bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired turnover of hyperfused mitochondria in severe axonal neuropathy due to a novel DRP1 mutation
Authors: Longo Fabiana , Benedetti Sara , Zambon Alberto A , Sora Maria Grazia Natali , Di Resta Chiara , De Ritis Daniele , Quattrini Angelo , Maltecca Francesca , Ferrari Maurizio , Previtali Stefano Carlo
Published: August 2019

Mitochondria undergo continuous cycles of fusion and fission in response to physiopathological stimuli. The key player in mitochondrial fission is dynamin-related protein 1 (DRP1), a cytosolic protein encoded by dynamin 1-like (DNM1L) gene, which relocalizes to the outer mitochondrial membrane, where it assembles, oligomerizes and drives mitochondrial division upon guanosine-5′-triphosphate (GTP) hydrolysis. Few DRP1 mutations have been described so far, with patients showing complex and variable phenotype ranging from early death to encephalopathy and/or optic atrophy. The disease is the consequence of defective mitochondrial fission due to faulty DRP1 function. However, the underlying molecular mechanisms and the functional consequences at mitochondrial and cellular level remain elusive. Here we report on a 5-year-old girl presenting psychomotor developmental delay, global hypotonia and severe ataxia due to axonal sensory neuropathy harboring a novel de novo heterozygous missense mutation in the GTPase domain of DRP1 (NM_012062.3:c.436G>A, NP_036192.2: p.D146N variant in DNM1L). Patient’s fibroblasts show hyperfused/balloon-like giant mitochondria, highlighting the importance of D146 residue for DRP1 function. This dramatic mitochondrial rearrangement phenocopies what observed overexpressing DRP1-K38A, a well-known experimental dominant negative version of DRP1. In addition, we demonstrated that p.D146N mutation has great impact on peroxisomal shape and function. The p.D146N mutation compromises the GTPase activity without perturbing DRP1 recruitment or assembly, causing decreased mitochondrial and peroxisomal turnover. In conclusion, our findings highlight the importance of sensory neuropathy in the clinical spectrum of DRP1 variants and, for the first time, the impact of DRP1 mutations on mitochondrial turnover and peroxisomal functionality.
Tame Tori in p-Adic Groups and Good Semisimple Elements
Authors: Fintzen Jessica
Published: August 2019

Let $G$ be a reductive group over a non-archimedean local field $k$. We provide necessary conditions and sufficient conditions for all tori of $G$ to split over a tamely ramified extension of $k$. We then show the existence of good semisimple elements in every Moy–Prasad filtration coset of the group $G(k)$ and its Lie algebra, assuming the above sufficient conditions are met.
Effect of Seasonal Malaria Chemoprevention on Immune Markers of Exhaustion and Regulation
Authors: Attaher Oumar , Zaidi Irfan , Kwan Jennifer L , Issiaka Djibrilla , Samassekou Mamoudou B , Cisse Kadidia B , Coulibaly Barou , Keita Sekouba , Sissoko Sibiri , Traore Tiangoua , Diarra Kalifa , Diarra Bacary S , Dembele Adama , Kanoute Moussa B , Mahamar Almahamoudou , Barry Amadou , Fried Michal , Dicko Alassane , Duffy Patrick E
Published: August 2019

Background

Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells.

Methods

In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry.

Results

Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC.

Conclusions

These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction.

Clinical Trials Registration

NCT02504918.
Preventing Infection by Human Cytomegalovirus
Authors: Plotkin Stanley A
Published: August 2019

The way to a successful vaccine against human cytomegalovirus is hampered by the peculiar biology of this infection. However, some candidate vaccines have been shown to protect seronegative women and transplant recipients, and we should know soon whether they can prevent congenital infection.
Optimal lysine in diets for high-yielding lactating sows1
Authors: Hojgaard Camilla K , Bruun Thomas S , Theil Peter K
Published: August 2019

The objective of the current study was to determine the optimal concentration of dietary standardized ileal digestible (SID) Lys required to maximize litter gain and minimize sow BW loss in modern high-yielding lactating sows when SID CP was kept constant across dietary treatments. A total of 396 parity 1 to 5 sows (L × Y, DanBred, Herlev, Denmark) were included in the study from day 3 after farrowing until weaning at day 26. Sows were allocated to 6 dietary treatments increasing in SID Lys concentration (6.19, 6.90, 7.63, 8.33, 9.04, and 9.76 g/kg). Diets were isoenergetic (14.04 MJ ME/kg as-fed). Litters were standardized to 14 piglets at day 3 ± 2 d postpartum. At day 3 ± 2 d and at day 26 ± 3 d in lactation, litter weight, and sow BW and back fat were registered. On a subsample of 72 parity 2 to 4 sows, litters were additionally weighed at days 10 and 17 ± 3 d, and milk and blood were sampled at day 3 ± 2 d, and 10, 17 and at 24 ± 3 d in lactation. For the 72 sows, body pools of fat and protein were also determined at days 3 ± 2 and 26 ± 3 d using the D2O dilution technique. All data were analyzed as a randomized complete block design using PROC MIXED in SAS. Furthermore, data were subjected to linear and quadratic polynomial contrasts. Variables with quadratic or linear effects or days in milk × treatment interactions were selected for analysis in PROC NLMIXED using linear broken-line models to evaluate optimal SID Lys concentrations. Only models that converged and the best fitting models were included. Average daily litter gain increased until a breakpoint at 8.11 g/kg of SID Lys (as-fed). At and above the breakpoint, multiparous and primiparous sows had litter gains of 3.36 and 2.93 kg/d, respectively. Weaning litter size (13.0 ± 0.1) was similar between the 6 dietary treatments (P = 0.28). Lactation sow BW loss was minimized to 0.17 kg/d at 9.05 g/kg of SID Lys and sow body protein loss was minimized to 0.23 kg at 9.22 g/kg of SID Lys. Linear broken-line analyses showed that for 3, 10, 17, and 24 DIM, plasma urea was minimized at 7.02, 8.10, 8.73, and 8.32 g/kg of SID Lys, respectively, and milk fat was maximized at 7.80 g/kg of SID Lys. In conclusion, in our conditions, high-yielding lactating sows required 8.11 g/kg of SID Lys to maximize litter gain and 9.05 g/kg of SID Lys to minimize sow BW loss. Based on plasma urea, the optimal dietary concentration of SID Lys was lowest in week 1, intermediate in week 2 and 4, and greatest in week 3 of lactation.
The rare case of De Garengeot hernia: femoral hernia containing perforated appendicitis
Authors: Ying Lei , Yahng Jeong-Moh John
Published: August 2019

Femoral hernias account for ~4% of all groin hernias but are much more common in females, especially those over the age of 70. Risk of incarceration is overall low but can include structures such as bowel, omentum, bladder, ovary and very rarely, the appendix. The subset of femoral hernias containing the vermiform appendix is known as de Garengeot hernias. We describe a rare case of an 87-year-old female patient who presented with an incarcerated right femoral hernia confirmed on contrast-enhanced computed tomography scan of the abdomen and pelvis, with subsequent open hernia reduction revealing a perforated necrotic appendix with pus contained in the hernia sac. Histopathology revealed acute appendicitis with increased stromal fibrosis suggestive of a chronic process. Pre-operative diagnosis of de Garengeot hernias remains challenging due to their non-specific presentation and attenuated clinical symptoms, and most diagnoses are made intraoperatively.
Knotted nasogastric tube: a rare, overlooked yet preventable complication
Authors: Monib Sherif , ElKorety Mohamed , Jibrin Umar , Dhungana Drishya , Thomson Simon
Published: August 2019

Nasogastric tubes (NGTs) have long been used for various indications, most commonly to decompress the stomach of its contents in intestinal obstruction or after abdominal surgery, to provide enteral feeding or to allow enteral liquid medication administration. Recently greater importance has been given to the correct placement NGTs to avoid serious complications. We present a case of a spontaneously knotted NGT that was identified and safely removed without complications, but which may have resulted from suboptimal placement. We discuss this case to raise awareness of this complication and how to minimize the likelihood of it happening and improve patient outcome.
Case comment: responding to the implausible, incredible and highly improbable stories defendants tell: a Bayesian interpretation of the Venray murder ruling
Authors: Jellema Hylke
Published: August 2019

In criminal trials, defendants often offer alternative explanations of the facts when they plead for their innocence. In its ruling on the Venray murder case, the Dutch Supreme Court dealt with the question when and how courts can reject such alternative explanations. According to the Supreme court, while courts should typically refer to evidence that refutes the explanation, they can also argue that the explanation ‘did not become plausible’ or that it is ‘not credible’. Finally, courts can state that an explanation is so ‘highly improbable’ that it requires no response. However, the Supreme Court did not explain these terms, leading to confusion about how they ought to be interpreted. This case comment offers a Bayesian interpretation according to which these three terms relate to (i) the posterior probability of the explanation, (ii) the credibility of the defendant, and (iii) how obvious it is that the explanation is improbable. This interpretation clarifies the Supreme Courts ruling and ties it to the criminal law system’s goals of error minimization and of producing understandable decisions efficiently.
Responsible Gambling and Its Stakeholders
Authors: Shaffer Howard J. , Blaszczynski Alexander , Ladouceur Robert , Collins Peter , Fong Davis
Published: August 2019

Robert Ladouceur and Alex Blaszczynski convened this working group and established the early agenda and direction for the International Group on Responsible Gambling and our scholarly publications. The Reno Model provided the seminal architecture for understanding, creating, and implementing responsible gambling activities and programs. This model stimulated considerable growth and interest in responsible gambling activities around the world. From this growth, the authors’ international working group on responsible gambling emerged. The primary purpose of this group and this book is to discuss and formulate guidelines, elaborate principles, and stimulate discussion related to responsible gambling policies and their evaluation. The group considered the views of a variety of key stakeholders who are obligated to minimize harm and protect consumers, such as regulators, governments, academics, clinicians, individuals, gamblers, and the general community). This chapter provides an overview about their viewpoints and insights about responsible gambling.
Responsible Gambling
Authors: Reilly Christine
Published: August 2019

This chapter reviews the current research base and analyzes the strengths and weaknesses of responsible gambling programs in practice and makes recommendations for strengthening these programs. Regulators and the gaming industry have increasingly recognized the importance of responsible gambling activities. Suggestions are given for researchers working in the responsible gambling field. A list of minimal requirements for a responsible gambling program is offered. There are multiple interventions available for operators to build a comprehensive responsible gambling program, but the missing ingredient is scientific research designed to develop new programs and to evaluate existing programs for safety and efficacy. More research on responsible gambling will benefit all stakeholders.
Responsible Gambling from a Nonprofit Perspective
Authors: Wiebe Jamie , Kelly Jon
Published: August 2019

This chapter presents the Responsible Gambling Council’s perspective on the evolution of responsible gambling as a concept and as a set of programs. This perspective in some ways reflects the Canadian experience managing the growth and diversification of gambling during the past two decades. The Council, because of its unique positioning and perspective, has been able to advocate for the enhancement of responsible gambling and to contribute many practical solutions to the field. This chapter uses the experience of the Council’s experience as a window into the theories the surround responsible gambling, the drivers that propel it forward, and the challenges that must be addressed to continue its progress. The authors stress the importance of defining program goals and evaluation methods, defining an audience, and matching the message to the audience.
Motivation and Stages of Change
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

Research has identified different stages that clients may go through as they change a substance use problem. These stages include precontemplation, contemplation, preparation, action, and maintenance (relapse prevention). The goals of this chapter are to learn these different stages, to identify the immediate and long-term consequences of either quitting or continuing to use substances, and to learn strategies to increase the client’s motivation for change.
Managing Thoughts of Using Substances
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

Thoughts of using alcohol, tobacco, or other drugs are common. Anyone who stops using a substance will think about it again. It’s a normal part of the change process to think about something that one once enjoyed or on which one became addicted. Thoughts of using are often associated with other recovery issues such as cravings, social pressures, family and interpersonal conflicts, and upsetting feelings. Specific thoughts can contribute to urges or cravings or to feelings such as depression or anger. Challenging and changing such thoughts can help us stay sober and feel better about ourselves and our lives. The goals of this chapter are to identify and practice controlling thoughts of using to decrease the risk of relapse and to learn to use a variety of coping strategies to manage thoughts of using.
Dealing with Family and Interpersonal Problems
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

Problems and conflicts in family and interpersonal relationships are common in recovery and can contribute to relapse if clients don’t have a plan to deal with them. Conflict, tension, and disagreements are normal parts of human relationships. Not addressing these head-on sets us up to feel angry, frustrated, and unhappy. Sometimes interpersonal problems are obvious, and other times they can be subtle, covert, or hidden. The goals of this chapter are for clients to identify and address conflicts in their families and interpersonal relationships, to examine their usual style of relating to others, and to begin to formulate and use strategies for resolving conflicts.
Building a Recovery Support System
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

A recovery support system consists of people and organizations that provide help and support in a client’s efforts to stop using alcohol, tobacco, or other drugs. A positive support system is associated with a better outcome and has many benefits. It enables clients to gain from the strength, hope, experience, and advice of others who care about their recovery. Although self-reliance is helpful in long-term recovery, in the early stages, reliance on others can make a big difference in whether or not a client uses alcohol or other drugs. The goals of this chapter are to learn the benefits of having a recovery support system, to identify people and organizations that can provide support, to work to overcome barriers to asking for help, and to learn strategies for creating and using an effective recovery support system.
Medications for Substance Use Disorders
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

Medications can help clients safely and comfortably withdraw from substances such as alcohol, opiates, or sedatives if they have a physical addiction. The medicines used will depend on the drug or drugs on which they are dependent. Medication-assisted treatment is the use of medications approved by the US Food and Drug Administration, in combination with counseling and behavioral therapies, to provide a whole-client approach to the treatment of opioid, alcohol, or tobacco use disorders. The goals of this chapter are to learn about types of medication that aid recovery from a substance use disorder, to understand the reasons why some people may have problems with medication, to learn about withdrawal symptoms and medications that help, to understand the effects of drug and alcohol use on psychiatric medications, and to determine whether or not a client needs medication to help with his or her substance disorder.
Relapse Management
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

If clients have a lapse or relapse, they can use it as a learning experience to help strengthen their recovery. They can try to figure out their warning signs and factors that led to the lapse or relapse, and they can use it as a motivator to change and to do things differently in recovery. Clients should always inform their therapist or counselor if they have a lapse or relapse so that they can work together to figure out what caused it and how to get back on track. The goals of this chapter are to determine and evaluate the reasons for a client lapse or relapse, to analyze the warning signs, to learn the steps to take when facing a lapse crisis, and, for those with an opioid addiction, to protect themselves from drug overdose.
Strategies for Balanced Living
Authors: Daley Dennis C. , Douaihy Antoine
Published: August 2019

Balance refers to the ability to reasonably manage the different aspects of our lives. Balanced living is not only healthy but also serves as a protection against relapse. Balance can lead to happiness and provide opportunities for personal growth. Although some areas of life may get temporarily out of balance due to demands of work or family, the goal is to strive for a balance that works for the client and that can accommodate periods of imbalance. The goals of this chapter are to understand the benefits of living a balanced lifestyle, to determine the overall balance in one’s life, to learn how to keep a daily inventory to catch problems and relapse warning signs early, to develop a weekly schedule of activities to add structure to our lives, and to create a list of pleasant activities.
Intermediate Sessions
Authors: Foa Edna B. , Hembree Elizabeth A. , Rothbaum Barbara Olasov , Rauch Sheila A. M.
Published: August 2019

Beginning around Session 5 or 6, emotional processing of the trauma memories can be made more efficient by having the patient focus primarily or exclusively on the most currently distressing parts of the trauma, which the authors term the “hot spots.” The therapist helps the patient identify his hot spots and then select one to begin the imaginal exposure. This should be one of the most distressing parts, if not the most distressing part, of the trauma. Therapy continues with the focus on the patient’s hot spots during the imaginal exposure until each has been sufficiently processed, as reflected by diminished Subjective Units of Distress Scale (SUDS) levels and the patient’s behavior (e.g., body movement, facial expression). This may take several sessions, depending on the number of hot spots, the patient’s pace, and the amount of time spent listening to exposure recordings as homework.
Characteristics of solar wind rotation
Authors: Li K J , Feng W
Published: August 2019

Over 54 yr of hourly mean value of solar wind velocity from 1963 November 27 to 2017 December 31 are used to investigate characteristics of the rotation period of solar wind through autocorrelation analysis. Solar wind of high velocity is found to rotate faster than low-velocity wind, while its rotation rate increases with increasing velocity, but in contrast for solar wind of low velocity, its rotation rate decreases with increasing velocity. Our analysis shows that solar wind of a higher velocity statistically possesses a faster rotation rate for the entire solar wind. The yearly rotation rate of solar wind velocity does not follow the Schwable cycle, but it is significantly negatively correlated to yearly sunspot number when it leads by 3 yr. Physical explanations are proposed to these findings.
On the contamination of the global 21 cm signal from polarized foregrounds
Authors: Spinelli Marta , Bernardi Gianni , Santos Mario G
Published: August 2019

Global (i.e. sky-averaged) 21 cm signal experiments can measure the evolution of the universe from the Cosmic Dawn to the Epoch of Reionization. These measurements are challenged by the presence of bright foreground emission that can be separated from the cosmological signal if its spectrum is smooth. This assumption fails in the case of single polarization antennas as they measure linearly polarized foreground emission - which is inevitably Faraday rotated through the interstellar medium. We investigate the impact of Galactic polarized foregrounds on the extraction of the global 21 cm signal through realistic sky and dipole simulations both in a low frequency band from 50 to 100 MHz, where a 21 cm absorption profile is expected, and in a higher frequency band (100 − 200 MHz). We find that the presence of a polarized contaminant with complex frequency structure can bias the amplitude and the shape of the reconstructed signal parameters in both bands. We investigate if polarized foregrounds can explain the unexpected 21 cm Cosmic Dawn signal recently reported by the EDGES collaboration. We find that unaccounted polarized foreground contamination can produce an enhanced and distorted 21 cm absorption trough similar to the anomalous profile reported by Bowman et al. (2018), and whose amplitude is in mild tension with the assumed input Gaussian profile (at ∼1.5σ level). Moreover, we note that, under the hypothesis of contamination from polarized foreground, the amplitude of the reconstructed EDGES signal can be overestimated by around 30%, mitigating the requirement for an explanation based on exotic physics.
Disc formation in magnetized dense cores with turbulence and ambipolar diffusion
Authors: Lam Ka Ho , Li Zhi-Yun , Chen Che-Yu , Tomida Kengo , Zhao Bo
Published: August 2019

Discs are essential to the formation of both stars and planets, but how they form in magnetized molecular cloud cores remains debated. This work focuses on how the disc formation is affected by turbulence and ambipolar diffusion (AD), both separately and in combination, with an emphasis on the protostellar mass accretion phase of star formation. We find that a relatively strong, sonic turbulence on the core scale strongly warps but does not completely disrupt the well-known magnetically induced flattened pseudo-disc that dominates the inner protostellar accretion flow in the laminar case, in agreement with previous work. The turbulence enables the formation of a relatively large disc at early times with or without AD, but such a disc remains strongly magnetized and does not persist to the end of our simulation unless a relatively strong AD is also present. The AD-enabled discs in laminar simulations tend to fragment gravitationally. The disc fragmentation is suppressed by initial turbulence. The AD facilitates the disc formation and survival by reducing the field strength in the circumstellar region through magnetic flux redistribution and by making the field lines there less pinched azimuthally, especially at late times. We conclude that turbulence and AD complement each other in promoting disc formation. The discs formed in our simulations inherit a rather strong magnetic field from its parental core, with a typical plasma-β of order a few tens or smaller, which is 2–3 orders of magnitude lower than the values commonly adopted in magnetohydrodynamic simulations of protoplanetary discs. To resolve this potential tension, longer term simulations of disc formation and evolution with increasingly more realistic physics are needed.
WALTZ-DB 2.0: an updated database containing structural information of experimentally determined amyloid-forming peptides
Authors: Louros Nikolaos , Konstantoulea Katerina , De Vleeschouwer Matthias , Ramakers Meine , Schymkowitz Joost , Rousseau Frederic
Published: August 2019

Transition of soluble proteins into insoluble amyloid fibrils is driven by self-propagating short sequence stretches. However, accurate prediction of aggregation determinants remains challenging. Here, we describe WALTZ-DB 2.0, an updated and significantly expanded open-access database providing information on experimentally determined amyloid-forming hexapeptide sequences (http://waltzdb.switchlab.org/). We have updated WALTZ-DB 2.0 with new entries, including: (i) experimental validation of an in-house developed dataset of 229 hexapeptides, using electron microscopy and Thioflavin-T binding assays; (ii) manual curation of 98 amyloid-forming peptides isolated from literature. Furthermore, the content has been expanded by adding novel structural information for peptide entries, including sequences of the previous version. Using a computational methodology developed in the Switch lab, we have generated 3D-models of the putative amyloid fibril cores of WALTZ-DB 2.0 entries. Structural models, coupled with information on the energetic contributions and fibril core stabilities, can be accessed through individual peptide entries. Customized filtering options for subset selections and new modelling graphical features were added to upgrade online accessibility, providing a user-friendly interface for browsing, downloading and updating. WALTZ-DB 2.0 remains the largest open-access repository for amyloid fibril formation determinants and will continue to enhance the development of new approaches focused on accurate prediction of aggregation prone sequences.
Political Investment Cycles of State-Owned Enterprises
Authors: Li Qingyuan , Lin Chen , Xu Li
Published: August 2019

Using a large panel of more than 140,000 state-owned enterprises (SOEs), this study examines SOEs’ investment behavior surrounding 82 national elections in 25 European countries between 2001 and 2015. We find that SOEs increase their corporate investment by about 29% of the sample average during national election years. This effect is more pronounced in fixed timing and closely contested elections. The effect is also stronger in countries with low institutional quality, more centralized political systems, and state-controlled banking systems. In contrast, we find the matched non-SOEs significantly decrease their corporate investment during national election years. (JEL G18, G30, G32, E22)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR)
Authors: Orbai Ana-Maria , Ogdie Alexis , Gossec Laure , Tillett William , Leung Ying Ying , Gao Jingjing , Trivedi Mona , Tasset Chantal , Meuleners Luc , Besuyen Robin , Hendrikx Thijs , Coates Laura C
Published: August 2019

Objective

To examine the effects of filgotinib, an oral, selective Janus kinase 1 inhibitor, on health-related quality of life (HRQoL) using the Psoriatic Arthritis Impact of Disease (PsAID)9 questionnaire in active PsA.

Methods

Patients were randomized 1 : 1 to filgotinib 200 mg or placebo once daily for 16 weeks in EQUATOR, a multicentre, double-blind, phase 2 randomized controlled trial. HRQoL was assessed with PsAID9 at Weeks 4 and 16. Change from baseline in total and individual domain scores, plus the proportions of patients achieving minimal clinically important improvement (MCII; ⩾3 points) and patient-accepted symptom status (PASS; score <4), were evaluated. Correlation with the 36-item short-form health survey (SF-36) was investigated.

Results

One hundred and thirty-one patients were randomized to filgotinib or placebo. Filgotinib effects on PsAID9 were observed from Week 4. At Week 16, mean (s.d.) change from baseline in PsAID9 was –2.3 (1.8) and –0.8 (2.2) for filgotinib and placebo, respectively (least-squares mean of group difference –1.48 [95% CI –2.12, –0.84], P < 0.0001), with significant improvements in all domains vs placebo. Significantly more patients on filgotinib achieved MCII (group difference 25.4% [95% CI 8.92, 39.99], P = 0.0022) and PASS (group difference 29.6% [95% CI 10.65, 45.60], P = 0.0018) at Week 16 vs placebo. Similar improvements in SF-36 were observed, with moderate to strong negative correlation between PsAID9 and SF-36.

Conclusion

Filgotinib significantly improved HRQoL vs placebo in patients with active PsA, as measured by PsAID9. To our knowledge, EQUATOR is the first randomized controlled trial to evaluate PsAID9.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show, NCT03101670.
Review of research on high-speed railway aerodynamics in China
Authors: Tian Hong-qi
Published: August 2019

High-speed railway aerodynamics is the key basic science for solving the bottleneck problem of high-speed railway development. This paper systematically summarizes the aerodynamic research relating to China’s high-speed railway network. Seven key research advances are comprehensively discussed, including train aerodynamic drag-reduction technology, train aerodynamic noise-reduction technology, train ventilation technology, train crossing aerodynamics, train/tunnel aerodynamics, train/climate environment aerodynamics, and train/human body aerodynamics. Seven types of railway aerodynamic test platform built by Central South University are introduced. Five major systems for a high-speed railway network—the aerodynamics theoretical system, the aerodynamic shape (train, tunnel, and so on) design system, the aerodynamics evaluation system, the 3D protection system for operational safety of the high-speed railway network, and the high-speed railway aerodynamic test/computation/analysis platform system—are also introduced. Finally, eight future development directions for the field of railway aerodynamics are proposed. For over 30 years, railway aerodynamics has been an important supporting element in the development of China’s high-speed railway network, which has also promoted the development of high-speed railway aerodynamics throughout the world.
Structure of the germarium and female germ-cell clusters in Thulinius ruffoi (Bertolani, 1982) (Tardigrada: Eutardigrada: Parachela)
Authors: Janelt Kamil , Jezierska Marta , Student Sebastian , Poprawa Izabela
Published: August 2019

Thulinius ruffoi is a freshwater species that has the ability to reproduce via parthenogenesis. A meroistic polytrophic ovary is present in this species. Analyses of the germarium structure, and formation and organization of female germ-cell clusters were performed using light, confocal laser scanning, transmission electron and serial block-face scanning electron microscopy. The germarium is the small, anterior part of an ovary that contains putative germ-line stem cells. In the studied species, the female germ-cell clusters are large and branched. Only one cell in each cluster develops into an oocyte, while all the other cells become trophocytes. In this paper, we present the ﬁrst report on the presence of F-actin as a component of the intercellular bridges that connect the cells in the germ-cell cluster of T. ruffoi. Moreover, our results show that the female germ-cell clusters are formed as the result of both synchronous and asynchronous divisions and that their organization can vary not only between individuals of the investigated species, but also that clusters developing simultaneously within the same ovary can have a different spatial organization.
Bifocal Compression–Distraction for Combined Bone and Soft-Tissue Defects in Post-traumatic Tibial Nonunion
Authors: Thakeb Mootaz F. , Fayyad Tamer A. , ElGebeily Mohamed A. , Diab Ramy A. , El Zahlawy Hany , Sharafeldin Mohamed S. , Al Kersh Mohamed A.
Published: August 2019

Objective:

To compare 2 distraction osteogenesis techniques in post-traumatic tibial nonunion patients with composite bone and soft-tissue defects.

Design:

Nonrandomized prospective, case series, single-center study.

Setting:

Department of Orthopaedics and Traumatology, Limb Reconstruction Unit, El-Helal hospital, Cairo, Egypt.

Participants:

Fifty post-traumatic tibial nonunion patients with composite bone and soft-tissue defects.

Intervention:

Twenty-five patients were treated using bone transport (BT) technique, and 25 patients were treated using acute shortening (AS) and distraction technique.

Outcome Measurements:

The external fixation index (EFI); functional and bone results; and complication rates.

Results:

All patients were followed for a minimum of 18 months after removal of their Ilizarov frame. AS and BT groups were followed up for a mean of 19.7 and 20.3 months, respectively. The mean bone gap after resection and debridement was 4 cm in AS group and 5.9 cm in BT group (P = 0.06). The mean EFI was statistically significant and lower in the AS group compared with BT group (P = 0.03). There were no other statistically significant differences between either intervention groups.

Conclusions:

Both techniques achieved comparable good to excellent results, and the differences in number of complications and ASAMI scores for bone or function were not statistically significant. Yet, it appears that the AS technique may be superior because it has a significantly lower EFI. This may not be feasible in all cases, however, because the AS technique is limited by the defect size and the condition of the surrounding soft tissues.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Cardiac Rehabilitation Utilization During an Acute Cardiac Hospitalization
Authors: Pack Quinn R. , Priya Aruna , Lagu Tara , Pekow Penelope S. , Berry Robert , Atreya Auras R. , Ades Philip A. , Lindenauer Peter K.
Published: August 2019

Background:

Inpatient cardiac rehabilitation (ICR) programs provide important services to hospitalized patients by delivering risk factor education, daily ambulation, and facilitation of referral to outpatient cardiac rehabilitation. However, little is known about ICR utilization or practice patterns.

Methods:

We examined the use of ICR, between January 2007 and June 2011, in a geographically and structurally diverse sample of US hospitals (Premier, Inc).

Results:

Among 458 hospitals, there were 1 343 537 admissions with a qualifying diagnosis for outpatient cardiac rehabilitation. Formal ICR was available at 223 (49%) of these hospitals. Overall, patient utilization of ICR was low (21.2%) and varied by indication. Utilization was highest in those undergoing cardiac surgery (43.3%) and lowest in patients with medically managed myocardial infarction (15.6%) or heart failure (10.6%). A larger bed count, the presence of cardiac interventional services, and Midwest location were associated with increased likelihood of a hospital having an ICR program. In multivariable hierarchical analysis adjusting for known hospital characteristics among hospitals that provided ICR, multiple patient factors were associated with a lower likelihood of ICR utilization, including older age, more comorbidities, female sex, and Medicare insurance, but unspecified hospital characteristics explained the vast majority of the variability.

Conclusions:

We found substantial variation in the delivery of ICR across US hospitals and by patient condition. Overall, only a minority of eligible patients ever received ICR and fewer than half of hospitals treating cardiac patients provided formal ICR services. This substantial gap in the secondary prevention of heart disease warrants further investigation and intervention.
Risk Factors for Influenza Virus Related Severe Lower Respiratory Tract Infection in Children
Authors: Eşki Aykut , Öztürk Gökçen Kartal , Gülen Figen , Çiçek Candan , Demir Esen
Published: August 2019

Background:

Influenza virus is one of the most common respiratory pathogens for all age groups and may cause seasonal outbreaks. Our aim was to identify risk groups and factors associated with severe clinical course including mortality in children with influenza-related lower respiratory tract infection (LRTI).

Methods:

We conducted a retrospective study in children hospitalized with influenza virus LRTI from 2008 to 2018. Data on demographic features, influenza type, viral coinfection, primary and secondary bacterial infections (SBIs), time of onset of antiviral treatment, comorbidities, hospitalization length, pediatric intensive care unit admission/invasive mechanical ventilation (IMV) need and mortality were collected from medical records.

Results:

There were 280 patients hospitalized with LRTI and median hospitalization length was 9 days. Congenital heart disease, neuromuscular disease, SBIs and late-onset antiviral treatment were independent risk factors for prolonged hospital stay (P < 0.05). Pediatric intensive care unit admission was present in 20.4% (57) of the patients and 17.1% (48) of all patients required IMV. SBIs, lymphopenia, neutrophilia, immunosuppression and human bocavirus coinfection were independent risk factors for IMV support (P < 0.05). Eighteen patients died and immunosuppression, lymphopenia and SBIs were independent risk factors for mortality (P < 0.05).

Conclusions:

Presence of comorbidity, SBIs, neutrophilia and lymphopenia at admission identified as risk factors for severe influenza infections including need for IMV and death. Although several studies showed that antiviral treatment reduce hospitalization, complications and mortality, there is a lack of prospective trials and patients for antiviral therapy should be carefully chosen by the clinician.
The Use of Colistin for the Treatment of Multidrug-resistant Gram-negative Infections in Neonates and Infants
Authors: Nakwan Narongsak , Chokephaibulkit Kulkanya , Imberti Roberto
Published: August 2019

In this review, we report the available data regarding efficacy, safety and pharmacokinetics of colistin in the treatment of multidrug-resistant Gram-negative bacteria in neonates and infants. Seventeen clinical studies, involving 312 patients, and 3 pharmacokinetics studies were identified. Blood stream infection was the most common source of infection, followed by pneumonia and meningitis/ventriculitis. In most cases, colistin was administered in association with other antibiotics. The most common route of administration was intravenous, with colistimethate doses ranging from 25,000 to 225,000 IU/kg/day divided into 2 or 3 doses. A recent pharmacokinetic study suggested that the appropriate intravenous dose should be >150,000 IU/kg/day. Microbiologic cure was obtained in 94.2% of patients and survival was 76.6%. The combination of intraventricular and intravenous colistin should be used in meningitis/ventriculitis. Nebulized colistin should be used as adjunctive treatment, but not as monotherapy. Nephrotoxicity and apnea were reported in 5.8% and 3.9% of patients respectively.The use of colistin for multidrug-resistant Gram-negative infections in neonates and infants is effective and safe, but the quality of studies is moderate. The optimal intravenous dose should be higher than that indicated in most reports.
Involvement of the Cochlear Aqueduct by Jugular Paraganglioma Is Associated With Sensorineural Hearing Loss
Authors: Patel Neil S. , Link Michael J. , Driscoll Colin L. W. , Neff Brian A. , Van Gompel Jamie J. , Lane John I. , Carlson Matthew L.
Published: August 2019

Objective:

The etiology of sensorineural hearing loss (SNHL) in patients with jugular paraganglioma (JP) whose tumors lack inner ear fistulae or vestibulocochlear nerve involvement is unknown. Recent literature has proposed that occlusion of the inferior cochlear vein may be causative. Herein, we assess the association between radiologic involvement of the cochlear aqueduct (CA) and the development of SNHL.

Study Design:

Blinded, retrospective review of imaging and audiometry.

Setting:

Tertiary center.

Patients:

Adults with JP.

Intervention(s):

None.

Main Outcome Measures:

Asymmetric SNHL was assessed continuously as the difference in bone conduction pure-tone average (BCPTA) between ears and as a categorical variable (≥15 dB difference at two consecutive frequencies, or a difference in speech discrimination score of ≥15%). Involvement of the CA was considered present if there was evidence of medial T2 fluid signal loss, contrast enhancement, or bony erosion/expansion.

Results:

Of 30 patients meeting inclusion criteria, 15 (50%) had asymmetric SNHL. CA involvement was observed in 87% of patients with asymmetric SNHL compared with 13% in those with symmetric hearing (p = 0.0001). Univariate analysis demonstrated that age, sex, and tumor volume were not associated with asymmetric SNHL. The median difference in BCPTA between ears in patients with CA involvement was 21.3 dB HL compared to 1.2 dB HL in those without CA involvement (p < 0.0001). Regression analysis demonstrates that enhancement within the CA is associated with a BCPTA difference of 19.4 dB HL (p = 0.0006).

Conclusions:

Cochlear aqueduct involvement by JP is associated with SNHL in the absence of inner ear fistula, vestibulocochlear nerve involvement, or brainstem compression. Correlation with operative findings or histopathologic evidence of tumor involvement may validate this intriguing imaging finding.
Microbiome Analysis of Cholesteatoma by Gene Sequencing
Authors: Weiss Joshua P. , Antonelli Patrick J. , Dirain Carolyn O.
Published: August 2019

Objective:

To compare the microbial flora of cholesteatoma and normal middle ears using gene-based sequencing analysis.

Study Design:

Controlledex vivohuman study.

Setting:

Academic, tertiary medical center.

Subjects and Methods:

Brush, swab, and tissue samples were each taken from cholesteatoma matrix and uninvolved tissue in patients with previously untreated, acquired cholesteatoma (n = 19) or middle ear mucosa from patients undergoing cochlear implantation with no history of cholesteatoma or previous middle ear surgery (control; n = 12). DNA was isolated from specimens then 16S rRNA gene sequencing was performed.

Results:

There was no difference in microbial yield between the sampling methods. Cholesteatoma specimens had lower relative abundance of 14 bacterial species compared with controls includingAcidovorax sp.,Bacillus sp.,Masillia sp.,Moraxella osloensis,Phenylobacterium conjunctum,Sphingomonas sp., andStaphylococcus epidermidis(allp < 0.05).Alternariasp. were present on nearly all the specimens.Alternariasp. andCladosporium herbarum(bothp ≤ 0.05) were lower in the cholesteatoma compared with control group. There was no difference in the relative abundance of any bacteria or fungi between the cholesteatoma matrix and uninvolved middle ear mucosa.

Conclusions:

Microbiome of cholesteatoma matrix is largely similar to adjacent mucosa. This differs from healthy ears. Further study is needed to understand if middle ear microbiome may impact cholesteatoma pathogenesis or treatment.
Pressure Transmission to the Inner Ear by Mastoid Palpation After Transmastoid Surgery for Superior Canal Dehiscence
Authors: Tanavde Ved A. , Creighton Francis X. , Ward Bryan K. , Carey John P.
Published: August 2019

Objective:

To discuss an effect of transmastoid repair of superior semicircular canal dehiscence and its resolution using a mastoid titanium mesh plate.

Patients:

A 53-year-old woman with a history of superior canal dehiscence syndrome (SCDS) and subsequent transmastoid repair experienced dizziness and a loud, drum-like sound in her repaired ear when touching the ear. Palpating the skin over the mastoid defect reproduced the symptoms and could be observed on binocular microscopy as tympanic membrane deformation synchronous with mastoid palpation.

Intervention (s):

Surgery to place a titanium mesh cranioplasty plate over the mastoid cavity.

Main Outcome Measure (s):

Reduction in dizziness and auditory symptoms when palpating the mastoid.

Results:

In follow-up 2 months after surgery, palpation of the left mastoid no longer results in vertigo or hearing a loud sound. Hearing and vestibular function remained unchanged.

Conclusions:

Despite resolution of SCDS symptoms after transmastoid plugging and resurfacing of the superior semicircular canal involving mastoidectomy, patients can be bothered by dizziness and vertigo when pressing on the mastoid soft tissue envelope. This acts like a balloon that, when compressed, changes middle ear pressure and moves the tympanic membrane and can even cause alternobaric vertigo. This can be avoided or resolved by rigidly reconstructing the defect in the mastoid bone.
Concurrent Treatment With Intratympanic Dexamethasone for Moderate-Severe Through Severe Bell's Palsy
Authors: Inagaki Akira , Minakata Toshiya , Katsumi Sachiyo , Murakami Shingo
Published: August 2019

Objective:

To determine whether early intervention with intratympanic steroid injection, known as concurrent intratympanic steroid therapy, is effective as a supplement to systemic steroid therapy for treating moderate-severe to severe Bell's palsy.

Design:

An open-label historical control trial.

Setting:

Tertiary referral center.

Participants:

A total of 35 Bell's palsy patients presenting with House–Brackmann grade IV or higher were treated with intratympanic steroid therapy concurrent with standard systemic treatment and compared with 108 patients treated with standard systemic therapy alone started within 7 days of onset.

Interventions:

In the concurrent intratympanic steroid therapy group, patients received both 410 mg of prednisolone (standard dose) and 1.65 mg of intratympanic dexamethasone for 10 consecutive days. Patients in the control group received the standard dose, or more, of systemic prednisolone. Both groups were additionally treated with valacyclovir.

Main Outcomes and Measures:

The primary outcome measure was restoration of a House–Brackmann score of grade I.

Results:

The rate of recovery to House–Brackmann Grade I was higher for the concurrent intratympanic steroid therapy group than for the control group (94% vs 73%, p = 0.008). The adjusted odds ratio was 5.47 (95% confidence interval: 1.18–25.21, p = 0.029).

Conclusions:

The recovery rate was higher for concurrent intratympanic steroid therapy treatment than for standard-of-care control treatment, regardless of whether steroid with lower or equivalent glucocorticoid action was administered. This result suggests that concurrent treatment with intratympanic steroid therapy is a potentially beneficial supplement to systemic steroid administration.