bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013
Authors: Friedrich Michaela-Elena , Winkler Dietmar , Konstantinidis Anastasios , Huf Wolfgang , Engel Rolf , Toto Sermin , Grohmann Renate , Kasper Siegfried
Published: August 2019

Background

Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome.

Methods

This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients.

Results

A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine.

Conclusions

Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.
Maternal Envelope gp41 Ectodomain-Specific Antibodies Are Associated With Increased Mother-to-Child Transmission of Human Immunodeficiency Virus-1
Authors: Naiman Nicole E , Slyker Jennifer , Nduati Ruth , Overbaugh Julie M
Published: August 2019

Mother-to-child transmission of human immunodeficiency virus (HIV) occurs in the setting of maternal and passively acquired antibodies, providing a unique window into immune correlates of HIV risk. We compared plasma antibody binding to HIV antigens between 51 nontransmitting mother-infant pairs and 21 transmitting mother-infant pairs. Plasma antibody binding to a variety of gp41 ectodomain-containing antigens was associated with increased odds of transmission. Understanding the reasons why gp41 ectodomain-targeting antibodies are associated with transmission risk will be important in determining whether they can directly enhance infection or whether their presence reflects a redirecting of the humoral response away from targeting more protective epitopes.
Analysis of intestinal immunity and flora in a collagen-induced mouse arthritis model: differences during arthritis progression
Authors: Nemoto Nobuhito , Takeda Yuji , Nara Hidetoshi , Araki Akemi , Gazi Md Yeashin , Takakubo Yuya , Naganuma Yasushi , Takagi Michiaki , Asao Hironobu
Published: August 2019

Intestinal immunity and flora are reported to be associated with the onset of rheumatoid arthritis. However, differences in the intestinal immunity and flora dynamics between the initial peak and relapse of arthritis have not been investigated. Here we analyzed the lymphocyte populations in different lymphoid tissues, the IgA in feces, and the intestinal flora at the initial peak and the relapse phase of arthritis in a collagen-induced arthritis (CIA) mouse model. In this model compared with the control group, the percentage of RORγt+CD4+ T cells in the mesenteric lymph nodes (mLN) was increased at the initial peak but decreased at the relapse stage of arthritis, and the opposite changes were observed in the spleen. The percentage of Foxp3+CD4+ T cells was unchanged at the initial peak in both tissues but increased only in the mLN at the relapse stage. The IgA in feces increased with the progression of arthritis, and bacterial analysis revealed that some specific bacterial families were changed at the peak and relapse stages of arthritis. Finally, the immune dynamics under different arthritic conditions were examined by integrating these factors using principal component analysis (PCA). PCA showed that the immunological and intestinal flora profiles were different between the initial peak and the relapse of the arthritis. Our findings suggest that the intestinal immunity and the environment change drastically with the progress of arthritis.
Impact of a national guideline on use of knee arthroscopy: An interrupted time-series analysis
Authors: Kiadaliri Ali , Bergkvist Dan , Dahlberg Leif E , Englund Martin
Published: August 2019

Objective

To assess the impact of the Swedish health authority recommendation against the use of knee arthroscopy in patients aged ≥40 years with knee osteoarthritis (OA).

Design

Interrupted time series analysis.

Setting

Public health care in Skåne region.

Participants

Patients aged ≥40 years who underwent knee arthroscopy from January 2010 to December 2015.

Intervention(s)

National guideline’s recommendation against the use of knee arthroscopy in patients with knee OA.

Main Outcome Measure(s)

1) proportion of patients aged ≥40 years with a main diagnosis of Knee OA and/or degenerative meniscal lesions (DML) who underwent knee arthroscopy, and 2) overall knee arthroscopy rate per 100,000 Skåne population aged ≥40 years.

Results

A total of 6,155 knee arthroscopy were performed among people aged ≥40 years during study period. Of 42,044 patients with Knee OA/DML, 3,728 had knee arthroscopy. The recommendation was associated with reductions in the use of knee arthroscopy and two years after the recommendation, there was a reduction of 28.6% (95% CI: 9.3, 47.8) and 34.7% (23.9, 45.4) in proportion of Knee OA/DML patients with knee arthroscopy and the overall knee arthroscopy rate, respectively, relative to that expected if pre-recommendation trend continued. Our sensitivity analysis showed that the use of total knee replacement was stable over the study period.

Conclusion

The national recommendation was associated with reduction in use of knee arthroscopy in public health care in southern Sweden. However, still 4.5% of these patients underwent knee arthroscopy in 2015 implying that more efforts are required to achieve the recommended target.
E.H. Carr and IPE: An Essay in Retrieval
Authors: Germain Randall
Published: August 2019

Although the work of E.H. Carr has a prominent place in the scholarly history of international relations (IR), it is notably absent from the discipline of international political economy (IPE). This is puzzling, because Carr's analysis of international politics places a strong emphasis on the organic connection between politics and economics on an international scale. On this reading, his principal publications on IR can also be seen to chart a sophisticated conceptualization of what I want to label historical IPE. This essay retrieves such a reading of Carr for the discipline of IPE. It begins by interrogating the way in which Carr's work has been appropriated by modern IPE scholarship, in order to highlight the limited use made of the political economy dimension of his research. I then explore the historical and political economy aspects of Carr's writings to consider how his contribution might advance recent contemporary theoretical debate in the discipline. I pay particular attention to how his work charts an historical conception of IPE that can synthesize and move beyond the rationalist/constructivist binary that currently dominates theorizing in the discipline.
Informatics opportunities to involve patients in hospital safety: a conceptual model
Authors: Haldar Shefali , Mishra Sonali R , Pollack Ari H , Pratt Wanda
Published: August 2019

Objective

Inpatients could play an important role in identifying, preventing, and reporting problems in the quality and safety of their care. To support them effectively in that role, informatics solutions must align with their experiences. Thus, we set out to understand how inpatients experience undesirable events (UEs) and to surface opportunities for those informatics solutions.

Materials and Methods

We conducted a survey with 242 patients and caregivers during their hospital stay, asking open-ended questions about their experiences with UEs. Based on our qualitative analysis, we developed a conceptual model representing their experiences and identified informatics opportunities to support patients.

Results

Our 4-stage conceptual model illustrates inpatient experiences, from when they first encounter UEs, when they could intervene, when harms emerge, what types of harms they experience, and what they do in response to harms.

Discussion

Existing informatics solutions address the first stage of inpatients’ experiences by increasing their awareness of potential UEs. However, future researchers can explore new opportunities to fill gaps in support that patients experience in subsequent stages, especially at critical decision points such as intervening in UEs and responding to harms that occur.

Conclusions

Our conceptual model reveals the complex inpatient experiences with UEs, and opportunities for new informatics solutions to support them at all stages of their experience. Investigating these new opportunities could promote inpatients’ participation and engagement in the quality and safety of their care, help healthcare systems learn from inpatients’ experience, and reduce these harmful events.
Standardized ileal digestibility of amino acids in canola meal fed to gestating and lactating sows1
Authors: Velayudhan Deepak Ettungapladi , Hossain Manik M , Stein Hans H , Nyachoti C Martin
Published: August 2019

An experiment was conducted to determine the standardized ileal digestibility (SID) of CP and AA in solvent extracted canola meal (CM) fed to gestating and lactating sows without or with a multi-enzyme complex. Eight sows cannulated on day 40 of gestation were randomly assigned to 1 of 4 dietary treatments in a replicated 4 × 4 Latin square design. The 4 diets included 2 cornstarch-based diets with 31.3% CM as the only source of AA, without or with a multi-enzyme complex, a casein-cornstarch diet to determine ileal endogenous AA losses, and a phosphorus-free diet (phosphorus digestibility data reported elsewhere). All diets contained 0.3% titanium dioxide. Gestating sows were fed 3.0 kg/d of the respective experimental diets, whereas, during lactation, sows had ad libitum access to experimental diets. Ileal digesta samples were collected in midgestation, late gestation, and lactation. In each period, after 6-d acclimation to the experimental diets, on days 7 and 8, ileal digesta samples were collected continuously for 12 h. Results indicated that sows in lactation had greater apparent ileal digestibility (AID) of CP and all AA (P < 0.05) compared with sows in gestation. Enzyme supplementation improved (P < 0.05) the AID of histidine, lysine, methionine, valine, and alanine, and a tendency (P < 0.10) for improvement in AID was observed for arginine, isoleucine, tryptophan, and cysteine during lactation, but not during gestation. However, the SID of most AA was not affected by collection phase, but enzyme supplementation improved (P < 0.05) the SID of arginine, histidine, lysine, methionine, and valine during lactation. The SID of indispensable AA in CM fed to gestating and lactating sows were as follows: arginine, 89.2 and 91.3%; histidine, 93.1 and 94.0%; isoleucine, 85.9 and 87.0%; leucine, 89.2 and 89.2%; lysine, 87.0 and 87.7%; methionine, 92.2 and 93.2%; phenylalanine, 89.2 and 87.8%; threonine, 84.3 and 82.7%; tryptophan, 88.1 and 91.5%; valine, 85.9 and 84.3%. In conclusion, the SID of AA in CM fed to lactating sows may be improved if a mixture of carbohydrases is included in the diet, but under the conditions of this experiment, the carbohydrase mixture did not affect SID of AA in CM fed to gestating sows in midgestation or late gestation.
Observation of unexpected molecular binding activity for Mu phage tail fibre chaperones
Authors: Sakai Kohei , Iwazaki Takuma , Yamashita Eiki , Nakagawa Atsushi , Sakuraba Fumiya , Enomoto Atsushi , Inagaki Minoru , Takeda Shigeki
Published: August 2019

In the history of viral research, one of the important biological features of bacteriophage Mu is the ability to expand its host range. For extending the host range, the Mu phage encodes two alternate tail fibre genes. Classical amber mutation experiments and genome sequence analysis of Mu phage suggested that gene products (gp) of geneS (gpS = gp49) and gene S’ (gpS’ = gp52) are tail fibres and that gene products of geneU (gpU = gp50) and geneU’ (gpU’ = gp51) work for tail fibre assembly or tail fibre chaperones. Depending on the gene orientation, a pair of genes 49-50 or 52-51 is expressed for producing different tail fibres that enable Mu phage to recognize different host cell surface. Since several fibrous proteins including some phage tail fibres employ their specific chaperone to facilitate folding and prevent aggregation, we expected that gp50 or gp51 would be a specific chaperone for gp49 and gp52, respectively. However, heterologous overexpression results for gp49 or gp52 (tail fibre subunit) together with gp51 and gp50, respectively, were also effective in producing soluble Mu tail fibres. Moreover, we successfully purified non-native gp49-gp51 and gp52-gp50 complexes. These facts showed that gp50 and gp51 were fungible and functional for both gp49 and gp52 each other.
The eggplant transcription factor MYB44 enhances resistance to bacterial wilt by activating the expression of spermidine synthase
Authors: Qiu Zhengkun , Yan Shuangshuang , Xia Bin , Jiang Jing , Yu Bingwei , Lei Jianjun , Chen Changming , Chen Lin , Yang Yang , Wang Yongqing , Tian Shibing , Cao Bihao
Published: August 2019

SmMYB44 directly binds to the promoter of a spermidine synthase (SPDS) gene and activates its expression, governing spermidine biosynthesis and resistance to bacterial wilt in eggplant.
The impact of AGN on stellar kinematics and orbits in simulated massive galaxies
Authors: Frigo Matteo , Naab Thorsten , Hirschmann Michaela , Choi Ena , Somerville Rachel S , Krajnovic Davor , Davé Romeel , Cappellari Michele
Published: August 2019

We present a series of 10 × 2 cosmological zoom simulations of the formation of massive galaxies with and without a model for active galactic nucleus (AGN) feedback. Differences in stellar population and kinematic properties are evaluated by constructing mock integral field unit maps. The impact of the AGN is weak at high redshift when all systems are mostly fast rotating and disc-like. After z ∼ 1 the AGN simulations result in lower mass, older, less metal rich, and slower rotating systems with less discy isophotes – in general agreement with observations. 2D kinematic maps of in situ and accreted stars show that these differences result from reduced in-situ star formation due to AGN feedback. A full analysis of stellar orbits indicates that galaxies simulated with AGN are typically more triaxial and have higher fractions of x-tubes and box orbits and lower fractions of z-tubes. This trend can also be explained by reduced late in-situ star formation. We introduce a global parameter, ξ3, to characterize the anticorrelation between the third-order kinematic moment h3 and the line-of-sight velocity (Vavg/σ), and compare to ATLAS3D observations. The kinematic correlation parameter ξ3 might be a useful diagnostic for large integral field surveys as it is a kinematic indicator for intrinsic shape and orbital content.
Insights from the APOKASC determination of the evolutionary state of red-giant stars by consolidation of different methods
Authors: Elsworth Yvonne , Hekker Saskia , Johnson Jennifer A , Kallinger Thomas , Mosser Benoit , Pinsonneault Marc , Hon Marc , Kuszlewicz James , Miglio Andrea , Serenelli Aldo , Stello Dennis , Tayar Jamie , Vrard Mathieu
Published: August 2019

The internal working of low-mass stars is of great significance to both the study of stellar structure and the history of the Milky Way. Asteroseismology has the power to directly sense the internal structure of stars and allows for the determination of the evolutionary state – i.e. has helium burning commenced or is the energy generated only by the fusion in the hydrogen-burning shell? We use observational data from red-giant stars in a combination (known as APOKASC) of asteroseismology (from the Kepler mission) and spectroscopy (from SDSS/APOGEE). The new feature of the analysis is that the APOKASC evolutionary state determination is based on the comparison of diverse approaches to the investigation of the frequency-power spectrum. The high level of agreement between the methods is a strong validation of the approaches. Stars for which there is not a consensus view are readily identified. The comparison also facilitates the identification of unusual stars including those that show evidence for very strong coupling between p and g cavities. The comparison between the classification based on the spectroscopic data and asteroseismic data have led to a new value for the statistical uncertainty in APOGEE temperatures. These consensus evolutionary states will be used as an input for methods that derive masses and ages for these stars based on comparison of observables with stellar evolutionary models (‘grid-based modelling’) and as a training set for machine-learning and other data-driven methods of evolutionary state determination.
V1082-Sgr: A magnetic cataclysmic variable with a lobe-filling companion star
Authors: Xu Xiaojie , Shao Yong , Li Xiang-Dong
Published: August 2019

V1082 Sgr is a cataclysmic variable with accretion luminosity above 1034 erg s−1, indicating a mass-transfer rate above $10^{-9}\, \mathrm{M}_{\odot }$  yr−1. However, its K-type companion was suggested to be underfilling its Roche lobe (RL), making the high mass-transfer rate a mystery. In this work we propose a possible model to explain this discrepancy. The system is proposed to be an intermediate polar, with its K-type companion filling its RL. The mass of the white dwarf star is evaluated to be $0.77\pm 0.11\, \mathrm{M}_{\odot }$ from both X-ray continuum fitting and Fe line flux ratio measurements. We make numerical simulations to search for the possible progenitors of the system. The results show that a binary with an initial 1.5–2.5$\, \mathrm{M}_{\odot }$ companion in a one to two day orbit (or an initial 1.0–1.4$\, \mathrm{M}_{\odot }$ companion in a 3.2–4.1 d orbit) may naturally evolve to a cataclysmic variable with a $\sim 0.55 \pm 0.11\, \mathrm{M}_{\odot }$, Roche-lobe-filling companion in a 0.86 d orbit. The effective temperature of the donor star, the mass-transfer rate, and the derived V-band magnitude are all consistent with previous observations.
On the nature of the resonant drag instability of dust streaming in protoplanetary disc
Authors: Zhuravlev V V
Published: August 2019

The recently discovered resonant drag instability (RDI) of dust streaming in protoplanetary disc is considered as the mode coupling of subsonic gas-dust mixture perturbations. This mode coupling is coalescence of two modes with nearly equal phase velocities: inertial wave (IW) having positive energy and a streaming dust wave (SDW) having negative energy as measured in the frame of gas environment being at rest in vertical hydrostatic equilibrium. SDW is a trivial mode produced by the bulk streaming of dust, which transports perturbations of dust density. In this way, settling combined with radial drift of the dust makes possible coupling of SDW with IW and the onset of the instability. In accordance with the concept of the mode coupling, RDI growth rate is proportional to the square root of the coupling term of the dispersion equation, which itself is proportional to mass fraction of dust, f ≪ 1. This clarifies why RDI growth rate ∝f1/2. When SDW has positive energy, its resonance with IW provides an avoided crossing instead of the mode coupling. In the high wavenumber limit RDI with unbounded growth rate ∝f1/3 is explained by the triple mode coupling, which is coupling of SDW with two IW. It coexists with a new quasi-resonant instability accompanied by bonding of two oppositely propagating low-frequency IW. The mode coupling does not exist for dust streaming only radially in a disc. In this case RDI is provided by the obscured mechanism associated with the inertia of solids.
Stochastic Gene Expression Influences the Selection of Antibiotic Resistance Mutations
Authors: Sun Lei , Ashcroft Peter , Ackermann Martin , Bonhoeffer Sebastian
Published: August 2019

Bacteria can resist antibiotics by expressing enzymes that remove or deactivate drug molecules. Here, we study the effects of gene expression stochasticity on efflux and enzymatic resistance. We construct an agent-based model that stochastically simulates multiple biochemical processes in the cell and we observe the growth and survival dynamics of the cell population. Resistance-enhancing mutations are introduced by varying parameters that control the enzyme expression or efficacy. We find that stochastic gene expression can cause complex dynamics in terms of survival and extinction for these mutants. Regulatory mutations, which augment the frequency and duration of resistance gene transcription, can provide limited resistance by increasing mean expression. Structural mutations, which modify the enzyme or efflux efficacy, provide most resistance by improving the binding affinity of the resistance protein to the antibiotic; increasing the enzyme’s catalytic rate alone may contribute to resistance if drug binding is not rate limiting. Overall, we identify conditions where regulatory mutations are selected over structural mutations, and vice versa. Our findings show that stochastic gene expression is a key factor underlying efflux and enzymatic resistances and should be taken into consideration in future antibiotic research.
miRDB: an online database for prediction of functional microRNA targets
Authors: Chen Yuhao , Wang Xiaowei
Published: August 2019

MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented the new prediction algorithm into a web server, allowing custom target prediction with user-provided sequences. Another new database feature is the prediction of cell-specific miRNA targets. miRDB now hosts the expression profiles of over 1000 cell lines and presents target prediction data that are tailored for specific cell models. At last, a new web query interface has been added to miRDB for prediction of miRNA functions by integrative analysis of target prediction and Gene Ontology data. All data in miRDB are freely accessible at http://mirdb.org.
Safety and Effectiveness of the Pipeline Flex Embolization Device With Shield Technology for the Treatment of Intracranial Aneurysms: Midterm Results From a Multicenter Study
Authors: Trivelato Felipe Padovani , Wajnberg Eduardo , Rezende Marco Túlio Salles , Ulhôa Alexandre Cordeiro , Piske Ronie Leo , Abud Thiago Giansante , de Castro-Afonso Luís Henrique , Abath Carlos Gustavo Coutinho , Nakiri Guilherme Seizem , Araújo João Francisco Santoro , Silva José Laércio Júnior , Tosello Renato Tavares , Vanzin José Ricardo , Manzato Luciano Bambini , Baccin Carlos Eduardo , da Mota Bruno Anderson Araújo , Abud Daniel Giansante
Published: August 2019

BACKGROUND

The safety and efficacy of the first generation of the Pipeline Embolization Device (PED; Medtronic Inc) have been proven in large case series. Ischemic events are one of the most common complications following treatment of aneurysms with flow diverters. The new PED Flex with Shield technology (PED Shield; Medtronic Inc) was introduced to minimize the rate of complications.

OBJECTIVE

To evaluate the outcomes of patients harboring aneurysms treated with the PED Shield.

METHODS

This was an observational, prospective, single-arm multicenter study of patients treated with the PED Shield. The primary safety endpoint was the absence of major neurological complications and death. The secondary effectiveness endpoint was angiographic occlusion at 6 and 12 mo. Technical complications were also reported.

RESULTS

Between November 2017 and December 2018, 151 patients from 7 centers with 182 aneurysms were enrolled. The mean aneurysm size was 7.0 mm; 27 (14.8%) aneurysms were large, and 7 (3.8%) were giant. In 141 of 151 patients (93.4%), the primary endpoint was reached. The overall rate of periprocedural complications was 7.3%. Of the aneurysms, 79.7% met the study's secondary endpoint of complete occlusion at 6 mo and 85.3% at 12 mo.

CONCLUSION

The PED Shield is a safe and effective treatment for intracranial aneurysms. The results regarding total occlusion and ischemic complications did not differ from those obtained in case series using previous versions of the PED. Long-term follow-up and comparative studies are required to provide stronger conclusions regarding the reduced thrombogenicity of this device.
Pacifism in International Law
Authors: Moses Jeremy
Published: August 2019

The label of pacifism has been applied to a very wide range of political movements and ideologies that focus on nonviolence and the achievement of lasting peace. The varieties of pacifism, ranging from a commitment to absolute nonviolence to more contingent or non-absolute versions, cut across a range of ethical, political, and religious positions. The most famous and influential articulations of pacifism are found in the writings and work of revolutionary political activists such as Gandhi and Martin Luther King, but these bear little relation to international law in either theory or practice as they are primarily concerned with the establishment of new social relations within the state. In relation to international law, pacifism occupies a more limited and tangential position, with most of the focus falling on ambitious proposals for generating world peace through the development of international law, a field that is commonly given the label of “legal pacifism.” The aim of theorists and activists in this area is to bring about the outlawry or abolition of war through the development of international law and international institutions. Such proposals go further than existing arrangements under the United Nations insofar as they seek to avoid the authorization of war as an enforcement mechanism against aggressive states, but they fall well short of pacifist ideologies that reject all forms of violence. The practical highpoints for these approaches came with the establishment of the Permanent Court of Arbitration under the Hague Conventions of 1899 and 1907 and the signing of a multilateral treaty aimed at banning the recourse to war, the Kellogg-Briand Pact, in 1928. Other literatures that draw connections between international law and pacifism are more marginal to the discipline of international law. The extensive literature on the relationship between just war theory and pacifism, for example, may be seen as being situated in close relation to the Law of Armed Conflict and International Humanitarian Law, but this literature tends to avoid international legal questions and focuses more on the philosophical challenges posed by pacifism. Similarly, the pacifist orientation of activist groups campaigning for nuclear weapons treaties and bans is illustrative of an intersection between pacifism and international law that is less obvious and explicit than what we find in relation to legal or juridical pacifism. All, however, share a broad preference for nonviolent means of dispute resolution and seek avenues within international law for advancing that agenda.
Patchwork States: The Localization of State Territoriality on the South Sudan–Uganda Border, 1914–2014*
Authors: Leonardi Cherry
Published: August 2019

This paper takes a localized conflict over a non-demarcated stretch of the Uganda–South Sudan boundary in 2014 as a starting point for examining the history of territorial state formation on either side of this border since its colonial creation in 1914. It argues that the conflict was an outcome of the long-term constitution of local government territories as patches of the state, making the international border simultaneously a boundary of the local state. Some scholars have seen the limited control of central governments over their borderlands and the intensification of local territorialities as signs of African state fragmentation and failure. But the article argues that this local territoriality should instead be seen as an outcome of ongoing state-formation processes in which state territory has been co-produced through local engagement and appropriation. The paper is thus of wider relevance beyond African or postcolonial history, firstly in contributing a spatial approach to studies of state formation which have sought to replace centre–periphery models with an emphasis on the centrality of the local state. Secondly it advances the broader field of borderlands studies by arguing that international boundaries have been shaped by processes of internal territorialisation as well as by the specific dynamics of cross-border relations and governance. Thirdly it advocates a historical and processual approach to understanding territory, arguing that the patchwork of these states has been fabricated and reworked over the past century, entangling multiple, changing forms and scales of territory in the ongoing constitution of state boundaries.
On the Rise of FinTechs: Credit Scoring Using Digital Footprints
Authors: Berg Tobias , Burg Valentin , Gombović Ana , Puri Manju
Published: August 2019

We analyze the information content of a digital footprint—that is, information that users leave online simply by accessing or registering on a Web site—for predicting consumer default. We show that even simple, easily accessible variables from a digital footprint match the information content of credit bureau scores. A digital footprint complements rather than substitutes for credit bureau information and affects access to credit and reduces default rates. We discuss the implications for financial intermediaries’ business models, access to credit for the unbanked, and the behavior of consumers, firms, and regulators in the digital sphere. (JEL G20, G21, G29)
Early activation of fibroblasts is required for kidney repair and regeneration after injury
Authors: Zhou Dong , Fu Haiyan , Liu Shijia , Zhang Lu , Xiao Liangxiang , Bastacky Sheldon I. , Liu and Youhua
Published: August 2019

Acute kidney injury (AKI) is a devastating condition with high morbidity and mortality. AKI is characterized by tubular injury, inflammation, and vascular impairment. However, the role of interstitial fibroblasts in the pathogenesis of AKI is largely unknown. Here, we show that fibroblasts were activated, as defined by vimentin expression, at 1 h after AKI triggered by ischemia‐reperfusion injury (IRI). They rapidly entered the cell cycle with Ki‐67‐positive staining, which started at 1 h and peaked at 12 h after IRI, whereas tubular cell proliferation peaked at 3 d. The trigger for such an early activation of fibroblasts was identified as sonic hedgehog (Shh), which was rapidly induced in renal tubules and could target interstitial fibroblasts. Tubule‐specific knockout of Shh in mice inhibited fibroblast activation and aggravated kidney injury and functional decline after IRI. Likewise, pharmacologic inhibition of Shh signaling with cyclopamine also hindered fibroblast activation and exacerbated kidney damage. These studies uncover that tubule‐derived Shh triggers the early activation of fibroblasts, which is required for kidney repair and regeneration. Our findings for the first time illustrate a previously unrecognized importance of interstitial fibroblasts in conferring renal protection in AKI.—Zhou, D., Fu, H., Liu, S., Zhang L., Xiao, L., Bastacky, S. I., Liu, Y. Early activation of fibroblasts is required for kidney repair and regeneration after injury. FASEB J. 33, 12576–12587 (2019). www.fasebj.org
Immunotherapy for non-small cell lung cancer
Authors: Vafadar Sam
Published: August 2019

Immunotherapy is a new genre of treatment for patients with advanced cancer. Initially approved for use in metastatic melanoma, immunotherapy has found a significant place in treating non-small cell lung cancer (NSCLC). Clinical trials using several combinations of immunotherapy are underway to help to determine the best treatment for specific patient groups. This article reviews approved uses of immunotherapy for NSCLC, immune-related toxicities, and explores the future direction of this treatment.
Current and emerging treatments for sickle cell disease
Authors: Monus Taylor , Howell Christopher M.
Published: August 2019

Sickle cell disease (SCD) is a group of inherited blood disorders affecting the hemoglobin, shortening the lifespan of erythrocytes, and causing them to take on a distinctive sickled shape that can lead to vaso-occlusion. Current treatment aims to reduce morbidity and mortality through hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation. This article reviews the disease process, typical presentations, complications, and acute and chronic treatment options.
Practical Guidance for Measuring and Reporting Surgical Margins in Vulvar Cancer
Authors: Kortekaas Kim E. , Van de Vijver Koen K. , van Poelgeest Mariëtte I.E. , Gilks C. Blake , Smit Vincent T.H.B.M. , Arif Saimah , Arora Deep , Faruqi Asma , Ganesan Raji , Griffin Nicholas R. , Hale Richard , Hock Yelin E. , Horn Lars-Christian , McCluggage W. Glenn , Mukonoweshuro Pinias , Park Kay J. , Rous Brian , Tanchel Bruce , Van Rompuy Anne-Sophie , van Schalkwyk Gerry , Vella Jo , Vergine Marco , Singh Naveena , Bosse Tjalling
Published: August 2019

Surgical resection with free surgical margins is the cornerstone of successful primary treatment of vulvar squamous cell carcinoma (VSCC). In general reexcision is recommended when the minimum peripheral surgical margin (MPSM) is <8 mm microscopically. Pathologists are, therefore, required to report the minimum distance from the tumor to the surgical margin. Currently, there are no guidelines on how to make this measurement, as this is often considered straightforward. However, during the 2018 Annual Meeting of the British Association of Gynaecological Pathologists (BAGP), a discussion on this topic revealed a variety of opinions with regard to reporting and method of measuring margin clearance in VSCC specimens. Given the need for uniformity and the lack of guidance in the literature, we initiated an online survey in order to deliver a consensus-based definition of peripheral surgical margins in VSCC resections. The survey included questions and representative diagrams of peripheral margin measurements. In total, 57 pathologists participated in this survey. On the basis of consensus results, we propose to define MPSM in VSCC as the minimum distance from the peripheral edge of the invasive tumor nests toward the inked peripheral surgical margin reported in millimeters. This MPSM measurement should run through tissue and preferably be measured in a straight line. Along with MPSM, other relevant measurements such as depth of invasion or tumor thickness and distance to deep margins should be reported. This manuscript provides guidance to the practicing pathologist in measuring MPSM in VSCC resection specimens, in order to promote uniformity in measuring and reporting.
Comparative Analysis of Single versus Stacked Free Flap Breast Reconstruction: A Single-Center Experience
Authors: Haddock Nicholas T. , Cho Min-Jeong , Teotia Sumeet S.
Published: August 2019

Background:

As breast reconstructive microsurgeons increase their available flap techniques with experience, the need for stacked and multiple flaps may generate an improved aesthetic outcome. The authors present their institutional experience of using single versus stacked free flap breast reconstruction.

Methods: One thousand seventy

flaps were performed on 509 patients from 2010 to 2018 by two senior surgeons at a single university hospital. Three hundred eighty-eight flaps were either stacked profunda artery perforator (PAP) flaps, four-flap flaps [bilateral PAP plus bilateral deep inferior epigastric perforator (DIEP) flap], or double-pedicle DIEP/superficial inferior epigastric perforator flaps. Six hundred eighty-two flaps were either unilateral or bilateral DIEP or PAP flap (one flap per breast). Demographics, patient comorbidities, and flap complications were compared between the two groups.

Results:

Of the 509 patients, 359 underwent single DIEP or PAP flap (one flap per breast) and 150 patients underwent stacked free flaps. The stacked flap group had statistically lower body mass index, higher rates of radiation therapy, longer procedure time, smaller flaps, higher deep venous thrombosis rates, and higher take-back rates compared with the single flap group. There were no statistical differences in the rates of flap loss (2.2 percent in stacked flaps versus 1.1 percent in single flaps), wound complication, hematoma, or pulmonary embolism.

Conclusions:

Autologous breast reconstruction is the gold standard for natural and durable breast reconstruction, often giving superior aesthetic outcomes and higher patient satisfaction. However, the true success of autologous breast reconstruction is limited to the amount of tissue available to provide total breast reconstruction. This study shows that stacked flap breast reconstruction is safe and has similar complication rates as single-flap breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Complications and Quality of Life following Reduction Mammaplasty in Adolescents and Young Women
Authors: Nuzzi Laura C. , Firriolo Joseph M. , Pike Carolyn M. , DiVasta Amy D. , Labow Brian I.
Published: August 2019

Background:

Adolescent reduction mammaplasty remains controversial because of concerns of postoperative breast growth, complications, and the effect on well-being. The authors sought to prospectively quantify early and late complications following reduction mammaplasty in adolescents and young women, and examine the intersection of surgical complications and postoperative health-related quality of life.

Methods:

From 2008 to 2017, female patients aged 12 to 21 years undergoing reduction mammaplasty were asked to complete the 36-Item Short-Form Health Survey (version 2), the Rosenberg Self-Esteem Scale, the Breast-Related Symptoms Questionnaire, and the Eating-Attitudes Test-26 preoperatively and postoperatively at 6 months and 1, 3, 5, and 7 years. Clinical evaluations using standardized forms assessed baseline and postoperative symptomatology, complications, and surgical outcomes.

Results:

In the authors’ sample of 512 participants, the most common complications included hypertrophic scarring (20.0 percent) and altered sensation of the nipple (8.4 percent) or breast (7.8 percent). Patient age, body mass index category, and amount of tissue resected did not significantly increase the odds of developing a complication. Significant postoperative improvements on the Rosenberg Self-Esteem Scale, the Breast-Related Symptoms Questionnaire, the Eating-Attitudes Test-26, and in all 36-Item Short-Form Health Survey domains (i.e., physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) were largely seen irrespective of whether complications occurred.

Conclusions:

Although complications following reduction mammaplasty were common, the vast majority were minor. Patients had significant postoperative improvements in their physical and psychosocial well-being regardless of whether they experienced a complication. Concerns for potential complication, especially in younger and overweight or obese patients, should not preclude otherwise healthy adolescents and young women from the benefits of reduction mammaplasty.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Long-Term Static and Dynamic Effects of Surgical Release of the Tear Trough Ligament and Origins of the Orbicularis Oculi in Lower Eyelid Blepharoplasty
Authors: Wong Chin-Ho , Mendelson Bryan
Published: August 2019

Background:

Release of the tear trough ligament and the origins of the orbicularis oculi is a key maneuver with many lower blepharoplasty techniques. The long-term static and dynamic effects of this release have not been studied previously.

Methods:

From December of 2012 to June of 2017, 105 patients were treated with the extended transconjunctival lower eyelid blepharoplasty with release of the tear trough ligament and fat redistribution as described previously. The long-term effect of the release was assessed by evaluating the effectiveness in correcting the tear trough deformity, the effect on the lower eyelid position, and the dynamic changes of the patient’s smile.

Results:

The mean patient age was 41 years (range, 23 to 62 years). The mean follow-up was 31 months (range, 12 to 53 months). The tear trough was effectively corrected with this maneuver. This release did not compromise the tarsoligamentous support of the lower eyelid, with no increase in scleral show in 99 percent of patients and with no patients developing ectropion. Functionally, the change in the action of the orbicularis oculi as a result of detachment of its origins resulted in a change in appearance of the smile. Elimination of the tethering at the tear trough ligament and the downward pull toward the medial suborbital maxilla resulted in elevation of the lid-cheek junction with smiling. Reduced efficiency of orbicularis contraction resulted in a diminished pretarsal bulge and in reduction of crow’s feet with smiling.

Conclusions:

The maneuver is effective in correcting the tear trough deformity while not weakening the lower eyelid tarsoligamentous support. Functionally, the patient’s smile became more youthful and rejuvenated, with less wrinkling and elevation of the lid-cheek junction with smiling.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Efficacy of Botulinum Toxin in Treating Asian Indian Patients with Masseter Hypertrophy: A 4-Year Follow-Up Study
Authors: Shome Debraj , Khare Stuti , Kapoor Rinky
Published: August 2019

Background:

Asian Indians usually have wide lower faces because of masseter hypertrophy. The authors evaluated the efficacy of botulinum toxin type A in long-term management of bilateral masseter hypertrophy in Asian Indian patients.

Methods:

Fifty patients were enrolled in the study and injected with 30 U of botulinum toxin type A to each side of the face, at baseline. Based on masseter muscle thickness and response to the injections, 25 patients underwent a second injection session at week 12, and the other 25 patients underwent additional third sessions, at week 24 after the first injection, respectively. Standardized photography and ultrasonography were performed to assess facial contour and masseter muscle thickness at baseline and at 1-, 2-, 3-, and 4-year follow-ups. A p value < 0.05 was considered statistically significant.

Results:

The authors observed 12 percent (p < 0.0001) average masseter muscle size reduction at week 12. The maximum reduction (26.6 percent; p < 0.0001) was observed at week 24 for the patients who received two injections and maintained an average 24.43 percent (p < 0.0001) reduction until follow-up at year 4. Patients who received three injections exhibited very high reduction (42.52 percent; p < 0.0001) of masseter volume at week 36 and maintained an average 40.64 percent (p < 0.0001) reduced volume until year 4.

Conclusions:

Botulinum toxin type A treatment is effective for long-term management of bilateral masseter hypertrophy. Doses repeated at 12-week intervals accentuate masseter volume reduction and also help maintain reduced masseter volume for 4-year follow-up, with satisfactory facial contour.
Reconstruction of Posterior Mandibulectomy Defects in the Modern Era of Virtual Planning and Three-Dimensional Modeling
Authors: Chang Edward I. , Boukovalas Stefanos , Liu Jun , Largo Rene D. , Hanasono Matthew M. , Garvey Patrick B.
Published: August 2019

Background:

Posterior mandibulectomy defects can be reconstructed using either soft tissue or vascularized bone. The authors hypothesize that advances in computer-aided design and manufacturing (CAD-CAM) have resulted in osteocutaneous free flaps now proving superior to soft-tissue flaps.

Methods:

The authors conducted a retrospective review of all free flap reconstructions of posterior mandibulectomy defects where the condyle was resected from 2005 to 2016.

Results:

Overall, 291 patients (mean age, 56.9 years; mean body mass index, 26.2 kg/m2) underwent posterior mandible reconstruction with 169 soft-tissue flaps and 122 osteocutaneous free flaps (90 free-hand versus 32 CAD-CAM). Forty patients (13.7 percent) required two free flaps to reconstruct the defect, most commonly a fibula osteocutaneous flap for the mandibulectomy defect and a soft-tissue flap for external coverage. Postoperatively, there were no differences in the incidence of trismus between soft-tissue versus vascularized bone flaps; however, malocclusion was most common in patients with soft-tissue flaps (p < 0.001). Patients with CAD-CAM bone reconstruction experienced significantly less malocclusion (p < 0.001), were more likely to progress to a regular diet (p = 0.001), and trended to having superior speech (p = 0.057) compared with the other cohorts. There were six total flap losses, with no difference between soft-tissue and bony flaps.

Conclusions:

Although reconstruction of posterior mandibulectomy defects should be based on the patient’s comorbidities, surgeon comfort, and available resources, patients undergoing reconstruction of posterior mandibulectomy defects reconstructed with CAD-CAM–assisted fibulas experienced superior postoperative function compared with soft-tissue flaps or free-hand fibula flaps.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.