bluuebunny/crossref_metadata_2025 huggingface dataset:
Morbus Hirschsprung
Authors: Lacher M.
Published: February 2018

Der Morbus Hirschsprung ist ein häufiges kinderchirurgisches Krankheitsbild.

Auch wenn eine Vielzahl von genetischen Mutationen beschrieben wurde, besteht die Trias der Diagnosestellung weiterhin in der sorgfältigen Anamnese, Kolon-Kontrastmitteluntersuchung und Rektumbiopsie.

Die Durchzugsoperation hat zum Ziel, den aganglionären Darm zu entfernen und die intestinale Passage durch Anastomosierung des innervierten Darms mit dem Analkanal unmittelbar oberhalb der Linea dentata zu rekonstruieren, sodass der Analkanal und die Sphinkterfunktion erhalten bleiben. Zu den häufigsten Techniken gehören die Operationen nach Swenson, Soave (de la Torre) und Duhamel. Diese können auch laparoskopisch assistiert durchgeführt werden.

Obwohl der Morbus Hirschsprung durch Resektion des aganglionären Darmes primär gut zu behandeln ist, ist die Langzeitmorbidität hoch. Diese wird vor allem durch die fort-bestehende Obstipation bis hin zur Stuhlinkontinenz oder rezidivierende Episoden einer Enterokolitis bestimmt. Durch eine zielgerichtete Diagnostik und multidisziplinäre Behandlung können diese Symptome meist im Verlauf mehrerer Jahre erfolgreich behandelt werden.

Der Pädiater spielt beim Erkennen und Management dieser Kinder eine wichtige Rolle.
Psychosoziale Aspekte der Stuhlinkontinenz
Authors: Klitzing K. v. , Scholz D.
Published: February 2018

Stuhlkontinenz ist nach WHO-Definition die erlernte Fähigkeit, Stuhlgang willentlich ortund zeitgerecht abzusetzen (1). Zum Erwerb dieser sozialen Kompetenz muss das Kind den Konflikt zwischen Autonomie und Konformität lösen. Der lustvolle Umgang mit den Ausscheidungen wird dem Ekelregime unterworfen. Misslingt dieser Entwicklungsschritt, ist die gesellschaftliche Teilhabe gefährdet. Das Ringen um Sauberkeitsprinzipien stellt die pädagogischen Fähigkeiten der Eltern auf die Probe. Die von Eltern bei der eigenen Reinlichkeitserziehung erlebten Emotionen werden in Familien mit stuhlinkontinenten Kindern reaktiviert. Subklinische psychische Symptome bis hin zu manifesten psychischen Störungen finden sich bei stuhlinkontinenten Kindern und deren Familienangehörigen deutlich häufiger als in der Normalbevölke-rung. Sie können sowohl Ursache und aufrechterhaltender Faktor als auch Folge der kindlichen Symptomatik und der damit verbundenen familiären Interaktionsproblematik sein. Sekundäre Stuhlinkontinenz kann durch Belastungssituationen ausgelöst werden. Invasive Diagnostik und rigide Behandlungsschemata können traumatisieren und dysfunktionales Verhalten chronifizieren.
Hautkrebsprävention und Sonnenschutzcreme: ein Update
Authors: Lademann J. , Patzelt A. , Zastrow L. , Meinke M. , Darvin M. , Knorr F.
Published: February 2018

In den letzten Jahren sind die Hautkrebsraten weltweit gestiegen. Die Anwendung von Sonnenschutzmitteln ist eine weit verbreitete Strategie in der Prävention gegen Hautkrebs, Sonnenbrand und Photoalterung. Es sollten kombinierte Breitbandfiltersysteme mit hoher Wirkung gegen UV-B- und UV-A-Strahlung eingesetzt werden. Weitere Studien sind notwendig, um die Entwicklung von Sonnenschutzmitteln gegen die ebenfalls schädlichen IRA-Strahlen voranzutreiben. Obwohl die regelmäßige Anwendung von Sonnenschutzmitteln ein wesentlicher Bestandteil in der Hautkrebsprävention ist, sollten insbesondere bei Kindern kombinierte Schutzmaßnahmen angewendet werden: Sonnenkarenz bei starker Sonneneinstrahlung, textiler Sonnenschutz, Aufenthalt im Schatten und die Anwendung von Sonnenschutzmitteln.
Editorial
Authors: Reimer Jens
Published: February 2018

Sehr geehrte Leserinnen und Leser,

die Suche nach Glück bewegt uns in den letzten Dekaden zunehmend. Als Faktoren, die zum Glück beitragen, sind soziale Fürsorge, Generosität, Redlichkeit, Gesundheit, Freiheit, Einkommen und gute Regierungsführung zu nennen. Im Weltglücksreport 2017 nehmen 3 skandinavische Länder, nämlich Norwegen, Dänemark und Island, die Toppositionen ein.
Orientation towards otherness in the social and literary spaces of today’s Europe
Authors: Arias Rosario , Bryla Martyna
Published: February 2018

Abstract

This paper addresses current narratives on refugees and Muslim others within the social and literary spaces of today’s Europe. Drawing on Sara Ahmed and others, it sets out to better comprehend what lies behind European fears of the other and, in doing so, raise questions about the ways of facing those who are desperately knocking on Europe’s door.
Integrity and Its counterfeits: implications for economy, business and management
Authors: Sun William , Robinson Simon , Polowczyk Paweł Łukasz
Published: February 2018

Abstract

While the concept of integrity has long been explored by great philosophers and thinkers, its application in modern and postmodern business and economic contexts has been underdeveloped. Little have been done to address the vagueness and paradoxicality of integrity and its shadow reality of counterfeits. The thematic collection, which this paper complements, entitled ‘Integrity and Its Counterfeits: Implications for Economy, Business and Management’, makes a contribution towards filling the gap between the abstract concept of integrity and its application into business and economy, with a particular attention on the ambiguous, equivocal and diverse meanings of the concept, the complex and dynamic practicality of integrity, and the grey and dark areas of business out of integrity. This article introduces the background of the research theme and provides exemplary debates and emerging avenues of discussion on this topic.
Invited Article: An active terahertz polarization converter employing vanadium dioxide and a metal wire grating in total internal reflection geometry
Authors: Liu Xudong , Chen Xuequan , Parrott Edward P. J. , Han Chunrui , Humbert Georges , Crunteanu Aurelian , Pickwell-MacPherson Emma
Published: February 2018

Active broadband terahertz (THz) polarization manipulation devices are challenging to realize, but also of great demand in broadband terahertz systems. Vanadium dioxide (VO2) shows a promising phase transition for active control of THz waves and provides broadband polarization characteristics when integrated within grating-type structures. We creatively combine a VO2-based grating structure with a total internal reflection (TIR) geometry providing a novel interaction mechanism between the electromagnetic waves and the device, to realize a powerful active broadband THz polarization-controlling device. The device is based on a Si-substrate coated with a VO2 layer and a metal grating structure on top, attached to a prism for generating the TIR condition on the Si-VO2-grating interface. The grating is connected to electrodes for electrically switching the VO2 between its insulating and conducting phases. By properly selecting the incident angle of the THz waves, the grating direction, and the incident polarization state, we first achieved a broadband intensity modulator under a fused silica prism with an average modulation depth of 99.75% in the 0.2-1.1 THz region. Additionally, we realized an active ultra-broadband quarter-wave converter under a Si prism that can be switched between a 45° linear rotator and a quarter wave converter in the 0.8-1.5 THz region. This is the first demonstration of an active quarter-wave converter with ultra-broad bandwidth performance. Our work shows a highly flexible and multifunctional polarization-controlling device for broadband THz applications.
Exploring the diversity of Asian Cryptocercus (Blattodea : Cryptocercidae): species delimitation based on chromosome numbers, morphology and molecular analysis
Authors: Bai Qikun , Wang Lili , Wang Zongqing , Lo Nathan , Che Yanli
Published: February 2018

Woodroaches from the genus Cryptocercus Scudder, 1862 are known to display low levels of morphological divergence, yet significant genetic divergence and variability in chromosome number. Compared with Cryptocercus taxa from North America, the diversity of the genus in Asia has received relatively little attention. We performed morphological and karyotypic examinations of multiple taxa from several previously unsampled mountainous areas of central and south-western China, and identified nine candidate species primarily on the basis of chromosome number. We then investigated diversity across all Asian Cryptocercus, through phylogenetic analyses of 135 COI sequences and 74 28S rRNA sequences from individuals of 28 localities, including species delimitation analysis in General Mixed Yule Coalescent (GMYC) and Automatic Barcode Gap Discovery (ABGD). Phylogenetic results indicated that individuals from the same locality constituted well supported clades. The congruence of GMYC and ABGD results were in almost perfect accord, with 28 candidate species described on the basis of karyotypes (including the nine identified in this study). We provide evidence that each valley population in the Hengduan Mountains contains a separate evolving lineage. We conclude that the principal cause of the rich Cryptocercus diversity in China has been the uplift of the Qinghai-Tibet Plateau.
Integration and authority: rescuing the ‘one thought too many’ problem
Authors: Smyth Nicholas
Published: February 2018

Four decades ago, Bernard Williams accused Kantian moral theory of providing agents with ‘one thought too many’. The general consensus among contemporary Kantians is that this objection has been decisively answered. In this paper, I reconstruct the problem, showing that Williams was not principally concerned with how agents are to think in emergency situations, but rather with how moral theories are to be integrated into recognizably human lives. I show that various Kantian responses to Williams provide inadequate materials for solving this ‘integration problem’, and that they are correspondingly ill-positioned to account for the authority of morality, as Williams suspected all along.
Critical assessment 30: Grain growth – Unresolved issues
Authors: Rios P. R. , Zöllner D.
Published: February 2018

Grain growth is a broad field of study that covers several scientifically and technically interesting characteristics. Normal grain growth kinetics and its associated parabolic growth law and self-similar size distributions, grain boundary pinning, abnormal grain growth, the effect of triple junctions and quadruple points as well as grain growth in thin films are the most important current topics of grain growth research. In this critical assessment of grain growth in metals, we present and discuss some of the most important unresolved issues that have been a subject of research for many years.
Enhancing protein fold determination by exploring the complementary information of chemical cross-linking and coevolutionary signals
Authors: dos Santos Ricardo N , Ferrari Allan J R , de Jesus Hugo C R , Gozzo Fábio C , Morcos Faruck , Martínez Leandro
Published: February 2018

Motivation

Elucidation of protein native states from amino acid sequences is a primary computational challenge. Modern computational and experimental methodologies, such as molecular coevolution and chemical cross-linking mass-spectrometry allowed protein structural characterization to previously intangible systems. Despite several independent successful examples, data from these distinct methodologies have not been systematically studied in conjunction. One challenge of structural inference using coevolution is that it is limited to sequence fragments within a conserved and unique domain for which sufficient sequence datasets are available. Therefore, coupling coevolutionary data with complimentary distance constraints from orthogonal sources can provide additional precision to structure prediction methodologies.

Results

In this work, we present a methodology to combine residue interaction data obtained from coevolutionary information and cross-linking/mass spectrometry distance constraints in order to identify functional states of proteins. Using a combination of structure-based models (SBMs) with optimized Gaussian-like potentials, secondary structure estimation and simulated annealing molecular dynamics, we provide an automated methodology to integrate constraint data from diverse sources in order to elucidate the native conformation of full protein systems with distinct complexity and structural topologies. We show that cross-linking mass spectrometry constraints improve the structure predictions obtained from SBMs and coevolution signals, and that the constraints obtained by each method have a useful degree of complementarity that promotes enhanced fold estimates.

Availability and implementation

Scripts and procedures to implement the methodology presented herein are available at https://github.com/mcubeg/DCAXL.

Supplementary information

Supplementary data are available at Bioinformatics online.
ssbio: a Python framework for structural systems biology
Authors: Mih Nathan , Brunk Elizabeth , Chen Ke , Catoiu Edward , Sastry Anand , Kavvas Erol , Monk Jonathan M , Zhang Zhen , Palsson Bernhard O
Published: February 2018

Working with protein structures at the genome-scale has been challenging in a variety of ways. Here, we present ssbio, a Python package that provides a framework to easily work with structural information in the context of genome-scale network reconstructions, which can contain thousands of individual proteins. The ssbio package provides an automated pipeline to construct high quality genome-scale models with protein structures (GEM-PROs), wrappers to popular third-party programs to compute associated protein properties, and methods to visualize and annotate structures directly in Jupyter notebooks, thus lowering the barrier of linking 3D structural data with established systems workflows.

Availability and implementation

ssbio is implemented in Python and available to download under the MIT license at http://github.com/SBRG/ssbio. Documentation and Jupyter notebook tutorials are available at http://ssbio.readthedocs.io/en/latest/. Interactive notebooks can be launched using Binder at https://mybinder.org/v2/gh/SBRG/ssbio/master?filepath=Binder.ipynb.

Supplementary information

Supplementary data are available at Bioinformatics online.
Draft genomes of two blister beetles Hycleus cichorii and Hycleus phaleratus
Authors: Wu Yuan-Ming , Li Jiang , Chen Xiang-Sheng
Published: February 2018

Background

Commonly known as blister beetles or Spanish fly, there are more than 1500 species in the Meloidae family (Hexapoda: Coleoptera: Tenebrionoidea) that produce the potent defensive blistering agent cantharidin. Cantharidin and its derivatives have been used to treat cancers such as liver, stomach, lung, and esophageal cancers. Hycleus cichorii and Hycleus phaleratus are the most commercially important blister beetles in China due to their ability to biosynthesize this potent vesicant. However, there is a lack of genome reference, which has hindered development of studies on the biosynthesis of cantharidin and a better understanding of its biology and pharmacology.

Results

We report 2 draft genomes and quantified gene sets for the blister beetles H. cichorii and H. phaleratus, 2 complex genomes with >72% repeats and approximately 1% heterozygosity, using Illumina sequencing data. An integrated assembly pipeline was performed for assembly, and most of the coding regions were obtained. Benchmarking universal single-copy orthologs (BUSCO) assessment showed that our assembly obtained more than 98% of the Endopterygota universal single-copy orthologs. Comparison analysis showed that the completeness of coding genes in our assembly was comparable to other beetle genomes such as Dendroctonus ponderosae and Agrilus planipennis. Gene annotation yielded 13 813 and 13 725 protein-coding genes in H. cichorii and H. phaleratus, of which approximately 89% were functionally annotated. BUSCO assessment showed that approximately 86% and 84% of the Endopterygota universal single-copy orthologs were annotated completely in these 2 gene sets, whose completeness is comparable to that of D. ponderosae and A. planipennis.

Conclusions

Assembly of both blister beetle genomes provides a valuable resource for future biosynthesis of cantharidin and comparative genomic studies of blister beetles and other beetles.
The Neurologic Examination
Authors: Adams Andrea C.
Published: February 2018

The neurologic examination is the most important part of the evaluation of a patient who has neurologic symptoms or disease. The information obtained from the history and physical examination is needed to generate a differential diagnosis, to select the appropriate diagnostic tests, and to initiate appropriate therapy.
Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation
Authors: Stahl David
Published: February 2018

This chapter provides a summary of a landmark study in critical care medicine. Does the daily interruption of continuous sedative infusions in critically ill patients receiving mechanical ventilation decrease the duration of mechanical ventilation and the duration of stay in the intensive care unit (ICU)? This chapter describes the study designed to answer that question including funding, study location, patient population, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant context and studies, discusses implications, and concludes with a relevant clinical case. This was the first randomized-controlled trial to demonstrate that daily sedation interruption for mechanically ventilated medical ICU patients is safe and may reduce the duration of mechanical ventilation and length of stay in the ICU.
A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus
Authors: Sanders Jason L. , Lee Jarone
Published: February 2018

Generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, and multiple agents have been advocated for the initial treatment. The VA Status Epilepticus Cooperative Study Group conducted a randomized, blinded trial comparing intravenous diazepam followed by phenytoin, lorazepam, phenobarbital, or phenytoin as first-line treatment for GCSE. In the intention-to-treat analysis, no significant difference in treatment was observed across all groups for patients with either overt GCSE or subtle GCSE. Among patients with verified-diagnosis overt GCSE, lorazepam was most successful at achieving cessation of seizures, though no difference was observed among patients with verified-diagnosis subtle GCSE. Results from this trial and two others establish benzodiazepines as the favored first line treatment of GCSE. Investigations are ongoing comparing benzodiazepines to newer antiepileptic drugs. The Established Status Epilepticus Trial will be the first randomized trial comparing fosphenytoin, levetiracetam, and valproic acid for benzodiazepine-refractory status epilepticus in children and adults.
Intracranial Pressure Monitoring in Severe Traumatic Brain Injury
Authors: Peponis Thomas , King David R.
Published: February 2018

The study “A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury” published by Chesnut et al. aimed to resolve the debatable issue of the benefit of intracranial-pressure (ICP) monitoring in patients with severe traumatic brain injury (TBI). The authors designed a randomized controlled trial that was conducted in Latin America. A total of 324 patients admitted with severe TBI were randomly assigned to two groups. The first group (n = 157) was managed with ICP monitoring, using an intraparenchymal monitor. The goal was to keep the ICP below 20 mm Hg. Management of patients comprising the second group (n = 167) was based solely on serial clinical examinations and imaging tests. It was hypothesized that ICP-monitoring would result in increased survival rates, plus improved functional and neuropsychological status at 6-months after the injury. Additionally, the authors hypothesized that complication rates would be decreased and the ICU length of stay shorter.
Comparison of Two Fluid-Management Strategies in Acute Lung Injury
Authors: Gaudet Ross , Kalman Rebecca
Published: February 2018

This chapter provides a summary of the landmark study known as the FACTT Trial. Does a conservative versus liberal fluid-management protocol reduce death from any cause at 60 days in patients with acute lung injury? Starting with that question, the chapter describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. Although conservative fluid management in patients with acute lung injury had a similar profile with respect to adverse events as did a liberal fluid management, the conservative fluid strategy did improve lung function and shorten the duration of mechanical ventilation and intensive care length of stay.
Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients
Authors: Cobas Miguel , Grillo Melissa
Published: February 2018

The efficacy of stress ulcer prophylaxis for the prevention of gastrointestinal bleeding in the critically ill has led to its widespread use. Side effects and cost of prophylaxis necessitate targeting the therapy to those patients most likely to benefit. A prospective multicenter cohort study was conducted to evaluate potential risk factors for stress ulceration in patients admitted to intensive care units. Two strong independent risk factors for bleeding were identified: respiratory failure and coagulopathy. Since few critically ill patients have clinically significant gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion), prophylaxis can safely be withheld unless they require mechanical ventilation or have a coagulopathy.
Glutamine and Antioxidants in Critically Ill Patients
Authors: Liu Yuk Ming , Lee Jarone
Published: February 2018

The REDOXS trial evaluated whether supplementation with glutamine and antioxidants would be beneficial in critically-ill patients. Antioxidants included selenium, vitamin E, vitamin C and zinc. The REDOXS trial was a large randomized clinical trial that included over 40 intensive care units (ICU) in North American and Europe. An earlier study led the REDOXS trial group to hypothesize that there would be a mortality benefit with early nutritional supplementation. 1223 patients were enrolled and randomized to receive glutamine, antioxidants, both or placebo. The final study results demonstrated no clinical benefit from the nutritional supplementation and surprisingly indicated an increased mortality at 28 days for those patients given glutamine.
Bronchoscopy with Bronchoalveolar Lavage versus Endotracheal Aspiration for the Diagnosis of Ventilator-Associated Pneumonia
Authors: Rasul Samad , Kaufman David C.
Published: February 2018

This study looked at the optimal approach to diagnose ventilator associated pneumonia (VAP). This was an important topic to study as VAP is known to be associated with higher mortality rate, longer stays in the intensive care unit (ICU) and higher utilization of resources for treatment. This multicenter trial included 740 patients in 28 ICUs in Canada and the United States. Mechanically ventilated, immunocompetent, adult patients with suspected VAP were randomized to undergo either bronchoalveolar lavage (BAL) with quantitative cultures of the BAL fluid or endotracheal aspiration with nonquantitative culture of the aspirate. No difference in 28 day mortality was noted between the two study groups. Both diagnostic strategies led to similar clinical outcomes and overall use of antibiotics. Immunocompromised patients and those colonized with certain resistant organisms were excluded from this trial.
Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units (PRORATA Trial)
Authors: De Moraes Alice Gallo , Schiavo Dante
Published: February 2018

This chapter provides a summary of the landmark study known as the PRORATA trial. Does a procalcitonin (PCT)-based strategy to treat suspected bacterial infections in ICU patients reduce antibiotic exposure without adverse outcomes? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The study suggests that critically ill patients managed with a PCT-guided antibiotic strategy to treat suspected bacterial infections results in more antibiotic-free days than those managing patients with clinical guidelines alone. The mortality of patients in the PCT arm was non-inferior to those in the control group at day 28 and at day 60. The strategy could be beneficial for reducing antibiotic resistance in the ICU.
An Intervention to Decrease Catheter-Related Bloodstream Infections in the ICU
Authors: Maxey-Jones Courtney , Bittner Edward
Published: February 2018

As part of the Keystone Intensive Care Unit project a bundle of evidence-based interventions was introduced in ICUs across the state of Michigan with the goal of decreasing catheter-related bloodstream infections (CRBI). The bundle included (1) hand washing, (2) full barrier precautions during placement of central venous catheters, (3) skin cleaning with chlorhexidine, (4) if possible, avoidance of femoral site, and (5) removing unnecessary central venous catheters. Post implementation rates of catheter-related bloodstream infections were compared to baseline data. The results showed a decrease from a baseline median rate of 2.7 infections per 1000 catheter-days to a median rate of 0 infections per 1000 catheter-days, which was sustained over 18 months of follow-up.
Proximal Humerus Fractures
Authors: Sanchez-Sotelo Joaquin
Published: February 2018

Fractures of the proximal humerus are common. A relatively large number of these injuries will heal with nonoperative treatment without major residual pain or functional loss. However, internal fixation or arthroplasty leads to a much better outcome for selected fractures. The orthopedic surgeon dealing with these injuries is faced with three challenges. First, it is difficult to understand these fractures based on imaging studies and to select those patents that will do better with surgery. Second, internal fixation and arthroplasty for proximal humerus fractures are difficult procedures and fraught with technical complications. And third, complications often require challenging salvage procedures.
The healthy settings approach: Healthy Cities and environmental health indicators
Authors: de Leeuw Evelyne , Webster Premila
Published: February 2018

‘Healthy Cities’ is a global movement in urban health that grew from a Canadian initiative in the mid-1980s to a World Health Organization programme. Healthy Cities are characterized by a strong commitment to values such as sustainability, solidarity, justice, and participation embedded in a vision that embraces ecological and community perspectives. The movement comes in different manifestations around the world; this chapter focuses mostly on the European evidence base and discusses efforts that have been made over three decades to establish validated sets of indicators to measure and assess urban health and Healthy Cities. True to the nature of the movement, indicators are both socioecological and biomedical, qualitative, and quantitative. This presents challenges to validity and applicability across urban environments.
The throat
Authors: Perry Mike
Published: February 2018

This chapter looks at diseases and conditions of the throat that may present acutely to an emergency department, general practice, or ward. It aims to equip the reader with the necessary knowledge to enable them to quickly and accurately triage and diagnose common clinical problems. Referral pathways and management are also discussed. Generally speaking, patients do not present with a ready-made diagnosis, but rather with either a symptom located to an anatomical region (e.g. toothache, lump, or headache), or an obvious problem (e.g. nose bleed or injury). This is the starting point (‘Common presentations’ and ‘Common problems and their causes’). The next section (‘Useful questions and what to look for’) lists key diagnostic elements in relation to each symptom. The remainder of each chapter details how to examine each site, useful investigations (emergency department and outpatients), and some notes on the conditions themselves. This is a useful aid for the non-specialist and those preparing for clinical examinations.
Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies
Authors: Grebely Jason , Feld Jordan J , Wyles David , Sulkowski Mark , Ni Liyun , Llewellyn Joe , Mir Heshaam M , Sajed Nika , Stamm Luisa M , Hyland Robert H , McNally John , Brainard Diana M , Jacobson Ira , Zeuzem Stefan , Bourlière Marc , Foster Graham , Afdhal Nezam , Dore Gregory J
Published: February 2018

Background

Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST.

Methods

Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible.

Results

Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%).

Conclusion

Sofosbuvir-based therapies are effective and safe in patients receiving OST.
Efficacy and Outcomes of Posterior Inferior Cerebellar Artery (PICA) Bypass for Proximal PICA and Vertebral Artery-PICA Aneurysms: A Case Series
Authors: Rennert Robert C , Strickland Ben A , Ravina Kristine , Bakhsheshian Joshua , Fredrickson Vance , Tenser Matthew , Amar Arun , Mack William , Carey Joseph , Russin Jonathan J
Published: February 2018

BACKGROUND

Nonsaccular vertebral artery (VA) and posterior inferior cerebellar artery (PICA) aneurysms have high morbidity and mortality rates and are difficult to treat using standard microsurgical or endovascular techniques. Definitive revascularization can require clip trapping and/or vessel sacrifice, with PICA bypass. The published surgical experience with these approaches is limited. We herein review our recent surgical experience with PICA revascularization for complex PICA and VA/PICA aneurysms.

OBJECTIVE

To determine the efficacy and outcomes of PICA bypass for revascularization of nonsaccular PICA and VA/PICA aneurysms.

METHODS

Retrospective analysis of an institutional review board-approved, prospective database was performed to identify patients with PICA and VA/PICA aneurysms treated with PICA bypass at a single institution. Demographic information, aneurysm characteristics, temporary clip time, and neurological outcomes were recorded.

RESULTS

Ten cases of PICA revascularization were performed for both ruptured (n = 8) and unruptured (n = 2) nonsaccular proximal PICA or VA/PICA aneurysms. Seven cases were performed without vessel grafts; 3 cases required harvest of the descending branch of the lateral femoral circumflex artery. Mean temporary clip time was 38 min (range 27-50 min). Good outcomes (Glasgow Outcomes Scale score of 5) were achieved in 70% (n = 7) of patients at time of discharge; the remaining patients had a Glasgow Outcomes Scale of 3. Two bypass-related complications occurred in this series; a hematoma at the graft harvest site requiring evacuation, and severe bypass graft spasm requiring multiple endovascular treatments.

CONCLUSION

PICA bypass can be a safe, effective, and highly customizable tool for the revascularization of patients with nonsaccular proximal PICA and VA/PICA aneurysms.
Temporal Bone Meningo-Encephalic-Herniation: Etiological Categorization and Surgical Strategy
Authors: Grinblat Golda , Dandinarasaiah Manjunath , Prasad Sampath Chandra , Piras Gianluca , Piccirillo Enrico , Fulcheri Andrea , Sanna Mario
Published: February 2018

Objective:

To study the clinical presentation, intraoperative findings and surgical management in meningo-encephalic-herniation (MEH) based on the etiology.

Study Design:

A retrospective clinical study and is a follow-up on the previously published report in 2009.

Setting:

A quaternary referral otology and skull base center

Patients and Methods:

The inclusion criteria were intraoperatively verified MEH in patients with a minimum follow-up of 12 months, which yielded 262 operated ears. The data were extracted regarding demographics, laterality, clinical presentation, past surgeries, contralateral-ear condition, intraoperative findings, complications, recurrences, revision-surgeries, audiometric-data, and follow-up.

Results:

The mean age at surgery was 49.7 years with the involvement of right-ear in 53.8% of patients. Lesions were categorized based on the etiology as chronic-otitis-media with/without cholesteatoma-MEH (COM/CHOL-MEH)-47.7%, iatrogenic-MEHs −20.9%; traumatic-MEHs −8% and spontaneous-MEHs −23.3%. At presentation, hearing loss (100 and 98.2%) and otorrhea (65.6 and 49.1%) were predominant in COM/CHOL-MEHs and iatrogenic-MEHs, respectively. On the other hand, meningitis (23.9 and 14.3%) and cerebrospinal fluid-leak (52.4 and 42.8%) were more pronounced in spontaneous and traumatic MEHs, respectively. Surgical approaches included 1) transmastoid, 2) middle-cranial-fossa-approach, 3) combined, and 4) middle-ear-obliteration (MEO) techniques. A total of 52.8% of COM/CHOL-MEHs and 49.1% of iatrogenic-MEHs underwent MEO. Middle-cranial-fossa approach was predominantly used in spontaneous-MEHs (52.5%) and traumatic-MEHs (38.1%). The defect was mostly single (75.2%). Smaller, multiple, bilateral lesions were more common in spontaneous-MEHs with tegmen-tympani involvement (57.4%).

Conclusion:

Incorporating etiology into MEHs is a key-step that can be used as a guidance in choosing the right surgery. MEO is a part of armamentarium, and should be used whenever needed, if the objective is performing a definitive surgery.
Overview of aldosterone-related genetic syndromes and recent advances
Authors: Zennaro Maria-Christina , Fernandes-Rosa Fabio L. , Boulkroun Sheerazed
Published: February 2018

Purpose of review

Primary aldosteronism is the most common form of secondary hypertension. Early diagnosis and treatment are key to cure of hypertension and prevention of cardiovascular complications. Recent genetic discoveries have improved our understanding on the pathophysiology of aldosterone production and triggered the development of new diagnostic procedures and targeted treatments for primary aldosteronism.

Recent findings

Different inherited genetic abnormalities distinguish specific forms of familial hyperaldosteronism. Somatic mutations are found not only in aldosterone-producing adenoma (APA), leading to primary aldosteronism, but also in aldosterone producing cell clusters of normal and micronodules from image-negative adrenal glands. Genetic knowledge has allowed the discovery of surrogate biomarkers and specific pharmacological inhibitors. Ageing appears to be associated with dysregulated and relatively autonomous aldosterone production.

New biochemical markers and pharmacological approaches may allow preoperative identification of somatic mutation carriers and use of targeted treatments.
In-Depth Characterization of the Effects of Cigarette Smoke Exposure on the Acute Trauma Response and Hemorrhage in Mice
Authors: Hartmann Clair , Gröger Michael , Noirhomme Jan-Philipp , Scheuerle Angelika , Möller Peter , Wachter Ulrich , Huber-Lang Markus , Nussbaum Benedikt , Jung Birgit , Merz Tamara , McCook Oscar , Kress Sandra , Stahl Bettina , Calzia Enrico , Georgieff Michael , Radermacher Peter , Wepler Martin
Published: February 2018

Introduction:

Hemorrhagic shock accounts for a large amount of trauma-related mortality. The severity of trauma can be further aggravated by an additional blunt chest trauma (TxT), which independently contributes to mortality upon the development of an acute lung injury (ALI). Besides, cigarette smoke (CS) exposure before TxT enhanced posttraumatic inflammation, thereby aggravating ALI. We therefore aimed to characterize the impact of an acute and/or chronic lung injury on organ dysfunction in a murine model of traumatic hemorrhagic shock (HS).

Methods:

After 3 weeks of CS exposure, anesthetized mice underwent HS with/without TxT. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain mean arterial pressure ≥50 mmHg. Lung mechanics and gas exchange were assessed together with systemic hemodynamics, metabolism, and acid-base status. Postmortem blood and tissue samples were analyzed for cytokine and chemokine levels, protein expression, mitochondrial respiration, and histological changes.

Results:

CS exposure and HS alone coincided with increased inflammation, decreased whole blood sulfide concentrations, and decreased diaphragmatic mitochondrial respiration. CS-exposed mice, which were subjected to TxT and subsequent HS, showed hemodynamic instability, acute kidney injury, and high mortality.

Conclusions:

Chronic CS exposure per se had the strongest impact on inflammatory responses. The degree of inflammation was similar upon an additional TxT, however, mice presented with organ dysfunction and increased mortality rates. Hence, in mice the degree of inflammation may be dissociated from the severity of organ dysfunction or injury.
Dynamic sporulation gene co-expression networks for Bacillus subtilis 168 and the food-borne isolate Bacillus amyloliquefaciens: a transcriptomic model
Authors: Omony Jimmy , de Jong Anne , Krawczyk Antonina O. , Eijlander Robyn T. , Kuipers Oscar P.
Published: February 2018

Sporulation is a survival strategy, adapted by bacterial cells in response to harsh environmental adversities. The adaptation potential differs between strains and the variations may arise from differences in gene regulation. Gene networks are a valuable way of studying such regulation processes and establishing associations between genes. We reconstructed and compared sporulation gene co-expression networks (GCNs) of the model laboratory strain Bacillus subtilis 168 and the food-borne industrial isolate Bacillus amyloliquefaciens. Transcriptome data obtained from samples of six stages during the sporulation process were used for network inference. Subsequently, a gene set enrichment analysis was performed to compare the reconstructed GCNs of B. subtilis 168 and B. amyloliquefaciens with respect to biological functions, which showed the enriched modules with coherent functional groups associated with sporulation. On basis of the GCNs and time-evolution of differentially expressed genes, we could identify novel candidate genes strongly associated with sporulation in B. subtilis 168 and B. amyloliquefaciens. The GCNs offer a framework for exploring transcription factors, their targets, and co-expressed genes during sporulation. Furthermore, the methodology described here can conveniently be applied to other species or biological processes.
E-learning for introductory Computer Science concept on recursion applying two types of feedback methods in the learning assessment
Authors: Mondigo Lynnard , Lao Demelo Madrazo
Published: February 2018

Purpose

The purpose of this paper is to develop a web-based interactive learning object (ILO) of introductory Computer Science (CS) concept on recursion and compare two feedback methods in the learning assessment part.

Design/methodology/approach

Test driven development (TDD) approach was used to develop ILO. The authors adapted Multimedia Educational Resource for Learning and Online Teaching (MERLOT) standard instrument to evaluate ILO’s effectiveness as an e-learning tool. Three respondents, from a list of pre-identified prospective evaluators, were randomly chosen and served as raters for MERLOT, while 32 student-respondents coming from first-year Math and CS undergraduate majors were randomly assigned to each ILO version implementing either one of the two feedback methods.

Findings

ILO obtained mean ratings above 4 (in scale 1-5) in three MERLOT criteria, namely, potential effectiveness as teaching tool, ease of use, and quality of content, which is rated highest (mean=4.40, SD=0.53). The study also revealed that immediate feedback increases retention while delayed feedback improves generating new knowledge. Respondents who viewed the ILO implementing immediate feedback in their first session had statistically significantly higher scores (mean=8.25, SD=0.80) than those who viewed with delayed feedback (mean=7.63, SD=0.89). In their second session, the same observation was noted although with higher mean scores. These results give evidence that the developed ILO met standards in e-learning material and showed evidence of its effectiveness with preferably implementing immediate feedback.

Research limitations/implications

Although the developed ILO can now be used in school as supplementary learning material in teaching the concept of recursion in an introductory CS subject, a pilot testing of the web-based ILO using a larger sample of respondents to validate its effectiveness for online distance learning educational material can be pursued. Furthermore, in designing and creating an ILO, the provision of feedback during the assessment stage is necessary for effecting learning.

Originality/value

The study was a first to develop ILO for CS topic on recursion. The paper also compared which of two known feedback methods is best to implement in an ILO.
Localisation in an emerging Gulf economy
Authors: Jabeen Fauzia , Faisal Mohd Nishat , Katsioloudes Marios
Published: February 2018

Purpose

The purpose of this paper is twofold: first, to understand Emirati nationals’ perceptions of the role of workforce localisation policies in their professional aspirations and growth and, second, to determine the role of higher education and job attributes in the achievement of their goals. The study uses a hierarchy-based model/road map to improve localisation efforts by attempting to aid understanding of the relationships and barriers hindering these processes.

Design/methodology/approach

The study follows a two-stage process. In the first stage, a questionnaire-based survey was administered to 207 Emirati postgraduate students from public and private universities based in two major Emirates: Abu Dhabi and Dubai. The sample data were analysed by basic descriptive statistics in the form of cross-relationships and rank correlation tests. In the second stage, an interpretive structural modelling approach was used to develop a hierarchy-based structural model of the barriers to localisation.

Findings

Emiratis younger than 30 years old consider localisation as an enabling factor in their professional success in contrast to those older than 30 years old. The results also indicate that working female Emiratis have significantly more positive attitudes regarding the contribution of localisation towards their professional success than that of their male counterparts. However, both genders see a mismatch in efforts being made to better equip themselves for the workplace. The hierarchy-based model delineates variables that could contribute to making localisation a successful employment programme in the United Arab Emirates (UAE).

Research limitations

The findings of this study relate to the UAE. However, there are similar localisation programmes that have been implemented in other Gulf Cooperation Council states. Hence, while the results of this study are relevant to the UAE, they may not be generalisable to the entire Gulf region.

Practical implications

It is proposed that the research findings and the structural model of relationships may help policy makers develop suitable strategies to strengthen the Emirati localisation programme.

Originality/value

This study makes a contribution to the literature and can serve as a guide to policy makers for localisation programmes. This is achieved by analysing the attitude of UAE nationals studying at higher education institutions. Furthermore, the study presents a hierarchy-based model of the barriers to localisation that explains the root causes of the problem.
How brand-oriented strategy affects the financial performance of B2B SMEs
Authors: Anees-ur-Rehman Muhammad , Wong Ho Yin , Sultan Parves , Merrilees Bill
Published: February 2018

Purpose

This study aims to examine the relationship between brand orientation and financial performance in business-to-business (B2B) small- and medium-sized enterprises (SMEs). It examines the impact of brand-oriented strategy on financial performance through four branding constructs, namely, internal branding, brand communication, brand awareness and brand credibility.

Design/methodology/approach

A questionnaire-based survey was conducted to collect data from 250 Finnish B2B SMEs. Confirmatory factor analysis was performed to examine the validity of the constructs, whereas structural equation modeling was used to test proposed hypotheses of the study.

Findings

The results suggest that brand orientation improves the effectiveness of brand communication and internal branding in building brand awareness and credibility. Brand awareness emphasizes an external route through brand communication, whereas brand credibility emphasizes an internal route through internal branding. Brand awareness has a positive impact on brand credibility, and brand credibility has a positive impact on financial performance, highlighting the importance of both brand performance components for financial performance.

Originality/value

This study addresses the research gap in the B2B branding literature regarding the role of branding in enhancing financial performance. The results suggest that brand-oriented strategy can contribute to financial performance through brand awareness and brand credibility in the context of B2B SMEs.