. In this population, whose reference standard measure of pain is the patient’s self-report, the inability to communicate clearly does not negate a patient’s pain experience or the need for appropriate pain management (5). Severe pain negatively affects critically ill adults (6) beyond its unpleasant experience dimension. Implementation of assessment-driven and standardized pain management protocols improves ICU outcomes and clinical practice (5,6). Carefully titrated analgesic dosing is important in balancing the benefits versus risks of opioid exposure (7–10). Protocol-Based Pain Assessment and Management Question. Should we use a protocol-based (analgesia/analgosedation) pain assessment and management programs in the care of adult ICU patients when compared with usual care? Good practice statement. Management of pain for adult ICU patients should be guided by routine pain assessment and pain should be treated before a sedative agent is considered. Recommendation. We suggest using an assessment-driven, protocol-based, stepwise approach for pain and sedation management in critically ill adults (conditional recommendation, moderate quality of evidence). Remarks. For this recommendation, analgosedation is defined as either analgesia-first sedation (i.e., an analgesic [usually an opioid] is used before a sedative to reach the sedative goal) or analgesia-based sedation (i.e., an analgesic [usually an opioid] is used instead of a sedative to reach the sedative goal). The implementation of this recommendation infers that institutions should have an assessment-driven protocol that mandates regular pain and sedation assessment using validated tools, provides clear guidance on medication choice and dosing, and makes treating pain a priority over providing sedatives. Our pooled analysis suggests that protocol-based (analgesia/analgosedation) pain and sedation assessment and management programs compared with usual therapy reduce sedative requirements, duration of mechanical ventilation, ICU length of stay (LOS), and pain intensity (5,11–31). Panel members issued a conditional recommendation because the benefits of a protocol-based approach were not observed across all critical outcomes. Pharmacologic Adjuvants to Opioid Therapy. Opioids remain a mainstay for pain management in most ICU settings; however, their side effects preoccupy clinicians because important safety concerns, such as sedation, delirium, respiratory depression, ileus, and immunosuppression, may increase ICU LOS and worsen post-ICU patient outcome. The panel generally supports the use of multimodal pharmacotherapy as a component of an analgesia-first approach to spare/minimize opioid and sedative use and optimize analgesia and rehabilitation (32), as described below. Acetaminophen Question. Should acetaminophen be used as an adjunct to an opioid (vs an opioid alone) for pain management in critically ill adults? Recommendation. We suggest using acetaminophen as an adjunct to an opioid to decrease pain intensity and opioid consumption for pain management in critically ill adults (conditional recommendation, very low quality of evidence). When compared with placebo in the perioperative period, use of IV acetaminophen 1 g every 6 hours was associated with reduced pain intensity and opioid consumption 24 hours after surgery (33,34). The risk for IV acetaminophen-associated hypotension may preclude its use in some patients (35). Given these findings, the panel suggests using acetaminophen (IV, oral, or rectal) to decrease pain intensity and opioid consumption when treating pain in critically ill patients, particularly in patients at higher risk for opioid-associated safety concerns. Nefopam Question. Should nefopam be used either as an adjunct or a replacement for an opioid (vs an opioid alone) for pain management in critically ill adults? Recommendation. We suggest using nefopam (if feasible) either as an adjunct or replacement for an opioid to reduce opioid use and their safety concerns when treating pain in critically ill adults (conditional recommendation, very low quality of evidence). Nefopam is a nonopioid analgesic; a 20-mg dose has an analgesic effect comparable to 6 mg of IV morphine (36). Nefopam has potential safety advantages over opioids and other nonopioid analgesics (e.g., cyclooxygenase 1 selective nonsteroidal anti-inflammatory drugs) because it has no detrimental effects on hemostasis, gastric mucosal integrity, renal function, vigilance, ventilatory drive, and intestinal motility. However, nefopam use can be associated with tachycardia, glaucoma, seizure, and delirium. Although not available in the United States or Canada, nefopam is a low-cost drug that is used in nearly 30 countries. In cardiac surgery patients, nefopam’s analgesic effect resembles IV fentanyl when delivered as patient-controlled analgesia, with less nausea (37). Ketamine Question. Should ketamine be used as an adjunct to an opioid (vs an opioid alone) for pain management in critically ill adults? Recommendation. We suggest using low-dose ketamine (1–2 µg/kg/hr) as an adjunct to opioid therapy when seeking to reduce opioid consumption in postsurgical adults admitted to the ICU (conditional recommendation, very low quality of evidence). IV ketamine, although shown to reduce opioid requirements among abdominal surgery patients admitted to the ICU, was not shown to improve patients’ self-reported pain intensity (38). Reduced opioid consumption is only a surrogate for better patient-centered outcomes. The frequency of side effects (i.e., nausea, delirium, hallucinations, hypoventilation, pruritus, and sedation) was similar between the ketamine and control groups. Although indirect evidence from randomized controlled trials (RCTs) in non-ICU patients supports a role for ketamine as an analgesic adjuvant to opioid therapy, evidence evaluating its role in the ICU for this indication currently remains limited. Neuropathic pain medications Question. Should a neuropathic pain medication (e.g., gabapentin, carbamazepine, and pregabalin) be used as an adjunct to an opioid (vs an opioid alone) for pain management in critically ill adults? Recommendations. We recommend using a neuropathic pain medication (e.g., gabapentin, carbamazepine, and pregabalin) with opioids for neuropathic pain management in critically ill adults (strong recommendation, moderate quality of evidence). We suggest using a neuropathic pain medication (e.g., gabapentin, carbamazepine, and pregabalin) with opioids for pain management in ICU adults after cardiovascular surgery (conditional recommendation, low quality of evidence). Neuropathic pain medications as an adjuvant to opioid therapy have been evaluated in critically ill adults with Guillain-Barré syndrome or who have recently undergone cardiac surgery (39–42). Across both populations, their use significantly reduced opioid consumption within 24 hours of their initiation. Among cardiac surgery patients, neuropathic pain medication use did not affect time to extubation or ICU LOS (41,42). Panel members estimated that neuropathic agents had negligible costs and were widely available although the possible sedative and cognitive effects of these agents could preclude their use in some patients. These drugs require the ability for patients to swallow or have enteral access. Agitation/Sedation Sedatives are frequently administered to critically ill patients to relieve anxiety and prevent agitation-related harm (2). These medications may predispose patients to increased morbidity (43–46). In addition to the healthcare provider determining the specific indication for the sedative use, the patient’s current and subsequent sedation status should be continuously assessed using valid and reliable scales (47–49). The 2013 guidelines (2) suggested targeting light levels of sedation or using daily awakening trials (44,50–52), and minimizing benzodiazepines (53), to improve short-term outcomes (e.g., duration of mechanical ventilation and ICU LOS). In addition, sedation delivery paradigms and specific sedative medications can have an important effect on post-ICU outcomes including 90-day mortality, physical functioning, and neurocognitive and psychologic outcomes. Light Sedation Question. Does light sedation (vs deep sedation), regardless of the sedative agent(s) used, significantly affect outcomes in critically ill mechanically ventilated adults? Recommendation. We suggest using light sedation (vs deep sedation) in critically ill, mechanically ventilated adults (conditional recommendation, low quality of evidence). The 2013 guidelines’ ungraded statement associated maintaining a light level of sedation with shortened time to extubation and ICU LOS (2). Although the previous guideline defined light sedation as a Richmond Agitation-Sedation Scale (RASS) scale score of greater than or equal to –2 and eye opening of at least 10 seconds (50), this level of sedation is probably deeper than that required for mechanically ventilated patient management in an ICU. No universally accepted definition of light sedation exists. For studies that used scales, such as the RASS (48), a RASS score of –2 to +1 (or its equivalent using other scales) was defined as light sedation in the studies evaluated by this panel. The outcomes evaluated differ from the short-term outcomes assessed in the 2013 guidelines (2) in their consideration of post-ICU discharge measurements. Light sedation was associated with a shorter time to extubation (51,54,55) and a reduced tracheostomy rate (50). Light sedation was not associated with a reduction in 90-day mortality (44,50,53), delirium prevalence (44,54), posttraumatic stress disorder incidence (31,50), or self-extubation (44,50,53,55). No RCTs evaluated the impact of light versus deep sedation on cognitive or physical functioning. Choice of Sedative. Sedation indication, goal, clinical pharmacology, and acquisition cost are important determinants in choosing a sedative agent. The 2013 guidelines suggest (conditionally) that nonbenzodiazepine sedatives (either propofol or dexmedetomidine) are preferable to benzodiazepine sedatives (either midazolam or lorazepam) in critically ill, mechanically ventilated adults because of improved short-term outcomes, such as ICU LOS, duration of mechanical ventilation, and delirium (2). For the 2018 guidelines (1), we considered both short- and long-term outcomes as critical in our evaluation. Questions. Should propofol, when compared with a benzodiazepine, be used for sedation in critically ill, mechanically ventilated adults? Should dexmedetomidine, when compared with a benzodiazepine, be used for sedation in critically ill, mechanically ventilated adults? Should dexmedetomidine, when compared with propofol, be used for sedation in critically ill, mechanically ventilated adults? Recommendation. We suggest using either propofol or dexmedetomidine over benzodiazepines for sedation in critically ill, mechanically ventilated adults (conditional recommendation, low quality of evidence). We evaluated the effect of propofol versus a benzodiazepine, dexmedetomidine versus a benzodiazepine, and propofol versus dexmedetomidine in three separate analyses for the outcomes deemed critical. In most studies, benzodiazepines were administered as continuous infusions and not intermittent boluses. We combined studies using midazolam and lorazepam. A shortened time to light sedation of at least 4 hours and time to extubation of at least 8–12 hours (one nursing shift) were deemed clinically significant. Compared with a benzodiazepine, propofol use was associated with a shorter time to light sedation in seven RCTs (56–62) and a shorter time to extubation in nine RCTs (56,57,61, 67). Only one RCT assessed delirium and found no difference (61). No data were available for other critical outcomes. Although propofol was associated with a higher risk of self-extubation, the CI for this outcome was wide and it remains unclear if harm resulted (i.e., need for reintubation). Dexmedetomidine, when compared with a benzodiazepine infusion (one study used intermittent boluses), was associated with a shorter duration of mechanical ventilation in five RCTs (53,67–70) and ICU of stay in three RCTs (53,68,71). Delirium prevalence was evaluated in four RCTs (53,68,69,71); the Midazolam versus Dexmedetomidine (MIDEX) (69) trial data could not be pooled as delirium was assessed only once, 48 hours after sedation discontinuation. Dexmedetomidine was associated with a significant reduction in delirium in the three remaining pooled RCTs that evaluated delirium bid throughout the ICU stay (53, 68, 71). The Safety and Efficacy of Dexmedetomidine Compared With Midazolam (53) and Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) (68) studies both demonstrated a greater incidence of bradycardia in the dexmedetomidine group; neither study found that intervention was required for the bradycardia. We evaluated three RCTs comparing dexmedetomidine and propofol; none of the three demonstrated any difference in time to extubation (67, 69, 72). No data were available for other critical outcomes. A single RCT, the Propofol versus Dexmedetomidine (PRODEX) study, showed that delirium incidence was decreased with dexmedetomidine at the single time point of 48 hours after sedation cessation (69). Patients could communicate more if with dexmedetomidine when compared with propofol (69). No were in bradycardia or hypotension between patients with propofol versus dexmedetomidine (69). sedative choice were not assessed as both propofol and dexmedetomidine acquisition costs are than when they were both propofol and dexmedetomidine practice was considered and dexmedetomidine may not be the unique sedative when deep sedation or is Panel members that the desirable and of propofol (vs dexmedetomidine) were they issued a conditional recommendation to use either agent for sedation of critically ill adults. Delirium Delirium is in critically ill adults. Delirium is a clinical most studies its using such as the Assessment for the ICU or the Delirium Delirium can be for patients and and is associated with cognitive increased ICU and LOS, and greater costs and Question. Should a (vs no such be used to reduce delirium in critically ill adults? Recommendation. We suggest using a intervention that is on not risk for delirium, and and in critically ill adults (conditional recommendation, low quality of evidence). Remarks. These are not to reduce or delirium (e.g., cognitive use of improve (e.g., minimizing light and improve (i.e., reduced sedation), reduce (e.g., early and reduce and/or (e.g., use of such as or eye The intervention studies, many of which were not evaluated a of the use of such significantly reduced delirium ICU duration of delirium in patients who it ICU LOS and mortality all decreased intervention the and Delirium and was significantly associated with less delirium in a study When a and a on assessment and of and was evaluated in a study, and delirium was also assessed using the an analysis showed that in were significantly associated with reduced mortality and more ICU or delirium effects were not in the Delirium Question. Should a agent (vs no use of this be used to delirium in all critically ill adults with Recommendation. We suggest not using an or a A (i.e., a to delirium (conditional recommendation, low quality of evidence). A of 2) and a 1) this This evidence suggests that the use of the an or a was not associated with a shorter duration of delirium, mechanical ventilation or ICU LOS, or decreased Although this recommendation the use of agents in the of delirium, the short-term use of or an in patients may be a of evidence, for those patients who experience significant to the of a delirium, such as and/or or who are and have that may be to or However, all agents should be the of the patient’s Dexmedetomidine Recommendation. We suggest using dexmedetomidine for delirium in mechanically ventilated adults is (conditional recommendation, low quality of evidence). A single randomized trial evaluated role as a for patients from to the study patients and was early because the was Although dexmedetomidine (vs was associated with a but increase in hours within of its use did not affect either ICU or LOS, or patients’ at Immobility and of critical frequently experience many long-term including can in of critically ill patients and is associated with in patients’ long-term physical functioning, and quality of important risk for is The and benefits of rehabilitation and delivered in the ICU have been evaluated as potential to and physical functioning. highlighted in the 2013 guidelines may be as a delirium management important between analgesic and sedation and pain and sedation status with patients in in the ICU Question. For critically ill adults, is rehabilitation or either or in or outcomes compared with usual a or Recommendation. We suggest rehabilitation or in critically ill adults (conditional recommendation, low quality of evidence). Remarks. is a of to optimize and reduce in with a is a of intervention within rehabilitation that the of patients and with a of patient outcomes. This recommendation supports over usual care or similar with a reduced reduced or The implementation of this recommendation will be by particularly related to in the of appropriate and to across We a of RCTs that our and on five critical outcomes. significantly improved at ICU discharge and significantly reduced duration of mechanical ventilation A but not in quality of using the within of discharge was observed across four RCTs had no effect on mortality or short-term physical The incidence of for patients was very low on five trials and outcomes function, and of to and related could not be evaluated to insufficient was assessed as to and to be on In addition, indirect evidence with a with panel members (including an ICU patient suggests that patients benefits Given the of either or and the low quality of evidence, panel members that the desirable for patients probably the Sleep is a and a of for many critically ill patients Sleep in the ICU can be and is by increased light and decreased and eye The of critical delirium, and is but it is important and is an of In addition to has been to to ICU delirium duration of mechanical ventilation and neurocognitive Pharmacologic Question. Should a medication (i.e., dexmedetomidine, or (vs no use of a be used to improve in critically ill adults? Recommendation. We no recommendation the use of to improve in critically ill adults recommendation, very low quality of evidence). randomized trials evaluating the of were of the studies a in quality, but the panel that the data were insufficient to a The of in the United States is not and concerns as to the quality and of the have prevented many from adding it to their however, associated with effects (e.g., sedation and and Dexmedetomidine Recommendation. We no recommendation the use of dexmedetomidine at to improve recommendation, low quality of evidence). randomized trials compared dexmedetomidine to placebo in critically ill mechanically ventilated and in critically ill, ventilated patients not a continuous sedative infusion Dexmedetomidine (vs increased and decreased 1 in both however, neither demonstrated a decrease in or an increase in deep or A not in our these with to and when dexmedetomidine was administered in mechanically ventilated ICU patients a sedative infusion is for a critically ill adult dexmedetomidine may be a because of its potential to improve Propofol Recommendation. We suggest not using propofol to improve in critically ill adults (conditional recommendation, low quality of evidence). RCTs compared propofol to benzodiazepines and one compared propofol to placebo No in with propofol compared with propofol was associated with side and respiratory depression, mechanical Although we recommend using propofol for the of in the critically ill, this recommendation does not to its use in patients or continuous Question. Should a protocol be used to improve in critically ill adults? Recommendation. We suggest using a protocol in critically ill adults (conditional recommendation, very low quality of evidence). The protocols for in their all and to patients and two use of Among the two a more complex of one a guideline that the use of medications to and/or delirium and in over a In all studies, protocols were to all ICU patients and did not a of patients to have RCT in surgery patients demonstrated that and improved self-reported quality the three studies, one found an in in a ICU the other two did not analysis of the three studies demonstrated an reduction in the prevalence of delirium with a of the or of are in and delirium be from the the of the of this executive summary to provide the most clinically and by of the PADIS guidelines that and should using when care for critically ill adults. The recommendation by data and to the the of was for by the panelists and patients in the We that the 2018 PADIS guideline (1) will the delivery of care delirium, and and the of patient-centered research across of these important critical care

A cDNA that encodes type VIII adenylyl cyclase has been isolated from two rat brain libraries. The open reading frame encodes a 1248-amino acid protein predicted to have two sets of six transmembrane spans and two putative nucleotide binding domains as is characteristic of other mammalian adenylyl cyclases. Two type VIII messages are detected in rat brain with estimated sizes of 5.5 and 4.4 kilobases. In situ hybridization indicates that the type VIII messages are most abundantly expressed in the granule cells of the dentate gyrus, the pyramidal cells of hippocampal fields CA1-CA3, the entorhinal cortex, and the piriform cortex. Hybridization is also detected in the neocortex, the amygdaloid complex, and regions of the thalamus and hypothalamus. Stable expression of the type VIII cDNA in human embryonal kidney cells leads to the appearance of a novel 165-kDa glycoprotein in the membrane fraction. Stimulation of these cells with agents that increase intracellular Ca2+ results in up to 43-fold increases in cAMP accumulation over that of control cells transfected with the expression vector. Addition of isoproterenol alone does not lead to type VIII-specific effects in intact cells. Adenylyl cyclase activity in membranes prepared from type VIII-transformed cells is stimulated up to 40-fold by the addition of Ca2+/calmodulin (EC50 = 53 nM calmodulin). The addition of activated recombinant alpha subunit of Gs synergistically increases the Ca2+/calmodulin-stimulated activity. A possible role for type VIII adenylyl cyclase in long-term potentiation is discussed.

Currently available data describing the gene expression and regulation, secretion, distribution, and protein chemistry of osteopontin (OPN) all are consistent with the notions of this protein functioning as an inhibitor of mineralization and/or as a mediator of cell-matrix and matrix-matrix/mineral adhesion (cohesion) during the formation, turnover, and repair of normal and pathological mineralized tissues. The properties and overall integrity of mineralized tissues are in part dictated by the nature of their interfaces--sites where organic and inorganic components of the extracellular matrix interact to provide biomechanical strength, regulate mineral ion homeostasis, and influence cellular events involved in mineralized tissue modeling, remodeling, and repair. High-resolution, colloidal-gold immunocytochemistry has been used to characterize the proteinaceous composition of these interfaces and to establish that the phosphorylated sialoprotein, OPN, is a major component found at these sites where it accumulates as a dense, planar "coating" of organic material termed either a cement line or a lamina limitans. Structural/functional features of OPN predict an ability of this protein to regulate calcification in the matrix proper of mineralized tissues and to participate, more specifically, in cell-matrix and matrix-matrix/mineral adhesion in laminae limitantes and cement lines, respectively. From the ultrastructural immunocytochemical data presented herein for OPN illustrating the cellular expression and extracellular matrix distribution of this protein, it is demonstrated that the production of OPN is one of the earliest, and latest, secretory activities of the osteoblast lineage and that this activity manifests itself morphologically as a cement line or a lamina limitans, respectively, at bone matrix interfaces. In laminae limitantes at bone surfaces, OPN appears to be involved in osteoclast adhesion and possibly haptotaxis. An OPN-containing cement line is also present at hard tissue interfaces in rat tooth, against osseointegrated titanium and hydroxyapatite implants and at the margins of surgically created bone defects--and there may influence biological adhesion in a manner similar to that proposed for normal bone. It is suggested, therefore, that in addition to its potential for influencing cell adhesion/dynamics in bones and teeth, OPN in cement lines may act as an interfacial adhesion promoter between apposing substrates, therein maintaining the overall integrity of bone during the bone remodeling sequence and "bonding" dissimilar tissues (or biocompatible materials) together in biological composites such as teeth and osseointegrated implants.

To successfully accomplish a behavioral goal such as reaching for an object, an animal must solve two related problems: to decide which object to reach and to plan the specific parameters of the movement. Traditionally, these two problems have been viewed as separate, and theories of decision making and motor planning have been developed primarily independently. However, neural data suggests that these processes involve the same brain regions and are performed in an integrated manner. Here, a computational model is described that addresses both the question of how different potential actions are specified and how the brain decides between them. In the model, multiple potential actions are simultaneously represented as continuous regions of activity within populations of cells in frontoparietal cortex. These representations engage in a competition for overt execution that is biased by modulatory influences from prefrontal cortex. The model neural populations exhibit activity patterns that correlate with both the spatial metrics of potential actions and their associated decision variables, in a manner similar to activities in parietal, prefrontal, and premotor cortex. The model therefore suggests an explanation for neural data that have been hard to account for in terms of serial theories that propose that decision making occurs before action planning. In addition to simulating the activity of individual neurons during decision tasks, the model also reproduces key aspects of the spatial and temporal statistics of human choices and makes a number of testable predictions.