bluuebunny/crossref_metadata_2025 huggingface dataset:
Don’t abandon RCTs in IVF. We don’t even understand them
Authors: Wilkinson J , Brison D R , Duffy J M N , Farquhar C M , Lensen S , Mastenbroek S , van Wely M , Vail A
Published: September 2019

The conclusion of the Human Fertilisation and Embryology Authority that ‘add-on’ therapies in IVF are not supported by high-quality evidence has prompted new questions regarding the role of the randomized controlled trial (RCT) in evaluating infertility treatments. Critics argue that trials are cumbersome tools that provide irrelevant answers. Instead, they argue that greater emphasis should be placed on large observational databases, which can be analysed using powerful algorithms to determine which treatments work and for whom. Although the validity of these arguments rests upon the sciences of statistics and epidemiology, the discussion to date has largely been conducted without reference to these fields. We aim to remedy this omission, by evaluating the arguments against RCTs in IVF from a primarily methodological perspective. We suggest that, while criticism of the status quo is warranted, a retreat from RCTs is more likely to make things worse for patients and clinicians.
Contrasting the variability in spatial distribution of two juvenile flatfishes in relation to thermal stanzas in the eastern Bering Sea
Authors: Yeung Cynthia , Cooper Daniel W
Published: September 2019

Groundfish species in the Bering Sea are undergoing pronounced changes in spatial distribution and abundance due to warming ocean temperatures. The main drivers of interannual variability in this ecosystem are the alternating warm and cold thermal stanzas. Yellowfin sole (Limanda aspera; YFS) and northern rock sole (Lepidopsetta polyxystra; NRS) are commercially-valuable flatfishes in the Bering Sea and are among the most dominant groundfish species there in numbers and biomass. We examined the variability in the spatial distribution and abundance of juvenile NRS and YFS in relation to the ice and temperature conditions associated with warm-cold thermal shifts from 1982 to 2017. The goal was to assess the implications of the fluctuating thermal environment for Bering Sea flatfish production. We found ice cover and bottom temperature indices in the preceding 1 to 3 years to be the best predictors of NRS juvenile distribution. In contrast, these indices were not significantly correlated with YFS juvenile distribution, which could be an artifact of their relatively low availability to sampling. A warm stanza, as the Bering Sea is currently in, is expected to favor high numbers of NRS juveniles and the northward expansion of their distribution.
Long-term continuous flow mechanical biventricular support: 9 years and counting
Authors: Gude Einar , Hoel Tom N , Sørensen Gro , Broch Kaspar , Meyer Anders , Fiane Arnt E
Published: September 2019

We report 2 continuous flow HeartWareTM left ventricular assist devices successfully used in a patient with advanced heart failure of giant cell myocarditis origin in a biventricular configuration. Despite technical challenges of adapting a left ventricular assist device engineered for systemic pressure to function as a right ventricular assist device, the addition of dynamic banding on the right ventricular assist device outflow graft allowed successful adaptation of afterload. This patient has now been on biventricular configuration support for 9 years, and remains stable to this day.
Sevoflurane provides better haemodynamic stability than propofol during right ventricular ischaemia–reperfusion
Authors: Haraldsen Pernille , Cunha-Goncalves Doris , Metzsch Carsten , Algotsson Lars , Lindstedt Sandra , Ingemansson Richard
Published: September 2019

OBJECTIVES

To assess whether sevoflurane provides better haemodynamic stability than propofol in acute right ventricular (RV) ischaemia–reperfusion.

METHODS

Open-chest pigs (mean ± standard deviation, 68.8 ± 4.2 kg) anaesthetized with sevoflurane (n = 6) or propofol (n = 6) underwent 60 min of RV free wall ischaemia and 150 min of reperfusion. Haemodynamic parameters and blood flow in the 3 major coronary arteries were continuously monitored. Biomarkers of cardiac ischaemia were analysed.

RESULTS

Mean arterial pressure and stroke volume decreased, whereas pulmonary vascular resistance increased equally in both groups. Heart rate increased 7.5% with propofol (P < 0.05) and 17% with sevoflurane (P < 0.05). At reperfusion, left atrial pressure and systemic vascular resistance decreased with sevoflurane. While RV stroke work (mmHg·ml) and cardiac output (l·min−1) decreased in the propofol group (4.2 ± 1.2 to 2.9 ± 1.7 and 2.65 ± 0.44 to 2.28 ± 0.56, respectively, P < 0.05 both), they recovered to baseline levels in the sevoflurane group (4.1 ± 1.5 to 4.0 ± 1.5 and 2.77 ± 0.6 to 2.6 ± 0.5, respectively, P > 0.05). Circumflex and left anterior descending coronary artery blood flow decreased in both groups. Right coronary artery blood flow (ml·min−1) decreased with propofol (38 ± 9 to 28 ± 9, P < 0.05), but not with sevoflurane (28 ± 11 to 28 ± 17, P > 0.05). Biomarkers of cardiac ischaemia increased in both groups.

CONCLUSIONS

Compared to propofol, sevoflurane-anaesthetized pigs showed higher RV stroke work, cardiac output and right coronary artery blood flow during reperfusion. These findings warrant a clinical trial of sevoflurane in RV ischaemia in humans.
Big data, observational research and P-value: a recipe for false-positive findings? A study of simulated and real prospective cohorts
Authors: Veronesi Giovanni , Grassi Guido , Savelli Giordano , Quatto Piero , Zambon Antonella
Published: September 2019

Background

An increasing number of observational studies combine large sample sizes with low participation rates, which could lead to standard inference failing to control the false-discovery rate. We investigated if the ‘empirical calibration of P-value’ method (EPCV), reliant on negative controls, can preserve type I error in the context of survival analysis.

Methods

We used simulated cohort studies with 50% participation rate and two different selection bias mechanisms, and a real-life application on predictors of cancer mortality using data from four population-based cohorts in Northern Italy (n = 6976 men and women aged 25–74 years at baseline and 17 years of median follow-up).

Results

Type I error for the standard Cox model was above the 5% nominal level in 15 out of 16 simulated settings; for n = 10 000, the chances of a null association with hazard ratio = 1.05 having a P-value < 0.05 were 42.5%. Conversely, EPCV with 10 negative controls preserved the 5% nominal level in all the simulation settings, reducing bias in the point estimate by 80–90% when its main assumption was verified. In the real case, 15 out of 21 (71%) blood markers with no association with cancer mortality according to literature had a P-value < 0.05 in age- and gender-adjusted Cox models. After calibration, only 1 (4.8%) remained statistically significant.

Conclusions

In the analyses of large observational studies prone to selection bias, the use of empirical distribution to calibrate P-values can substantially reduce the number of trivial results needing further screening for relevance and external validity.
Personality Factors Differentiating Selective Approach, Selective Avoidance, and the Belief in the Importance of Silencing Others: Further Evidence for Discriminant Validity
Authors: Tsfati Yariv
Published: September 2019

Recent research proposed self-report measures tapping three different strategies used by people to place themselves within an ideologically homogeneous information environment: selective approach, selective avoidance, and the belief in the importance of silencing others (BISO). Using online survey data collected in Israel (n = 749), the present investigation explores the discriminant validity of these constructs. Confirmatory factor model comparisons support their empirical differentiation. In addition, it is argued that the constructs are empirically different given the fact that they correlate differently with personality factors. BISO is more strongly and positively associated with authoritarianism. Selective avoidance is more strongly negatively associated with openness to experience. Selective approach was positively associated with empathy, with which selective avoidance was negatively associated.
Antipartyism and Public Opinion toward Presidential Unilateral Actions: The Case of Taiwan in 2017
Authors: Tsai Tsung-han , Yu Ching-hsin
Published: September 2019

In this article, we examine how antipartyism influences the public’s preferences for the tools of presidential power by focusing on the case of Taiwan, which is a president-parliamentary system. We distinguish two types of antipartyism: general antipartyism and reactive antipartyism. The former refers to the general perception of political parties, whereas the latter involves the functions of parties in modern democracy. According to the analysis results, we find that general antipartyism is positively associated with support for the president’s power to unilaterally appoint judges. In contrast, reactive antipartyism leads to less support for executive privilege, unilateral judicial appointments, and the authority to direct agency implementation of policies passed by the legislature.
A novel approach to the Lindelöf hypothesis
Authors: Fokas A S
Published: September 2019

Lindelöf’s hypothesis, one of the most important open problems in the history of mathematics, states that for large $t$, Riemann’s zeta function $\zeta (1/2+it)$ is of order $O(t^{\varepsilon })$ for any $\varepsilon>0$. It is well known that for large $t$, the leading order asymptotics of the Riemann zeta function can be expressed in terms of a transcendental exponential sum. The usual approach to the Lindelöf hypothesis involves the use of ingenious techniques for the estimation of this sum. However, since such estimates cannot yield an asymptotic formula for the above sum, it appears that this strategy cannot lead to the proof of Lindelöf’s hypothesis. Here a completely different approach is introduced. In particular, a novel linear integral equation is derived for $|\zeta (\sigma +it)|^2, \ 0<\sigma <1$ whose asymptotic analysis yields asymptotic results for a certain Riemann zeta-type double exponential sum. This sum has the same structure as the sum describing the leading asymptotics of $|\zeta (\sigma +it)|^2$, namely it involves $m_1^{-\sigma -it}m_2^{-\sigma -it}$, but its summation limits are different than those of the sum corresponding to $|\zeta (\sigma +it)|^2$. The analysis of the above integral equation requires the asymptotic estimation of four different integrals denoted by $I_1,I_2,\tilde{I}_3,\tilde{I}_4$, as well as the derivation of an exact relation between certain double exponential sums. Here the latter relation is derived, and also the rigourous analysis of the first two integrals $I_1$ and $I_2$ is presented. For the remaining two integrals, formal results are only derived that suggest a possible roadmap for the derivation of rigourous asymptotic results of the above double exponential sum, as well as for other sums associated with $|\zeta (\sigma +it)|^2$. Additional developments suggested by the above novel approach are also discussed.
Bergman-Harmonic Functions on Classical Domains
Authors: Xiao Ming
Published: September 2019

We study Bergman-harmonic functions on classical domains from a new point of view in this paper. We first establish a boundary pluriharmonicity result for Bergman-harmonic functions on classical domains: a Bergman-harmonic function $u$ on a classical domain $D$ must be pluriharmonic on germs of complex manifolds in the boundary of $D$ if $u$ has some appropriate boundary regularity. Next we give a new characterization of pluriharmonicity on classical domains which may shed a new light on future study of Bergman-harmonic functions. We also prove characterization results for Bergman-harmonic functions on type I domains.
Human Cytomegalovirus Infection in Women With Preexisting Immunity: Sources of Infection and Mechanisms of Infection in the Presence of Antiviral Immunity
Authors: Britt William J
Published: September 2019

Human cytomegalovirus (HCMV) infection remains an important cause of neurodevelopmental sequelae in infants infected in utero. Unique to the natural history of perinatal HCMV infections is the occurrence of congenital HCMV infections (cCMV) in women with existing immunity to HCMV, infections that have been designated as nonprimary maternal infection. In maternal populations with a high HCMV seroprevalence, cCMV that follows nonprimary maternal infections accounts for 75%–90% of all cases of cCMV infections as well as a large proportion of infected infants with neurodevelopmental sequelae. Although considerable effort has been directed toward understanding immune correlates that can modify maternal infections and intrauterine transmission, the source of virus leading to nonprimary maternal infections and intrauterine transmission is not well defined. Previous paradigms that included reactivation of latent virus as the source of infection in immune women have been challenged by studies demonstrating acquisition and transmission of antigenically distinct viruses, a finding suggesting that reinfection through exposure to an exogenous virus is responsible for some cases of nonprimary maternal infection. Additional understanding of the source(s) of virus that leads to nonprimary maternal infection will be of considerable value in the development and testing of interventions such as vaccines designed to limit the incidence of cCMV in populations with high HCMV seroprevalence.
Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation
Authors: Boonyaratanakornkit Jim , Vivek Meghana , Xie Hu , Pergam Steven A , Cheng Guang-Shing , Mielcarek Marco , Hill Joshua A , Jerome Keith R , Limaye Ajit P , Leisenring Wendy , Boeckh Michael J , Waghmare Alpana
Published: September 2019

Background

Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized.

Methods

Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection.

Results

Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0).

Conclusions

High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.
Promoting Compliance with Human Rights: The Performance of the United Nations’ Universal Periodic Review and Treaty Bodies
Authors: Carraro Valentina
Published: September 2019

What mechanisms facilitate state compliance with human rights? This article proposes and applies a model to assess the extent to which two United Nations human rights mechanisms—the Universal Periodic Review (UPR) and the state reporting procedure of the treaty bodies—are perceived as capable of stimulating compliance with human rights, and why. It does so by identifying a set of goals potentially achieved by these organizations—generating pressure, stimulating learning, providing an accurate overview of states’ performance, and delivering practically feasible recommendations—and testing the extent to which reaching these goals is seen to facilitate compliance with human rights. It concludes that the treaty bodies’ perceived strength lies in providing states with learning opportunities and an accurate overview of their internal situations. In contrast, the UPR is deemed particularly strong in generating peer and public pressure on states. From a theoretical point of view, this article shows that, under certain conditions, the three main theoretical schools on compliance—enforcement, management, and constructivist—offer credible explanations for states’ performance in implementing human rights recommendations, with the enforcement school faring relatively better than the other two. Data were collected by means of forty semi-structured interviews and an online survey.
Microlevel Security after Armed Conflict: A New Framework for Analyzing Risks and Benefits of Peacebuilding Processes
Authors: Guthrey Holly L
Published: September 2019

The maintenance and/or achievement of security is of paramount importance within settings recovering from armed conflict; however existing studies in the field of peacebuilding do not sufficiently explore how various processes undertaken within peacebuilding programming result in different types of security outcomes at the individual and community level. In this article, I develop a novel conceptual framework for analyzing “microlevel” security risks and benefits of peacebuilding processes, through an adapted version of Johan Galtung's work on direct and structural violence. For the purposes of this article, the framework is applied in the context of “local” transitional justice (TJ) processes used in the aftermath of armed conflict, for which advocacy and implementation has increased in the recent past. Relying on a social psychological definition of security, I disaggregate components of direct and structural violence and use illustrative examples from existing empirical studies about the effects of local TJ processes in various settings to demonstrate ways in which these types of violence may be perpetuated, or initiated in new forms through these processes, thus posing security risks. The framework is further developed through the elucidation of factors that may help to repair the consequences of direct and structural violence and/or hinder the likelihood of their repetition, thematically conceptualized as physical and psychological welfare and social justice (respective to direct and structural violence) that I suggest link to security benefits. The framework is intended to provide new perspectives on understanding how peacebuilding processes may both promote and prevent security from being realized at the local level following armed conflict.
Desert seismic signal denoising by 2D compact variational mode decomposition
Authors: Li Yue , Li Linlin , Zhang Chao
Published: September 2019

Noise suppression and effective signal recovery are very important for seismic signal processing. The random noise in desert areas has complex characteristics due to the complex geographical environment; noise characteristics such as non-stationary, non-linear and low frequency. These make it difficult for conventional denoising methods to remove random noise in desert seismic records. To address the problem, this paper proposes a two-dimensional compact variational mode decomposition (2D-CVMD) algorithm for desert seismic noise attenuation. This model decomposes the complex desert seismic data into an finite number of intrinsic mode functions with specific directions and vibration characteristics. The algorithm introduces binary support functions, which can detect the edge region of the signal in each mode by penalizing the support function through the L1 and total variation (TV) norm. Finally, the signal can be reconstructed by the support functions and the decomposed modes. We apply the 2D-CVMD algorithm to synthetic and real seismic data. The results show that the 2D-CVMD algorithm can not only suppress desert low-frequency noise, but also recover the weak effective signal.
The Human Cost of the Weapons Trade: Small Arms Transfers and Recipient State Homicide
Authors: Martinez Machain Carla , Pickering Jeffrey
Published: September 2019

Empirical research has increasingly turned its attention to ways that international phenomena impact the human condition within countries. International influences have been shown to affect human rights, health, and quality of life within societies. They may also impact microlevel phenomena such as violent criminal behavior. In this study, we build on such recent scholarship and research that bridges the theoretical and empirical gap between international relations research and criminology. Our analysis examines the cross-national relationship between interstate small arms transfers and domestic homicide rates. We suspect that some proportion of weapons from the legal small arms trade find their way into the hands of societal actors and that a prevalence of firearms in society may be associated with elevated homicide rates. State strength should mitigate this relationship, as strong states should have greater ability to manage and to control legal arms shipments than their weaker counterparts. Cross-national empirical tests of small arms flows and homicide rates from 2000 to 2014 support our theoretical claims. They also demonstrate that legal small arms transfers impact only certain types of violent crimes.
Hosting Your Enemy: Accepting Refugees from a Rival State and Respect for Human Rights
Authors: Chu Tiffany S
Published: September 2019

This article argues that dynamics among rivals can affect how host states respond to refugees. Particularly, refugees from rival states can motivate host countries to promote inclusive action because they are exiled from an adversary. By treating refugees well and openly respecting their human rights, host states can, in effect, shame their rival, thereby undermining the adversary's legitimacy and discrediting the opposing government in the eyes of the international community. In the absence of a strategic rivalry, host governments do not have this incentive to support refugee human rights. Using statistical analyses, I find support for these hypotheses. In particular, the arrival of refugees from a neighboring rival state are associated with the strongest increase in respect for human rights within the host country, whereas refugees from a noncontiguous, nonrival state are related to a decrease in respect for human rights.
Detection of new methanol maser transitions associated with G358.93−0.03
Authors: MacLeod G C , Sugiyama K , Hunter T R , Quick J , Baan W , Breen S L , Brogan C L , Burns R A , Caratti o Garatti A , Chen X , Chibueze J O , Houde M , Kaczmarek J F , Linz H , Rajabi F , Saito Y , Schmidl S , Sobolev A M , Stecklum B , van den Heever S P , Yonekura Y
Published: September 2019

We report the detection of new 12.178, 12.229, 20.347, and 23.121 GHz methanol masers in the massive star-forming region G358.93−0.03, which are flaring on similarly short time-scales (days) as the 6.668 GHz methanol masers also associated with this source. The brightest 12.178 GHz channel increased by a factor of over 700 in just 50 d. The masers found in the 12.229 and 20.347 GHz methanol transitions are the first ever reported and this is only the fourth object to exhibit associated 23.121 GHz methanol masers. The 12.178 GHz methanol maser emission appears to have a higher flux density than that of the 6.668 GHz emission, which is unusual. No associated near-infrared flare counterpart was found, suggesting that the energy source of the flare is deeply embedded.
PP4 phosphatase cooperates in recombinational DNA repair by enhancing double-strand break end resection
Authors: Villoria María Teresa , Gutiérrez-Escribano Pilar , Alonso-Rodríguez Esmeralda , Ramos Facundo , Merino Eva , Campos Adrián , Montoya Alex , Kramer Holger , Aragón Luis , Clemente-Blanco Andrés
Published: September 2019

The role of Rad53 in response to a DNA lesion is central for the accurate orchestration of the DNA damage response. Rad53 activation relies on its phosphorylation by Mec1 and its own autophosphorylation in a manner dependent on the adaptor Rad9. While the mechanism behind Rad53 activation has been well documented, less is known about the processes that counteract its activity along the repair of a DNA adduct. Here, we describe that PP4 phosphatase is required to avoid Rad53 hyper-phosphorylation during the repair of a double-strand break, a process that impacts on the phosphorylation status of multiple factors involved in the DNA damage response. PP4-dependent Rad53 dephosphorylation stimulates DNA end resection by relieving the negative effect that Rad9 exerts over the Sgs1/Dna2 exonuclease complex. Consequently, elimination of PP4 activity affects resection and repair by single-strand annealing, defects that are bypassed by reducing Rad53 hyperphosphorylation. These results confirm that Rad53 phosphorylation is controlled by PP4 during the repair of a DNA lesion and demonstrate that the attenuation of its kinase activity during the initial steps of the repair process is essential to efficiently enhance recombinational DNA repair pathways that depend on long-range resection for their success.
A Comparative Study of Fibromyalgia, Rheumatoid Arthritis, Spondyloarthritis, and Sjögren’s Syndrome; Impact of the Disease on Quality of Life, Psychological Adjustment, and Use of Coping Strategies
Authors: Bucourt Emilie , Martaillé Virginie , Goupille Philippe , Joncker-Vannier Isabelle , Huttenberger Brigitte , Réveillère Christian , Mulleman Denis , Courtois and Robert
Published: September 2019

Background

Fibromyalgia, rheumatoid arthritis, spondyloarthritis, and Sjögren’s syndrome are chronic rheumatic diseases with very different clinical characteristics, but which share symptoms such as pain and fatigue. The aim of the study was to examine the impact of the disease on psychological adaptation in fibromyalgia compared with other rheumatic diseases (rheumatoid arthritis, spondyloarthritis, and Sjögren’s syndrome).

Methods

In a multicenter study, 165 women with rheumatic diseases (48 with fibromyalgia, 47 with rheumatoid arthritis, 47 with spondyloarthritis, 23 with Sjögren’s syndrome) completed the General Health Questionnaire–28 (emotional distress), Fatigue Severity Scale (fatigue), Fibromyalgia Impact Questionnaire (impact of the disease), Coping Strategies Questionnaire (coping), and Mini International Neuropsychiatric Interview (comorbidity with DSM IV axis-I disorders). We used the Kruskal-Wallis test, Mann-Whitney U test, and chi2 test to compare comorbid anxiety and depressive disorders and to compare the impact of the disease on patients’ mental well-being and daily life and adjustment (coping strategies).

Results

Anxiety and depressive disorders were more common in fibromyalgia patients; they had higher scores on impact of the disease, physical symptoms, pain, and fatigue than rheumatoid arthritis patients and reported more fatigue than patients with spondyloarthritis. Overall, they used more maladaptive coping strategies (less use of distancing from pain than patients with rheumatoid arthritis and spondyloarthritis, less use of ignoring pain sensations, and more use of catastrophizing than those with rheumatoid arthritis). No differences were found between fibromyalgia and Sjögren’s syndrome on impact and adjustment.

Conclusions

Compared with other rheumatic diseases, fibromyalgia has a greater impact on daily life; patients have more difficulty adjusting to the disease and generally use poorer strategies to cope with pain.
The ‘Territory of the Union’ in EU Citizenship Law: Charting a Route from Parallel to Integrated Narratives
Authors: Shuibhne Niamh Nic
Published: September 2019

This paper examines the growing significance of the ‘territory of the Union’ in EU citizenship law and asks what it reveals about Union citizenship in the wider system of the EU legal order. In doing so, it builds on scholarship constructing the idea of ‘personhood’ in EU law by adding a complementary dimension of ‘place-hood’. The analysis is premised on territory as a place within—but also beyond—which particular legal qualities are both produced by and reflect shared objectives or values. In that respect, the paper offers a comprehensive ‘map’ of Union territory as a legal construct, with the aim of uncovering what kind of legal place the territory of the Union constitutes as well as the extent to which it is dis-connectable from the territories of the Member States. It also considers how Union territory relates to what lies ‘outside’. It will be shown that different narratives of Union territory have materialized in the case law of the Court of Justice. However, it is argued that these segregated lines of reasoning should be integrated, both to reflect and to progress a composite understanding of Union territory as a place in which concerns for Union citizens, for Member States, and for the system underpinning the EU legal order are more consistently acknowledged and more openly weighed.
Increased Fibrogenic Gene Expression in Multifidus Muscles of Patients With Chronic Versus Acute Lumbar Spine Pathology
Authors: Shahidi Bahar , Fisch Kathleen M. , Gibbons Michael C. , Ward Samuel R.
Published: September 2019

Study Design.

Prospective observational study-basic science (Level 1).

Objective.

The aim of this study was to compare expression of functional groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways between paraspinal muscle biopsies from individuals with acute and chronic lumbar spine pathology.

Summary of Background Data.

Low back pain is a complex and multifactorial condition that affects a majority of the general population annually. Changes in muscle tissue composition (i.e., fatty and fibrotic infiltration) are a common feature in individuals with lumbar spine pathology associated with low back pain, which often results in functional loss. Understanding the molecular underpinnings of these degenerative changes in different phases of disease progression may improve disease prevention and treatment specificity.

Methods.

Intraoperative biopsies of the multifidus muscle were obtained from individuals undergoing surgery for acute (<6-month duration) or chronic (>6-month duration) lumbar spine pathology. Expression of 42 genes related to myogenesis, atrophy, adipogenesis, metabolism, inflammation, and fibrosis were measured in 33 samples (eight acute, 25 chronic) using qPCR, and tissue composition of fat, muscle, and fibrosis was quantified using histology.

Results.

We found that tissue composition of the biopsies was heterogeneous, resulting in a trend toward lower RNA yields in biopsies with higher proportions of fat (r <−0.39, P < 0.1). There were no significant differences in gene expression patterns for atrophy (P > 0.635), adipogenesis (P > 0.317), myogenesis (P > 0.320), or inflammatory (P > 0.413) genes after adjusting for the proportion of muscle, fat, and connective tissue. However, in the fibrogenesis pathway, we found significant upregulation of CTGF (P = 0.046), and trends for upregulation of COL1A1 (P = 0.061), and downregulation of MMP1 and MMP9 (P = 0.061) in the chronic group.

Conclusion.

There is increased fibrogenic gene expression in individuals with chronic disease when compared to acute disease, without significant differences in atrophic, myogenic, adipogenic, or inflammatory pathways, suggesting increased efforts should be made to prevent or reverse fibrogenesis to improve patient function in this population.

Level of Evidence: N/A
Granulocyte–Macrophage Colony-Stimulating Factor Inhalation Therapy for Severe Pulmonary Alveolar Proteinosis
Authors: Zhen Genshen , Li Duo , Jiang Jian , Weng Yibing
Published: September 2019

Background:

Some patients with pulmonary alveolar proteinosis (PAP) still present with high recurrence rate after large-volume whole lung lavage (WLL). Granulocyte–macrophage colony-stimulating factor (GM-CSF) has been proved to be effective for PAP, but clinical research on GM-CSF inhalation therapy combined with WLL for severe PAP is rare in Asia.

Study Question:

This study aimed to investigate the clinical efficacy of GM-CSF inhalation combined with WLL in Chinese patients with PAP.

Study Design:

We performed regression analysis on 33 patients with severe PAP who underwent WLL alone or WLL combined with GM-CSF inhalation. The patients were put into 2 groups, WLL group and GM-CSF/WLL group.

Measures and Outcomes:

Physiologic, serologic, and radiologic features of the 2 groups at different time points after treatment and the recurrence rates at 1-year follow-up were compared.

Results:

There were no significant differences in lung function, blood gas analysis indices, and lung CT between the 2 groups after 1-week treatment (P > 0.05). After 3-month treatment, the GM-CSF/WLL group showed significantly faster improvement in FEV1%Pred (P = 0.028), FVC%Pred (P = 0.014), PaO2 (P = 0.022), PA-aO2 (P = 0.009), PaO2/FiO2 (P = 0.025), 6-minute walking test (P = 0.002), and lung CT parameters (P < 0.05) compared with the WLL group. The recurrence rate at the 1-year follow-up in the GM-CSF/WLL group (5.5%) was significantly higher than that in the WLL group (46.67%; P < 0.05).

Conclusions:

GM-CSF inhalation therapy combined with WLL is an effective treatment for patients with severe PAP, with further improvement in lung function at the base of WILL as well as reduction on re-WLL incidence.
Gastrointestinal Symptoms in Infants of Mothers With a Psychiatric History and the Role of Depression and Bonding
Authors: de Kruijff Ineke , Choenni Vandhana , Groeneweg Jasja T. , Vlieger Arine M. , Benninga Marc A. , Kok Rianne , Kamperman Astrid M. , Lambregtse‐van den Berg Mijke P.
Published: September 2019

Objectives:

Gastroesophageal reflux (GER), excessive crying, and constipation are common gastrointestinal symptoms in infancy of multifactorial origin in which psychosocial stress factors play an important role. The aims of this observational study were to investigate the presence of gastrointestinal symptoms in infants of mothers with or without a history of a psychiatric disorder, their association with maternal depressive symptoms, and the possible mediating role of bonding.

Methods:

One hundred one mothers with a history of a psychiatric disorder and 60 control mothers were included. Infant gastrointestinal symptoms, maternal depressive symptoms, and mother‐infant bonding were assessed using validated questionnaires and diagnostic criteria at 1.5 months postpartum.

Results:

The mean total score on the Infant Gastroesophageal Reflux Questionnaire Revised reported in infants of mothers with psychiatric disorder (13.4 standard deviation 5.4) was significantly higher than that in infants of control mothers (10.8 standard deviation 5.4;P= .003). No significant differences were found in the presence of excessive crying (modified Wessel criteria and subjective experience) and constipation (ROME IV criteria) between both groups. Infant GER was associated with maternal depressive symptoms (P= 0.027) and bonding problems (P= <0.001). Constipation was related to maternal depressive symptoms (P= 0.045), and excessive crying (Wessel and subjective criteria) was associated with bonding problems (P= 0.022 andP= 0.002, respectively). The effect of maternal depressive symptomatology on infant GER symptoms and excessive crying was mediated by bonding problems.

Conclusion:

Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother‐infant bonding is a mediating factor.
Risk Factors Associated With Increased Mortality From Intussusception in African Infants
Authors: Pindyck Talia , Parashar Umesh , Mwenda Jason M. , Tadesse Amezene , Armah George , Omore Richard , Ngwira Bagrey , Jani Bhavin , Mpabalwani Evans M. , Mbuwayesango Bothwell , Tate Jacqueline ,   African Intussusception Surveillance Network
Published: September 2019

Objectives:

Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception.

Methods:

Infants with intussusception from 7 sub‐Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital‐based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression.

Results:

A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2–3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0–1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9–6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3–0.7), and employment of a household member (OR 0.7; 95% CI 0.4–1.0) were protective against intestinal resection.

Conclusions:

Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub‐Saharan African countries to reduce morbidity and mortality from intussusception in these resource‐limited settings.
Team-Based Intervention to Reduce the Impact of Nonactionable Alarms in an Adult Intensive Care Unit
Authors: Yeh Justin , Wilson Ruth , Young Lufei , Pahl Lisa , Whitney Steven , Dellsperger Kevin C. , Schafer Pascha E.
Published: September 2019

Background:

Nonactionable alarms comprise over 70% of alarms and contribute a threat to patient safety. Few studies have reported approaches to translate and sustain these interventions in clinical settings.

Purpose:

This study tested whether an interprofessional team-based approach can translate and implement effective alarm reduction interventions in the adult intensive care unit.

Methods:

The study was a prospective, cohort, pre- and postdesign with repeated measures at baseline (preintervention) and post-phase I and II intervention periods. The settings for the most prevalent nonactionable arrhythmia and bedside parameter alarms were adjusted during phases I and II, respectively.

Results:

The number of total alarms was reduced by 40% over a 14-day period after both intervention phases were implemented. The most prevalent nonactionable parameter alarms decreased by 47% and arrhythmia alarms decreased by 46%.

Conclusions:

It is feasible to translate and sustain system-level alarm management interventions addressing alarm fatigue using an interprofessional team-based approach.
What Do We Know Now About Autologous Fat Grafting?
Authors: Gal Shaili , Xue Yunfeng , Pu Lee L. Q.
Published: September 2019

Autologous fat grafting has remained part of the plastic surgeon's armamentarium. Although there have been numerous articles written on this topic, its scientific basis has recently come under some scrutiny with authors questioning what we really know about fat grafting. This article reviews the various fat grafting techniques used today based on the volume and specific need of the patient. Moreover, this review acts as a guideline to the plastic and reconstructive surgeon to choose the fat grafting technique tailored to the specific goal of the procedure. Once volume of fat and the final goal of the procedure is determined, fat grafting becomes a more individualized approach for our patients. While fat grafting is not a cookie-cutter procedure, it can be defined by the volume needed and divided into 3 categories of small, mega or large, and nanofat grafting techniques. A discussion of these 3 main categories of fat grafting techniques will be presented, along with a discussion of the mechanisms of adipocyte survival after transplant based on the graft survival and graft replacement theories. Finally, the role of adipose-derived stem cells in fat grafting based on clinical studies will be delineated. It is our hope to provide the most updated information on what do we know now about autologous fat grafting.
Radiation-Induced Skin Fibrosis
Authors: Borrelli Mimi R. , Shen Abra H. , Lee Gordon K. , Momeni Arash , Longaker Michael T. , Wan Derrick C.
Published: September 2019

Radiotherapy (RT) has become an indispensable part of oncologic treatment protocols for a range of malignancies. However, a serious adverse effect of RT is radiodermatitis; almost 95% of patients develop moderate to severe skin reactions following radiation treatment. In the acute setting, these can be erythema, desquamation, ulceration, and pain. Chronically, soft tissue atrophy, alopecia, and stiffness can be noted. Radiodermatitis can delay oncologic treatment protocols and significantly impair quality of life. There is currently a paucity of effective treatment options and prevention strategies for radiodermatitis. Importantly, recent preclinical and clinical studies have suggested that fat grafting may be of therapeutic benefit, reversing detrimental changes to soft tissue following RT. This review outlines the damaging effects of RT on the skin and soft tissue as well as discusses available treatment options for radiodermatitis. Emerging strategies to mitigate detrimental, chronic radiation-induced changes are also presented.
Evidence-Based Gardening
Authors: Ching Ann Hui , Le Nicole , Norwich-Cavanaugh Amanda , Hsia Henry C.
Published: September 2019

Complex wounds are commonly thought to require aggressive surgical intervention to achieve healing. However, optimal healing results can often be achieved when greater emphasis is placed on optimizing patient factors prior to any surgical intervention. A retrospective review was performed of pressure ulcers and complex wound cases treated over 5 years at the Yale New Haven Wound Center. Optimal healing including clinical resolution of osteomyelitis and improved scarring was achieved when patient factors, such as glucose control and nutrition, were optimized. Surgical intervention can be more effective and even avoided entirely with the appropriate focus on optimizing patient factors.
Use of Negative Pressure Wound Therapy in Surgical Site Infection During Pregnancy
Authors: Escobar-Vidarte María Fernanda , Messa Adriana , Nieto Albaro Jose , Echavarría Maria Paula , Carvajal Javier Andres , Fernández Paula Andrea
Published: September 2019

BACKGROUND:

Surgical site infections (SSIs) are a known cause of morbidity and mortality; however, evidence related to management of SSIs during pregnancy is sparse.

CASE:

A 26-year-old female patient with an adnexal cystic lesion underwent laparotomy at 19 weeks of pregnancy. She experienced a late SSI 10 days after initial surgery, necessitating surgical debridement. She was treated with multiple surgical interventions for wound irrigations and wound closure assisted by a negative pressure wound therapy.

CONCLUSION:

Negative pressure wound therapy was used for treatment of an SSI during pregnancy without causing premature delivery or requiring a cesearan section.
Tapeworm manipulation of copepod behaviour: parasite genotype has a larger effect than host genotype
Authors: Benesh Daniel P.
Published: September 2019

Compared with uninfected individuals, infected animals can exhibit altered phenotypes. The changes often appear beneficial to parasites, leading to the notion that modified host phenotypes are extended parasite phenotypes, shaped by parasite genes. However, the phenotype of a parasitized individual may reflect parasitic manipulation, host responses to infection or both, and disentangling the contribution of parasite genes versus host genes to these altered phenotypes is challenging. Using a tapeworm (Schistocephalus solidus) infecting its copepod first intermediate host, I performed a full-factorial, cross-infection experiment with five host and five parasite genotypes. I found that a behavioural trait modified by infection, copepod activity, was affected by both host and parasite genotype. There was no clear evidence for host genotype by parasite genotype interactions. Several observations indicated that host behaviour was chiefly determined by parasite genes: (i) all infected copepods, regardless of host or parasite genotype, exhibited behavioural changes, (ii) parasitism reduced the differences among copepod genotypes, and (iii) within infected copepods, parasite genotype had twice as large an effect on behaviour as host genotype. I conclude that the altered behaviour of infected copepods primarily represents an extended parasite phenotype, and I discuss how genetic variation in parasitic host manipulation could be maintained.
The avalanche-like behaviour of large-scale haemodynamic activity from wakefulness to deep sleep
Authors: Bocaccio H. , Pallavicini C. , Castro M. N. , Sánchez S. M. , De Pino G. , Laufs H. , Villarreal M. F. , Tagliazucchi E.
Published: September 2019

Increasing evidence suggests that responsiveness is associated with critical or near-critical cortical dynamics, which exhibit scale-free cascades of spatio-temporal activity. These cascades, or ‘avalanches’, have been detected at multiple scales, from
in vitro
and
in vivo
microcircuits to voltage imaging and brain-wide functional magnetic resonance imaging (fMRI) recordings. Criticality endows the cortex with certain information-processing capacities postulated as necessary for conscious wakefulness, yet it remains unknown how unresponsiveness impacts on the avalanche-like behaviour of large-scale human haemodynamic activity. We observed a scale-free hierarchy of co-activated connected clusters by applying a point-process transformation to fMRI data recorded during wakefulness and non-rapid eye movement (NREM) sleep. Maximum-likelihood estimates revealed a significant effect of sleep stage on the scaling parameters of the cluster size power-law distributions.
Post hoc
statistical tests showed that differences were maximal between wakefulness and N2 sleep. These results were robust against spatial coarse graining, fitting alternative statistical models and different point-process thresholds, and disappeared upon phase shuffling the fMRI time series. Evoked neural bistabilities preventing arousals during N2 sleep do not suffice to explain these differences, which point towards changes in the intrinsic dynamics of the brain that could be necessary to consolidate a state of deep unresponsiveness.
Information processing by endoplasmic reticulum stress sensors
Authors: Stroberg Wylie , Eilertsen Justin , Schnell Santiago
Published: September 2019

The unfolded protein response (UPR) is a collection of cellular feedback mechanisms that seek to maintain protein folding homeostasis in the endoplasmic reticulum (ER). When the ER is ‘stressed’, through either high protein folding demand or undersupply of chaperones and foldases, stress sensing proteins in the ER membrane initiate the UPR. Recently, experiments have indicated that these signalling molecules detect stress by being both sequestered by free chaperones and activated by free unfolded proteins. However, it remains unclear what advantage this bidirectional sensor control offers stressed cells. Here, we show that combining positive regulation of sensor activity by unfolded proteins with negative regulation by chaperones allows the sensor to make a more informative measurement of ER stress. The increase in the information capacity of the combined sensing mechanism stems from stretching of the active range of the sensor, at the cost of increased uncertainty due to the integration of multiple signals. These results provide a possible rationale for the evolution of the observed stress-sensing mechanism.