bluuebunny/crossref_metadata_2025 huggingface dataset:
A single-arm study to evaluate skin tolerance, effectiveness and adherence to use of an alcohol-based hand rub solution among hospital nurses
Authors: Ripabelli Giancarlo , Tamburro Manuela , Guerrizio Giuliana , Fanelli Incoronata , Agnusdei Concetto Paolo , Sammarco Michela Lucia
Published: May 2019

Background:

Hand hygiene is considered as the most important strategy for preventing healthcare infections.

Objective:

In this single-arm study, skin tolerance, effectiveness and prolonged efficacy, and adherence to use an alcohol-based hand rub (ABHR) solution among hospital nurses was evaluated.

Methods:

Nurses were recruited in the main hospital of Molise Region, Central Italy. Skin reactions during 12-week follow-up were self-reported by nurses and, when occurring examined by hospital dermatologist. Samples were collected from palms and fingertips before and after ABHR, also at random times during work.

Results:

Dermatological reactions were not reported by 20 nurses (15 female and 5 male, aged 30–59 years) after product use. Microbial counts decreased by 99% (2Log10) in 75%, with higher reduction in palm than fingertips (99% vs 70% respectively). Analysis of six randomly collected samples after 10–20 and 30–40 min from the last use showed a satisfactory prolonged efficacy.

Discussion:

Beyond high effectiveness to reduce transient microbiota, no skin reactions were observed, likely due to the camomile, thyme and eucalyptus extracts contained within the gel. This study, addressing technical questions of a commercialised product, provides useful information for public health authorities faced with a choice of hand disinfectants, evaluating cost-effectiveness and cost-benefit in the light of the huge amount of these products needed at hospital level.
Current trends in the application of non-invasive genetic sampling to study Neotropical birds: Uses, goals, and conservation potential
Authors: Baus Isaura , Miño Carolina Isabel , Monge Otto
Published: May 2019

The non-invasive collection of biological samples has proven useful to study a diverse array of research topics worldwide. Here, we present a systematic bibliographical synthesis exploring how the non-invasive collection of genetic samples has been used to study avian populations in the Neotropics. We searched international online databases for scientific publications, spanning from 2007 to 2017, to describe the trends and identify the sample types used, species studied, and research questions addressed. The analysis of 21 articles showed that shed feathers were most frequently used (66.7% of articles), followed by carcasses (14.2%), eggs (9.5%), and non-invasively obtained blood (4.8%); one study used both feces and shed feathers. Most studies addressed population genetic issues (38.1%), followed by species identification (28.6%), phylogenetic questions (14.3%), molecular sexing (9.5%), and parentage analyses (9.5%). Brazil produced almost half (47.6%) of the publications retrieved. Despite an increasing interest in using non-invasive sampling to study Neotropical avifauna, its application is still largely concentrated in the most developed countries in this region and to explore a limited number of questions. A more regular use of non-invasive sampling would help advance the knowledge of ecological, behavioral, genetic, and evolutionary aspects of Neotropical birds. Investigating the extent of human–wildlife conflict, such as impact of road-kills, illegal traffic, and collision with aerial infrastructure or unmanned vehicles, is an underexplored avenue of research in which this method could be of much help. Non-invasive genetic sampling can help tackle conservation problems and pave the way to scientifically informed conservation policies in this avian biodiversity hotspot.
Malnutrition definitions in clinical practice: To be E43 or not to be?
Authors: Phillips Wendy , Doley Jennifer , Boi Kelli
Published: May 2019

Malnutrition is a disease that imposes a significant healthcare cost burden in the United States, especially when left undiagnosed and untreated for an extended period of time. This article discusses traditional malnutrition diagnostic criteria for adults and why registered dietitian nutritionists and physicians should no longer use these criteria to determine nutrition status. It concludes with the malnutrition clinical characteristics currently accepted in the United States and globally, with implications for practice. Clinical documentation specialists and medical coders can use this information to better interpret medical record documentation and assign the correct International Classification of Diseases, 10th Revision, Clinical Modification codes to the coding abstract.
Protests, Regulations, and Environmental Accountability in Cambodia
Authors: Young Sokphea
Published: May 2019

In the realm of global environmental governance, accountability has been key to the debate concerning pervasive environmental deterioration. Among the factors underlying this deterioration, a perceived challenge is the lack of clear mechanisms for identifying to whom the actors in environmental governance in general, and in other sectors, for example, hydropower, agricultural land, mining, and infrastructure in particular, are accountable to for their actions. To investigate the challenge of this situation, this article explores the ways in which the protest movements of grass-roots communities and non-governmental organizations endeavour to hold government and foreign corporations accountable for the actions they have taken which have contributed to environmental degradation in Cambodia. Drawing on two case studies, this article argues that these protest movements have played an increasing role in requiring environmental accountability from both government and corporations.
Naturally Occurring Homoisoflavonoids: Phytochemistry, Biological Activities, and Synthesis (Part II)
Authors: Abegaz Berhanu M , Kinfe Henok H
Published: May 2019

This review documents all the new homoisoflavonoids (HIFs) that have been reported since 2007, whose total number has grown from 159 in 2007 to 295 at the present time. This review contains their structures, biological sources, plant parts they are obtained from, and, if reported, their optical rotations and melting points. The same classification is followed as an earlier review to ease reference to both reviews. This review takes note of the recent revision of plant families that were known to contain HIFs that have now been merged into one big family, Asparagaceae. Homoisoflavonoids also occur in Fabaceae and others. Two taxa, Ophiopogoan japonicus (Asparagaceae) and Caesalpinia sappan (Fabaceae), have been the source of many HIFs. These are briefly summarized. The biological properties of HIFs are also reviewed under the topics such as antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and cytotoxic. The review also surveys the total synthesis of natural HIFs. All new compounds are classified and tabulated following the same style as the previous review.

Dedicated to Professor Andrew Paul Krapcho on the occasion of his 87th Birthday.
Structure of the SARS-Unique Domain C From the Bat Coronavirus HKU4
Authors: Staup Andrew J. , De Silva Ivon U. , Catt Justin T. , Tan Xuan , Hammond Robert G. , Johnson Margaret A.
Published: May 2019

Coronaviruses (CoVs) that cause infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome phylogenetically originate from bat CoVs. The coronaviral nonstructural protein 3 (nsp3) has been implicated in viral replication, polyprotein cleavage, and host immune interference. We report the structure of the C domain from the SARS-Unique Domain of bat CoV HKU4. The protein has a frataxin fold, consisting of 5 antiparallel β strands packed against 2 α helices. Bioinformatics analyses and nuclear magnetic resonance experiments were conducted to investigate the function of HKU4 C. The results showed that HKU4 C engages in protein-protein interactions with the nearby M domain of nsp3. The HKU4 C residues involved in protein-protein interactions are conserved in group 2c CoVs, indicating a conserved function.
NMR Methods to Characterize Protein-Ligand Interactions
Authors: Maity Sanhita , Gundampati Ravi Kumar , Suresh Kumar Thallapuranam Krishnaswamy
Published: May 2019

Structural information pertaining to the interactions between biological macromolecules and ligands is of potential significance for understanding of molecular mechanisms in key biological processes. Recently, nuclear magnetic resonance (NMR) spectroscopic techniques has come of age and has widened its scope to characterize binding interactions of small molecules with biological macromolecules especially, proteins. NMR spectroscopy-based techniques are versatile due to their ability to examine weak binding interactions and for rapid screening the binding affinities of ligands with proteins at atomic resolution. In this review, we provide a broad overview of some of the important NMR approaches to investigate interactions of small organic molecules with proteins.
Triterpenoid Saponins From the Root Bark of Haplocoelum congolanum
Authors: Pertuit David , Mitaine-Offer Anne-Claire , Miyamoto Tomofumi , Tanaka Chiaki , Tran Duy Khang , Delaude Clément , Lacaille-Dubois Marie-Aleth
Published: May 2019

Two undescribed triterpenoid saponins together with 5 known ones were isolated from the root bark of Haplocoelum congolanum Hauman. Their structures were elucidated by spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance experiments in combination with mass spectrometry as 3- O-(4- O-[3-hydroxy-3-methylglutaryl])-α-l-arabinopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyloleanolic acid and 3- O-α-l-arabinofuranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyloleanolic acid.
Child poverty in rich contexts: The example of Sweden
Authors: Andersson Bruck Kjerstin
Published: May 2019

In international comparisons, Sweden is one of the countries with the lowest number of children growing up in poverty; its material standard is high, and welfare services are extensive and heavily subsidised. How child poverty can be understood in that context is interrogated in the article. The point of departure for the discussion is Swedish Save the Children’s 2013 anti-poverty campaign Fattigskolan [Poverty School]. The campaign presents child poverty from the vantage point of a welfare state and is informative for understanding normative discourses on childhood. Childhood is investigated as a social imagination that both structures children’s and parents’ everyday lives and organises society. It is argued that the dominant social imagination is based on a middle-class fantasy permeating the organisation of the welfare state. The elements of this fantasy are critical to understanding child poverty.
Lung cancer screening patient–provider discussion: Where do we stand and what are the associated factors?
Authors: Chalian Hamid , Khoshpouri Pegah , Iranmanesh Arya M , Mammarappallil Joseph G , Assari Shervin
Published: May 2019

Objective:

The primary objective of this study was to estimate the percentage of individuals possibly eligible for lung cancer screening that report having discussed screening with a health care provider. The secondary objective was to investigate the associated factors of having patient–provider lung cancer screening discussion.

Methods:

Data from the Health Information National Trends Survey 2017 were used ( n = 3217). Lung cancer screening eligibility was based on the criteria utilized by the Centers for Medicare and Medicaid Services. Gender, race, educational attainment, health insurance coverage, and usual source of health care were covariates. Current or former smokers ages 55–77 ( n = 706) were considered potentially eligible for lung cancer screening (dependent variable).

Results:

Only 12.24% of individuals potentially eligible for lung cancer screening report prior discussion regarding lung cancer screening with a health care provider. Being eligible for lung cancer screening based on Centers for Medicare and Medicaid Services eligibility criteria was positively associated with the odds of a patient–provider lung cancer screening discussion (odds ratio = 3.95, 95% confidence interval = 2.48–6.30). Unlike gender, race, education, or insurance coverage, a usual source of health care was positively associated with a patient–provider screening discussion (odds ratio = 2.48, 95% confidence interval = 1.31–4.70).

Conclusion:

Individuals potentially eligible for lung cancer screening are more likely to have screening discussions with a health care provider. Having a usual source of health care may increase the odds of such a discussion, while patients are not discriminated based on race, gender, education, and insurance coverage. However, the relatively low rate (12.24%) of reported patient–provider lung cancer screening discussion indicates that significant barriers still remain.
An unusual case of complicated rhinosinusitis of the sphenoid sinus involving the cavernous sinus and skull base: Endoscopic sinus surgery and medical therapy
Authors: Fadda Gian Luca , D’Eramo Anna , Gned Dario , Succo Giovanni , Galizia Andrea , Cavallo Giovanni
Published: May 2019

Isolated sphenoid sinus diseases are generally asymptomatic and relatively uncommon with the potential for serious complications. Patients with this condition should be monitored closely and treated aggressively and either diagnostic or therapeutic intent is often indicated. In the management of a complex, life-threatening condition that involves many different fields of expertise, the otolaryngologist plays a key role in orchestrating different specialists and gaining direct access to the affected area, thus taking the first and essential step towards diagnosis and therapy. Because of the superiority of computed tomography in defining the bony margins and the superior soft tissue resolution of magnetic resonance imaging, these two techniques should be used in a complementary manner in the evaluation of isolated sphenoid sinus disease in addition to mapping the lesion better and identifying intracranial and intraorbital extent. We report an unusual case of isolated rhinosinusitis of the sphenoid sinus involving the cavernous sinus, pterygoid fossae and masticatory space in an immunocompetent patient.
School Counselors’ Roles and Responsibilities in Bullying Prevention: A National Survey
Authors: Swank Jacqueline M. , Smith-Adcock Sondra , Weaver Jo Lauren
Published: May 2019

We examined school counselors’ perceptions of their roles and responsibilities in addressing bullying. This study also investigated the prevalence of bullying prevention training, policies and laws, and various school problems. School counselors reported differences between their perceptions of their roles and responsibilities and what they believe are their principals’ expectations of school counselors. We discuss the results, implications for school counselors, and recommendations for research.
Life Choices of Emerging Adults in India
Authors: Mitra Deeya , Arnett Jeffrey Jensen
Published: May 2019

Emerging adulthood is marked by important decisions about life choices. These life choices have their roots in sociocultural and historical contexts. The present study used a mixed methodology, concept mapping, to understand the tasks that are deemed as important by emerging adults in India. Study 1 comprised five focus group discussions with individuals between 18 and 29 years ( N = 40, M age = 23) providing insights on the range of life choices. Study 2 ( N = 60, M age = 23) incorporated rating and sorting methodologies to derive cluster maps. Eight clusters emerged. In order of importance: responsibility toward family, independence/autonomy, financial security, education/career, parental expectations, romantic relationships, community and faith, and societal norms. Influences on decision-making of these life choices included self, others, circumstantial, and external. Findings have implications for adaptation to social change and overall well-being in emerging adulthood.
A novel method in assessing lower limb motor function
Authors: Khanfar Aws , Al Qaroot Bashar , Alsousi Ahmed , Zughoul Basheer , Al Elaumi Ahmad , Hamdan Mohammad , Safi Rami
Published: May 2019

Purpose:

To propose a novel, accurate, and easy to perform test replacing the manual muscle testing. Our target is to develop a valuable tool for identification of patients with neurological motor impairment precisely, rapidly, and easily.

Methods:

We have randomly selected patients presenting to the clinic complaining of back pain with or without lower limb symptoms. These patients were asked to walk on their heels and on their toes. Being unable to walk on heels and/or toes, the patient is considered to have positive test result (abnormal finding). After that, a full and thorough neurological examination was performed on every patient by an orthopedic resident doctor. We looked specifically to the correlation between the ability to do toe–heel walking with the results of the detailed neurological examination.

Results:

Toe–heel walking test was able to detect all patients with weakness in their lower limb musculature. The results from the current investigation indicate a very high Pearson correlation of 0.95 ( p = 0.001) between the toe–heel test and manual muscle testing.

Conclusion:

Toe–heel walking test is superior to detailed neurological examination in identification of patients with weakness, sphincter problem, and/or positive straight leg raising test. This test is both simple and rapidly performed test, which can be easily done by any health-care provider. Owing to its ease, this test is not restricted to medical doctors, but it could be accurately performed by any health-care provider such as nurses and physiotherapists. This will enable us to decrease the referral to the specialty clinic and to decrease the overall cost.
A Randomized Study of Passive versus Active PrEP Patient Navigation for a Heterogeneous Population at Risk for HIV in South Florida
Authors: Doblecki-Lewis Susanne , Butts Stefani , Botero Valeria , Klose Katherine , Cardenas Gabriel , Feaster Daniel
Published: May 2019

Effective approaches to promoting pre-exposure prophylaxis (PrEP) and linkage to PrEP care among those who may benefit the most from PrEP has proven to be a major challenge. We designed and pilot tested a strengths-based case management (SBCM) intervention for PrEP linkage. Adults interested in PrEP and meeting criteria (n = 61) were randomized to passive referral (control) or active SBCM (treatment). Outcomes measured were completion of provider visit, initiation of PrEP, and time to initiation of PrEP. Overall, 34% initiated PrEP by 12 weeks: 9 (29%) in the control group and 12 (40%) in the treatment group. The mean time to PrEP initiation was 13.1 weeks (95% confidence interval, 12.0-14.2) with no difference between groups ( P = .382). There was a 21% difference in achieving a provider visit between the treatment and control groups (53.3% versus 32.3%) by 12 weeks ( P = .096). Participants encountered financial, logistical, social, and provider-related barriers to PrEP access. Strengths-based case management–based patient navigation is a promising strategy for assisting PrEP seekers in obtaining a medical provider visit and initiating PrEP.
Progress and Challenges in “Getting to Zero” New HIV Infections in Miami, Florida
Authors: Escudero Daniel Javier , Bennett Brady , Suarez Sarah , Darrow William Ward , Mayer Kenneth Hugh , Seage George Richard
Published: May 2019

Objectives:

Miami has the highest rate of new HIV diagnoses in the United States. We examined the early successes and challenges in fulfilling recommendations made by the Miami-Dade County HIV/AIDS Getting to Zero Task Force, formed by local experts in 2016.

Methods:

We used a host of surveillance data, published empirical studies, public reports, and unpublished data from partners of the Task Force to evaluate progress and challenges in meeting the recommendations.

Results:

Improvements in prevention and care included routinized HIV testing in emergency departments, moving the linkage-to-care benchmark from 90 to 30 days, increased viral suppression, and awareness of pre-exposure prophylaxis. However, treatment enrollment, viral suppression, and pre-exposure prophylaxis uptake remained low.

Conclusions:

Recommendations from the Task Force provide excellent guidance for implementing evidence-based HIV prevention in Miami, yet success in achieving the recommendations will require continued or increased support in many public health sectors in South Florida.
Ventricular Ectopy and Arrhythmia Characteristics for Persons Living with HIV and Uninfected Controls
Authors: Meyer Alexander , Dandamudi Sanjay , Achenbach Chad , Lloyd-Jones Donald , Feinstein Matthew
Published: May 2019

Background:

Persons with HIV have elevated risk for cardiovascular disease, but little is known about the risk of ventricular ectopy and ventricular tachycardia (VE/VT) for HIV-infected (HIV+) persons.

Methods:

We evaluated the presence and anatomic origin of VE/VT for HIV+ persons and controls by screening a cohort using International Classification of Diseases codes and adjudicating positive screens by chart review. We sought to evaluate (1) presence of VE/VT and (2) likely anatomic origin of the VE/VT based on electrocardiogram.

Results:

There was no significant difference in the prevalence of VE/VT for HIV+ or uninfected persons. Among HIV+ persons, worse HIV control was associated with significantly greater odds of VE/VT. Exploratory analyses suggested that HIV+ persons may have a greater likelihood of VE/VT originating from the left ventricle.

Conclusion:

Although worse HIV control was associated with higher odds of VE/VT among persons with HIV, odds of VE/VT were not higher for persons with HIV than uninfected persons.
Demographic Engineering and Population Alteration in Iranian Kurdistan
Authors: Hassaniyan Allan
Published: May 2019

Studying the Iranian Kurdish question reveals the importance of the geopolitical location of the Kurdish region, which has left a massive impact on the framework and capability of the contemporary Kurdish national movement. Aware of this fact, different ruling regimes of Iran, considering territorial threats associated with the Kurdish nationalistic movement, implemented different policies of systematic “demographic engineering,” aimed at reducing the capability of the Kurdish claim for autonomy. Some aspects of the policy of demographic engineering implemented during the Safavid and the Pahlavi dynasties have been examined. Based on this, the article argues that the geopolitical location of the Kurdish region, as a buffer zone between the Ottoman and Safavid dynasties, has diminished and continues to undermine the capability of the Kurdish struggle for autonomy in Iran.
Exploring the Provider Preferences of Multiracial Patients
Authors: Snyder Cyndy R , Truitt Anjali R
Published: May 2019

Background:

Patient–provider race concordance has been argued as one way to improve patient–provider communication, patient satisfaction, and even patient outcomes. However, much of this literature focuses on or assumes that both patients and providers identify with only one race.

Objective:

The purpose of this study was to understand multiracial patients’ preferences in choosing a health-care provider.

Methods:

We conducted 15 interviews and 3 focus groups. We performed a directed content analysis to understand participants’ expressed preferences.

Results:

Thirty-one participants shared their health-care preferences. Participants described proximity to their homes or work, convenience in terms of availability, and health insurance coverage as reasons for selecting a provider. The majority articulated preferences related to provider gender and race. However, participants noted key barriers to receiving care from their preferred providers.

Conclusion:

This study highlights the preferences for health-care providers and the factors influencing those preferences and decisions among multiracial individuals. Findings illustrate the need to increase health workforce diversity, especially among primary care providers. Findings also show the need for increased empathy and cultural sensitivity among health-care professionals.
Clay mineral dating of displacement on the Sronlairig Fault: implications for Mesozoic and Cenozoic tectonic evolution in northern Scotland
Authors: Kemp Simon J. , Gillespie Martin R. , Leslie Graham A. , Zwingmann Horst , Campbell S. Diarmad G.
Published: May 2019

Temporary excavations during the construction of the Glendoe Hydro Scheme above Loch Ness in the Highlands of Scotland exposed a clay-rich fault gouge in Dalradian Supergroup psammite. The gouge coincides with the mapped trace of the subvertical Sronlairig Fault, a feature related in part to the Great Glen and Ericht–Laidon faults, which had been interpreted to result from brittle deformation during the Caledonian orogeny (c. 420–390 Ma). Exposure of this mica-rich gouge represented an exceptional opportunity to constrain the timing of the gouge-producing movement on the Sronlairig Fault using isotopic analysis to date the growth of authigenic (essentially synkinematic) clay mineralization. A series of fine-size separates was isolated prior to K–Ar analysis. Novel, capillary-encapsulated X-ray diffraction analysis was employed to ensure nearly perfect, random orientation and to facilitate the identification and quantification of mica polytypes. Coarser size fractions are composed of greater proportions of the 2M1 illite polytype. Finer size fractions show increasing proportions of the 1M illite polytype, with no evidence of 2M1 illite in the finest fractions. A series of Illite Age Analysis plots produced excellent R2 values with calculated mean ages of 296 ± 7 Ma (Late Carboniferous–Early Permian) for the oldest (2M1) illite and 145 ± 7 Ma (Late Jurassic–Early Cretaceous) for the youngest (1M) illite. The Late Carboniferous–Early Permian (Faulting event 1) age may represent resetting of earlier-formed micas or authigenesis during dextral displacement of the Great Glen Fault Zone (GGFZ). Contemporaneous WNW(NW)–ESE(SE) extension was important for basin development and hydrocarbon migration in the Pentland Firth and Moray Firth regions. The Late Jurassic–Early Cretaceous (Faulting event 2) age corresponds with Moray Firth Basin development and indicates that the GGFZ and related structures may have acted to partition the active extension in the Moray Firth region from relative inactivity in the Pentland Firth area at this time. These new age dates demonstrate the long-lived geological activity on the GGFZ, particularly so in post-Caledonian times where other isotopic evidence for younger tectonic overprints is lacking.
Evaluation of the efficacy of halloysite nanotubes in the removal of acidic and basic dyes from aqueous solution
Authors: Ngulube Tholiso , Gumbo Jabulani Ray , Masindi Vhahangwele , Maity Arjun
Published: May 2019

The present work describes the removal of Direct Red 81, Methyl Orange, Methylene Blue and Crystal Violet from aqueous solution using halloysite nanotubes. The clay mineral was physicochemically characterized using various methods. The influences of pH, interaction time, initial dye concentration, adsorbent amount and temperature on adsorption were monitored and interpreted. Although previous work has shown that acidic pH conditions favour the adsorption of pollutants from aqueous systems by clay materials, in this study maximum removal was possible over a wide range of pH conditions (pH ≥2–12). Adsorption was very rapid, and equilibrium was attained within 30 min. For all four dyes studied, chemical reaction seemed significant in the rate-controlling step, and the pseudo-second-order chemical reaction kinetics provided the best correlation of the experimental data. Thermodynamically, the process was spontaneous, with Gibbs energy decreasing with increasing temperature. Halloysite would be suitable for removing dyes from aqueous solution. This was further tested by using the halloysite nanotubes for the removal of complex dyes from printing and ink industry effluents.
Reliability of Violent Death Certification in One Coroner's District
Authors: Barraclough B. M.
Published: May 2019

Classifications given to self-inflicted deaths between 1959 and 1972 by a coroner and his deputy were compared for differences in the use of the suicide, accident, and open verdict definitions. The coroners varied in their use of the open verdict and the suicide verdict for poisoning cases but not for deaths from other causes.
The Evaluation of a Questionnaire Measuring Severity of Alcohol Dependence*
Authors: Hilton Margaret R. , Lokare V. G.
Published: May 2019

This paper is concerned with the evaluation of the Hilton Drinking Behaviour Questionnaire (HDBQ), which is based on the proposition that although there are wide variations in the types of problems caused by alcohol abuse there are certain symptoms which are generally considered to indicate ‘alcoholism’. Also that there is an identifiable pattern of symptom development in the acquisition of dependence.

The HDBQ proved to be a unidim.ensional scale which was valid and reliable as a m.easure of alcoholfsm, All items significantly discritninated between the alcoholic and control groups, and total scores correlated highly with those on the Alcadd test and with quantity-frequency measures of drinking. The theoretical and clinical implication of the results are discussed.
A Retrospective Study of Operationally Defined Hysterics
Authors: Almgren P.-E. , Nordgren L. , Skantze H.
Published: May 2019

A group of psychiatric patients were operationally defined as ‘hysterics’ by their reliance on the perceptual defence mechanism of repression, as disclosed in a valid psychological test. Most of them had dependency conflicts. Only half of them, almost exclusively female, had received the clinical diagnosis hysteria, the diagnosis being apparently founded on bodily complaints, overt aggression, and absence of depressive mood and anxiety. Lack of these characteristics in patients resorting to repression and with dependency conflicts results in diagnostic uncertainty. Clinical and test data justified the separation from operationally defined hysterics of three small subgroups: one with brain dysfunction, one with regressive psychosis, and one with non-regressive schizophrenia. Relevant diagnostic clues in the psychological tests and in the clinical picture are discussed.
The Predictability of Speech in Schizophrenic Patients
Authors: Rutter D. R. , Wishner J. , Kopytynska Hanka , Button Mary
Published: May 2019

Previous research has suggested that schizophrenic speech is less predictable than normal speech. Two experiments designed to test the suggestion are reported, both of them based on Cloze Procedure. In the first, raters were asked to predict ten passages of schizophrenic speech and ten passages of normal speech under fourth-word deletion. No difference between the two types of passage was found. In the second, a modified form of presentation was introduced which prevented raters making use of the text which follows a blank. Once again, no difference was revealed between the schizophrenic and normal passages, and this was true for both the new and traditional forms of presentation, and for both fourth-word and fifth-word deletion patterns. The investigation is discussed in the light of previous findings, and a number of suggestions concerning methodology and forms of analysis are made for future research.
The Relationship Between Korsakov's Syndrome and ‘Alcoholic Dementia’
Authors: Cutting John
Published: May 2019

Fifty cases of Korsakov's syndrome and 13 of ‘alcoholic dementia’ were identified from hospital records with the aim of examining the claim of each to be regarded as a clinical entity. Korsakov's syndrome, as diagnosed, was not homogeneous and comprised two groups. One resembled cases labelled as ‘alcoholic dementia’: the onset was gradual, the patients were older women with poorer intellectual functioning and there was a better outcome. The other group conformed to the conventional notion of Korsakov's syndrome, with preservation of intellect and a poor outcome. The combined group of gradual-onset cases and ‘alcoholic dementia’ was not entirely homogeneous. Within it were patients with ‘accelerated psychological deterioration’, others with Korsakov's syndrome superimposed on this pre-existing psychological deficit, and some with subacute confusional states.
Depression: Inside and Outside the Hospital Setting
Authors: Pilowsky I. , Spence N. D.
Published: May 2019

Twenty general practice patients selected for treatment with tricyclic antidepressants were matched with an equal number of psychiatric in-patients who had been admitted to hospital for depressive illnesses. In order to assess their depressive status, the Levine-Pilowsky (LPD) questionnaire was administered to both groups. It was found that although patients from each setting reported the same degree of depressive severity, the pattern of their LPD responses differed significantly. Twice as many hospital patients were assigned to either Class A (‘non-endogenous depression’) or Class B (‘endogenous depression) compared to the general practice patients, most of whom were classified as Class C (‘non depressed’). These results indicate the importance of distinguishing between depressive severity and depressive classification when comparing patients encountered outside the hospital setting with those who are in-patients.
The Extraverting Effect of Treatment in a Therapeutic Community for Drug Abusers
Authors: Wilson Stephen , Kennard David
Published: May 2019

Two measures of extraversion were administered routinely to a group of drug dependent offenders, on admission, after six months and after one year's treatment in a therapeutic community. On admission the sample was relatively introverted. During the treatment there was a progressive move towards extraversion, and after one year's residence there was a significant change in the direction of extraversion. It is suggested that this change constitutes an important factor in the success of this type of treatment.
An Adolescent Unit Assessed: A Consumer Survey
Authors: Wells P. G. , Morris A. , Jones R. M. , Allen D. J.
Published: May 2019

The paper describes the therapeutic programme of the Young People's Unit, Macclesfield. Admission is based on a therapeutic contract agreed with the youngster and family. Data on the first 150 admission to the Unit are presented. The information was collected from all referring agencies and a sample of youngsters and parents after an average period of two years since discharge. Results were similar to those of other follow-up studies of discharges from adolescent units, i.e. 78 per cent of neurotic disorders, 53 per cent of mixed neurotic and conduct disorders and 47 per cent of conduct disorders showed improvement. There was a high incidence of recurrence of the most significant presenting symptom (72 per cent). Nevertheless, referrers and youngsters showed a positive attitude to the treatment experience. The possible relationship of this to the contract system is discussed. A longer period of stay was found to correlate positively with improvement in conduct disorders. There is a need for further research into what aspects of a treatment milieu produce significant and lasting changes in conduct disorders.
SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx).
Authors: Rugo Hope S. , Im Seock-Ah , Wright Gail Lynn Shaw , Escriva-de-Romani Santiago , DeLaurentiis Michelino , Cortes Javier , Bahadur Shakeela Wazeen , Haley Barbara B. , Oyola Raul H. , Riseberg David A. , Musolino Antonino , Cardoso Fatima , Curigliano Giuseppe , Kaufman Peter A. , Pegram Mark D. , Edlich Sutton , Hong Sam , Rock Edwin P. , Gradishar William John
Published: May 2019

1000

Background: Pretreated HER2+ MBC lacks a defined standard of care, although T is commonly used. M has similar HER2 binding and antiproliferative effects as T. By contrast, M’s Fc region is engineered to increase affinity for both alleles of the activating Fc receptor (FcR), CD16A, and decrease affinity for the inhibitory FcR, CD32B. The low affinity CD16A-158F allele (~85% of population) has been associated with diminished clinical response to T. In a Phase 1 trial, M demonstrated acceptable safety, anti-tumor activity, and evidence of HER2-specific antibody and T-cell responses. Methods: SOPHIA (NCT02492711), a randomized, open-label P3 trial, enrolled pts with HER2+ MBC after pertuzumab and 1–3 lines of prior Tx for MBC. Pts were randomized 1:1 to M (15 mg/kg IV q3w + C) or T (6 [8 for loading dose] mg/kg IV q3w + C), stratified by met sites (≤2, > 2), lines of Tx for met disease (≤2, > 2), and C choice (standard dose capecitabine, eribulin, gemcitabine, or vinorelbine). Primary endpoints are central blinded PFS and OS, assessed sequentially using the stratified log-rank test. Objective response rate (ORR) was a secondary endpoint. 257 PFS events were required to provide 90% power to show PFS superiority at 2-sided α = 0.05. Results: Intent-to-treat analysis (536 pts: M 266; T 270) occurred after 265 PFS events. M prolonged PFS over T (median 5.8 vs 4.9 mo, hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P= 0.033). Treatment effects were more pronounced in pts with CD16A genotypes containing a 158F allele (median PFS 6.9 vs 5.1 mo, HR, 0.68; 95% CI, 0.52–0.90; P= 0.005). In 524 pts with baseline measurable disease (M 262; T 262), ORR was higher with M (22%; 95% CI, 17.3-27.7%) vs T (16%; 95% CI 11.8-21.0%). Safety profiles were comparable in 529 pts who received study therapy. Grade ≥3 AEs and serious AEs occurred in 138 (52%) and 39 (15%) vs 128 (48%) and 46 (17%) pts on M vs T, respectively. PFS data cutoff: 10/10/18. Conclusions: In combination with chemotherapy in pretreated HER2+ MBC, M improves PFS over T with comparable safety. CD16A genotyping suggests a differential benefit in patients with a 158F allele. OS data are maturing. Clinical trial information: NCT02492711.
Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia/lymphoma: Results of DFCI 11-001.
Authors: Vrooman Lynda M. , Blonquist Traci M. , Supko Jeffrey G. , Hunt Sarah K. , O'Brien Jane E. , Kay-Green Samantha , Athale Uma H. , Clavell Luis Antonio , Cole Peter D. , Harris Marian H. , Kelly Kara M. , Laverdiere Caroline , Leclerc Jean-Marie , Michon Bruno , Welch Jennifer JG , Stevenson Kristen E. , Neuberg Donna S. , Sallan Stephen E. , Silverman Lewis B.
Published: May 2019

10006

Background: DFCI ALL Consortium Protocol 11-001 assessed the efficacy and toxicity of Calaspargase pegol (SC-PEG), a novel pegylated asparaginase (ASP) formulation with longer half-life, compared with standard pegaspargase (SS-PEG). Methods: Patients (pts) aged 1-21 years with newly diagnosed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) were eligible. At study entry, pts were randomly assigned to receive either intravenous SS-PEG or SC-PEG, 2500 IU/m2/dose. Pts received 1 dose during the first treatment month. Beginning week 7, SS-PEG was administered every 2 weeks for 15 doses, SC-PEG every 3 weeks for 10 doses (30 weeks). Serum asparaginase activity (SAA) (considered therapeutic at ≥ 0.1 IU/mL) was assessed 4, 11, 18, and 25 days after the induction dose and before each post-induction dose. End-induction minimal residual disease (MRD) was assessed in ALL pts by IGH/TCR PCR. Results: Between 2012-2015, 239 eligible pts enrolled (230 ALL, 9 LL); 120 assigned to SS-PEG, 119 to SC-PEG. After dose 1, SAA remained ≥ 0.1 IU/mL in ≥ 95% of pts on both arms through day 18. Median SAA was higher (0.319 IU/mL vs 0.056 IU/mL) and more pts had therapeutic SAA (88% vs 17%, p˂0.001) with SC-PEG vs SS-PEG 25 days after dose 1. Post-induction, median nadir SAA (NSAA) were similar ( > 1.0 IU/mL) for both arms. There was no difference in rates of ASP-allergy, pancreatitis, thrombosis, hyperbilirubinemia, osteonecrosis, or infection. Of 230 evaluable pts, 99% of SS-PEG and 95% of SC-PEG pts achieved complete remission (p = 0.12). For B ALL pts, there was no difference in frequency of high end-induction MRD (10.3% SS-PEG, 9.5% SC-PEG, p = 1.0). With 4-year median follow-up, 4-year event-free survival (EFS) (90% confidence interval) for SS-PEG was 90.2% (84.3, 93.9), 87.7% (81.5, 91.9) for SC-PEG (p = 0.78); overall survival (OS) was 95.6% (91.0, 97.9) for SS-PEG, 94.8% (90.0, 97.3) for SC-PEG (p = 0.74). Conclusions: Every 3-week SC-PEG had similar EFS, OS, safety profile, and NSAA compared with every 2-week SS-PEG. The high NSAA observed for both preparations suggest dosing strategies can be further optimized. These data informed FDA approval of SC-PEG for pediatric pts. Clinical trial information: NCT01574274.
Phase 1/1B trial to assess the activity of entrectinib in children and adolescents with recurrent or refractory solid tumors including central nervous system (CNS) tumors.
Authors: Robinson Giles W. , Gajjar Amar J. , Gauvain Karen Marie , Basu Ellen M. , Macy Margaret E , Maese Luke Devon , Sabnis Amit J. , Foster Jennifer Haunani , Shusterman Suzanne , Yoon Janet , Weiss Brian D. , Abdelbaki Mohamed , Farid-Kapadia Mufiza , Meneses-Lorente Georgina , Cardenas Alison , Hutchinson Katherine , Bergthold Guillaume , Chow Maneval Edna , Fox Elizabeth , Desai Ami Vijay
Published: May 2019

10009

Background: Entrectinib is a CNS-penetrant oral inhibitor of TrkA/B/C, ROS1 and ALK tyrosine kinases. We report the efficacy of entrectinib in children with recurrent/refractory solid or CNS tumors. Methods: Patients ≤ 20y old with recurrent/refractory solid tumors were eligible. After determination of the recommended dose in all-comers, disease-specific expansion cohorts of CNS and solid tumors harboring target aberrations in NTRK1/2/3, ROS1 or ALK, and neuroblastoma (NBL), regardless of mutation spectrum, were enrolled. Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using RANO for CNS tumors, RECIST for solid tumors, and Curie score for NBL. Results: Between May 2016 and October 2018, 29 patients aged 4.9m–20y (median 7y) were enrolled and 28 were evaluated for response. Entrectinib was well tolerated. Dose limiting toxicities were elevated creatinine, dysgeusia, fatigue and pulmonary edema. The recommended dose was 550 mg/m2 daily. All responses occurred at doses ≥ 400 mg/m2. In CNS tumors (n = 6), all high-grade with gene fusions: 1 achieved a CR ( ETV6-NTRK3); 3 achieved a PR ( TPR-NTRK1, EEF1G-ROS1, EML1-NTRK2); 1 achieved an unconfirmed PR ( GOPC-ROS1); and 1 has yet to be evaluated ( KANK1-NTRK2). In extracranial solid tumors (n = 8), 6 had a fusion of whom 1 achieved a CR ( DCTN1-ALK) and 5 achieved a PR ( TFG1-ROS1, EML4-NTRK3, ETV6-NTRK3, KIF5B-ALK, ETV6-NTRK3). In NBL (n = 15): 1 achieved a CR ( ALK F1174L). Median duration of therapy was 85d (6–592d) for all patients; 56d (6–338d) for non-responders; and 281d (56–592d) for responders. Median time to response was 57d (30–58d). Conclusions: Entrectinib produced striking, rapid and durable responses in all children with refractory CNS and solid tumors harboring NTRK1/2/3, ROS1 or ALK fusions (11 out of 11) as well as in an ALK-mutated NBL. No responses were seen in tumors lacking aberrations in target kinases. These results support the continued evaluation of entrectinib as a targeted therapeutic in solid tumors with NTRK1/2/3, ROS1 and ALK fusions, especially in high-grade CNS neoplasms. Clinical trial information: NCT02650401.
Larotrectinib efficacy and safety in pediatric TRK fusion cancer patients.
Authors: van Tilburg Cornelis Martinus , DuBois Steven G. , Albert Catherine Michelle , Federman Noah , Nagasubramanian Ramamoorthy , Geoerger Birgit , Orbach Daniel , Bielack Stefan S. , Shukla Neerav Narendra , Turpin Brian , Casanova Michela , Spunt Sheri L. , Qamoos Hope , Nanda Shivani , Childs Barrett H. , Cox Michael Craig , Pappo Alberto S. , Laetsch Theodore Willis , Mascarenhas Leo
Published: May 2019

10010

Background: TRK fusions involving NTRK1, NTRK2, and NTRK3 genes have been identified in a broad range of pediatric and adult malignancies. Larotrectinib, a highly-selective oral TRK inhibitor, was well tolerated and showed encouraging antitumor activity in 17 pediatric patients (pts) with TRK fusion cancer (Laetsch et al, Lancet Oncol 2018). Here, we present data on the clinical efficacy and safety of larotrectinib in 38 pediatric pts with TRK fusion cancer from an expanded dataset. Methods: Pediatric pts enrolled in two larotrectinib clinical trials (NCT02637687, NCT02576431) with TRK fusion cancer detected by local testing were included; pts with primary CNS tumors were excluded from this report. Larotrectinib was administered until complete surgical resection, disease progression, withdrawal, or unacceptable toxicity. Disease status was investigator-assessed using RECIST v1.1. Data cutoff: July 30, 2018. Results: As of July 30, 2018, 38 children and adolescents < 18 y with TRK fusion cancer were enrolled. Median age was 2.3 y (range 0.1–14.0); 14 (37%) were < 1 y. 18 (47%) had infantile fibrosarcoma, 15 (39%) other soft tissue sarcoma, 2 (5%) thyroid cancer and 1 (3%) each had gastrointestinal stromal tumor, melanoma, or mesoblastic nephroma. TRK fusions involved NTRK1, 2, and 3 in 18 (47%), 2 (5%), and 18 (47%) pts, respectively. Half of the pts had metastatic disease and half locally advanced disease at entry. 26 pts (68%) had received prior systemic therapy (median lines: 1 [range 0–4]) and 6 were treatment-naïve. In 34 evaluable pts, the overall response rate was 94%: 12 CRs, 18 confirmed PRs, and 2 PRs pending confirmation; 2 had stable disease. Median duration of response had not been reached (range 1.6+ to 26.7+ months); 84% > 1 y. At data cutoff, 28 pts (74%) remained on treatment; 4 pts discontinued due to complete surgical resection and 4 due to disease progression while on therapy, 2 of whom initially responded (PR). Adverse events were mostly grade 1–2. Conclusions: Larotrectinib treatment resulted in a high and durable response rate in pediatric pts with TRK fusion cancer together with a favorable safety profile. Routine testing for NTRK gene fusions in pediatric cancer pts is recommended in the appropriate clinical context. Clinical trial information: NCT02637687 and NCT02576431.