bluuebunny/crossref_metadata_2025 huggingface dataset:
12. Market abuse
Authors: French Derek
Published: September 2019

This chapter deals with abuses committed in the trading of shares, with particular reference to insider dealing and market manipulation, and the laws intended to control them. The chapter considers forms of control to prevent market abuse under three key pieces of legislation: Regulation (EU) No 596/2014, the Criminal Justice Act 1993 and the Financial Services Act 2012. It looks at regulations governing disclosure to regulated markets and the fiduciary duty of directors, and offences involving insider dealing and creating a false market. The chapter analyses a particularly significant case: Percival v Wright [1902] 2 Ch 421.
Patterns in abundance and size of sharks in northwestern Australia: cause for optimism
Authors: Braccini Matias , Molony Brett , Blay Nick
Published: September 2019

Reliable information for population assessments is rare for sharks. We quantified patterns in catch rates and mean size for numerous tropical and subtropical species from 15 years of fishery-independent surveys (2002–2017) in northwestern Australia. This study region represents an area of ~0.8 million km2 which was closed to commercial shark fishing from 1993 or 2005 onward due to the very high State-wide catches of sandbar (Carcharhinus plumbeus) and dusky (Carcharhinus obscurus) sharks. A total of 43 shark and ray species were sampled, with sandbar shark being the most commonly caught species, followed by milk (Rhizoprionodon acutus), spot-tail (Carcharhinus sorrah), tiger (Galeocerdo cuvier), blacktip (Carcharhinus limbatus and Carcharhinus tilstoni), dusky and sliteye (Loxodon macrorhinus) sharks, and scalloped hammerhead (Sphyrna lewini). For sandbar shark, catch rates increased between 2008 and 2017 whereas for other taxa catch rates were mostly stable (albeit fluctuating). Mean size at capture fluctuated across years with no particular trends. Unlike for other parts of the world, catch rates and mean size of northwestern Australian sharks have been stable or increased in recent years. Though most shark species have conservative life histories, when science, management and enforcement work synergistically, sustainable resource use, recovery and conservation outcomes can all be achieved.
Transapical septal myectomy in the beating heart via a minimally invasive approach: a feasibility study in swine
Authors: Fang Jing , Wang Rui , Liu Hongyun , Su Yunshu , Chen Jun , Han Xiujuan , Wei Yupeng , Chen Yue , Cheng Lin , Wei Xiang
Published: September 2019

OBJECTIVES

The aim of this study was to establish an original transapical septal myectomy procedure that can be performed in the beating heart via a minimally invasive approach for the treatment of hypertrophic obstructive cardiomyopathy.

METHODS

We designed an original intracardiac septum resection device to conduct off-pump septal myectomy in swine. A subxiphoid minithoracotomy was performed to access the apex of the heart. This resection device was inserted into the left ventricular outflow tract of the heart via the apex. The basal anteroseptal myocardium beneath the right aortic cusp was identified using a combination of transoesophageal and transthoracic echocardiography and then resected and collected by the device.

RESULTS

Six consecutive operations were successfully and accurately performed using the custom-made device under echocardiographic guidance. All pigs survived and appeared to be normal until planned euthanasia 1 week after operation. A 300–700 mg portion of the septal myocardium was resected from the normal swine heart. Echocardiography and electrocardiogram revealed no abnormalities after resection. One exception was the fifth pig, in which mild annular regurgitation of the aortic valve occurred after repetitive resection. Postmortem necropsy demonstrated that all resections were correctly located at the basal anteroseptal septum beneath the right aortic cusp.

CONCLUSIONS

Our study provides the first proof-of-concept evidence for a novel beating heart transapical septal myectomy procedure, which showed promising translational potential for the treatment of hypertrophic obstructive cardiomyopathy. This procedure would probably reduce operative risks and improve outcomes and reduce the demanding expertise required to perform conventional surgical myectomy.
Cell-Free Hemoglobin Is Associated With Increased Vascular Resistance and Reduced Peripheral Perfusion in Severe Malaria
Authors: Kingston Hugh W F , Ghose Aniruddha , Rungpradubvong Voravut , Satitthummanid Sudarat , Herdman M Trent , Plewes Katherine , Ishioka Haruhiko , Leopold Stije J , Sinha Ipsita , Intharabut Benjamas , Piera Kim , McNeil Yvette , Mohanty Sanjib , Maude Richard J , White Nicholas J , Day Nicholas P J , Yeo Tsin W , Hossain Md Amir , Anstey Nicholas M , Dondorp Arjen M
Published: September 2019

Background

In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria.

Methods

Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The systemic vascular resistance index (SVRI) was estimated from the echocardiographic cardiac index and the mean arterial pressure.

Results

SVRI and hematocrit levels were lower and plasma CFH and asymmetric dimethylarginine levels were higher in patients with malaria, compared with healthy participants. In multivariate linear regression models for mean arterial pressure or SVRI in patients with severe malaria, hematocrit and CFH but not asymmetric dimethylarginine were significant predictors. The SVRI was lower in patients with suspected bacterial sepsis than in those with severe malaria, after adjustment for hematocrit and age. Plasma CFH levels correlated positively with the core-peripheral temperature gradient and plasma lactate levels and inversely with the perfusion index. Impaired peripheral perfusion, as reflected by a low perfusion index or a high core-peripheral temperature gradient, predicted mortality in patients with severe malaria.

Conclusions

CFH is associated with mean arterial pressure, SVRI, and peripheral perfusion in patients with severe malaria. This may be mediated through the nitric oxide scavenging potency of CFH, increasing basal vascular tone and impairing tissue perfusion.
Adenoviral Infections in Singapore: Should New Antiviral Therapies and Vaccines Be Adopted?
Authors: Coleman Kristen K , Wong Chui Ching , Jayakumar Jayanthi , Nguyen Tham T , Wong Abigail W L , Yadana Su , Thoon Koh C , Chan Kwai Peng , Low Jenny G , Kalimuddin Shirin , Dehghan Shoaleh , Kang June , Shamsaddini Amirhossein , Seto Donald , Su Yvonne C F , Gray Gregory C
Published: September 2019

Background

A number of serious human adenovirus (HAdV) outbreaks have been recently reported: HAdV-B7 (Israel, Singapore, and USA), HAdV-B7d (USA and China), HAdV-D8, -D54, and -C2 (Japan), HAdV-B14p1 (USA, Europe, and China), and HAdV-B55 (China, Singapore, and France).

Methods

To understand the epidemiology of HAdV infections in Singapore, we studied 533 HAdV-positive clinical samples collected from 396 pediatric and 137 adult patients in Singapore from 2012 to 2018. Genome sequencing and phylogenetic analyses were performed to identify HAdV genotypes, clonal clusters, and recombinant or novel HAdVs.

Results

The most prevalent genotypes identified were HAdV-B3 (35.6%), HAdV-B7 (15.4%), and HAdV-E4 (15.2%). We detected 4 new HAdV-C strains and detected incursions with HAdV-B7 (odds ratio [OR], 14.6; 95% confidence interval [CI], 4.1–52.0) and HAdV-E4 (OR, 13.6; 95% CI, 3.9–46.7) among pediatric patients over time. In addition, immunocompromised patients (adjusted OR [aOR], 11.4; 95% CI, 3.8–34.8) and patients infected with HAdV-C2 (aOR, 8.5; 95% CI, 1.5–48.0), HAdV-B7 (aOR, 3.7; 95% CI, 1.2–10.9), or HAdV-E4 (aOR, 3.2; 95% CI, 1.1–8.9) were at increased risk for severe disease.

Conclusions

Singapore would benefit from more frequent studies of clinical HAdV genotypes to identify patients at risk for severe disease and help guide the use of new antiviral therapies, such as brincidofovir, and potential administration of HAdV 4 and 7 vaccine.
Using REDCap and Apple ResearchKit to integrate patient questionnaires and clinical decision support into the electronic health record to improve sexually transmitted infection testing in the emergency department
Authors: Ahmad Fahd A , Payne Philip R O , Lackey Ian , Komeshak Rachel , Kenney Kenneth , Magnusen Brianna , Metts Christopher , Bailey Thomas
Published: September 2019

Objective

Audio-enhanced computer-assisted self-interviews (ACASIs) are useful adjuncts for clinical care but are rarely integrated into the electronic health record (EHR). We created a flexible framework for integrating an ACASIs with clinical decision support (CDS) into the EHR. We used this program to identify adolescents at risk for sexually transmitted infections (STIs) in the emergency department (ED). We provide an overview of the software platform and qualitative user acceptance.

Materials and Methods

We created an ACASI with a CDS algorithm to identify adolescents in need of STI testing. We offered it to 15- to 21-year-old patients in our ED, regardless of ED complaint. We collected user feedback via the ACASI. These were programmed into REDCap (Research Electronic Data Capture), and an iOS application utilizing Apple ResearchKit generated a tablet compatible representation of the ACASI for patients. A custom software program created an HL7 (Health Level Seven) message containing a summary of responses, CDS recommendations, and STI test orders, which were transmitted to the EHR.

Results

In the first year, 1788 of 6227 (28.7%) eligible adolescents completed the survey. Technical issues led to decreased use for several months. Patients rated the system favorably, with 1583 of 1787 (88.9%) indicating that they were “somewhat” or “very comfortable” answering questions electronically and 1291 of 1787 (72.2%) preferring this format over face-to-face interviews or paper questionnaires.

Conclusions

We present a novel use for REDCap to combine patient-answered questionnaires and CDS to improve care for adolescents at risk for STIs. Our program was well received and the platform can be used across disparate patients, topics, and information technology infrastructures.
DNA persistence in predator saliva from multiple species and methods for optimal recovery from depredated carcasses
Authors: Piaggio Antoinette J , Shriner Susan A , Young Julie K , Griffin Doreen L , Callahan Peggy , Wostenberg Darren J , Gese Eric M , Hopken Matthew W
Published: September 2019

Molecular forensics is an important component of wildlife research and management. Using DNA from noninvasive samples collected at predation sites, we can identify predator species and obtain individual genotypes, improving our understanding of predator–prey dynamics and impacts of predators on livestock and endangered species. To improve sample collection strategies, we tested two sample collection methods and estimated degradation rates of predator DNA on the carcasses of multiple prey species. We fed carcasses of calves (Bos taurus) and lambs (Ovis aires) to three captive predator species: wolves (Canis lupus), coyotes (C. latrans), and mountain lions (Puma concolor). We swabbed the carcass in the field, as well as removed a piece of hide from the carcasses and then swabbed it in the laboratory. We swabbed all tissue samples through time and attempted to identify the predator involved in the depredation using salivary DNA. We found the most successful approach for yielding viable salivary DNA was removing hide from the prey and swabbing it in the laboratory. As expected, genotyping error increased through time and our ability to obtain complete genotypes decreased over time, the latter falling below 50% after 24 h. We provide guidelines for sampling salivary DNA from tissues of depredated carcasses for maximum probability of detection.
Topical Review: Enhancing Understanding of the Clinical Meaningfulness of Outcomes to Assess Treatment Benefit from Psychological Therapies for Children with Chronic Pain
Authors: Palermo Tonya M , Kashikar-Zuck Susmita , Lynch-Jordan Anne
Published: September 2019

Objective

Despite the availability of measures for assessing physical, psychological, and health impact in children with chronic pain, there are not established guidelines for interpretation of children’s pain outcomes following psychological treatment. The purpose of this topical review is to discuss clinical significance as a neglected area of consideration in pediatric chronic pain assessment and to make recommendations on how the field can move toward benchmarking on core outcome domains.

Method

We review definitions of clinical significance and examples of several methodologies that have been used in other populations or are emerging in pediatric chronic pain including anchor-based methods, distribution-based methods, or multimethod approaches.

Results

Few measures across pediatric chronic pain outcome domains have established clinical significance of scores to interpret meaningful change following treatment limiting the interpretability of findings from clinical trials. In the context of clinical practice, several efforts to examine clinical significance to improve the translation of evidence-based measurement into standard clinical decision-making exist.

Conclusions

Recommendations are provided to encourage additional validation efforts of outcome measures in pediatric chronic pain and to encourage authors to report clinical significance in clinical trials of psychological interventions for pediatric chronic pain.
Strategies for Bringing Mindfulness to Emerging Adults
Authors: Rogers Holly , Maytan Margaret
Published: September 2019

Chapter 3 explores general strategies that are useful for teaching mindfulness to emerging adults. Traditional methods of teaching mindfulness and meditation are not always effective for engaging emerging adults. Often, students are enthusiastic about the idea of learning mindfulness, but they then have a hard time actually developing the skills in any meaningful way. This chapter looks at techniques that have proven useful for engaging the students in the study and practice of mindfulness. The strategies are divided into three categories: strategies related to the organization and structure of the class, strategies related to general teaching techniques, and strategies for dealing with typical student reactions. Each of these categories is fully explored, and examples of how to implement the various strategies are provided.
Structure and Logistics
Authors: Rogers Holly , Maytan Margaret
Published: September 2019

Considering the format, structure, and logistics of the Koru course, one is struck by how even these practical aspects of the model make it possible for students to learn the practice and skills being taught. A critical aspect of the model is the emphasis on both meditation and mindfulness-based stress-management skills. This chapter describes the structure and logistics involved in teaching Koru mindfulness. The following elements are reviewed: class structure, including the number and length of classes; recruitment; registration using the Koru teacher dashboard; communication with students; setting; structure; class commitments; and tools for teaching including the Koru mobile app.
Managing Substance Use Disorder
Authors: Daley Dennis C. , Douaihy Antoine B.
Published: September 2019

This practitioner guide reviews screening, assessment, and treatment of substance use disorders (SUDs). It is designed to accompany Managing Your Substance Use Disorder: Client Workbook and A Family Guide to Coping with Substance Use Disorders. The latter guide was added because each person with a SUD affects the family and concerned significant others. The information and strategies that the authors present can be used with clients who have any type of SUD. The guide focuses on strategies to reduce or stop substance use and change behaviors that challenge recovery. The information presented is derived from research, clinical, and recovery literature and from the authors’ extensive experience developing and managing a large continuum of clinical services, providing direct care, conducting quality improvement initiatives, participating in clinical trials, and teaching all disciplines in a large medical center and the community. This guide discusses professional approaches and attitudes toward individuals with SUDs, assessment, diagnostic formulation, psychosocial and pharmacotherapeutic treatments, and mutual support programs. It provides an overview of the recovery and relapse processes and practical strategies to address issues associated with SUDs. This guide is for practitioners from any discipline who encounter individuals with SUDs in addiction, mental health, psychiatric, private practice, or other settings such as social services and the criminal justice system. Even medical practitioners who do not specialize in addiction treatment can benefit from the information in this guide because individuals with SUDs are found in all types of healthcare settings.
Screening, Assessment, and Diagnosis
Authors: Daley Dennis C. , Douaihy Antoine
Published: September 2019

Screening is a process used to identify individuals who may be at risk for a substance use problem by having them answer a few questions about their use of alcohol, tobacco, or other drugs. An extensive assessment of substance use disorders (SUDs) requires a multidimensional approach and differs from other mental health assessments in that detailed information is obtained on patterns of alcohol or other drug use, negative consequences of use, physiological and behavioral dependence, cognitive impairment, motivation for change, potential effects of substances on psychiatric disorders, attitudes and beliefs about continued use and abstinence, and the client’s strengths, resources, and social support networks. Diagnosis determines whether a client meets criteria for a SUD, which in turn may affect treatment planning and access to services. The best approach to diagnosis is through a comprehensive clinical interview and identifying criteria that match a client’s symptomatology.
Stages of Change and Using Therapy or Counseling
Authors: Daley Dennis C. , Douaihy Antoine
Published: September 2019

Motivation is a dynamic process that is affected by interpersonal interactions. A fundamental component of treatment is to strengthen the client’s motivation for change. The objectives of this chapter are to introduce the client to the concept of stages of change and motivation for change, to help the client identify his or her current stage of change and the issues to address in recovery, to review strategies to help the client deal with low motivation, and to identify therapy-sabotaging behaviors and positive coping strategies.
Building a Recovery Support System
Authors: Daley Dennis C. , Douaihy Antoine
Published: September 2019

Healthy and supportive relationships with family, friends, and peers or other recovering individuals offer many potential benefits. The pressure to use substances decreases, the tendency to isolate oneself lessens, there are opportunities to reach out for help and support in times of stress or need, and there are opportunities to share mutual interests or experiences. Organizations can also be a major part of a client’s recovery support system. There are, however, numerous barriers to asking for help and support. The objectives of this chapter are to review the client’s social support system to identify the nature of current relationships, to identify the benefits of a recovery support system, to identify specific individuals and organizations that the client can include in his or her support network, and to help the client become aware of and overcome barriers to asking for help and support.
Mutual Support Programs and Recovery Clubs
Authors: Daley Dennis C. , Douaihy Antoine
Published: September 2019

There are many paths to recovery, and mutual support programs (MSPs) are one of the most common paths taken. MSPs offer a community of recovery in which individuals with substance abuse disorders (SUDs) help and support each other in numerous ways. The most widely available MSPs are the 12-step programs of Alcoholics Anonymous (AA), Narcotics Anonymous (NA), Cocaine Anonymous (CA), Crystal Meth Anonymous (CMA), Marijuana Anonymous (MA), and Heroin Anonymous (HA). AA and NA are available throughout the world, whereas the other 12-step programs are less accessible. Although some clients participate throughout their lives in MSPs, others use them for only a specific period of time. Clients vary in their needs for involvement in MSPs. The objectives of this chapter are to provide clients with information about mutual support programs and recovery clubs, to help clients identify drawbacks and benefits of attending MSPs and recovery clubs, and to help clients identify specific MSPs that can enhance their recovery.
Applying Ethical Theories to Genetic Counseling Practice
Authors: Biesecker Barbara B. , Peters Kathryn F. , Resta Robert
Published: September 2019

Genetic counseling engenders thorny ethical issues that expand as genetic testing technology continues to evolve. Genetic counselors are frequently faced with bioethical dilemmas that, by their very nature, are not easily resolved. This chapter reviews some of the common ethical frameworks for considering ethically complex situations—deontology, casuistry, principilism, and feminist ethics. These ethical approaches are illustrated by applying them to a case of a mother who is a BRCA mutation carrier and is trying to make a decision about genetic testing for her fourteen-year-old daughter. No one ethical framework will be applicable to all genetic counseling dilemmas, but familiarity with these different approaches can help counselors better understand the value of each approach in assessing a variety of clinical situations. A model is presented showing how to manage, think about, and think through ethical dilemmas.
Asymptomatic Cervical Carotid Stenosis
Authors: Vakharia Kunal , Natarajan Sabareesh K. , Shallwani Hussain , Levy Elad I.
Published: September 2019

Abstract: This chapter discusses the evaluation and management of asymptomatic carotid stenosis. Surgical and endovascular management of carotid artery disease continues to progress. With lifestyle modifications and medical management, the stroke risk without surgical intervention has been decreased; however, in patients with significant carotid stenosis, surgical intervention has still been shown to decrease the stroke risk by nearly half. A thorough understanding of the arterial and venous anatomy is essential for surgical planning. Carotid endarterectomy for asymptomatic carotid artery disease has been validated through prospective clinical trials to help dramatically reduce the risk of stroke. Endovascular management through carotid artery angioplasty and stenting is another option that continues to undergo evaluation in the asymptomatic patient population.
Transverse Sinus Arteriovenous Fistula Presenting with Tinnitus
Authors: Morrison John F. , Siddiqui Adnan H.
Published: September 2019

Abstract: Arteriovenous fistulae present in any of a number of characteristic locations in the brain, such as the ethmoidal region, the petrosal sinus, and the transverse sinus and torcula. The fistula is an abnormal connection between an artery and vein. While there are multiple accepted classification systems, the risk they represent to the patient depends primarily on the degree of reflux of the venous drainage back to the cortex of the brain. While the inflow and outflow may be very complex, isolation of the fistulous point where this abnormal connection occurs is the key to successful treatment. This may be achieved through either endovascular or open surgical techniques deoending on the anatomy.
Ruptured Conus Medullaris Arteriovenous Malformation
Authors: Lee Michaela H. , Liebelt Brandon D. , Nakaji Peter , Spetzler Robert F.
Published: September 2019

Abstract: Conus medullaris arteriovenous malformations are an exceedingly rare cause of neurological deficit. They occupy the tip of the spinal cord and can generate motor, sensorty, bowel, bladder, or sexual function deficits. Because of the complex vascular supply of the caudal aspect of the spinal cord, which usually includes multiple feeders from both the anterior and posterior spinal arteries, management may be endovascular, microsurgical, or both. Making the proper diagnosis and distinguishing it from other similar pathologies such as arteriovenous fistula is critical. As with other spinal arteriovenous malformations, it is usually not necessary to pursue the nidus into the spinal cord parenchyma at the time of surgery. This chapter discusses the diagnosis and management of this rare disorder.
Obstetric Critical Care
Authors: Popovich Marc J.
Published: September 2019

This chapter is intended to review content that is seen less often on an examination but that still may be pertinent for every intensivist. Obstetric critical care questions are usually integrated into broader surgical and infectious topics, and the goal of this chapter is specifically to cover this content with detail in lieu of having it show up as “grab bag” questions in other topical chapters (although this occurs as well). Nonetheless, questions on these topics should be expected on the examination and are common pitfalls for those undergoing certification. Obstetric patients may be admitted to any ICU that cares for surgical patients and as this population has a unique set of clinical needs and presenting pathology. Knowledge of the content in this chapter has practical implications for patient care and is justifiably covered in the certification exam.
Right to Die
Authors: Ford Elizabeth
Published: September 2019

Chapter 7 describes three cases that involve an individual’s right, in certain circumstances, to choose death. Cruzan v. Missouri is more specifically about a right to refuse life-sustaining treatment and surrogate decision-making; Washington v. Glucksberg and Vacco v. Quill are physician-assisted suicide cases, both decided on the same day by the U.S. Supreme Court and both declaring the practice unconstitutional.
Sexual Harassment
Authors: Levin Andrew P. , Rotter Merrill
Published: September 2019

Chapter 19 describes cases that involve sexual harassment in the workplace. As a group, they have defined and applied such important concepts as a “hostile work environment” and “quid pro quo,” and have established standards that forensic practitioners need to know when conducting evaluations for cases involving sexual harassment. The cases in this chapter are Meritor Bank v. Vinson, Harris Forklift Systems, Inc. and Oncale v. Sundowner Offshore Services, Inc.
Criminal Competencies
Authors: Grover Matthew W. , Cucolo Heather Ellis , Rotter Merrill
Published: September 2019

Chapter 22 includes cases that are important for one of the staples of forensic psychiatric practice, competence to stand trial evaluations. Knowledge of the legal standards required for one to defend oneself, either with or without an attorney, is necessary for a practitioner to be able to capably assess whether a mental illness prevents a defendant from participating in the adjudication process. The cases in this chapter are Dusky v. U.S., Wilson v. U.S., Jackson v. Indiana, Drope v. Missouri, Godinez v. Moran, Cooper v. Oklahoma and Indiana v. Edwards. The newest case (Trueblood v. Washington State Department of Social and Helth Services) looks at the practical issue of the wait time for competency restoration treatment as a potential constitutional violation.
Insanity
Authors: Frischer Katya
Published: September 2019

Chapter 25 relates to what is probably the most recognized, but perhaps the most rare, evaluation performed by a forensic professional. The pursuit of an insanity defense today is challenging and, in some states, not even permissible. These cases illustrate the evolution of the various state standards for establishing insanity (and therefore acquittal) for criminal defendants with mental illness. The following cases are included in this chapter: M’Naghten’s Case, Durham v. U.S., Washington v. U.S., Frendak v. U.S., Jones v. U.S., U.S. v. Torniero, Foucha v. Louisiana and Clark v. Arizona.
Immigration
Authors: Colley Jeremy , Cucolo Heather Ellis
Published: September 2019

Chapter 29 includes cases related to the rights of individuals subject to immigration proceedings, with particular focus on the right to be made aware of the potential immigration consequences of taking a guilty, competence to participate in the proceedings, and the related right to representation where competence is in question. While criminal case recommendations are beyond the purview of forensic practitioners, those involved in mental health diversion programs should be aware of the potential consequences of diversion participation for defendants at risk of deportation. In addition, forensic evaluators are called upon to opine about the impact of mental illness and/or cognitive disability on competence to participate in the immigration proceedings. The cases in this chapter include Padilla v. Kentucky and Matter of M-A-M.
Tissue typing
Authors: Spickett Gavin
Published: September 2019

Covering tissue typing, this chapter describes key elements for tissue matching, a key element for successful transplantation. Methods for detecting pre-formed circulating antibodies, serological tests, and genotyping are all described. Techniques including RFLP, PCR, sequence-specific primer are explained, along with a look forward to next-generation sequencing.
Fractal statistics in young star clusters: structural parameters and dynamical evolution
Authors: Hetem Annibal , Gregorio-Hetem Jane
Published: September 2019

We used fractal statistics to quantify the degree of observed substructures in a sample of 50 embedded clusters and more evolved open clusters (< 100 Myr) found in different galactic regions. The observed fractal parameters were compared with N-body simulations from the literature, which reproduce star-forming regions under different initial conditions and geometries that are related to the cluster's dynamical evolution. Parallax and proper motion from Gaia-DR2 were used to accurately determine cluster membership by using the Bayesian model and cross-entropy technique. The statistical parameters $\mathcal {Q}$, $\overline{m}$ and $\overline{s}$ were used to compare observed cluster structure with simulations. A low level of substructures ($\mathcal {Q} \lt $ 0.8) is found for most of the sample that coincides with simulations of regions showing fractal dimension D ∼ 2–3. Few clusters (<20 per cent) have uniform distribution with a radial density profile (α < 2). A comparison of $\mathcal {Q}$ with mass segregation (ΛMSR) and local density as a function of mass (ΣLDR) shows the clusters coinciding with models that adopt supervirial initial conditions. The age–crossing time plot indicates that our objects are dynamically young, similar to the unbound associations found in the Milky Way. We conclude that this sample may be expanding very slowly. The flat distribution in the $\mathcal {Q}$–age plot and the absence of trends in the distributions of ΛMSR and ΣLDR against age show that in the first 10 Myr the clusters did not change structurally and seem not to have expanded from a much denser region.
Insights into the physics when modelling cold gas clouds in a hot plasma
Authors: Sander Bastian , Hensler Gerhard
Published: September 2019

This paper aims at studying the reliability of a few frequently raised, but not proven, arguments for the modelling of cold gas clouds embedded in or moving through a hot plasma and at sensitizing modellers to a more careful consideration of unavoidable acting physical processes and their relevance. At first, by numerical simulations we demonstrate the growing effect of self-gravity on interstellar clouds and, by this, moreover argue against their initial set-up as homogeneous. We apply the adaptive-mesh refinement code flash with extensions to metal-dependent radiative cooling and external heating of the gas, self-gravity, mass diffusion, and semi-analytic dissociation of molecules, and ionization of atoms. We show that the criterion of Jeans mass or Bonnor–Ebert mass, respectively, provides only a sufficient but not a necessary condition for self-gravity to be effective, because even low-mass clouds are affected on reasonable dynamical time-scales. The second part of this paper is dedicated to analytically study the reduction of heat conduction by a magnetic dipole field. We demonstrate that in this configuration, the effective heat flow, i.e. integrated over the cloud surface, is suppressed by only 32 per cent by magnetic fields in energy equipartition and still insignificantly for even higher field strengths.
UBR5 interacts with the replication fork and protects DNA replication from DNA polymerase η toxicity
Authors: Cipolla Lina , Bertoletti Federica , Maffia Antonio , Liang Chih-Chao , Lehmann Alan R , Cohn Martin A , Sabbioneda Simone
Published: September 2019

Accurate DNA replication is critical for the maintenance of genome integrity and cellular survival. Cancer-associated alterations often involve key players of DNA replication and of the DNA damage-signalling cascade. Post-translational modifications play a fundamental role in coordinating replication and repair and central among them is ubiquitylation. We show that the E3 ligase UBR5 interacts with components of the replication fork, including the translesion synthesis (TLS) polymerase polη. Depletion of UBR5 leads to replication problems, such as slower S-phase progression, resulting in the accumulation of single stranded DNA. The effect of UBR5 knockdown is related to a mis-regulation in the pathway that controls the ubiquitylation of histone H2A (UbiH2A) and blocking this modification is sufficient to rescue the cells from replication problems. We show that the presence of polη is the main cause of replication defects and cell death when UBR5 is silenced. Finally, we unveil a novel interaction between polη and H2A suggesting that UbiH2A could be involved in polη recruitment to the chromatin and the regulation of TLS.
Structural insights into synthetic ligands targeting A–A pairs in disease-related CAG RNA repeats
Authors: Mukherjee Sanjukta , Błaszczyk Leszek , Rypniewski Wojciech , Falschlunger Christoph , Micura Ronald , Murata Asako , Dohno Chikara , Nakatani Kazuhiko , Kiliszek Agnieszka
Published: September 2019

The trinucleotide repeat expansion disorders (TREDs) constitute of a group of >40 hereditary neurodegenerative human diseases associated with abnormal expansion of repeated sequences, such as CAG repeats. The pathogenic factor is a transcribed RNA or protein whose function in the cell is compromised. The disorders are progressive and incurable. Consequently, many ongoing studies are oriented at developing therapies. We have analyzed crystal structures of RNA containing CAG repeats in complex with synthetic cyclic mismatch-binding ligands (CMBLs). The models show well-defined interactions between the molecules in which the CMBLs mimic nucleobases as they form pseudo-canonical base pairs with adenosine residues and engage in extensive stacking interactions with neighboring nucleotides. The binding of ligands is associated with major structural changes of the CAG repeats, which is consistent with results of biochemical studies. The results constitute an early characterization of the first lead compounds in the search for therapy against TREDs. The crystallographic data indicate how the compounds could be further refined in future biomedical studies.
A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: Clinical Trial Protocol
Authors: Takami Hirokazu , Nassiri Farshad , Moraes Fabio Y , Zadeh Gelareh , Bernstein Mark , Conrad Tatiana , Berlin Alejandro , Laperriere Normand , Millar Barbara-Ann , Shultz David Benjamin , Kongkham Paul
Published: September 2019

BACKGROUND

Brain metastases which require resection are treated with surgery followed by whole brain radiation therapy or postoperative cavity boost stereotactic radiosurgery (POCBS). Recently a novel strategy using neoadjuvant stereotactic radiosurgery (NaSRS) followed by resection was reported, demonstrating lower rates of postoperative leptomeningeal dissemination (LMD) and symptomatic radiation toxicity compared to a comparative cohort of patients treated with postoperative SRS.

OBJECTIVE

To determine if the rate of symptomatic radiation toxicity at 1 yr in patients who receive NaSRS differs significantly from historical rates for patients treated with POCBS.

METHODS

This is a multi-center, non-randomized, open phase II clinical trial. A total of 30 patients with up to 10 brain metastases, at least 1 of which is appropriate for surgical resection, will be enrolled for over 4 yr. All enrolled patients will be assigned to receive NaSRS followed by surgery.

EXPECTED OUTCOME

This study will clarify whether symptomatic radiation toxicity caused by NaSRS is significantly decreased compared to historical rates associated with POCBS. Secondary endpoints will include 1-yr local control (LC) of the treated lesion, 1-yr rates of LMD, median survival and 2-yr rates of progression-free and overall survival. Tertiary analyses will include correlation between LC and radiation toxicity with pretreatment clinical factors, serum markers, radiomic features, and molecular assessments of the resected tumors.

DISCUSSION

This prospective study will determine the toxicity associated with NaSRS and provide additional quantitative metrics of efficacy for future comparative trials.
Cost of Readmissions Following Anterior Cervical Discectomy and Fusion: Insights from the Nationwide Readmissions Database
Authors: Goyal Anshit , Bhandarkar Archis R , Alvi Mohammed Ali , Kerezoudis Panagiotis , Yolcu Yagiz U , Habermann Elizabeth B , Sebastian Arjun S , Bydon Mohamad
Published: September 2019

BACKGROUND

Postoperative readmissions are a significant driver of variation in bundled care costs associated with cervical spine surgery.

OBJECTIVE

To determine the factors predicting the cost of readmission episodes following elective anterior cervical discectomy and fusion (ACDF).

METHODS

We queried the Healthcare Cost and Utilization Project Nationwide Readmissions Database for patients undergoing elective ACDF during 2012 to 2015. Multivariable linear regression was performed to establish the factors associated with the cost of each 30-/90-d readmission episode.

RESULTS

A total of 139 877 and 113 418 patients met inclusion criteria for the evaluation of 30- and 90-d readmissions, respectively. Among these, the national rates of 30- and 90-d readmission after an elective ACDF were 3% and 6%, respectively. The median cost of a 30- and 90-d readmission episode was $6727 (IQR: $3844-$13 529) and $8507 (IQR: $4567-$17 460), respectively. Relative predictor importance analysis revealed that the number of procedures at index admission (IA), length of stay at IA, and time elapsed between index surgical admission and readmission were the top predictors of both 30- and 90-d readmission costs (all P < .001). Although cervical myelopathy accounted for only 3.6% of all 30-d readmissions, it accounted for the largest share (8%) of 30-d readmission costs.

CONCLUSION

In this analysis from a national all-payer database, we determined the factors associated with the cost of readmissions following elective ACDF. These results are important in assisting policymakers and payers with a better risk adjustment in bundled care payment systems and for surgeons in implementing readmission cost-reduction efforts.
Performance Obligations to Improve Delivery of Hospital-Initiated Smoking Cessation Interventions: A Before-and-After Evaluation
Authors: Mullen Kerri A , Walker Kathryn L , Hobler Laura A , Wells George A , Moroz Isabella A , Pipe Andrew L , Patzer Karen , Aitken Debbie A , Reid Robert D
Published: September 2019

Introduction

This study evaluated whether introducing performance obligations (a policy intervention) to service agreements between hospitals (n = 15) and their local health authority: (1) improved provision of an evidence-based tobacco cessation intervention (the “Ottawa Model” for Smoking Cessation) and (2) changed the quality of the cessation intervention being delivered.

Methods

Interrupted time series analysis was used to evaluate the change in the proportion of smoker patients provided the Ottawa Model 3 years before and 3 years after introducing the performance obligations. Changes in secondary outcomes related to program quality were described using mean differences, risk differences, and risk ratios, as appropriate.

Results

The proportion and number of patients provided the Ottawa Model doubled in the 3-year period following introduction of the new policy—from 3453 patients (33.7%) in the year before to 6840 patients (62.8%) in the final assessment year. This resulted in a signification slope change (+9.2%; 95% confidence interval [CI] 4.5%, 13.9%; p = .01) between the pre- and post-obligation assessment periods, signifying the policy had a positive impact on performance. Quality and effectiveness of the in-hospital intervention remained steady.

Conclusions

Implementation of performance obligations by a healthcare funder increased delivery of an evidence-based smoking cessation intervention across multiple hospitals. Given the known health and economic impacts of smoking cessation interventions, health authorities and hospitals should consider pairing adoption of systematic interventions, like the Ottawa Model, with policy to enhance reach and impact.

Implications

• The hospital-based Ottawa Model for Smoking Cessation (OMSC) intervention has been shown to increase smoking abstinence, while reducing mortality and healthcare utilization.

• The uptake of systematic, evidence-based interventions, like the OMSC, by hospitals has been relatively low despite the known positive impacts.

• The introduction of smoking cessation performance obligations by a healthcare funder resulted in more patients receiving an OMSC intervention while in hospital, with no corresponding change in intervention quality or effectiveness.

• Healthcare funders and hospitals should consider pairing the adoption of effective, systematic interventions, like the OMSC, with policy to enhance reach and impact.
First clear detection of the CCS Zeeman splitting toward the pre-stellar core, Taurus Molecular Cloud 1
Authors: Nakamura Fumitaka , Kameno Seiji , Kusune Takayoshi , Mizuno Izumi , Dobashi Kazuhito , Shimoikura Tomomi , Taniguchi Kotomi
Published: September 2019

We report the first clear detection of the Zeeman splitting of a CCS emission line at 45 GHz toward the nearby pre-stellar dense filament, Taurus Molecular Cloud 1 (TMC-1). We observed HC$_3$N non-Zeeman lines simultaneously with the CCS line, and did not detect any significant splitting of the HC$_3$N lines. Thus, we conclude that our detection of CCS Zeeman splitting is robust. The derived line-of-sight magnetic field strength is about $117 \pm 21 \, \mu$G, which corresponds to a normalized mass-to-magnetic flux ratio of 2.2 if we adopt an inclination angle of 45$^\circ$. Thus, we conclude that the TMC-1 filament is magnetically supercritical. Recent radiative transfer calculations of the CCS and HC$_3$N lines along the line of sight suggest that the filament is collapsing with a speed of $\sim$0.6 km s$^{-1}$, which is comparable to three times the isothermal sound speed. This infall velocity appears to be consistent with the evolution of a gravitationally infalling core.
Efficacy and Safety of Extracorporeal Shockwave Therapy for Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis
Authors: Wang Ying-Chun , Huang Hsuan-Ti , Huang Peng-Ju , Liu Zi-Miao , Shih Chia-Lung
Published: September 2019

Objective

The objective of this study was to assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) for treatment of knee osteoarthritis (OA) using a systemic review and meta-analysis.

Methods

An extensive search of relevant articles from electronic databases Pubmed, Embase, and Cochrane Library from inception to March 2019 was conducted. The treatment outcomes (visual analog scale [VAS] and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) of the included articles were pooled to calculate effect sizes. The assessment of heterogeneity among articles was evaluated using I2. Statistical analyses were conducted using RevMan software.

Results

The results showed that the ESWT group had significant improvement in pain relief compared with the control group through 12 months based on WOMAC and VAS scores. Compared with the baseline level, the patients had significant improvement in pain relief at most follow-up points (one week to 12 months) based on WOMAC and VAS scores. The patients showed significant improvement in physical function at six- and 12-month follow-up when compared with the control group and for all follow-up (one to 12 months) when compared with the baseline level. Additionally, only minor complications were observed after ESWT treatment.

Conclusions

The use of ESWT for treatment of knee OA had a beneficial effect on pain relief and physical function improvement for up to 12 months, and only minor complications occurred after ESWT treatment. However, there remains a lack of clarity regarding the frequency and dosage levels of ESWT required to achieve the maximum improvement.
Enhanced Itch Intensity Is Associated with Less Efficient Descending Inhibition Processing for Itch But Not Pain Attenuation in Chronic Dermatology Patients
Authors: Granot Michal , Yakov Sarit , Ramon Michal
Published: September 2019

Objectives

The study aims were 1) to investigate the direction of mutual inhibitory pathways on itch intensity by utilizing conditioned pain modulation paradigms for pain and itch attenuation and 2) to explore whether itch severity is affected by the individual pain sensitivity profile, as well as pain scores reported during the tests and the past week.

Design

Cross-sectional.

Setting

Testing was conducted at the Department of Dermatology, Rambam Health Care Campus.

Subjects

Forty patients suffering from chronic skin disorders associated with itch and treated in the Dermatology Clinic at Rambam Health Care Campus participated in the study.

Methods

Efficacy of descending inhibition was evaluated by two conditioned pain modulation (CPM) paradigms: by pruriception (CPMItch) induced by cold and heat as counterstimuli to inhibit itch intensity and by nociception (CPMPain). Severity and interference of clinical pain were assessed using the Brief Pain Inventory (BPI).

Results

Robust CPMItch responses were obtained following the various noxious stimulations. No associations were observed between CPMPain and CPMItch, itch severity, skin disease severity, and clinical pain symptoms. According to the linear regression model, itch severity was independently associated with less efficient CPMItch (B = –0.750, P < 0.001) and more efficient CPMPain (B = 0.031, P = 0.016), which affects itch in opposing manners.

Conclusions

Findings indicate that the intrinsic capacity to inhibit pain and itch by exposure to exogenous noxious stimuli autonomously affects itch intensity in an opposing manner. These findings may shed new light on the mutual mechanistic similarity and dissimilarity between pain and itch and their hierarchy.