bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Concepts in Debridement: Science and Strategies
Authors: Anghel Ersilia L. , DeFazio Michael V. , Barker Jenny C. , Janis Jeffrey E. , Attinger Christopher E.
Published: August 2016

Background:

The establishment of a healthy wound bed through adequate debridement of infected, senescent, and/or devitalized tissue is central to the progression of normal wound healing. Although a variety of surgical and nonsurgical strategies have been proposed, none have proven completely effective in all settings. This review focuses on the principles and techniques of modern debridement practices employed in the management of complex wounds.

Methods:

A comprehensive review of the PubMed/Medline and Ovid databases was performed to identify basic science and clinical studies using key words most relevant to biofilm, debridement, and wound healing. English language articles that were peer reviewed and that met the standard of evidence-based medicine were included. Level of evidence for various debridement approaches was rated utilizing the American Society of Plastic Surgeons Rating Levels of Evidence and Grading Recommendations.

Results:

The value of both operative and nonoperative debridement techniques, their indications, and limitations are described. With an emphasis placed on surgical debridement, this review highlights technical adjuncts that can be used to optimize wound bed preparation, including preoperative topical staining of the wound, as well as the use of color-guided endpoints to prevent removal of excess healthy tissue. The indications for using temporizing measures for wound control such as negative pressure wound therapy with and without installation are also discussed.

Conclusion:

Optimal management requires a multimodal approach that centers around operative debridement and incorporates the use of adjunctive measures to facilitate the removal of infected tissue, biofilm, and/or senescent cells that impede the progression of normal wound healing.
What Heals Hidradenitis Suppurativa: Surgery, Immunosuppression, or Both?
Authors: Falola Reuben A. , DeFazio Michael V. , Anghel Ersilia L. , Mitnick Carol Deane B. , Attinger Christopher E. , Evans Karen K.
Published: August 2016

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin that is a significant source of impaired quality-of-life for affected individuals. For patients with refractory disease, radical resection of all involved tissue may offer the only potential option for a cure. However, high rates of recurrence after wide local excision have led investigators to seek alternative therapeutic combinations. We present our experience and a literature review.

Methods:

A comprehensive literature review (1982–2016) was performed on PubMed and Ovid MEDLINE, using key words relevant to HS.

Results:

A total of 1842 publications were identified, and 15 publications were included in this review on: surgical intervention (n = 10), biologic therapy (n = 4), and joint surgical and biologic treatment (n = 1) of HS. The treatment type, level of evidence, and key findings are assessed and discussed.

Conclusions:

Recent trials demonstrating the safety and efficacy of biologic therapy alone in patients with moderate-to-severe HS have spurred questions regarding the potential utility of these agents as adjuncts to more traditional surgical interventions. The results of the literature search advocate a role for radical resection and biologic therapy in the setting of moderate-to-severe disease. Preliminary results from limited case series suggest a potential role for combined management in the setting of advanced, recalcitrant disease.
Modalities to Treat Venous Ulcers: Compression, Surgery, and Bioengineered Tissue
Authors: Gould Lisa J. , Dosi Garima , Couch Kara , Gibbons Gary W. , Howell Raelina S. , Brem Harold , Tomic-Canic Marjana
Published: August 2016

Background:

Venous leg ulcers (VLUs) represent the most common ulcers of the lower extremity. VLUs are notorious for delayed and prolonged healing with high rates of recurrence. Most patients with VLUs also have significant comorbidities that interfere with primary wound healing. Thus, caring for patients with VLUs requires an interdisciplinary approach that addresses the abnormal venous anatomy and the downstream effects that lead to inflammation, ulceration, and a hostile wound microenvironment.

Methods:

The current literature regarding venous ulcer treatment with an emphasis on compression, surgical options, and use of bioengineered tissue was reviewed. A combination of society guidelines, Cochrane reviews, and over 80 primary articles with high-level evidence were utilized to develop this summary and algorithm for an integrated approach to treating patients with venous ulcers. Details regarding compression modalities and venous diagnostic imaging are presented to help the clinician understand the rationale for using these technologies.

Results:

The comprehensive approach to the patient with chronic venous insufficiency (CVI) includes advances in compression, diagnostics, minimally invasive surgical treatment of venous disease, wound bed preparation, and bioengineered skin and soft tissue substitutes. An algorithm that incorporates early treatment of the ulcer and the venous disease leading to healing with prevention of recurrence is presented.

Conclusions:

Utilizing guidelines that incorporate evidence-based modalities will lead to the highest quality outcomes with the most appropriate resource utilization. A proactive approach to treating venous disease will alleviate suffering and prevent the long-term sequelae of CVI.
Biology and Biomarkers for Wound Healing
Authors: Lindley Linsey E. , Stojadinovic Olivera , Pastar Irena , Tomic-Canic Marjana
Published: August 2016

Background:

As the population grows older, the incidence and prevalence of conditions that lead to a predisposition for poor wound healing also increase. Ultimately, this increase in nonhealing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has and will continue to be the leading pathway to the discovery of therapeutic targets, as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of nonhealing patients for whom biomarker-guided approaches may aid in healing.

Methods:

A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches.

Results:

Currently, biomarkers are being identified using biomaterials sourced locally from human wounds and/or systemically using high-throughput “omics” modalities (genomic, proteomic, lipidomic, and metabolomic analysis). In this review, we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum, including those measured in tissue specimens, for example, β-catenin and c-myc, wound fluid, matrix metalloproteinases and interleukins, swabs, wound microbiota, and serum, for example, procalcitonin and matrix metalloproteinases.

Conclusions:

Identification of numerous potential biomarkers using different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity and consistent implementation of these biomarkers, as well as an emphasis on efficacious follow-up therapeutics, is necessary for transition of this technology to clinically feasible point-of-care applications.
Current Concepts in Tissue Engineering: Skin and Wound
Authors: Tenenhaus Mayer , Rennekampff Hans-Oliver
Published: August 2016

Background:

Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing.

Methods:

Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included.

Results:

Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption.

Conclusions:

Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.
What Role Does Function Play in Deciding on Limb Salvage versus Amputation in Patients With Diabetes?
Authors: Wukich Dane K. , Raspovic Katherine M.
Published: August 2016

Background:

Patients with diabetic foot disease are at an increased risk for lower extremity amputation (LEA), premature mortality, and reduced health-related quality of life. In the setting of chronic infection, significant tissue loss, and/or an unstable deformity, limb salvage may not be possible, and major amputation is necessary.

Methods:

The primary goal of this study was to review the literature with an emphasis on the functional aspects associated with successful limb salvage versus major LEA. A secondary goal was to review the epidemiology, quality of life, mortality, and energy expenditure associated with diabetic foot disease.

Results:

After major LEA, patients with diabetes are 3 times more likely to die within 1 year of surgery compared with patients who have not undergone LEA. Only two thirds of diabetic patients who undergo major LEA will ambulate with a prosthesis. This increased risk of death is not fully explained by complications of diabetes mellitus such as heart attack, stroke, or kidney failure. Preservation of lower extremity function is the primary goal of treatment, and reconstructive surgery should strive to achieve a plantigrade foot that is ulcer free and stable. Patients who have undergone successful limb salvage fear major amputation more than death. The energy costs of ambulation after LEA increase as the site of LEA becomes more proximal.

Conclusions:

Major LEA is a devastating complication in patients with diabetes. Once amputation becomes medically necessary, preoperative evaluation with a clinic specializing in amputations is very beneficial for these patients.
An Update on the Appropriate Role for Hyperbaric Oxygen: Indications and Evidence
Authors: Fife Caroline E. , Eckert Kristen A. , Carter Marissa J.
Published: August 2016

Background:

Among advanced therapeutic interventions for wounds, hyperbaric oxygen therapy (HBOT) has the unique ability to ameliorate tissue hypoxia, reduce pathologic inflammation, and mitigate ischemia reperfusion injury. Most of the conditions for which it is utilized have few successful alternative treatments, and the morbidity and mortality associated with treatment failure are significant. Data on the efficacy and effectiveness of HBOT were reviewed, comparative effectiveness research of HBOT was explained, and a new paradigm for the appropriate use of HBOT was described.

Methods:

Systematic reviews and randomized controlled trials that have evaluated HBOT were reviewed.

Results:

Although numerous small randomized controlled trials provide compelling support for HBOT, the physics of the hyperbaric environment create significant barriers to trial design. The electronic health record infrastructure created to satisfy mandatory quality and registry reporting requirements as part of healthcare reform can be harnessed to facilitate the acquisition of real world data for HBOT comparative effectiveness studies and clinical decision support.

Conclusions:

Predictive models can identify patients unlikely to heal spontaneously and most likely to benefit from HBOT. Although electronic health records can automate the calculation of predictive models making them available at the point of care, using them in clinical decision making is complicated. It is not clear whether stakeholders will support the allocation of healthcare resources using mathematical models, but the current patient selection process mandates a 30-day delay for all patients who might benefit and allows treatment for at least some patients who cannot benefit.
Wound Healing: Part I. Basic Science
Authors: Janis Jeffrey E. , Harrison Bridget
Published: August 2016

Learning Objectives:

After studying this article, the participant should be able to: 1. Describe the basic physiologic events in normal wound healing. 2. Understand the differences in healing among skin, bone, cartilage, and tendon. 3. Identify factors that may compromise or delay wound healing. 4. Describe methods for optimal closure of a wound.

Understanding the physiology and pathophysiology of normal wound healing and potential impediments to its end will allow the plastic surgeon to maximize postoperative outcomes and, in some instances, avoid unnecessary surgical interventions. Continuous advancements in our understanding of this process require frequent reviews of available data to permit reliable, evidence-based recommendations for clinical application. This is the first of a two-part article summarizing the science and clinical recommendations necessary for successful wound healing.
The Effect of Light-Intensity Cycling on Mood and Working Memory in Response to a Randomized, Placebo-Controlled Design
Authors: Lindheimer Jacob B. , O'Connor Patrick J. , McCully Kevin K. , Dishman Rod K.
Published: August 2016

Objective

Prior attempts to measure psychological responses to exercise are potentially limited by a failure to account for participants' expectations, the absence of a valid exercise placebo, and demand characteristics. The purpose of this study was to explore the main and interactive effects of a manipulation designed to increase expectations about the psychological benefits of an acute bout of active, light-intensity (treatment), and passive (placebo) cycling on mood and cognition. Demand characteristics were attenuated during recruitment, informed consent, and interactions with test administrators by communicating to participants that the study purpose was to assess the effects of active and passive cycling on respiration, heart rate, and muscle activation.

Methods

A repeated-measures, randomized, placebo-controlled design (n = 60) was used with cycling (active, passive) and information (informed, not informed) as between-subjects factors. State anxiety, feelings of energy, and working memory (percent accuracy and reaction time for correct responses) were measured at baseline (time 1), immediately after cycling (time 2) and 20 minutes after cycling (time 3).

Results

Most participants did not guess the purpose of the study (~92%) or expect a reduction in state anxiety (85%) or an increase in energy (80%) or cognitive performance (~93%). Mood and cognitive performance were not improved by active or passive cycling (all p values ≥ .12).

Conclusions

The methods used here to disguise the experimental hypotheses provide a potential framework for reducing demand characteristics and placebo responses in future investigations of psychological responses to exercise.
Brief Report: The Right People, Right Places, and Right Practices: Disparities in PrEP Access Among African American Men, Women, and MSM in the Deep South
Authors: Elopre Latesha , Kudroff Kachina , Westfall Andrew O. , Overton Edgar T. , Mugavero Michael J.
Published: August 2016

Disproportionate rates of HIV are observed in Black women and men, especially in the Southern United States. We observed limited uptake of preexposure prophylaxis (PrEP) services in our Southern community among these groups, particularly Black men who have sex with men relative to new HIV cases in Birmingham, AL; 18% accessed PrEP services compared with 50% of new HIV cases. Further research is needed to understand PrEP access and uptake in high-risk populations.
Role of Ultrasound in Complications of Hematopoetic Stem Cell Transplantation
Authors: Chauhan Anil , Faizi Nauroze A. , Chen Yin Jie , Jones Lisa P. , Garg Naveen , Bhosale Priya R.
Published: August 2016

Hematopoetic stem cell transplantation (HSCT) is an established therapeutic option for both malignant and nonmalignant indications, whose incidence has continued to increase in recent years. Because of its lower cost and lack of radiation exposure, ultrasound examination is often the first-line imaging modality in evaluating patients both before and after HSCT. It is important for radiologists to be aware of sonographic manifestations of the complications that may arise from HSCT. In this study, we will review the basics of HSCT, the role of imaging, and ultrasound examination findings in common and uncommon complications arising from HSCT.
Clinical Significance of Totally Laparoscopic Distal Gastrectomy: A Comparison of Short-term Outcomes Relative to Open and Laparoscopic-assisted Distal Gastrectomy
Authors: Nishimura Sho , Oki Eiji , Tsutsumi Satoshi , Tsuda Yasuo , Sugiyama Masahiko , Nakashima Yuichiro , Sonoda Hideto , Ohgaki Kippei , Saeki Hiroshi , Maehara Yoshihiko
Published: August 2016

Background:

Laparoscopic distal gastrectomy has become an established minimally invasive treatment for gastric cancer since it was first reported in 1994.

Materials and Methods:

We retrospectively assessed the clinical outcomes of 248 patients who had undergone open distal gastrectomy (ODG), laparoscopic-assisted distal gastrectomy (LADG), and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer.

Results and Conclusions:

TLDG showed superiority in terms of blood loss, reconstruction options, and postoperative recovery compared with ODG and LADG. Especially, the mean operating time in the TLDG group was significantly shorter than that of the LADG group (P=0.003). Book-binding technique used in TLDG was one of the reasons of this result. The only inferior aspect of TLDG was the longer operating time compared with ODG; TLDG had no disadvantages compared with LADG. Although the operating time and long-term outcome remain problems, we suggest that TLDG has the potential to serve as an optimal operative method.
Meteorological responses in the atmospheric boundary layer over southern England to the deep partial eclipse of 20 March 2015
Authors: Burt Stephen
Published: August 2016

A wide range of surface and near-surface meteorological observations were made at the University of Reading’s Atmospheric Observatory in central southern England (latitude 51.441° N, longitude 0.938° W, altitude 66 m above mean sea level) during the deep partial eclipse on the morning of 20 March 2015. Observations of temperature, humidity, radiation, wind speed and direction, and atmospheric pressure were made by computerized logging equipment at 1 Hz, supplemented by an automated cloud base recorder sampling at 1 min intervals and a high-resolution (approx. 10 m vertical interval) atmospheric sounding by radiosonde launched from the same location during the eclipse. Sources and details of each instrumental measurement are described briefly, followed by a summary of observed and derived measurements by meteorological parameter. Atmospheric boundary layer responses to the solar eclipse were muted owing to the heavily overcast conditions which prevailed at the observing location, but instrumental records of the event documented a large (approx. 80%) reduction in global solar radiation, a fall in air temperature of around 0.6°C, a decrease in cloud base height, and a slight increase in atmospheric stability during the eclipse. Changes in surface atmospheric moisture content and barometric pressure were largely insignificant during the event.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Using the ionospheric response to the solar eclipse on 20 March 2015 to detect spatial structure in the solar corona
Authors: Scott C. J. , Bradford J. , Bell S. A. , Wilkinson J. , Barnard L. , Smith D. , Tudor S.
Published: August 2016

The total solar eclipse that occurred over the Arctic region on 20 March 2015 was seen as a partial eclipse over much of Europe. Observations of this eclipse were used to investigate the high time resolution (1 min) decay and recovery of the Earth’s ionospheric E-region above the ionospheric monitoring station in Chilton, UK. At the altitude of this region (100 km), the maximum phase of the eclipse was 88.88% obscuration of the photosphere occurring at 9:29:41.5 UT. In comparison, the ionospheric response revealed a maximum obscuration of 66% (leaving a fraction,
Φ
, of uneclipsed radiation of 34±4%) occurring at 9:29 UT. The eclipse was re-created using data from the
Solar Dynamics Observatory
to estimate the fraction of radiation incident on the Earth’s atmosphere throughout the eclipse from nine different emission wavelengths in the extreme ultraviolet (EUV) and X-ray spectrum. These emissions, having varying spatial distributions, were each obscured differently during the eclipse. Those wavelengths associated with coronal emissions (94, 211 and 335 Å) most closely reproduced the time varying fraction of unobscured radiation observed in the ionosphere. These results could enable historic ionospheric eclipse measurements to be interpreted in terms of the distribution of EUV and X-ray emissions on the solar disc.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Atmospheric changes from solar eclipses
Authors: Aplin K. L. , Scott C. J. , Gray S. L.
Published: August 2016

This article reviews atmospheric changes associated with 44 solar eclipses, beginning with the first quantitative results available, from 1834 (earlier qualitative accounts also exist). Eclipse meteorology attracted relatively few publications until the total solar eclipse of 16 February 1980, with the 11 August 1999 eclipse producing the most papers. Eclipses passing over populated areas such as Europe, China and India now regularly attract scientific attention, whereas atmospheric measurements of eclipses at remote locations remain rare. Many measurements and models have been used to exploit the uniquely predictable solar forcing provided by an eclipse. In this paper, we compile the available publications and review a subset of them chosen on the basis of importance and novelty. Beyond the obvious reduction in incoming solar radiation, atmospheric cooling from eclipses can induce dynamical changes. Observations and meteorological modelling provide evidence for the generation of a local eclipse circulation that may be the origin of the ‘eclipse wind’. Gravity waves set up by the eclipse can, in principle, be detected as atmospheric pressure fluctuations, though theoretical predictions are limited, and many of the data are inconclusive. Eclipse events providing important early insights into the ionization of the upper atmosphere are also briefly reviewed.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Numerical simulations of the impact of the 20 March 2015 eclipse on UK weather
Authors: Clark P. A.
Published: August 2016

Short lead-time forecasts using the operational United Kingdom variable-resolution (UKV) configuration of the Met Office’s numerical weather prediction model, with horizontal grid-length 1.5 km over the UK, with and without a representation of the 20 March 2015 eclipse, have been used to simulate the impact of the eclipse on UK weather. The major impact was surface-driven through changes to surface heat and moisture fluxes that changed the boundary-layer development. In cloud-free areas, the nocturnal stable boundary layer persisted or quickly re-established during the eclipse. Surface temperatures were reduced by 7–8°C, near-surface air temperature by 1–3°C, and near-surface winds were backed, typically by 20°. Impacts on wind speed were small and variable, and would have been very difficult to detect. Smaller impacts occurred beneath cloud. However, the impact was enhanced because most of the incoming radiation that reached the surface was driving surface sensible heat flux rather than moisture flux, and the near-surface air temperature impact (0.5–1°
C
) agrees reasonably well with observations. The modelled impact of the eclipse was substantially reduced in urban areas due to their large thermal inertia. Experience from other assessments of the model suggests that this lack of response may be exaggerated. Surface impacts propagated upwards and downstream with time, resulting in a complex pattern of response, though generally near-surface temperature differences persisted for many hours after the eclipse. The impact on atmospheric pressure fields was insufficient to account for any significant perturbations to the wind field when compared with the direct impacts of surface stress and boundary-layer mixing.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Satellite observations of surface temperature during the March 2015 total solar eclipse
Authors: Good Elizabeth
Published: August 2016

The behaviour of remotely sensed land surface temperatures (LSTs) from the spinning-enhanced visible and infrared imager (SEVIRI) during the total solar eclipse of 20 March 2015 is analysed over Europe. LST is found to drop by up to several degrees Celcius during the eclipse, with the minimum LST occurring just after the eclipse mid-point (median=+1.5 min). The drop in LST is typically larger than the drop in near-surface air temperatures reported elsewhere, and correlates with solar obscuration (
r
=−0.47; larger obscuration = larger LST drop), eclipse duration (
r
=−0.62; longer duration = larger LST drop) and time (
r
=+0.37; earlier eclipse = larger LST drop). Locally, the LST drop is also correlated with vegetation (up to
r
=+0.6), with smaller LST drops occurring over more vegetated surfaces. The LSTs at locations near the coast and at higher elevation are also less affected by the eclipse. This study covers the largest area and uses the most observations of eclipse-induced surface temperature drops to date, and is the first full characterization of satellite LST during an eclipse (known to the author). The methods described could be applied to Geostationary Operational Environmental Satellite (GOES) LST data over North America during the August 2017 total solar eclipse.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
On the detection and attribution of gravity waves generated by the 20 March 2015 solar eclipse
Authors: Marlton G. J. , Williams P. D. , Nicoll K. A.
Published: August 2016

Internal gravity waves are generated as adjustment radiation whenever a sudden change in forcing causes the atmosphere to depart from its large-scale balanced state. Such a forcing anomaly occurs during a solar eclipse, when the Moon’s shadow cools part of the Earth’s surface. The resulting atmospheric gravity waves are associated with pressure and temperature perturbations, which in principle are detectable both at the surface and aloft. In this study, surface pressure and temperature data from two UK sites at Reading and Lerwick are examined for eclipse-driven gravity wave perturbations during the 20 March 2015 solar eclipse over northwest Europe. Radiosonde wind data from the same two sites are also analysed using a moving parcel analysis method, to determine the periodicities of the waves aloft. On this occasion, the perturbations both at the surface and aloft are found not to be confidently attributable to eclipse-driven gravity waves. We conclude that the complex synoptic weather conditions over the UK at the time of this particular eclipse helped to mask any eclipse-driven gravity waves.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Eclipse-induced wind changes over the British Isles on the 20 March 2015
Authors: Gray S. L. , Harrison R. G.
Published: August 2016

The British Isles benefits from dense meteorological observation networks, enabling insights into the still-unresolved effects of solar eclipse events on the near-surface wind field. The near-surface effects of the solar eclipse of 20 March 2015 are derived through comparison of output from the Met Office’s operational weather forecast model (which is ignorant of the eclipse) with data from two meteorological networks: the Met Office’s land surface station (MIDAS) network and a roadside measurement network operated by Vaisala. Synoptic-evolution relative calculations reveal the cooling and increase in relative humidity almost universally attributed to eclipse events. In addition, a slackening of wind speeds by up to about 2 knots in already weak winds and backing in wind direction of about 20° under clear skies across middle England are attributed to the eclipse event. The slackening of wind speed is consistent with the previously reported boundary layer stabilization during eclipse events. Wind direction changes have previously been attributed to a large-scale ‘eclipse-induced cold-cored cyclone’, mountain slope flows, and changes in the strength of sea breezes. A new explanation is proposed here by analogy with nocturnal wind changes at sunset and shown to predict direction changes consistent with those observed.

This article is part of the themed issue ‘Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse’.
Haemophilus influenzae type a as a cause of paediatric septic arthritis
Authors: Thorgrimson Joelle , Ulanova Marina
Published: August 2016

Introduction:

Incidence rates of invasive Haemophilus influenzae serotype b disease have decreased significantly since the introduction of the Hib vaccine; however, the rates in indigenous populations remain disproportionately high, specifically in the paediatric population. Additionally, with the decline of type b invasive infections, there has been a rebound in the incidence of invasive infections caused by other strains of H. influenzae, particularly serotype a.

Case presentation:

We present a paediatric case of septic arthritis caused by H. influenzae type a in a toddler that was fully resolved following antibiotic therapy. This report adds to other reports of septic arthritis in indigenous populations as shown through a review of recently documented H. influenzae type a septic arthritis cases.

Conclusion:

Socio-economic risk factors for invasive H. influenzae type a disease, such as poverty, poor housing conditions, overcrowding, smoking and substance abuse during pregnancy, as well as the need for H. influenzae type a immunization of vulnerable populations, are discussed.
Influence of cognitive control on semantic representation
Authors: Keung Waitsang , Osherson Daniel , Cohen Jonathan D.
Published: August 2016

The neural representation of an object can change depending on its context. For instance, a horse may be more similar to a bear than to a dog in terms of size, but more similar to a dog in terms of domesticity. We used behavioral measures of similarity together with representational similarity analysis and functional connectivity of fMRI data in humans to reveal how the neural representation of semantic knowledge can change to match the current goal demand. Here we present evidence that objects similar to each other in a given context are also represented more similarly in the brain and that these similarity relationships are modulated by context specific activations in frontal areas.

Significance statement

The judgment of similarity between two objects can differ in different contexts. Here we report a study that tested the hypothesis that brain areas associated with task context and cognitive control modulate semantic representations of objects in a task-specific way.

We first demonstrate that task instructions impact how objects are represented in the brain. We then show that the expression of these representations is correlated with activity in regions of frontal cortex widely thought to represent context, attention and control.

In addition, we introduce spatial variance as a novel index of representational expression and attentional modulation. This promises to lay the groundwork for more exacting studies of the neural basis of semantics, as well as the dynamics of attentional modulation.
Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank
Authors: Howard David M. , Hall Lynsey S. , Hafferty Jonathan D. , Zeng Yanni , Adams Mark J. , Clarke Toni-Kim , Porteous David J. , Nagy Reka , Hayward Caroline , Smith Blair H. , Murray Alison D. , Ryan Niamh M. , Evans Kathryn L. , Haley Chris S. , Deary Ian J. , Thomson Pippa A. , McIntosh Andrew M.
Published: August 2016

Genome-wide association studies using genotype data have had limited success in the identification of variants associated with major depressive disorder (MDD). Haplotype data provide an alternative method for detecting associations between variants in weak linkage disequilibrium with genotyped variants and a given trait of interest. A genome-wide haplotype association study for MDD was undertaken utilising a family-based population cohort, Generation Scotland: Scottish Family Health Study (n = 18 773), as a discovery cohort with UK Biobank used as a population-based cohort replication cohort (n = 25 035). Fine mapping of haplotype boundaries was used to account for overlapping haplotypes potentially tagging the same causal variant. Within the discovery cohort, two haplotypes exceeded genome-wide significance (P < 5 × 10-8) for an association with MDD. One of these haplotypes was nominally significant in the replication cohort (P < 0.05) and was located in 6q21, a region which has been previously associated with bipolar disorder, a psychiatric disorder that is phenotypically and genetically correlated with MDD. Several haplotypes with P < 10-7in the discovery cohort were located within gene coding regions associated with diseases that are comorbid with MDD. Using such haplotypes to highlight regions for sequencing may lead to the identification of the underlying causal variants.
Neuronal gamma-band synchronization regulated by instantaneous modulations of the oscillation frequency
Authors: Lowet E. , Roberts M. J. , Peter A. , Gips B. , De Weerd P.
Published: August 2016

Neuronal gamma-band synchronization shapes information flow during sensory and cognitive processing. A common view is that a stable and shared frequency over time is required for robust and functional synchronization. To the contrary, we found that non-stationary instantaneous frequency modulations were essential for synchronization. First, we recorded gamma rhythms in monkey visual area V1, and found that they synchronized by continuously modulating their frequency difference in a phase-dependent manner. The frequency modulation properties regulated both the phase-locking and the preferred phase-relation between gamma rhythms. Second, our experimental observations were in agreement with a biophysical model of gamma rhythms and were accurately predicted by the theory of weakly coupled oscillators revealing the underlying theoretical principles that govern gamma synchronization. Thus, synchronization through instantaneous frequency modulations represents a fundamental principle of gamma-band neural coordination that is likely generalizable to other brain rhythms.
Thousands of primer-free, high-quality, full-length SSU rRNA sequences from all domains of life
Authors: Karst Søren M. , Dueholm Morten S. , McIlroy Simon J. , Kirkegaard Rasmus H. , Nielsen Per H. , Albertsen Mads
Published: August 2016

Ribosomal RNA (rRNA) genes are the consensus marker for determination of microbial diversity on the planet, invaluable in studies of evolution and, for the past decade, high-throughput sequencing of variable regions of ribosomal RNA genes has become the backbone of most microbial ecology studies. However, the underlying reference databases of full-length rRNA gene sequences are underpopulated, ecosystem skewed1, and subject to primer bias2, which hamper our ability to study the true diversity of ecosystems. Here we present an approach that combines reverse transcription of full-length small subunit (SSU) rRNA genes and synthetic long read sequencing by molecular tagging, to generate primer-free, full-length SSU rRNA gene sequences from all domains of life, with a median raw error rate of 0.17%. We generated thousands of full-length SSU rRNA sequences from five well-studied ecosystems (soil, human gut, fresh water, anaerobic digestion, and activated sludge) and obtained sequences covering all domains of life and the majority of all described phyla. Interestingly, 30% of all bacterial operational taxonomic units were novel, compared to the SILVA database (less than 97% similarity). For the Eukaryotes, the novelty was even larger with 63% of all OTUs representing novel taxa. In addition, 15% of the 18S rRNA OTUs were highly novel sequences with less than 80% similarity to the databases. The generation of primer-free full-length SSU rRNA sequences enabled eco-system specific estimation of primer-bias and, especially for eukaryotes, showed a dramatic discrepancy between thein-silicoevaluation and primer-free data generated in this study. The large amount of novel sequences obtained here reaffirms that there is still vast, untapped microbial diversity lacking representatives in the SSU rRNA databases and that there might be more than millions after all1, 3. With our new approach, it is possible to readily expand the rRNA databases by orders of magnitude within a short timeframe. This will, for the first time, enable a broad census of the tree of life.
MINT: A multivariate integrative method to identify reproducible molecular signatures across independent experiments and platforms
Authors: Rohart F. , Eslami A. , Matigian N. , Bougeard S. , Lê Cao K-A.
Published: August 2016

Background

Molecular signatures identified from high-throughput transcriptomic studies often have poor reliability and fail to reproduce across studies. One solution is to combine independent studies into a single integrative analysis, additionally increasing sample size. However, the different protocols and technological platforms across transcriptomic studies produce unwanted systematic variation that strongly confounds the integrative analysis results. When studies aim to discriminate an outcome of interest, the common approach is a sequential two-step procedure; unwanted systematic variation removal techniques are applied prior to classification methods.

Results

To limit the risk of overfitting and over-optimistic results of a two-step procedure, we developed a novel multivariate integration method,MINT, that simultaneously accounts for unwanted systematic variation and identifies predictive gene signatures with greater reproducibility and accuracy. In two biological examples on the classification of three human cell types and four subtypes of breast cancer, we combined high-dimensional microarray and RNA-seq data sets and MINT identified highly reproducible and relevant gene signatures predictive of a given phenotype. MINT led to superior classification and prediction accuracy compared to the existing sequential two-step procedures.

Conclusions

MINTis a powerful approach and the first of its kind to solve the integrative classification framework in a single step by combining multiple independent studies.MINTis computationally fast as part of the mixOmics R CRAN package, available athttp://www.mixOmics.org/mixMINT/andhttp://cran.r-project.org/web/packages/mixOmics/.
Opponent surrounds explain diversity of contextual phenomena across visual modalities
Authors: Mély David A. , Serre Thomas
Published: August 2016

Asbtract

Context is known to affect how a stimulus is perceived. A variety of illusions have been attributed to contextual processing — from orientation tilt effects to chromatic induction phenomena, but their neural underpinnings remain poorly understood. Here, we present a recurrent network model of classical and extra-classical receptive fields that is constrained by the anatomy and physiology of the visual cortex. A key feature of the model is the postulated existence of two spatially disjoint near-vs. far-extra-classical regions with complementary facilitatory and suppressive contributions to the classical receptive field. The model accounts for a variety of contextual illusions, reveals commonalities between seemingly disparate phenomena, and helps organize them into a novel taxonomy. It explains how center-surround interactions may shift from attraction to repulsion in tilt effects, and from contrast to assimilation in induction phenomena. The model further explains enhanced perceptual shifts generated by a class of patterned background stimuli that activate the two opponent extra-classical regions cooperatively. Overall, the ability of the model to account for the variety and complexity of contextual illusions provides computational evidence for a novel canonical circuit that is shared across visual modalities.
SNP analysis implicates role of cytosine methylation in introducing consequential mutations inVibrio choleraegenomes
Authors: Sharda Mohak , Seshasayee Aswin Sai Narain , Khedkar Supriya
Published: August 2016

Epigenetic modifications play a key role in gene regulation and in recognition of self DNA in bacteria. In-spite of their positive role in cell survival, modifications like cytosine methylation incur a mutational cost. Cytosine methylation, specifically 5-methylcytosine, is prone to hydrolytic deamination which leads to C → T and G → A transitions. Here, we first study the abundance of mutagenic cytosine methylation target motifs and show that bacteria likeVibrio choleraemight use motif avoidance as a strategy to minimize the mutational effect of deamination of methylated cytosine. Second by performing SNP analysis on whole genome sequence data fromVibrio choleraepatient isolates we show a) high abundance of cytosine methylation-dependent mutations in the cytosine methylation target motif RCCGGY, b) 95% of these C → T and G → A transitions in the coding region lead to non-synonymous substitutions and c) many of these transitions are associated with membrane proteins and are implicated in virulence. Thus, our SNP analysis ofV. choleraegenomes implicates the role of cytosine methylation in generating genotypic diversity with adaptive potential.
Information theory and the phenotypic complexity of evolutionary adaptations and innovations
Authors: Wagner Andreas
Published: August 2016

Two main lines of research link information theory to evolutionary biology. The first focuses on organismalphenotypes, and on the information that organisms acquire about their environment. The second connects information-theoretic concepts togenotypicchange. The genotypic and phenotypic level can be linked by experimental high-throughput genotyping and computational models of genotype-phenotype relationships. I here use a simple information-theoretic framework to compute a phenotype’s information content (its phenotypic complexity), and the information gain or change that comes with a new phenotype. I apply this framework to experimental data on DNA-binding phenotypes of multiple transcription factors. Low phenotypic complexity is associated with a biological system’s ability to discover novel phenotypes in evolution. I show that DNA duplications lower phenotypic complexity, which illustrates how information theory can help explain why gene duplications accelerate evolutionary adaptation. I also demonstrate that with the right experimental design, sequencing data can be used to infer the information gain associated with novel evolutionary adaptations, for example in laboratory evolution experiments. Information theory can help quantify the evolutionary progress embodied in the discovery of novel adaptive phenotypes.
Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation
Authors: Cohen Michael X , Gulbinaite Rasa
Published: August 2016

The so-called steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differential projection of neural activity to many non-invasively placed electrodes or sensors. Our approach is a combination and extension of existing multivariate source separation methods. We demonstrate that RESS performs well on both simulated and empirical data, and outperforms conventional SSEP analysis methods based on selecting electrodes with the strongest SSEP response. We also discuss the potential confound of overfitting—whereby the filter captures noise in absence of a signal. Matlab scripts are available to replicate and extend our simulations and methods. We conclude with some practical advice for optimizing SSEP data analyses and interpreting the results.
OrchID: a Generalized Framework for Taxonomic Classification of Images Using Evolved Artificial Neural Networks
Authors: Pereira Serrano , Gravendeel Barbara , Wijntjes Patrick , Vos Rutger A.
Published: August 2016

Taxonomic expertise for the identification of species is rare and costly. On-going advances in computer vision and machine learning have led to the development of numerous semi- and fully automated species identification systems. However, these systems are rarely agnostic to specific morphology, rarely can perform taxonomic “approximation” (by which we mean partial identification at least to higher taxonomic level if not to species), and frequently rely on costly scientific imaging technologies. We present a generic, hierarchical identification system for automated taxonomic approximation of organisms from images. We assessed the effectiveness of this system using photographs of slipper orchids (Cypripedioideae), for which we implemented image pre-processing, segmentation, and colour and shape feature extraction algorithms to obtain digital phenotypes for 116 species. The identification system trained on these digital phenotypes uses a nested hierarchy of artificial neural networks for pattern recognition and automated classification that mirrors the Linnean taxonomy, such that user-submitted photos can be assigned a genus, section, and species classification by traversing this hierarchy. Performance of the identification system varied depending on photo quality, number of species included for training, and desired taxonomic level for identification. High quality photos were scarce for some taxa and were under-represented in the training set, resulting in imbalanced network training. The image features used for training were sufficient to reliably identify photos to the correct genus but less so to the correct section and species. The outcomes of this project include a library of feature extraction algorithms calledImgPheno,a collection of scripts for neural network training calledNBClassify,a library for evolutionary optimization of artificial neural network construction calledAI::FANN::Evolvingand a planned web application calledOrchIDfor identification of user-submitted images. All project outcomes are open source and freely available.