The flow cytometry data file standard provides the specifications needed to completely describe flow cytometry data sets within the confines of the file containing the experimental data. In 1984, the first Flow Cytometry Standard format for data files was adopted as FCS 1.0. This standard was modified in 1990 as FCS 2.0 and again in 1997 as FCS 3.0. We report here on the next generation flow cytometry standard data file format. FCS 3.1 is a minor revision based on suggested improvements from the community. The unchanged goal of the standard is to provide a uniform file format that allows files created by one type of acquisition hardware and software to be analyzed by any other type.The FCS 3.1 standard retains the basic FCS file structure and most features of previous versions of the standard. Changes included in FCS 3.1 address potential ambiguities in the previous versions and provide a more robust standard. The major changes include simplified support for international characters and improved support for storing compensation. The major additions are support for preferred display scale, a standardized way of capturing the sample volume, information about originality of the data file, and support for plate and well identification in high throughput, plate based experiments. Please see the normative version of the FCS 3.1 specification in Supporting Information for this manuscript (or at http://www.isac-net.org/ in the Current standards section) for a complete list of changes.

BACKGROUND

The TransEurope FootRace 2009 (TEFR09) was one of the longest transcontinental ultramarathons with an extreme endurance physical load of running nearly 4,500 km in 64 days. The aim of this study was to assess the wide spectrum of adaptive responses in humans regarding the different tissues, organs and functional systems being exposed to such chronic physical endurance load with limited time for regeneration and resulting negative energy balance. A detailed description of the TEFR project and its implemented measuring methods in relation to the hypotheses are presented.

METHODS

The most important research tool was a 1.5 Tesla magnetic resonance imaging (MRI) scanner mounted on a mobile unit following the ultra runners from stage to stage each day. Forty-four study volunteers (67% of the participants) were cluster randomized into two groups for MRI measurements (22 subjects each) according to the project protocol with its different research modules: musculoskeletal system, brain and pain perception, cardiovascular system, body composition, and oxidative stress and inflammation. Complementary to the diverse daily mobile MR-measurements on different topics (muscle and joint MRI, T2*-mapping of cartilage, MR-spectroscopy of muscles, functional MRI of the brain, cardiac and vascular cine MRI, whole body MRI) other methods were also used: ice-water pain test, psychometric questionnaires, bioelectrical impedance analysis (BIA), skinfold thickness and limb circumference measurements, daily urine samples, periodic blood samples and electrocardiograms (ECG).

RESULTS

Thirty volunteers (68%) reached the finish line at North Cape. The mean total race speed was 8.35 km/hour. Finishers invested 552 hours in total. The completion rate for planned MRI investigations was more than 95%: 741 MR-examinations with 2,637 MRI sequences (more than 200,000 picture data), 5,720 urine samples, 244 blood samples, 205 ECG, 1,018 BIA, 539 anthropological measurements and 150 psychological questionnaires.

CONCLUSIONS

This study demonstrates the feasibility of conducting a trial based centrally on mobile MR-measurements which were performed during ten weeks while crossing an entire continent. This article is the reference for contemporary result reports on the different scientific topics of the TEFR project, which may reveal additional new knowledge on the physiological and pathological processes of the functional systems on the organ, cellular and sub-cellular level at the limits of stress and strain of the human body. Please see related articles: http://www.biomedcentral.com/1741-7015/10/76 and http://www.biomedcentral.com/1741-7015/10/77.

The sensory organs of the vertebrate head originate from simple ectodermal structures known as cranial placodes. All cranial placodes derive from a common domain adjacent to the neural plate, the preplacodal region, which is induced at the border of neural and non-neural ectoderm during gastrulation. Induction and specification of the preplacodal region is regulated by the fibroblast growth factor, bone morphogenetic protein, WNT, and retinoic acid signaling pathways, and characterized by expression of the EYA and SIX family of transcriptional regulators. Once the preplacodal region is specified, different combinations of local signaling molecules and placode-specific transcription factors, including competence factors, promote the induction of individual cranial placodes along the neural axis of the head region. In this review, we summarize the steps of cranial placode development and discuss the roles of the main signaling molecules and transcription factors that regulate these steps during placode induction, specification, and development. For further resources related to this article, please visit the WIREs website.

Aging is a natural process of organismal decay that underpins the development of myriad diseases and disorders. Extensive efforts have been made to understand the biology of aging and its regulation, but most studies focus solely on the host organism. Considering the pivotal role of the microbiota in host health and metabolism, we propose viewing the host and its microbiota as a single biological entity whose aging phenotype is influenced by the complex interplay between host and bacterial genetics. In this review we present how the microbiota changes as the host ages, but also how the intricate relationship between host and indigenous bacteria impacts organismal aging and life span. In addition, we highlight other microbiota-dependent mechanisms that potentially regulate aging, and present experimental animal models for addressing these questions. Importantly, we propose microbiome dysbiosis as an additional hallmark and biomarker of aging. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Metallic and metallic oxide nanoparticles (NPs) have been increasingly used for various bio-applications owing to their unique physiochemical properties in terms of conductivity, optical sensitivity, and reactivity. With the extensive usage of NPs, increased human exposure may cause oxidative stress and lead to undesirable health consequences. To date, various endogenous and exogenous sources of oxidants contributing to oxidative stress have been widely reported. Oxidative stress is generally defined as an imbalance between the production of oxidants and the activity of antioxidants, but it is often misrepresented as a single type of cellular stress. At the biological level, NPs can initiate oxidative stress directly or indirectly through various mechanisms, leading to profound effects ranging from the molecular to the disease level. Such effects of oxidative stress have been implicated owing to their small size and high biopersistence. On the other hand, cellular antioxidants help to counteract oxidative stress and protect the cells from further damage. While oxidative stress is commonly known to exert negative biological effects, measured and intentional use of NPs to induce oxidative stress may provide desirable effects to either stimulate cell growth or promote cell death. Hence, NP-induced oxidative stress can be viewed from a wide paradigm. Because oxidative stress is comprised of a wide array of factors, it is also important to use appropriate assays and methods to detect different pro-oxidant and antioxidant species at molecular and disease levels. WIREs Nanomed Nanobiotechnol 2016, 8:414-438. doi: 10.1002/wnan.1374 For further resources related to this article, please visit the WIREs website.

BACKGROUND

Patients interested in aesthetic plastic surgery procedures increasingly seek advice on social media and rely on easily accessible online information. The investigatory goal was to determine the impact of this phenomenon on the everyday aesthetic plastic surgery practice.

METHODS

Five hundred consecutive patients completed a questionnaire prior to their consultation with a plastic surgeon at our clinic. A questionnaire was also completed by 128 plastic surgeons practising in 19 different countries. A literature review was performed.

RESULTS

Almost all patients (95%) used the internet to collect information prior to consultation, for 68% of them it being their first search method. Social media were used by 46% of patients and 40% of these were strongly influenced when choosing a specific doctor. The majority of plastic surgeons (85%) thought the information found on social media could lead to unrealistic expectations. However, 45% of plastic surgeons believed that their consultations became easier after the advent of social media, 29% found them more difficult. A literature review showed a high percentage of poor quality internet websites regarding plastic surgery and an increase in use of social media among plastic surgeons.

CONCLUSIONS

The internet and social media play an important and growing role in plastic surgery. This results in more informed patients but may create unrealistic expectations. Even if the internet provides ample information, it cannot replace the face-to-face consultation, which always should remain a detailed process, covering both risks and limitations of alternative procedures. Available literature on how social media influences the medical practice is still scarce and further research is needed.

METHODS

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry's newly released Diabetes Strategy.After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report.To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,DIABETES STRATEGY EVIDENCE PLATFORM: Summary of Evidence-Based AnalysesContinuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based AnalysisBehavioural Interventions for Type 2 Diabetes: An Evidence-Based AnalysisBARIATRIC SURGERY FOR PEOPLE WITH DIABETES AND MORBID OBESITY: An Evidence-Based SummaryCommunity-Based Care for the Management of Type 2 Diabetes: An Evidence-Based AnalysisHome Telemonitoring for Type 2 Diabetes: An Evidence-Based AnalysisApplication of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario

OBJECTIVE

The objective of this report is to determine whether home telemonitoring and management of blood glucose is effective for improving glycemic control in adults with type 2 diabetes.

BACKGROUND

An aging population coupled with a shortage of nurses and physicians in Ontario is increasing the demand for home care services for chronic diseases, including diabetes. In recent years, there has also been a concurrent rise in the number of blood glucose home telemonitoring technologies available for diabetes management. The Canadian Diabetes Association (CDA) currently recommends self-monitoring of blood glucose for patients with type 2 diabetes, particularly for individuals using insulin. With the emergence of home telemonitoring, there is potential for improving the impact of self-monitoring by linking patients with health care professionals who can monitor blood glucose values and then provide guided recommendations remotely. The MAS has, therefore, conducted a review of the available evidence on blood glucose home telemonitoring and management technologies for type 2 diabetes. EVIDENCE-BASED ANALYSIS OF EFFECTIVENESS:

OBJECTIVE

Is home telemonitoring of blood glucose for adults with type 2 diabetes more efficacious in improving glycemic control (i.e. can it reduce HbA1c levels) in comparison to usual care?

METHODS

METHODS

METHODS

Must involve the frequent transmission of remotely-collected blood glucose measurements by patients to health care professionals for routine monitoring through the use of home telemonitoring technology.

METHODS

Monitoring must be combined with a coordinated management and feedback system based on transmitted data.

METHODS

Usual diabetes care as provided by the usual care provider (usual care largely varies by jurisdiction and study).

METHODS

Adults ≥18 years of age with type 2 diabetes.

RESULTS

≥6 months.

METHODS

≥30 patients total.PUBLICATION TYPE: Randomized controlled trials (RCTs), systematic reviews, and/or meta-analyses.PUBLICATION DATE RANGE: January 1, 1998 to January 31, 2009.

METHODS

Studies with a control group other than usual care.Studies published in a language other than English.Studies in which there is indication that the monitoring of patients' diabetic measurements by a health care professional(s) was not occurring more frequently in intervention patients than in control patients receiving usual care.

METHODS

The primary outcome of interest was a reduction in glycosylated hemoglobin (HbA1c) levels.

METHODS

A comprehensive literature search was performed in OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, CINAHL, The Cochrane Library, and INAHTA for studies published between January 1, 2007 and January 31, 2009. The search was designed as a continuation of a search undertaken for a systematic review by the Canadian Agency for Drugs and Technologies in Health, originally encompassing studies published from 1950 up until July of 2008 and which reviewed home telemonitoring in comparison to usual care for the management of type 1 and type 2 diabetes.

RESULTS

A total of eight studies identified by the literature search were eligible for inclusion (one was excluded post-hoc from analysis). Studies varied considerably on characteristics of design, population, and intervention/control. Of note, few trials limited populations to type 2 diabetics only, thus trials with mixed populations (type 1 and type 2) were included, though in such cases, the majority of patients (>60%) had type 2 diabetes. No studies restricted inclusion or analyses by diabetes treatment type (i.e. populations were mixed with respect to those on insulin therapy vs. not) and studies further varied on whether intervention was provided in addition to usual care or as a replacement. Lastly, trials often included blood glucose home telemonitoring as an adjunct to other telemedicine components and thus the incremental value of adding home telemonitoring remains unclear. The overall grading of the quality of evidence was low, indicating that there is uncertainty in the findings. Meta-analysis of the seven trials identified a moderate but significant reduction in HbA1c levels (~0.5% reduction) in favour blood glucose home telemonitoring compared to usual care for adults with type 2 diabetes). Subgroup analyses suggested differences in effect size depending on the type of intervention, however, these findings should be held under caution as the analyses were exploratory in nature and intervention components overlapped between subgroups. Executive Summary Table 1:Meta-Analyses of Reduction in HbA(1c) Values for Analyzed StudiesGroupEstimate of effect(95% Confidence Interval)Statistical Heterogeneity (I(2))FOLLOW-UP values All studies-0.48 [-0.70 to -0.26]45% Upload studies-0.39 [-0.66 to -0.13]48% Web entry studies-0.66 [-0.99 to -0.33]0%Change-from-baseline values (p=0.5) All studies-0.50 [-0.80 to -0.19]65% Upload studies-0.26 [-0.55 to 0.02]45% Web entry studies-0.78 [-1.14 to -0.43]0%Change-from-baseline values (p=0.65) All studies-0.52 [-0.82 to -0.21]73% Upload studies-0.25 [-0.51 to 0.01]46% Web entry studies-0.78 [-1.08 to -0.48]0%Change-from-baseline values (p=0.85) All studies-0.54 [-0.84 to -0.24]85% Upload studies-0.21 [-0.41 to 0.00]47% Web entry studies-0.81 [-1.11 to -0.51]49%

CONCLUSIONS

Based on low quality evidence, blood glucose home telemonitoring technologies confer a statistically significant reduction in HbA1c of ~0.50% in comparison to usual care when used adjunctively to a broader telemedicine initiative for adults with type 2 diabetes.Exploratory analysis suggests differences in effect sizes for the primary outcome when analyzing by subgroup; however, this should only be viewed as exploratory or hypothesis-generating only.Significant limitations and/or sources of clinical heterogeneity are present in the available literature, generating great uncertainty in conclusions.More robust trials in type 2 diabetics only, utilizing more modern technologies, preferably performed in an Ontario or a similar setting (given the infrastructure demands and that the standard comparator is usual care), while separating out the effects of other telemedicine intervention components, are needed to clarify the effect of emerging remote blood glucose monitoring technologies.

BACKGROUND

This prospective registry assessed the safety and efficacy of paclitaxel coated balloon (PCB) angioplasty for small vessel coronary artery disease in Europe and Asia with the intention to treat lesions without additional stenting. The use of PCBs in small vessels seems to be associated with favourable outcomes; however, prospective data for the use of PCBs without stenting are limited.

METHODS

The SeQuent Please Small Vessel 'PCB only' Registry was an international, prospective, multicentre registry enrolling patients with de novo lesions of small reference diameters (≥ 2.0 mm, ≤ 2.75 mm). The primary end point was clinically driven target lesion revascularisation (TLR) at 9 months. Secondary end points were acute technical success, in-hospital outcomes, 9-month major adverse cardiac events (MACE) (death, myocardial infarction, or TLR), and the occurrence of definite lesion and vessel thrombosis.

RESULTS

A total of 479 patients (66.1 ± 10.9 years, 36.7% diabetics) were enrolled, 105 (23.5%) with an acute coronary syndrome, 41 (9.2%) with ST elevation myocardial infarction (STEMI), and 60 (14.8%) with non-STEMI. The initial procedural success rate was 99.0%; 27 patients (6%) needed additional bare metal stent implantation. TLR at 9.4±1.7 months occurred in 14 patients (3.6%), while three patients (0.6%) had vessel thrombosis in non-target lesions. There was no cardiac death or coronary artery bypass graft surgery.

CONCLUSIONS

To date, this is the largest prospective study with PCBs in small vessel de novo lesions in unselected patients. Rates of TLR and MACE were low, suggesting the use of PCBs may be an attractive alternative treatment option to drug eluting stents in small vessels.

Bacteria are ubiquitous in the bovine uterus after parturition, but 50 years ago, cows tolerated these bacteria and few animals developed uterine disease. Now, up to 40% of dairy cattle develop postpartum uterine disease. Uterine disease causes infertility by compromising the function of not only the endometrium but also the ovary. Animals defend themselves against pathogens using tolerance and resistance mechanisms. Tolerance is the ability to limit the disease severity induced by a given pathogen burden. Resistance is the ability to limit the pathogen burden and is usually the function of immunity. Endometrial cells contribute to tolerance and have roles in innate immunity and the inflammatory response to pathogens. However, failures in endometrial tolerance and the character of the inflammatory response shape postpartum uterine disease. We propose that uterine health is more dependent on the ability of the endometrium to tolerate pathogens than the ability to resist invading bacteria. Expected final online publication date for the Annual Review of Animal Biosciences Volume 7 is February 15, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The lung is often overlooked as a metabolically active organ, yet biochemical studies have long demonstrated that glucose utilization surpasses that of many other organs, including the heart, kidney, and brain. For most cells in the lung, energy consumption is relegated to performing common cellular tasks, like mRNA transcription and protein translation. However, certain lung cell populations engage in more specialized types of energy-consuming behaviors, such as the beating of cilia or the production of surfactant. While many extrapulmonary diseases are now linked to abnormalities in cellular metabolism, the pulmonary community has only recently embraced the concept of metabolic dysfunction as a driver of respiratory pathology. Herein, we provide an overview of the major metabolic pathways in the lung and discuss how cells sense and adapt to low-energy states. Moreover, we review some of the emerging evidence that links alterations in cellular metabolism to the pathobiology of several common respiratory diseases. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Gene expression is a fundamental process that underlies development, homeostasis, and behavior of organisms. The fact that it relies on nucleic acid intermediates, which can specifically interact with complementary probes, provides an excellent opportunity for studying the multiple steps--transcription, RNA processing, transport, translation, degradation, and so forth--through which gene function manifests. Over the past three decades, the toolbox of nucleic acid science has expanded tremendously, making high-precision in situ detection of DNA and RNA possible. This has revealed that many--probably the vast majority of--transcripts are distributed within the cytoplasm or the nucleus in a nonrandom fashion. With the development of microscopy techniques we have learned not only about the qualitative localization of these molecules but also about their absolute numbers with great precision. Single-molecule techniques for nucleic acid detection have been transforming our views of biology with elementary power: cells are not average members of their population but are highly distinct individuals with greatly and suddenly changing gene expression, and this behavior of theirs can be measured, modeled, and thus predicted and, finally, comprehended. For further resources related to this article, please visit the WIREs website.

BACKGROUND

The authors have declared no conflicts of interest for this article.

The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Increasingly, studies are revealing that these chemicals impact host biology, either by acting on cells within the gastrointestinal tract or entering circulation and exerting their effects at distal sites within the body. Given the high level of functional diversity in the gut microbiome and the varied diets that we consume, the repertoire of microbiota-derived molecules within our bodies varies dramatically across individuals. Thus, the microbes in our gut and the metabolic end products they produce represent a phenotypic lever that we can potentially control to develop new therapeutics for personalized medicine. Here, we review current understanding of how microbes in the gastrointestinal tract contribute to the molecules within our gut and those that circulate within our bodies. We also highlight examples of how these molecules affect host physiology and discuss potential strategies for controlling their production to promote human health and to treat disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 15 is January 24, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. WIREs Syst Biol Med 2016, 8:517-535. doi: 10.1002/wsbm.1355 For further resources related to this article, please visit the WIREs website.

This review is based on a Cochrane systematic review entitled 'Interventions for replacing missing teeth: management of soft tissues for dental implants' published in The Cochrane Library (see http:// www.cochrane.org/ for information). Cochrane systematic reviews are regularly updated to include new research, and in response to comments and criticisms from readers. If you wish to comment on this review, please send your comments to the Cochrane website or to Marco Esposito. The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of the review authors, and are not necessarily shared by the Cochrane Collaboration.

OBJECTIVE

To evaluate whether flapless procedures are beneficial for patients and which is the ideal flap design, whether soft tissue correction/augmentation techniques are beneficial for patients and which are the best techniques, whether techniques to increase the peri-implant keratinised mucosa are beneficial for patients and which are the best techniques, and which are the best suturing techniques/ materials.

METHODS

The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched up to the 9th of June 2011 for randomised controlled trials (RCTs) of rootform osseointegrated dental implants, with a follow-up of at least 6 months after function, comparing various techniques to handle soft tissues in relation to dental implants. Primary outcome measures were prosthetic failures, implant failures and biological complications. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted at least in duplicate and independently by two or more review authors. The statistical unit was the patient and not the prosthesis, the procedure or the implant. RESULTS were expressed using risk ratios for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals (CI).

RESULTS

Seventeen potentially eligible RCTs were identified but only six trials with 138 patients in total could be included. The following techniques were compared in the six included studies: flapless placement of dental implants versus conventional flap elevation (2 trials, 56 patients), crestal versus vestibular incisions (1 trial, 10 patients), Erbium:YAG laser versus flap elevation at the second-stage surgery for implant exposure (1 trial, 20 patients), whether a connective tissue graft at implant placement could be effective in augmenting peri-implant tissues (1 split-mouth trial, 10 patients), and autograft versus an animal-derived collagen matrix to increase the height of the keratinised mucosa (1 trial, 40 patients). On a patient rather than per implant basis, implants placed with a flapless technique and implant exposures performed with laser lead to statistically significantly less postoperative pain than flap elevation. Sites augmented with soft tissue connective grafts had better aesthetics and thicker tissues. Both palatal autografts or the use of a porcine-derived collagen matrix are effective in increasing the height of keratinised mucosa at the cost of a 0.5 mm recession of peri-implant soft tissues. There were no other statistically significant differences for any of the remaining analyses.

CONCLUSIONS

There is limited weak evidence suggesting that flapless implant placement is feasible and has been shown to reduce patient postoperative discomfort in adequately selected patients, that augmentation at implant sites with soft tissue grafts is effective in increasing soft tissue thickness and improving aesthetics, and that one technique to increase the height of keratinised mucosa using autografts or an animal-derived collagen matrix was able to achieve its goal but at the cost of a worsened aesthetic outcome (0.5 mm of recession). There is insufficient reliable evidence to provide recommendations on which is the ideal flap design, the best soft tissue augmentation technique, whether techniques to increase the width of keratinised/attached mucosa are beneficial to patients or not, and which are the best incision/suture techniques/materials. Properly designed and conducted RCTs, with at least 6 months of follow-up, are needed to provide reliable answers to these questions.

Phosphorylation of fascin at serine 39 (phospho-S39-fascin) could inhibit its actin-binding and actin-bundling activities and decrease filopodia formation. However, the relationship between phospho-S39-fascin expression and clinicopathological parameters in tumors is still unknown. Here, Western blot analysis and IHC applied to tissue microarray technology were performed to examine the expression status of non-phosphorylated fascin (fascin) and phospho-S39-fascin and their impacts on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Fascin and phospho-S39-fascin expressions were tested by cytoplasmic staining. Among the 254 patients, 90 cases showed high expression of fascin and 87 cases showed high expression of phospho-S39-fascin. Survival analysis showed that high expression of fascin was significantly associated with a poor prognosis of the patients with ESCC (p=0.004). In contrast, high expression of phospho-S39-fascin correlated significantly with an improved outcome of patients (p=0.020). Multivariate analysis showed that both fascin and phospho-S39-fascin were independent prognostic factors. In a combined analysis, the patients with high expression of fascin and low expression of phospho-S39-fascin tumors had a shorter overall survival than those with high expression of both fascin and phospho-S39-fascin tumors (5-year overall survival rate: 28.7% vs 48.3%, p=0.068). Our results suggest that high expression of fascin correlates with poor outcome and that high expression of phospho-S39-fascin decreases the risk of poor prognosis in ESCC. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments.

To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer.

We conducted a literature search including a major electronic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE (Ovid), and Embase (Ovid); handsearching conference proceedings; checking references of included studies; use of the 'related citation' feature in PubMed and a search for ongoing studies in trial registries. As part of the living systematic review approach, we run searches continually, incorporating new evidence after it is identified. Last search date 14 May 2018.

Randomized controlled trials (RCTs) assessing the benefits and harms of long-term treatment with LMWHs, DOACs or VKAs in people with cancer and symptomatic VTE.

We extracted data in duplicate on study characteristics and risk of bias. Outcomes included: all-cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia, and health-related quality of life (QoL). We assessed the certainty of the evidence at the outcome level following the GRADE approach (GRADE handbook).

Of 15,785 citations, including 7602 unique citations, 16 RCTs fulfilled the eligibility criteria. These trials enrolled 5167 people with cancer and VTE.Low molecular weight heparins versus vitamin K antagonistsEight studies enrolling 2327 participants compared LMWHs with VKAs. Meta-analysis of five studies probably did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on mortality up to 12 months of follow-up (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.13; risk difference (RD) 0 fewer per 1000, 95% CI 45 fewer to 48 more; moderate-certainty evidence). Meta-analysis of four studies did not rule out a beneficial or harmful effect of LMWHs compared to VKAs on major bleeding (RR 1.09, 95% CI 0.55 to 2.12; RD 4 more per 1000, 95% CI 19 fewer to 48 more, moderate-certainty evidence) or minor bleeding (RR 0.78, 95% CI 0.47 to 1.27; RD 38 fewer per 1000, 95% CI 92 fewer to 47 more; low-certainty evidence), or thrombocytopenia (RR 0.94, 95% CI 0.52 to 1.69). Meta-analysis of five studies showed that LMWHs probably reduced the recurrence of VTE compared to VKAs (RR 0.58, 95% CI 0.43 to 0.77; RD 53 fewer per 1000, 95% CI 29 fewer to 72 fewer, moderate-certainty evidence).Direct oral anticoagulants versus vitamin K antagonistsFive studies enrolling 982 participants compared DOACs with VKAs. Meta-analysis of four studies may not rule out a beneficial or harmful effect of DOACs compared to VKAs on mortality (RR 0.93, 95% CI 0.71 to 1.21; RD 12 fewer per 1000, 95% CI 51 fewer to 37 more; low-certainty evidence), recurrent VTE (RR 0.66, 95% CI 0.33 to 1.31; RD 14 fewer per 1000, 95% CI 27 fewer to 12 more; low-certainty evidence), major bleeding (RR 0.77, 95% CI 0.38 to 1.57, RD 8 fewer per 1000, 95% CI 22 fewer to 20 more; low-certainty evidence), or minor bleeding (RR 0.84, 95% CI 0.58 to 1.22; RD 21 fewer per 1000, 95% CI 54 fewer to 28 more; low-certainty evidence). One study reporting on DOAC versus VKA was published as abstract so is not included in the main analysis.Direct oral anticoagulants versus low molecular weight heparinsTwo studies enrolling 1455 participants compared DOAC with LMWH. The study by Raskob did not rule out a beneficial or harmful effect of DOACs compared to LMWH on mortality up to 12 months of follow-up (RR 1.07, 95% CI 0.92 to 1.25; RD 27 more per 1000, 95% CI 30 fewer to 95 more; low-certainty evidence). The data also showed that DOACs may have shown a likely reduction in VTE recurrence up to 12 months of follow-up compared to LMWH (RR 0.69, 95% CI 0.47 to 1.01; RD 36 fewer per 1000, 95% CI 62 fewer to 1 more; low-certainty evidence). DOAC may have increased major bleeding at 12 months of follow-up compared to LMWH (RR 1.71, 95% CI 1.01 to 2.88; RD 29 more per 1000, 95% CI 0 fewer to 78 more; low-certainty evidence) and likely increased minor bleeding up to 12 months of follow-up compared to LMWH (RR 1.31, 95% CI 0.95 to 1.80; RD 35 more per 1000, 95% CI 6 fewer to 92 more; low-certainty evidence). The second study on DOAC versus LMWH was published as an abstract and is not included in the main analysis.Idraparinux versus vitamin K antagonistsOne RCT with 284 participants compared once-weekly subcutaneous injection of idraparinux versus standard treatment (parenteral anticoagulation followed by warfarin or acenocoumarol) for three or six months. The data probably did not rule out a beneficial or harmful effect of idraparinux compared to VKAs on mortality at six months (RR 1.11, 95% CI 0.78 to 1.59; RD 31 more per 1000, 95% CI 62 fewer to 167 more; moderate-certainty evidence), VTE recurrence at six months (RR 0.46, 95% CI 0.16 to 1.32; RD 42 fewer per 1000, 95% CI 65 fewer to 25 more; low-certainty evidence) or major bleeding (RR 1.11, 95% CI 0.35 to 3.56; RD 4 more per 1000, 95% CI 25 fewer to 98 more; low-certainty evidence).

For the long-term treatment of VTE in people with cancer, evidence shows that LMWHs compared to VKAs probably produces an important reduction in VTE and DOACs compared to LMWH, may likely reduce VTE but may increase risk of major bleeding. Decisions for a person with cancer and VTE to start long-term LMWHs versus oral anticoagulation should balance benefits and harms and integrate the person's values and preferences for the important outcomes and alternative management strategies.Editorial note: this is a living systematic review (LSR). LSRs offer new approaches to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

When the brain is presented with ambiguous visual stimuli supporting two interpretations, perception becomes bistable and alternates over time between one interpretation and the other. This process contains elements of competition (between the rivaling percepts) as well as inhibition, as the percepts are mutually exclusive so that one is always suppressed. This review covers the most widely studied form of bistable perception-binocular rivalry. Suppression in rivalry is covered in detail, including discussion of its general and specific components, its local nature and spatial organization, techniques for quantifying it, and the role of global feedback. The competitive dynamics of rivalry are discussed within the context of the classical 'adapting reciprocal inhibition' model of rivalry and recent evidence supporting this model is discussed. This model is contrasted with alternative models based on late competition and with hybrid models. Finally, the role of attention in rivalry is examined and commonalities with other forms of bistable perception are noted. WIREs Cogn Sci 2012, 3:87-103. doi: 10.1002/wcs.151 For further resources related to this article, please visit the WIREs website.

One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. Sadenosylmethionine is a potent aminopropyl and methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA. We propose that 1C metabolism functions as a key biochemical conduit between parental environment and epigenetic regulation of early development and that interindividual and ethnic variability in epigenetic-gene regulation arises because of genetic variants within 1C genes, associated epigenetic regulators, and differentially methylated target DNA sequences. We present evidence to support these propositions, drawing upon studies undertaken in humans and animals. We conclude that future studies should assess the epigenetic effects of cumulative (multigenerational) dietary imbalances contemporaneously in both parents, as this better represents the human experience. Expected final online publication date for the Annual Review of Animal Biosciences Volume 7 is February 15, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Placebo effects constitute a major part of treatment success in medical interventions. The nocebo effect also has a major impact, as it accounts for a significant proportion of the reported side effects for many treatments. Historically, clinical trials have aimed to reduce placebo effects; however, currently, there is interest in optimizing placebo effects to improve existing treatments and in examining ways to minimize nocebo effects to improve clinical outcome. To achieve these aims, a better understanding of the psychological and neurobiological mechanisms of the placebo and nocebo response is required. This review discusses the impact of the placebo and nocebo response in health care. We also examine the mechanisms involved in the placebo and nocebo effects, including the central mechanism of expectations. Finally, we examine ways to enhance placebo effects and reduce the impact of the nocebo response in clinical practice and suggest areas for future research. Expected final online publication date for the Annual Review of Psychology Volume 70 is January 4, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Positive affect (PA) is associated with better health across a wide range of physical health outcomes. This review reflects on why the study of PA is an essential component of our understanding of physical health and expands on pathways that connect these two variables. To encourage forward movement in this burgeoning research area, measurement and design issues in the study of PA and health are discussed, as are the connections between PA and a range of different health outcomes. Plausible biological, social, and behavioral pathways that allow for positive feelings to get under the skin and influence physical wellness are detailed and framed in the context of several theoretical models. Finally, new directions for the field and important methodological and interpretative considerations that are essential to moving this important research area forward are explored. Expected final online publication date for the Annual Review of Psychology Volume 70 is January 4, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Tendon is a uniaxial connective tissue component of the musculoskeletal system. Tendon is involved in force transmission between muscle and bone. Tendon injury is very common and debilitating but tendon repair remains a clinical challenge for orthopedic medicine. In vertebrates, tendon is mainly composed of type I collagen fibrils, displaying a parallel organization along the tendon axis. The tendon-specific spatial organization of type I collagen provides the mechanical properties for tendon function. In contrast to other components of the musculoskeletal system, tendon biology is poorly understood. An important goal in tendon biology is to understand the mechanisms involved in the production and assembly of type I collagen fibrils during development, postnatal formation, and healing processes in order to design new therapies for tendon repair. In this review we highlight the current understanding of the molecular and mechanical signals known to be involved in tenogenesis during development, and how development provides insights into tendon healing processes. WIREs Dev Biol 2016, 5:5-23. doi: 10.1002/wdev.201 For further resources related to this article, please visit the WIREs website.

Voltage-gated sodium and calcium channels are evolutionarily related transmembrane signaling proteins that initiate action potentials, neurotransmission, excitation-contraction coupling, and other physiological processes. Genetic or acquired dysfunction of these proteins causes numerous diseases, termed channelopathies, and sodium and calcium channels are the molecular targets for several major classes of drugs. Recent advances in the structural biology of these proteins using X-ray crystallography and cryo-electron microscopy have given new insights into the molecular basis for their function and pharmacology. Here we review this recent literature and integrate findings on sodium and calcium channels to reveal the structural basis for their voltage-dependent activation, fast and slow inactivation, ion conductance and selectivity, and complex pharmacology at the atomic level. We conclude with the theme that new understanding of the diseases and therapeutics of these channels will be derived from application of the emerging structural principles from these recent structural analyses. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.