bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of pre- and posttreatment average treatment effects with binary time-varying treatment using Stata
Authors: Cerulli Giovanni , Ventura Marco
Published: September 2019

In this article, we describe tvdiff, a community-contributed command that implements a generalization of the difference-in-differences estimator to the case of binary time-varying treatment with pre- and postintervention periods. tvdiff is flexible and can accommodate many actual situations, enabling the user to specify the number of pre- and postintervention periods and a graphical representation of the estimated coefficients. In addition, tvdiff provides two distinct tests for the necessary condition of the identification of causal effects, namely, two tests for the so-called parallel-trend assumption. tvdiff is intended to simplify applied works on program evaluation and causal inference when longitudinal data are available.
Speaking Stata: The last day of the month
Authors: Cox Nicholas J.
Published: September 2019

I discuss three related problems about getting the last day of the month in a new variable. Commentary ranges from the specifics of date and other functions to some generalities on developing code. Modular arithmetic belongs in every Stata user’s coding toolbox.
Review of Richard Valliant and Jill A. Dever’s Survey Weights: A Step-by-Step Guide to Calculation
Authors: Heeringa Steven G.
Published: September 2019

In this article, I review the Stata Press publication Survey Weights: A Step-by-Step Guide to Calculation by Valliant and Dever (2018).
A decomposition solution approach to the troops-to-tasks assignment in military peacekeeping operations
Authors: Chaudry Nadia , Vermedal Ingunn , Fagerholt Kjetil , Fauske Maria Fleischer , Stålhane Magnus
Published: September 2019

This paper considers the Peacekeeping Troops-to-Tasks Problem (PTTP). The PTTP deals with assigning battlegroup resources to a set of tasks associated with a given peacekeeping mission. The tasks may be spread across several locations, and have requirements regarding the time at which they can be handled, and the skills and skill levels needed to complete them. There is also a utility value related to each completed task that reflects its importance. The resources are bound by a hierarchy of command, limiting their movement in relation to one another. The aim is to decide which tasks to complete, when, and by whom. We present a mathematical compact model for the PTTP, which includes a number of complicating real-life factors. Due to the complexity of the compact model, it is difficult to solve large instances using a commercial solver. Therefore, we also propose a decomposition-based solution approach, with a decomposed model where possible travel routes for the resources are generated a priori. The computational study shows that the decomposed model has better performance than the compact model, and that it can be used as a good starting point for developing a useful decision support tool for military peacekeeping operations planning.
Magnetohydrodynamic velocity profile measurement for microelectromechanical systems micro-robot design
Authors: Flores-Fuentes Wendy , Valenzuela-Delgado Mónica , Cáceres-Hernández Danilo , Sergiyenko Oleg , Bravo-Zanoguera Miguel E , Rodríguez-Quiñonez Julio C , Hernández-Balbuena Daniel , Rivas-López Moisés
Published: September 2019

The development of microelectromechanical systems based on magnetohydrodynamic for micro-robot applications requires precise control of the micro-flow behavior. The micro-flow channel design and its performance under the influence of the Lorentz force is a critical challenge, the mathematical model of each magnetohydrodynamic device design must be experimentally validated before to be employed in the fabrication of microelectromechanical systems. For this purpose, the present article proposes the enhancement of a particle image velocimetry measurement process in a customized machine vision system. The particle image velocimetry measurements are performed for the micro-flow velocity profile mathematical model validation of a magnetohydrodynamic stirrer prototype. Data mining and filtering have been applied to a raw measurement database from the customized machine vision system designed to evaluate the magnetohydrodynamic stirrer prototype. Outlier’s elimination and smoothing have been applied to raw data to approximate the particle image velocimetry measurements output to the velocity profile mathematical model to increase the accuracy of a customized machine vision system for two-dimensional velocity profile measurements. The accurate measurement of the two-dimensional velocity profile is fundamental owing to the requirement of future enhancement of the customized machine vision system to construct the three-dimensional velocity profile of the magnetohydrodynamic stirrer prototype. The presented methodology can be used for measurement and validation in the design of microelectromechanical systems micro-robot design and any other devices that require micro-flow manipulation for tasks such as stirring, pumping, mixing, networking, propelling, and even cooling.
Different models for prediction of radical cystectomy postoperative complications and care pathways
Authors: Taylor Jacob , Meng Xiaosong , Renson Audrey , Smith Angela B. , Wysock James S. , Taneja Samir S. , Huang William C. , Bjurlin Marc A.
Published: September 2019

Background:

Radical cystectomy for bladder cancer has one of the highest rates of morbidity among urologic surgery, but the ability to predict postoperative complications remains poor. Our study objective was to create machine learning models to predict complications and factors leading to extended length of hospital stay and discharge to a higher level of care after radical cystectomy.

Methods:

Using the American College of Surgeons National Surgical Quality Improvement Program, peri-operative adverse outcome variables for patients undergoing elective radical cystectomy for bladder cancer from 2005 to 2016 were extracted. Variables assessed include occurrence of minor, infectious, serious, or any adverse events, extended length of hospital stay, and discharge to higher-level care. To develop predictive models of radical cystectomy complications, we fit generalized additive model (GAM), least absolute shrinkage and selection operator (LASSO) logistic, neural network, and random forest models to training data using various candidate predictor variables. Each model was evaluated on the test data using receiver operating characteristic curves.

Results:

A total of 7557 patients were identified who met the inclusion criteria, and 2221 complications occurred. LASSO logistic models demonstrated the highest area under curve for predicting any complications (0.63), discharge to a higher level of care (0.75), extended length of stay (0.68), and infectious (0.62) adverse events. This was comparable with random forest in predicting minor (0.60) and serious (0.63) adverse events.

Conclusions:

Our models perform modestly in predicting radical cystectomy complications, highlighting both the complex cystectomy process and the limitations of large healthcare datasets. Identifying the most important variable leading to each type of adverse event may allow for further strategies to model cystectomy complications and target optimization of modifiable variables pre-operative to reduce postoperative adverse events.
Biological therapies and their clinical impact in the treatment of systemic lupus erythematosus
Authors: Magro Rosalie
Published: September 2019

The development of biological therapies has had an impact on the management of several medical conditions. Their use in systemic lupus erythematosus (SLE), however, remains very limited. This review has summarized the evidence on the clinical effect of biologicals in SLE. Biological drugs with a number of targets have been studied in several phase II and III randomized controlled trials (RCTs). Positive results have been obtained in phase III RCTs with belimumab and this led to its license for active SLE. The clinical experience with belimumab has confirmed the efficacy and safety of belimumab in SLE. Promising results have been noted in phase II trials for blisibimod, sifalimumab, anifrolumab, and ustekinumab. Despite the fact that the RCTs with rituximab did not achieve their primary endpoint, clinical experience with rituximab is extensive and shows favorable clinical response in refractory renal and non-renal SLE. It is hoped that further ongoing phase III RCTs on a number of biological agents in SLE will highlight the potential role of other biologicals in the management of this challenging and heterogeneous condition.
The Impact of Artificial Intelligence on the Activities of a Futurist
Authors: van Belkom Rudy
Published: September 2019

Artificial intelligence (AI) has surpassed the level of science fiction; it is increasingly being used as an analysis tool in modern scientific research. AI is able to classify and cluster large amounts of data in a short time, which could potentially save a lot of time and money. Algorithms can also recognize patterns that scientists might overlook. These advantages are currently hardly exploited in futures studies. This article will focus on the impact of AI on the activities of a futurist. A distinction is made between predicting, exploring, and creating the future. The aim of this article is to discuss the possibilities and challenges of using AI in futures studies. One of the biggest challenges of using AI in futures studies is the dependence of AI on large amounts of data which are not available about the future. We therefore have to work with historical data. I emphasize that it is crucial for futurists to take advantage of the opportunities that AI offers in futures studies, but to be well aware of its disadvantages and limitations.
Combined Bone Marrow Aspirate and Platelet-Rich Plasma for Cartilage Repair: Two-Year Clinical Results
Authors: Hede Kris , Christensen Bjørn B. , Jensen Jonas , Foldager Casper B. , Lind Martin
Published: September 2019

Purpose

To evaluate the clinical and biological outcome of combined bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) on a collagen scaffold for treating cartilage lesions in the knee.

Methods and Materials

Ten patients (mean age 29.4 years, range 18-36) suffering from large full-thickness cartilage in the knee were treated with BMAC and PRP from January 2015 to December 2016. In a 1-step procedure autologous BMAC and PRP was seeded onto a collagen scaffold and sutured into the debrided defect. Patients were evaluated by clinical outcome scores (IKDC [International Knee Documentation Committee Subjective Knee Form], KOOS [Knee Injury and Osteoarthritis Outcome Score], and pain score using the Numeric Rating Scale [NRS]) preoperatively, after 3 months, and after 1 and 2 years. Second-look arthroscopies were performed ( n = 7) with biopsies of the repair tissue for histology. All patients had magnetic resonance imaging (MRI) preoperatively, after 1 year, and after 2 to 3.5 years with MOCART (magnetic resonance observation of cartilage repair tissue) scores evaluating cartilage repair.

Results

After 1 year significant improvements were found in IKDC, KOOS symptoms, KOOS ADL (Activities of Daily Living), KOOS QOL (Quality of Life), and pain at activity. At the latest follow-up significant improvements were seen in IKDC, KOOS symptoms, KOOS QOL, pain at rest, and pain at activity. MRI MOCART score for cartilage repair improved significantly from baseline to 1-year follow-up. Histomorphometry of repair tissue demonstrated a mixture of fibrous tissue (58%) and fibrocartilage (40%).

Conclusion

Treatment of cartilage injuries using combined BMAC and PRP improved subjective clinical outcome scores and pain scores at 1 and 2 years postoperatively. MRI and histology indicated repair tissue inferior to the native hyaline cartilage.
Pyeloplasty for pelviureteric obstruction junction obstruction
Authors: Starmer Benjamin , Weston Robin , Bromage Stephen
Published: September 2019

Pelviureteric junction obstruction (PUJO) is a common clinical presentation. Patients require investigation with biochemistry and imaging in the form of computed tomography and diuretic renography. The gold-standard pyeloplasty treatment is minimally invasive pyeloplasty. Here we discuss a typical presentation of PUJO and discuss key questions in the investigation, management and follow-up of this condition, including a review of the treatment options.

Level of evidence: 3a
Nursing Students’ Sleep Patterns and Perceptions of Safe Practice During Their Entrée to Shift Work
Authors: James Lois , Butterfield Patricia , Tuell Erica
Published: September 2019

Background: The transition into shift work represents a critical and challenging time point in a nurse’s career. The purpose of this study was to describe nursing students’ sleep patterns and perceptions of safe practice during their first semester of clinical rotations. Method: Repeated measures pertaining to the sleep patterns of 19 full-time junior undergraduate nursing students were measured before, during, and after their first clinical rotations. Sleep was measured using wrist activity monitors and sleep diaries for seven consecutive days at each time period. Students’ “self-efficacy” or belief in their ability to provide safe practice was measured for (a) patient care (preventing adverse events to patients) and (b) occupational health (preventing occupational injuries to themselves) using Bandura’s self-efficacy scales. Associations between students’ sleep, sleepiness, and their perceptions of safe practice were explored. Results: Nursing students’ self-efficacy scores regarding patient care (preventing adverse events) improved across the three time periods (from 80% before clinical rotation, to 84% during clinical rotation, to 87% after clinical rotation). Although lower overall, students’ self-efficacy scores regarding occupational health (preventing occupational injuries to themselves) also improved across the three time periods (from 71% before clinical rotation, to 76% during clinical rotation, to 77% after clinical rotation). Furthermore, increased sleepiness significantly predicted lower self-efficacy scores for both patient care and occupational health. Conclusion/Application to Practice: Sleepiness can impair nursing students’ confidence in their ability to practice safely.
Social Anxiety and Dynamic Social Reinforcement Learning in a Volatile Environment
Authors: Beltzer Miranda L. , Adams Stephen , Beling Peter A. , Teachman Bethany A.
Published: September 2019

Adaptive social behavior requires learning probabilities of social reward and punishment and updating these probabilities when they change. Given prior research on aberrant reinforcement learning in affective disorders, this study examines how social anxiety affects probabilistic social reinforcement learning and dynamic updating of learned probabilities in a volatile environment. Two hundred and twenty-two online participants completed questionnaires and a computerized ball-catching game with changing probabilities of reward and punishment. Dynamic learning rates were estimated to assess the relative importance ascribed to new information in response to volatility. Mixed-effects regression was used to analyze throw patterns as a function of social anxiety symptoms. Higher social anxiety predicted fewer throws to the previously punishing avatar and different learning rates after certain role changes, suggesting that social anxiety may be characterized by difficulty updating learned social probabilities. Socially anxious individuals may miss the chance to learn that a once-punishing situation no longer poses a threat.
Current Concepts in Rotator Cuff Repair Techniques: Biomechanical, Functional, and Structural Outcomes
Authors: Rossi Luciano A. , Rodeo Scott A. , Chahla Jorge , Ranalletta Maximiliano
Published: September 2019

There is substantial evidence indicating that double-row (DR) repair restores more of the anatomic rotator cuff footprint and is biomechanically superior to single-row (SR) repair. Transosseous-equivalent (TOE) techniques have shown biomechanical advantages when compared with traditional DR, including increased contact at the rotator cuff footprint, higher pressure at the tendon-bone interface, and increased failure strength. Several meta-analyses of evidence level 1 and 2 studies have shown a lower rate of failed/incomplete healing when DR repair was compared with SR repair types. There is some limited evidence that TOE techniques improve healing rates in large and massive tears as compared with SR and DR. Overall, most level 1 and 2 studies have failed to prove a significant difference between SR and DR repairs in terms of clinical outcomes. However, most studies include only short-term follow-up, minimizing the impact that the higher rate of retears/failed healing seen with SR repairs can have in the long term. There are no high-quality clinical studies comparing different DR configurations, and there are currently not enough clinical data to determine the functional advantages of various DR technique modifications over one another. Although numerous biomechanical and clinical studies comparing different rotator cuff repair techniques have been published in the past decade, none has achieved universal acceptance. It is essential for the orthopaedic surgeon to know in detail the available literature to be able to apply the most appropriate and cost-effective technique in terms of healing and functional outcomes. This review provides a critical analysis of the comparative biomechanical and clinical studies among SR, DR, and TOE techniques reported in the literature in the past decade.
An Update on Ocular Gene Therapy for Monogenic and Multifactorial Retinal Diseases
Authors: Hou Alice Y. , Kiss Szilárd
Published: September 2019

Monogenic and multifactorial retinal diseases are genetically and clinically diverse conditions that have historically shared an untreatable clinical course. In recent years, the advent of targeted treatments like gene therapy has enabled intraocular delivery of viral vectors, such as adeno-associated viruses and retroviruses, that establish long-term stable protein expression. Despite the innate distinctions between mainly monogenic disorders affecting the retina such as Leber congenital amaurosis (LCA), heterogeneous monogenic conditions like retinitis pigmentosa (RP), and multifactorial diseases such as age-related macular degeneration (AMD), gene therapy has shown great promise as a gene replacement or augmentation strategy to treat or halt these disorders. This review will present an overview of retinal gene therapy and provide a comprehensive analysis of past and current clinical trials for LCA, RP, and AMD. It will discuss the paradigm shift that has occurred in ophthalmic care thanks to the development of gene therapy, as well as its challenges for the future.
Following REDD+: Elite agendas, political temporalities, and the politics of environmental policy failure in Guyana
Authors: Hook Andrew
Published: September 2019

This article follows the journey of Guyana’s Reducing Emissions from Deforestation and Forest Degradation (REDD+) programme, from its promising emergence in 2009 as an ambitious, Norway-funded scheme worth US$250m to its near-abandonment by all actors ten years later. It is based on primary fieldwork conducted in Guyana in 2016 and 2017 and a deep review of the theoretical and empirical literature on REDD+ policy processes and the Norway–Guyana agreement. The article shows how, contrary to the mainstream understanding of environmental policy as a disinterested search for a rational, scientific solution, decisions governing REDD+ policy in Guyana were rather shaped throughout by the political objectives and calculations of a small number of opportunistic elite actors. It further shows how even the modest incarnation of REDD+ in Guyana (which ended up resembling more of a results-based aid programme than a Payment for Ecosystem Services scheme) was continually affected by political factors beyond the control of policy managers. These included fluctuations in the world gold price that led to an increase in mining activity and deforestation, the departure of a key international investor which caused the collapse of the flagship REDD+-funded Amaila Falls hydropower project, and legislative gridlock in Guyana generated by a hung Parliament. While not suggesting that REDD+ (or similar Payment for Ecosystem Services schemes) can never work, the article nonetheless illustrates the ways in which political objectives and unforeseen events can overwhelm substantive policy efforts towards fighting climate change. The findings also illustrate the dangers of prioritizing short-term ‘success stories’ over longer-term and more consultative environmental policy processes.
MMP9 inhibition increases erythropoiesis in RPS14-deficient del(5q) MDS models through suppression of TGF-β pathways
Authors: Youn Minyoung , Huang Haigen , Chen Cheng , Kam Sharon , Wilkes Mark C. , Chae Hee-Don , Sridhar Kunju J. , Greenberg Peter L. , Glader Bertil , Narla Anupama , Lin Shuo , Sakamoto Kathleen M.
Published: September 2019

Key Points

MMP9 inhibition improves erythropoiesis in RPS14-deficient del(5q) MDS models. Increased MMP9 expression in RPS14-deficient cells activates TGF-β signaling, resulting in defective erythroid developments.
Efficacy of emicizumab in a pediatric patient with type 3 von Willebrand disease and alloantibodies
Authors: Weyand Angela C. , Flood Veronica H. , Shavit Jordan A. , Pipe Steven W.
Published: September 2019

Key Points

Type 3 von Willebrand disease with alloantibodies is a rare clinical entity with few treatment options. Emicizumab prophylaxis in such patients may result in improved hemarthrosis control, lower cost, and enhanced quality of life.
Development of a predictive model for on-time arrival flight of airliner by discovering correlation between flight and weather data
Authors: Etani Noriko
Published: September 2019

An important business of airlines is to get customer satisfaction. Due to bad weather, a mechanical reason, and the late arrival of the aircraft to the point of departure, flights delay and lead to customer dissatisfaction. A predictive model of on-time arrival flight is proposed with using flight data and weather data. The key research in this paper is to discover the correlation between flight data and weather data. The relation between pressure pattern and flight data of Peach Aviation, which is LCC (low-cost carrier) in Japan, are clarified, and it is found that the sea-level pressures of 3 weather observation spots, which are Wakkanai as the most northern spot, Minami-Torishima as the most eastern spot, and Yonagunijima as the most western spot, can classify the pressure patterns. As a result, on-time arrival fight is predicted at 77% of the accuracy with using Random Forest Classifier of machine learning. Furthermore, feasibility of the predictive model is evaluated by developing a tool of on-time arrival flight prediction.
Positive End-Expiratory Pressure During Anesthesia for Prevention of Postoperative Pulmonary Complications: A Meta-analysis With Trial Sequential Analysis of Randomized Controlled Trials
Authors: Zhang Pengcheng , Wu Lingmin , Shi Xuan , Zhou Huanping , Liu Meiyun , Chen Yuanli , Lv Xin
Published: September 2019

BACKGROUND:

Whether intraoperative positive end-expiratory pressure (PEEP) can reduce the risk of postoperative pulmonary complications remains controversial. We performed a systematic review of currently available literature to investigate whether intraoperative PEEP decreases pulmonary complications in anesthetized patients undergoing surgery.

METHODS:

We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) that compared intraoperative PEEP versus zero PEEP (ZEEP) for postoperative pulmonary complications in adults. The prespecified primary outcome was postoperative pulmonary atelectasis.

RESULTS:

Fourteen RCTs enrolling 1238 patients met the inclusion criteria. Meta-analysis using a random-effects model showed a decrease in postoperative atelectasis (relative risk [RR], 0.51; 95% confidence interval [CI], 0.35–0.76; trial sequential analyses [TSA]-adjusted CI, 0.10–2.55) and postoperative pneumonia (RR, 0.48; 95% CI, 0.27–0.84; TSA-adjusted CI, 0.05–4.86) in patients receiving PEEP ventilation. However, TSA showed that the cumulative Z-curve of 2 outcomes crossed the conventional boundary but did not cross the trial sequential monitoring boundary, indicating a possible false-positive result. We observed no effect of PEEP versus ZEEP ventilation on postoperative mortality (RR, 1.78; 95% CI, 0.55–5.70).

CONCLUSIONS:

The evidence that intraoperative PEEP reduces postoperative pulmonary complications is suggestive but too unreliable to allow definitive conclusions to be drawn.
Educating Patients Regarding Pain Management and Safe Opioid Use After Surgery: A Narrative Review
Authors: Lee Bradley H. , Wu Christopher L.
Published: September 2019

In recent years, there have been escalating concerns related to the opioid epidemic. With a steadily increasing opioid supply, it is critical to provide proper education to patients who are prescribed these medications. Education should be emphasized as a means of ensuring safe use and potentially as a strategy for curbing the opioid supply. Patients who undergo surgery are frequently prescribed opioids for postoperative pain; however, the content and delivery of information related to usage is inconsistent and often inadequate. Lack of education on postoperative pain management and opioid use places patients at risk for poor compliance and worse pain control. Furthermore, patients are often not properly educated on opioid-related side effects and risks or about safe behaviors when taking medications. The majority of patients are also not informed about how to store and dispose of leftover medications. Patients who are prescribed opioids require education preoperatively to cover the topics of pain management, opioid-related side effects, and risks, storage, and disposal. Evidence from various studies demonstrates that educational interventions improve knowledge and potentially lead to safer behaviors and reduced opioid use. Education can be provided in various formats with each having unique advantages and limitations.
Development and Pilot Study of an iOS Smartphone Application for Perioperative Functional Capacity Assessment
Authors: Rubin Daniel S. , Dalton Allison , Tank Allyson , Berkowitz Mark , Arnolds David E. , Liao Chuanhong , Gerlach Rebecca M.
Published: September 2019

BACKGROUND:

Functional capacity assessment plays a core role in the preoperative evaluation. The Duke Activity Status Index (DASI) and the 6-minute walk test (6MWT) are 2 methods that have demonstrated the ability to evaluate functional capacity and predict perioperative outcomes. Smartphones offer a novel method to facilitate functional capacity assessment as they can easily administer a survey and accelerometers can track patient activity during a 6MWT. We developed a smartphone application to administer a 6MWT and DASI survey and performed a pilot study to evaluate the accuracy of a smartphone-based functional capacity tool in our Anesthesia and Perioperative Medicine Clinic.

METHODS:

Using the Apple ResearchKit software platform, we developed an application that administers a DASI survey and 6MWT on an iOS smartphone. The DASI was presented to the patient 1 question on the screen at a time and the application calculated the DASI score and estimated peak oxygen uptake (Vo
2). The 6MWT used the CMPedometer class from Apple’s core motion facility to retrieve accelerometer data collected from the device’s motion coprocessor to estimate steps walked. Smartphone estimated steps were compared to a research-grade pedometer using the intraclass correlation coefficient (ICC). Distance walked was directly measured during the 6MWT and we performed a multivariable linear regression with biometric variables to create a distance estimation algorithm to estimate distance walked from the number of steps recorded by the application.

RESULTS:

Seventy-eight patients were enrolled in the study and completed the protocol. Steps measured by the smartphone application as compared to the pedometer demonstrated moderate agreement with an ICC (95% CI) of 0.87 (0.79–0.92; P = .0001). The variables in the distance estimation algorithm included (β coefficient [slope], 95% CI) steps walked (0.43, 0.29–0.57; P < .001), stride length (0.38, 0.22–0.53; P < .001), age in years (−1.90, −3.06 to −0.75; P = .002), and body mass index (−2.59, −5.13 to −0.06; P = .045). The overall model fit was R
2 = 0.72, which indicates a moderate level of goodness of fit and explains 72% of the variation of distance walked during a 6MWT.

CONCLUSIONS:

Our pilot study demonstrated that a smartphone-based functional capacity assessment is feasible using the DASI and 6MWT. The DASI was easily completed by patients and the application clearly presented the results of the DASI to providers. Our application measured steps walked during a 6MWT moderately well in a preoperative patient population; however, future studies are needed to improve the smartphone application’s step-counting accuracy and distance estimation algorithm.
Luminal-contact-inhibition of epithelial basal stem cell multipotency in prostate organogenesis and homeostasis
Authors: Horton Corrigan , Liu Yueli , Yu Chuan , Xie Qing , Wang Zhu A.
Published: September 2019

Prostate epithelial basal cells are highly plastic in their luminal differentiation capability. Basal stem cells actively produce luminal cells during organogenesis, but become restricted in the adult prostate unless receiving oncogenic or inflammatory stimuli. Given that the number of luminal cells increases relative to basal cells through development and that equilibrium is reached in the adulthood, we hypothesize that a negative-feedback mechanism exists to inhibit basal-to-luminal differentiation. We provide evidence supporting this hypothesis by comparing murine prostatic growth in a tissue reconstitution assay with cell recombinants of different basal-to-luminal ratios. Additionally, in organoid culture, hybrid organoids derived from adjacent basal and luminal cells showed reduced basal stem cell activities, suggesting contact inhibition. Importantly, removal of adult luminal cells in vivo via either an inducible Cre/loxP-Dre/rox dual-lineage-tracing system or orthotopic trypsin injection led to robust reactivation of basal stem cell activities, which acts independent of androgen. These data illustrate the prostate organ as a distinctive paradigm where cell contact from differentiated daughter cells restricts adult stem cell multipotency to maintain the steady-state epithelial architecture.
Cadherin switch marks germ layer formation in the diploblastic sea anemone Nematostella vectensis
Authors: Pukhlyakova E. A. , Kirillova A. O. , Kraus Y. A. , Zimmermann B. , Technau U.
Published: September 2019

Morphogenesis is a shape-building process during development of multicellular organisms. During this process the establishment and modulation of cell-cell contacts play an important role. Cadherins, the major cell adhesion molecules, form adherens junctions connecting epithelial cells. Numerous studies in Bilateria have shown that cadherins are associated with the regulation of cell differentiation, cell shape changes, cell migration and tissue morphogenesis. To date, the role of Cadherins in non-bilaterians is unknown. Here, we study the expression and the function of two paralogous classical cadherins, cadherin1 and cadherin3, in the diploblastic animal, the sea anemone Nematostella vectensis. We show that a cadherin switch is accompanying the formation of germ layers. Using specific antibodies, we show that both cadherins are localized to adherens junctions at apical and basal positions in ectoderm and endoderm. During gastrulation, partial EMT of endodermal cells is marked by a step-wise down-regulation of cadherin3 and up-regulation of cadherin1. Knockdown experiments show that both cadherins are required for maintenance of tissue integrity and tissue morphogenesis. Thus, both sea anemones and bilaterians use independently duplicated cadherins combinatorially for tissue morphogenesis and germ layer differentiation.
GSK-3 modulates SHH-driven proliferation in postnatal cerebellar neurogenesis and medulloblastoma
Authors: Ocasio Jennifer K. , Bates Rolf Dale P. , Rapp Carolyn D. , Gershon Timothy R.
Published: September 2019

Cerebellar development requires regulated proliferation of cerebellar granule neuron progenitors (CGNPs). Inadequate CGNP proliferation causes cerebellar hypoplasia while excessive CGNP proliferation can cause medulloblastoma, the most common malignant pediatric brain tumor. Although Sonic Hedgehog (SHH) signaling is known to activate CGNP proliferation, the mechanisms down-regulating proliferation are less defined. We investigated CGNP regulation by GSK-3, which down-regulates proliferation in the forebrain, gut and breast by suppressing mitogenic WNT signaling. In striking contrast, we found that co-deleting Gsk-3α and Gsk-3β blocked CGNP proliferation, causing severe cerebellar hypoplasia. The GSK-3 inhibitor CHIR-98014 similarly down-regulated SHH-driven proliferation. Transcriptomic analysis showed activated WNT signaling and up-regulated Cdkn1a in Gsk-3-deleted CGNPs. Ctnnb co-deletion increased CGNP proliferation and rescued cerebellar hypo-proliferation in Gsk-3α/β mutants, demonstrating physiologic control of CGNPs by GSK-3, mediated through WNT. SHH-driven medulloblastomas similarly required GSK-3, as co-deleting Gsk-3α/β blocked tumor growth in medulloblastoma-prone SmoM2 mice. These data show that a GSK-3/WNT axis modulates the developmental proliferation of CGNPs and the pathologic growth of SHH-driven medulloblastoma. The requirement for GSK-3 in SHH-driven proliferation suggests that GSK-3 may be targeted for SHH-driven medulloblastoma therapy.
The Parkinson's disease gene PINK1 activates Akt via PINK1 kinase-dependent regulation of the phospholipid PI(3,4,5)P3
Authors: Furlong Rachel M. , Lindsay Andrew , Anderson Karen E. , Hawkins Phillip T. , Sullivan Aideen M. , O'Neill Cora
Published: September 2019

Akt signalling is central to cell survival, metabolism, protein and lipid homeostasis, and is impaired in Parkinson's disease (PD). Akt activation is reduced in the brain in PD, and by many PD-causing genes, including PINK1. This study investigated the mechanisms by which PINK1 regulates Akt signalling. Our results reveal for the first time that PINK1 constitutively activates Akt in a PINK1-kinase dependent manner in the absence of growth factors, and enhances Akt activation in normal growth medium. In PINK1-modified MEFs, agonist-induced Akt signalling failed in the absence of PINK1, due to PINK1 kinase-dependent increases in PI(3,4,5)P3 at both plasma membrane and Golgi being significantly impaired. In the absence of PINK1, PI(3,4,5)P3 levels did not increase in the Golgi, and there was significant Golgi fragmentation, a recognised characteristic of PD neuropathology. PINK1 kinase activity protected the Golgi from fragmentation in an Akt-dependent fashion. This study demonstrates a new role for PINK1 as a primary upstream activator of Akt via PINK1 kinase-dependent regulation of its primary activator PI(3,4,5)P3, providing novel mechanistic information on how loss of PINK1 impairs Akt signalling in PD.

This article has an associated First Person interview with the first author of the paper.
Incidence of internal mammary node in locally advanced breast cancer and its correlation with metastatic disease: a retrospective observational study
Authors: Singh Somesh , Ramani Subhash K , Rastogi Ashita , Thakur Meenakshi H
Published: September 2019

Objective:

To determine incidence of internal mammary nodes (IMN) at baseline CT of locally advanced breast cancer (LABC) and ascertain prognostic implication.

Methods and materials:

Retrospective review of all LABC patients from 1 January 2012 through 31 December 2014 was performed after approval from institutional review board. CTs of 182 patients enrolled were reviewed by two radiologists independently, and IMNs were documented based on size, location and relation with location of breast primary. 3-year follow-up was analysed and incidence of metastases was calculated as overall incidence, incidence in patients with and without discernible IMN at baseline imaging. Results are presented as numbers and percentages. Differences in metastases of two groups were compared using χ2 test. 95% CI was calculated and p < 0.05 was considered significant.

Results:

77 of 182 had identifiable IMN (42.3% incidence). Majority of identifiable nodes were on ipsilateral side of primary (incidence 90.90%) with higher incidence in patients with upper-outer quadrant tumours (55.9%). Majority were seen in second intercostal space (44.4%). 36 (19.7%) developed distant metastases within 3 years of therapy. Of these, 21 (27.3%) had IMN as compared with 15 (14.3 %) without IMN on baseline imaging. Patients with identifiable IMN on baseline CT had significantly higher incidence of distant metastases (p = 0.0321).

Conclusion:

Significant number LABC patients have identifiable IMN on baseline imaging with patients showing IMN on baseline CT showing significantly higher rate of metastatic disease following therapy.

Advances in knowledge:

Many LABC patients have identifiable IMNs on baseline imaging which show higher incidence of subsequent metastatic disease.
Gustatory dysfunction in relation to circumvallate papilla’s taste buds structure upon unilateral maxillary molar extraction in Wistar rats: an in vivo study
Authors: Mostafa Sana , Hakam Heba M. , El-motayam Amal
Published: September 2019

Background: The interaction between taste sensation and dentoalveolar innervation is still under research.  teeth loss can alter taste thresholds in humans, but the underlying mechanisms are still obscure. This study investigated the effect of unilateral maxillary molars extraction on the structure of circumvallate papilla in rats.

Methods: Thirty-two male Wister rats, aged 3-4 months were randomly distributed into four groups (one control and 3 experimental ) each including 8 animals. The rats were euthanized 3, 6 or 9 weeks following the procedure. The changes in trough length and the taste buds structure and number of both sides of CVP were investigated using routine histological examination followed by statistical analysis.

Results: the trough toward the extraction side was obviously shorter with a noticeable decrease of taste buds’ number than the non-extraction side. Taste buds were reduced in size and most of them showed signs of degeneration which was more evident in group II followed by group III, less deformity detected in group IV in comparison to the preceding 2 experimental groups. the non-extraction side of all experimental groups showed normal trough length and generally normal histology of taste buds.

 Conclusions: Maxillary molars extraction has a degenerative effect on the structure of  taste buds and gustatory epithelium which were more marked at the extraction side and showed improvement upon elongation of follow up period
Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection
Authors: Van Gerwen Olivia T. , Muzny Christina A.
Published: September 2019

Trichomonas vaginalisis the most common, curable non-viral sexually transmitted infection (STI) worldwide. Despite this burden of disease, it is not currently a reportable disease in the United States. Recent advances in the epidemiology, diagnosis, and management ofT. vaginalisinfection are described in this article. This includes updated global and U.S. prevalence data in women and men as well as recent epidemiological data in HIV-infected individuals and pregnant women. Advances in molecular diagnostics are also reviewed, as are data from recent clinical trials regarding the treatment of trichomonas in women.
How can we make better health decisions a Best Buy for all?
Authors: O'Brien Niki , Li Ryan , Isaranuwatchai Wanrudee , Dabak Saudamini Vishwanath , Glassman Amanda , Culyer Anthony J. , Chalkidou Kalipso
Published: September 2019

The World Health Organization (WHO) resolution calling on Member States to work towards achieving universal health coverage (UHC) has increased the need for prioritizing health spending. Such need will soon accelerate as low- and middle-income countries transition from external aid. Countries will have to make difficult decisions on how best to integrate and finance previously donor-funded technologies and health services into their UHC packages in ways that are equitable, and operationally and financially sustainable.

The International Decision Support Initiative (iDSI) is a global network of health, policy and economic expertise which supports countries in making better decisions about how best and how much to spend public money on healthcare. iDSI core partners include Center For Global Development, China National Health Development Research Center, Clinton Health Access Initiative, Health Intervention and Technology Assessment Program, Thailand / National Health Foundation, Imperial College London, Kenya Medical Research Institute, and the Norwegian Institute of Public Health. In May 2019, iDSI convened a roundtable entitled Why strengthening health systems to make better decisions is a Best Buy.

The event brought together members of iDSI, development partners and other organizations working in the areas of evidence-informed priority-setting, resource allocation and purchasing. The roundtable participants identified key challenges and activities that could be undertaken by the broader health technology assessment (HTA) community to further country-led capacity building, as well to foster deeper collaboration between the community itself.

HTA is a tool which can assist governments and development partners with evaluating alternative investment options in a defensible and accountable fashion. The definition and scope of HTA, and what it can achieve and support, can be presented more clearly and cohesively to stakeholders. Organizations engaging in HTA must develop deeper collaboration, and integrate existing collaborations, to ensure progress in developing HTA institutionalization globally is well organized and sustainable.
Design of tourism clusters: a systematic approach sinter
Authors: Кощеев Дмитрий , Koscheev Dmitriy , Исопескуль Ольга , Isopeskul' Ol'ga
Published: September 2019

The monograph is devoted to the phenomenon of tourism cluster as an economic model of design and management of tourism in the region. The author's method of theoretical analysis is presented, with the help of which the in-depth study of the concept of "tourist cluster" as a scientific category is realized. Holistic approaches to the interpretation of the essence of the concept of "tourist cluster"are identified. The approaches are described in a static position and in time dynamics, illustrate the historical development of the category in economic theory.
Developed and described the copyright system-and-sinter approach, the structure of which included: the interpretation of the concept of "tourist cluster" characteristic table, a graphical cluster model and methodology for identification and investigation of such systems.
The new methodology was tested on the example of the Perm region, but can be applied to other subjects of the Russian Federation.
For representatives of state and municipal authorities responsible for the implementation of the policy of tourism development; students studying in the areas of "Economy", "Tourism" and "State and municipal management"; all interested in the spatial development and development of tourism in the territory of the Russian Federation.
Level 2 Reformulation Linearization Technique–Based Parallel Algorithms for Solving Large Quadratic Assignment Problems on Graphics Processing Unit Clusters
Authors: Date Ketan , Nagi Rakesh
Published: September 2019

This paper discusses efficient parallel algorithms for obtaining strong lower bounds and exact solutions for large instances of the quadratic assignment problem (QAP). Our parallel architecture is comprised of both multicore processors and compute unified device architecture–enabled NVIDIA graphics processing units (GPUs) on the Blue Waters Supercomputing Facility at the University of Illinois at Urbana–Champaign. We propose novel parallelization of the Lagrangian dual ascent algorithm on the GPUs, which is used for solving a QAP formulation based on the level-2 reformulation linearization technique. The linear assignment subproblems in this procedure are solved using our accelerated Hungarian algorithm [Date K, Rakesh N (2016) GPU-accelerated Hungarian algorithms for the linear assignment problem. Parallel Computing 57:52–72.]. We embed this accelerated dual-ascent algorithm in a parallel branch-and-bound scheme and conduct extensive computational experiments on single and multiple GPUs, using problem instances with up to 42 facilities from the quadratic assignment problem library (QAPLIB). The experiments suggest that our GPU-based approach is scalable, and it can be used to obtain tight lower bounds on large QAP instances. Our accelerated branch-and-bound scheme is able to comfortably solve Nugent and Taillard instances (up to 30 facilities) from the QAPLIB, using a modest number of GPUs.
Interesting, Important, and Impactful Operations Management
Authors: Cachon Gérard P. , Girotra Karan , Netessine Serguei
Published: September 2019

Operations management has evolved since the founding of M&SOM: new departments have been created in our journals, new tracks have been established in our conferences, and new methodologies have been adopted in our research. Are these changes good for the field? To some, they seem detrimental, yielding a fragmented community that does not always speak the same language nor interact in any meaningful way. Others celebrate our expanded diversity and the new areas of research that it opens up. We argue that neither group is entirely wrong, nor entirely correct. Like the latter, we argue that we must contribute to a growing set of domains using all possible tools of inquiry. But sharing the concern of the former, we view fragmentation as a symptom of a problem. To get out of its rut, to have greater impact, the field needs to ask questions that are important and provide answers that are interesting. In particular, we should (i) avoid the trap of specificity (excellent answers to narrowly defined questions), (ii) expand our horizon beyond our (relatively) small field (connect and actively engage with diverse audiences), and (iii) be bold to pioneer new areas of inquiry. Operations management is at the heart of many of the big issues in society today, and we should be (and can be) central to the conversation.