bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment Design for Accuracy of Scores, Meaningfulness of Interpretations, and Fairness of Decision-Making in High-Stakes Educational Testing
Authors: Ercikan Kadriye , Allalouf Avi
Published: September 2016

Testing is used in decision-making in a variety of contexts worldwide. These include selection and screening of individuals for education programs (including higher education admissions), certification and licensing of professionals, and policymaking in schools and higher education. The consequences of testing-for example, being denied admission to education programs or authorization to practice specific professions-affect individuals, organizations, and jurisdictions. In every testing context, questions arise about the degree to which a test provides accurate and meaningful information for fair decision-making. Also, the use of assessment has been the target of specific criticism, including claims that the high-stakes nature of tests leads to “teaching to the test,” thereby reducing schools’ and districts’ control over K-12 education curricula, and that higher education admission tests lack a focus on subject matter knowledge. This chapter discusses the main areas of criticism and recommends several assessment design requirements that address them.
Session 3: Problem Solving Around OCD
Authors: Peris Tara S. , Piacentini John
Published: September 2016

This chapter describes the third session of treatment, wherein families begin to identify specific problems on which they’d like to work. Using their initial treatment skills (praise, emotion monitoring, and self-soothing), they work together to identify shared goals to achieve and to prioritize them. The chapter describes strategies for teaching families to use functional analysis to understand their target problems, along with steps for practicing family problem solving in session. Scaffolding and making changes gradually is emphasized.
LGB-Parent Families and the School Context
Authors: Goldberg Abbie E.
Published: September 2016

Children are influenced by multiple contexts, including their families and schools. Research on children with lesbian, gay, and bisexual (LGB) parents has primarily focused on their experiences within their families, with little attention to experiences in the school context. The lack of research on the family–school interface of LGB parent families is troubling because these families are vulnerable to marginalization, exclusion, and stigma in the broader society, which likely extend to the school environment. This chapter reviews research on the academic achievement, social functioning, and bullying of children with LGB parents. When relevant, the author emphasizes race/ethnicity, social class, geographic location, and other key social locations that may shape the experiences of LGB–parent families, then addresses research on LGB parents themselves, including their experiences in selecting and interacting with their children’s schools. The chapter ends with recommendations for educators and practitioners who may encounter LGB parent families.
Inextricably Linked
Authors: Snapp Shannon , Russell Stephen T.
Published: September 2016

Evidence suggests that inclusive curriculum has positive implications for students’ learning, well-being, and safety. Types of inclusive curricula, namely ethnic studies and LGBTQ-inclusive curricula, however, are currently being contested in schools throughout the United States. Twenty-three key informants (e.g., teachers, school board members, school administrators, community activists) in Arizona and California shared their three primary reasons that an inclusive curricular and pedagogical approach to teaching is important: (a) students are reflected in their learning, (b) violence against others lessens and school becomes hospitable to learning, and (c) students’ learning improves due to greater academic engagement and connection. While many key informants saw ethnic studies and LGBTQ-inclusive curriculum as “inextricably linked,” several indicated that the two classes are viewed as separate and distinct. The need for curriculum that aligns with social justice and intersectionality frameworks as well as coalitional advocacy is discussed.
Sexual and Gender Minorities and Bullying in Japan
Authors: Kasai Makiko
Published: September 2016

Japan does not have a cultural history of strong stigma against homosexuality and gender nonconformity in the ways that are true in West, but there is growing evidence that homophobia and transphobia do exist. In this chapter, the history of LGBT issues in Japan is overviewed, focusing mainly on the experiences of gay men and lesbians. Lately, more LGBT-related research has focused on studies on persons with gender identity disorder (GID) due to the approval of gender reassignment surgery as a treatment for GID. Many studies showed that sexual minority youth reported suicidal wishes or behavior because of bullying experiences, feelings of isolation, physical dysphoria, or internal homophobia or transphobia. Moreover, most teachers reported that they did not include any material on LGBT issues in classroom, thus highlighting an urgent need to educate school teachers on these issues.
Advocacy to Support Gender Identity Development in Schools in the Face of Organized Backlash
Authors: Fischer David , Bellinger L. Boyd , Horn Stacey S. , Sullivan Shannon L.
Published: September 2016

Supporting transgender and gender-nonconforming children and adolescents represents a challenge to schools and districts that are not prepared to do so. While much of the conversation focuses on the need for anti-bullying and anti-harassment policies, often what is left out are the support and accommodations necessary that allow transgender and gender-nonconforming children and adolescents to thrive, such as gender-neutral bathrooms, record keeping, name and pronoun usage, and gender-segregated activities. This chapter explores the process used by one safe schools organization in the United States to advocate for inclusive policies and the backlash that ensued when an opposition group began organizing against the passage of the policies. A summary of the process for passing the policies and subsequent organizing efforts to protect the district employee who supported the policies, along with the policies themselves, leads to implications for future organizing efforts.
Enumerated U.S. State Laws
Authors: Russell Stephen T. , Horn Stacey S. , Moody Raymond L. , Fields Amanda , Tilley Elizabeth
Published: September 2016

There is strong recent evidence that enumerated anti-bullying and nondiscrimination policies are an important foundation for promoting school policies that support the well-being of LGBTQ and all students. To understand factors associated with the passage of US state laws that included sexual orientation and gender identity (SOGI) in status enumeration, the authors conducted interviews with 33 key informants who were involved in policy advocacy in states with different policy enumeration outcomes. In addition to questions about strategies used in policy advocacy, results illuminate specific effective strategies and the conditions for successful SOGI policy advocacy. Key themes related to SOGI policy advocacy across the states under consideration included the relevance and response to a state’s distinct legislative climate and history, avoidance of fiscal impact of proposed legislation, coordinated and consistent communication and messaging, and the relevance of distinct approaches to the organization, strategy, and leadership for policy advocacy.
History of Group Therapies for People With Psychosis
Authors: Lecomte Tania , Leclerc Claude , Wykes Til
Published: September 2016

Group interventions have been offered in institutionalized settings for many decades. This chapter reviews the changes in goals and purposes for group therapies over the years. The chapter presents the goals, results and at times pitfalls of various group approaches. For instance, the book covers the first psychoanalytical groups offered to people with severe mental illness, followed by artistic and psychodrama groups. The chapter presents how the 1950’s saw the mergence of milieu therapy, closely followed by encounter groups. Specifically addressing people with severe mental illness, Yalom, and later Kanas, developed their models of inpatient group therapy, that are presented here. Finally, the chapter reviews some group approaches still used today, namely skills training, cognitive skills groups, peer support groups and dual-diagnosis groups.
Testing Hypotheses and Looking for Alternatives (Sessions 7 to 12)
Authors: Lecomte Tania , Leclerc Claude , Wykes Til
Published: September 2016

In this chapter we highlight the CBT for psychosis techniques needed for the second part of the therapy. We offer concrete examples of how to present the CBT model and techniques in a group setting, using short movies and neutral examples, before tackling personal beliefs. Most techniques and activities start from the outside in, meaning that to avoid threatening participants, they first practice the concepts with fictional examples before attempting to apply them to themselves. The chapter takes each session of the second section of the workbook and explains in detail the purpose of each activity, how to conduct it, and gives clinical examples to illustrate participants’ reactions to these sessions.
Coping and Competence (Sessions 19 to 24)
Authors: Lecomte Tania , Leclerc Claude , Wykes Til
Published: September 2016

This chapter describes the last section of the workbook. It explores the adoption of new and useful coping strategies for different contexts. Coping is not only about making it through a stressful situation but also implies daily strategies that can help prevent more serious difficulties in the long run. The focus is also on preventing mental illness relapse by encouraging insight into one’s warning signs of relapse, concentrating on protective factors, and recognizing which coping strategies are most useful for which difficulties or symptoms. The chapter takes each session of the fourth section of the workbook and explains in detail the purpose of each activity, how to conduct it, and gives clinical examples to illustrate participants’ reactions to these sessions.
Obstacles to Group CBT for Psychosis
Authors: Lecomte Tania , Leclerc Claude , Wykes Til
Published: September 2016

Various obstacles can be encountered during group CBTp, either before the therapy, during the therapy, or even after the therapy. This chapter offers concrete examples of different obstacles that can be met as well as specific solutions for each obstacle. Some of these obstacles are setting-specific, such as lack of support from management or staff resistance to a new group, whereas some are more therapist-related (e.g., feeling incompetent, not getting along with the co-therapist). Regarding obstacles that are more client-related, we present a list of commonly encountered difficult or challenging participants in group CBT for psychosis and offer suggestions regarding how to best deal with them. This chapter essentially offers a plethora of solutions to common obstacles and challenges met when delivering group CBT for psychosis.
On extreme transient events from rotating black holes and their gravitational wave emission
Authors: van Putten Maurice H. P. M. , Della Valle Massimo
Published: September 2016

The super-luminous object ASASSN-15lh (SN2015L) is an extreme event with a total energy Erad ≃ 1.1 × 1052 erg in blackbody radiation on par with its kinetic energy Ek in ejecta and a late time plateau in the UV, which defies a nuclear origin. It likely presents a new explosion mechanism for hydrogen-deprived supernovae. With no radio emission and no H-rich environment, we propose to identify Erad with dissipation of a baryon-poor outflow in the optically thick remnant stellar envelope produced by a central engine. By negligible time-scales of light crossing and radiative cooling of the envelope, SN2015L's light curve closely tracks the evolution of this engine. We here model its light curve by the evolution of black hole spin during angular momentum loss in Alvén waves to matter at the Inner Most Stable Circular Orbit (ISCO). The duration is determined by σ = MT/M of the torus mass MT around the black hole of mass M: σ ∼ 10−7 and σ ∼ 10−2 for SN2015L and, respectively, a long GRB. The observed electromagnetic radiation herein represents a minor output of the rotational energy Erot of the black hole, while most is radiated unseen in gravitational radiation. This model explains the high-mass slow-spin binary progenitor of GWB150914, as the remnant of two CC-SNe in an intra-day binary of two massive stars. This model rigorously predicts a change in magnitude Δm ≃ 1.15 in the light curve post-peak, in agreement with the light curve of SN2015L with no fine-tuning.
Synchrotron masers and fast radio bursts
Authors: Ghisellini G.
Published: September 2016

Fast radio bursts, with a typical duration of 1 ms and 1 Jy flux density at gigahertz frequencies, have brightness temperatures exceeding 1033 K, requiring a coherent emission process. This can be achieved by bunching particles in volumes smaller than the typical wavelength, but this may be challenging. Maser emission is a possibility. Under certain conditions, the synchrotron-stimulated emission process can be more important than true absorption, and a synchrotron maser can be created. This occurs when the emitting electrons have a very narrow distribution of pitch angles and energies. This process overcomes the difficulties of having extremely dense bunches of particles and relaxes the light-crossing time limits, since there is no simple relation between the actual size of the source and the observed variability time-scale.
RZ Leonis Minoris bridging between ER Ursae Majoris-type dwarf nova and nova-like system
Authors: Kato Taichi , Ishioka Ryoko , Isogai Keisuke , Kimura Mariko , Imada Akira , Miller Ian , Masumoto Kazunari , Nishino Hirochika , Kojiguchi Naoto , Kawabata Miho , Sakai Daisuke , Sugiura Yuki , Furukawa Hisami , Yamamura Kenta , Kobayashi Hiroshi , Matsumoto Katsura , Wang Shiang-Yu , Chou Yi , Ngeow Chow-Choong , Chen Wen-Ping , Panwar Neelam , Lin Chi-Sheng , Hsiao Hsiang-Yao , Guo Jhen-Kuei , Lin Chien-Cheng , Omarov Chingis , Kusakin Anatoly , Krugov Maxim , Starkey Donn R. , Pavlenko Elena P. , Antonyuk Kirill A. , Sosnjvskij Aleksei A. , Antonyuk Oksana I. , Pit Nikolai V. , Baklanov Alex V. , Babina Julia V. , Itoh Hiroshi , Padovan Stefano , Akazawa Hidehiko , Kafka Stella , de Miguel Enrique , Pickard Roger D. , Kiyota Seiichiro , Shugarov Sergey Yu. , Chochol Drahomir , Krushevska Viktoriia , Sekeráš Matej , Pikalova Olga , Sabo Richard , Dubovsky Pavol A. , Kudzej Igor , Ulowetz Joseph , Dvorak Shawn , Stone Geoff , Tordai Tamás , Dubois Franky , Logie Ludwig , Rau Steve , Vanaverbeke Siegfried , Vanmunster Tonny , Oksanen Arto , Maeda Yutaka , Kasai Kiyoshi , Katysheva Natalia , Morelle Etienne , Neustroev Vitaly V. , Sjoberg George
Published: September 2016

We observed RZ LMi, which is renowned for its extremely short (∼19 d) supercycle and is a member of a small, unusual class of cataclysmic variables called ER UMa-type dwarf novae, in 2013 and 2016. In 2016, the supercycles of this object substantially lengthened in comparison to the previous measurements to 35, 32, and 60 d for three consecutive superoutbursts. We consider that the object virtually experienced a transition to the nova-like state (permanent superhumper). This observed behavior reproduced the prediction of the thermal-tidal instability model extremely well. We detected a precursor in the 2016 superoutburst and detected growing (stage A) superhumps with a mean period of 0.0602(1) d in 2016 and in 2013. Combined with the period of superhumps immediately after the superoutburst, the mass ratio is not as small as in WZ Sge-type dwarf novae, having orbital periods similar to RZ LMi. By using least absolute shrinkage and selection operator (Lasso) two-dimensional power spectra, we detected possible negative superhumps with a period of 0.05710(1) d. We estimated an orbital period of 0.05792 d, which suggests a mass ratio of 0.105(5). This relatively large mass ratio is even above that of ordinary SU UMa-type dwarf novae, and it is also possible that the exceptionally high mass-transfer rate in RZ LMi may be a result of a stripped secondary with an evolved core in a system evolving toward an AM CVn-type object.
Molecular diagnosis and immunotherapy
Authors: Sastre Joaquín , Sastre-Ibañez Marina
Published: September 2016

Purpose of review

To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy.

Recent findings

As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy.

Molecular diagnosis, when used with other tools and patients’ clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.
The Angle Labor Pain Questionnaire
Authors: Angle Pamela , Kurtz-Landy Christine , Djordjevic Jasmine , Barrett Jon , Kibbe Alanna , Sriparamananthan Saiena , Lee Yuna , Hamata Lydia , Kiss Alex
Published: September 2016

Objectives:

The Angle Labor Pain Questionnaire (A-LPQ) is a new, condition-specific, multidimensional psychometric instrument that measures the most important dimensions of women’s childbirth pain experiences using 5 subscales: The Enormity of the Pain, Fear/Anxiety, Uterine Contraction Pain, Birthing Pain, and Back Pain/Long Haul. This study assessed the A-LPQ’s test-retest reliability during early active labor without pain relief.

Methods:

Two versions of the A-LPQ were randomly administered to laboring women during 2 test sessions separated by a 20-minute window. Participants were of mixed parity, contracting ≥3 minutes apart, cervical dilation ≤6 cm, and without pain relief. Changes in pain were rated using the Patient Global Impression of Change Scale. Overall pain intensity and pain coping were rated using the Numeric Rating Scale (NRS) and the Verbal Rating Scale (VRS) and the Pain Mastery Scale (PMS) respectively. A-LPQ test-retest reliability (primary outcome), Cronbach’s α, and concurrent validity with NRS, VRS, and PMS scores were assessed (n=104). Responsiveness was assessed in 55 women who reported changes in pain.

Results:

A-LPQ summary and subscale scores demonstrated good test-retest reliability (ICCs, 0.96 to 0.89), trivial to moderate sensitivity to change, and high responsiveness to minimal changes in pain (0.85 to 1.50). Cronbach’s α for A-LPQ summary scores was excellent (0.94) and ranged from 0.72 to 0.94 for subscales. Concurrent validity was supported by moderate to strong correlations with NRS and VRS scores for overall pain intensity and PMS scores for pain coping.

Discussion:

Findings support A-LPQ use for assessing women’s childbirth pain experiences.
Systemic vasculitis and the gut
Authors: Hatemi Ibrahim , Hatemi Gulen , Çelik Aykut F.
Published: September 2016

Purpose of review

Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed.

Recent findings

Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohn's disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behçet's syndrome. Refractory gastrointestinal involvement in Behçet's syndrome can be treated with thalidomide and/or TNF-α antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab.

Gastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behçet's syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives.
Durable Response of Metastatic Squamous Cell Carcinoma of the Skin to Ipilimumab Immunotherapy
Authors: Day Fiona , Kumar Mahesh , Fenton Linda , Gedye Craig
Published: September 2016

A 72-year-old male patient was receiving second-line chemotherapy for metastatic squamous cell carcinoma of the skin (SCCS) when he was diagnosed with concurrent metastatic melanoma (BRAF
G469E mutant). Chemotherapy was ceased and he was treated with 4 cycles of ipilimumab immunotherapy. The patient experienced clinical benefit and durable remission in both malignancies and remains free of cancer progression 8 months after the last cycle of ipilimumab. Response of SCCS to ipilimumab has not been previously described, however this case and recent reports of pembrolizumab efficacy confirm the critical role of the immune system in SCCS pathogenesis and suggest further exploration of checkpoint immunotherapy for the treatment of this disease.
Determination of Colistin and Colistimethate Levels in Human Plasma and Urine by High-Performance Liquid Chromatography–Tandem Mass Spectrometry
Authors: Bihan Kevin , Lu Qin , Enjalbert Manon , Apparuit Maxime , Langeron Olivier , Rouby Jean-Jacques , Funck-Brentano Christian , Zahr Noël
Published: September 2016

Background:

Colistin is a polypeptide antibiotic from the polymyxin E group used for the treatment of infections caused by multidrug-resistant gram-negative bacteria. The main constituents, accounting for approximately 85% of this mixture, are colistin A (polymyxin E1) and colistin B (polymyxin E2). The aim of this study was to develop and validate new and fast methods of quantification of colistin A and B and its precursors [colistin methanesulfonate sodium (CMS) A and B] by ultraperformance liquid chromatography–tandem mass spectrometry in plasma and urine with short pretreatment and run times.

Methods:

Chromatography was performed on an Acquity UPLC-MS/MS system (WATERS) with a WATERS Acquity UPLC C18 column (4.6 × 150 mm, 3.5 μm particle size). The pretreatment of samples consists of precipitation and extraction into microcolumns plate and HLB 96-well plate 30 μm–30 mg (OASIS) with a Positive Pressure-96 (WATERS).

Results:

Quantification was performed using a multiple reaction monitoring of the following transitions: m/z 390.9 → 385.1 for colistin A, m/z 386.2 → 101.0 for colistin B, and m/z 602.4 → 241.1 for polymyxin B1 sulfate. In plasma and urine, calibration curves were linear from 30 to 6000 ng/mL for colistin A and from 15 to 3000 ng/mL for colistin B. With an acceptable accuracy and precision, the lower limit of quantification were set at 24.0 ng/mL and 12.0 ng/mL for colistin A and B in plasma, and at 18.0 ng/mL and 9.0 ng/mL for colistin A and B in urine.

Conclusions:

These LC-MS/MS methods of quantification for colistin A and B and its precursors (CMS A and B) in plasma and urine are fast, simple, specific, sensitive, accurate, precise, and reliable. Furthermore, they are linear and repeatable. These procedures were successfully applied to a pharmacokinetic study of a critically ill patient suffering from ventilator-associated pneumonia, who was treated with nebulized CMS.
FOVEAL HYPOPLASIA: DIAGNOSIS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Sánchez-Vicente José L. , Contreras-Díaz Miguel , Llerena-Manzorro Laura , Rueda Trinidad , López-Herrero Fernando , Molina-Socola Fredy E. , Muñoz-Morales Ana , Rodríguez de la Rúa-Franch Enrique
Published: September 2016

Purpose:

To describe the clinical presentations and image findings of a patient with foveal hypoplasia.

Methods:

Observational case report of one patient. The clinical presentation of the patient was documented by fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography.

Results:

A 55-year-old healthy white female with bilateral foveal hypoplasia without nystagmus was presented. There were no signs suggestive of ocular albinism. Absence of foveal depression was noted on both clinical examination and optical coherence tomography. Lack of foveal avascular zone was confirmed on fluorescein angiography and optical coherence tomography angiography.

Conclusion:

To the best of our knowledge this is the first report of findings in foveal hypoplasia examined by angio-optical coherence tomography. Optical coherence tomography angiography is an easy, rapid, and noninvasive tool that allows imaging of the retinal microvasculature without intravenous dye injection.
Selective Serotonin Reuptake Inhibitors and Operative Bleeding Risk
Authors: Roose Steven P. , Rutherford Bret R.
Published: September 2016

Objective

This study aimed to review the data on the effect of selective serotonin reuptake inhibitors (SSRIs) on bleeding during or after operative procedures and to offer guidelines for clinical management.

Data Sources

Search of PubMed and MEDLINE for all articles in English from 1990–2016 with key words depression, antidepressants, bleeding, platelets, and operation.

Study Selection

Studies were included if they reported information on bleeding complications during operative or childbirth procedures in patients taking antidepressants.

Data Extraction

Because of the limited number and heterogeneity of studies with respect to the range of operative procedures and definition of bleeding complications, a qualitative approach was taken to summarize results rather than abstracting and aggregating data.

Results

The weight of the evidence is that SSRI use increases the risk of bleeding complications during and immediately after surgery. However, given the limited data, we cannot estimate the risk for a given patient having a given procedure.

Conclusions

Clinicians must consider the risk-to-benefit ratio of discontinuing an SSRI before an elective operative procedure. Discontinuing SSRI medications may result in discontinuation syndrome, symptom recrudescence, or relapse of depression, whereas continuing an SSRI during surgery exposes patients to significant bleeding risks. Antidepressant prescribers must be cognizant of and take responsibility for discussing this potential problem and considering different options. This issue must also be the responsibility of the doctor performing the procedure, but, frequently, it will be the prescribing physician who alerts the surgeon to the potential bleeding risk associated with SSRIs.
Evaluation of the Relationship Between Pharmacokinetics and the Safety of Aripiprazole and Its Cardiovascular Effects in Healthy Volunteers
Authors: Belmonte Carmen , Ochoa Dolores , Román Manuel , Cabaleiro Teresa , Talegón Maria , Sánchez-Rojas Sergio Daniel , Abad-Santos Francisco
Published: September 2016

Aims

The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval.

Methods

The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Blood pressure was measured at the following times: predose and 0.5, 2, 4, 6, and 8 hours postdose. An electrocardiogram was recorded at predose, 4, and 8 hours postdose.

Results

Area under the curve (AUC), maximum plasma concentration, half-life, and distribution volume corrected for weight were higher in women. Aripiprazole treatment produced a decrease of BP (9.3 mm Hg on systolic and 6.2 mm Hg on diastolic pressure) and an increase in HR (12.1 beats per minute) and QTc interval (9.1 milliseconds). There were sex differences in BP, HR, and QTc interval. Women and subjects with higher AUC and maximum plasma concentration values were more prone to experience adverse drug reactions and gastrointestinal adverse reactions. The AUC was related with systolic BP and diastolic BP decrease and HR increase but there was no relationship between aripiprazole concentrations and QTc increase.

Conclusions

Aripiprazole decreases BP and increases HR and QTc interval. Pharmacokinetics, pharmacodynamics, and safety of aripiprazole are affected by sex. There is a directly proportional relationship between pharmacokinetic parameters and adverse drug reactions and effect on BP and HR.
Mesenteric Tumor Deposits in Midgut Small Intestinal Neuroendocrine Tumors Are a Stronger Indicator Than Lymph Node Metastasis for Liver Metastasis and Poor Prognosis
Authors: Fata Cynthia R. , Gonzalez Raul S. , Liu Eric , Cates Justin M. , Shi Chanjuan
Published: September 2016

Mesenteric tumor deposits (MTDs) are not included in the American Joint Committee on Cancer (AJCC) staging system for midgut small intestinal neuroendocrine tumors (NETs). We examined the prognostic significance of MTDs associated with midgut NETs. Hematoxylin and eosin slides from 132 resected jejunal/ileal NETs were reviewed for AJCC tumor stage, lymph node (LN) metastasis, MTDs, and hepatic metastases. MTDs were defined as discrete irregular mesenteric tumor nodules discontinuous from the primary tumor. Clinical or pathologic evidence of metastases and survival data were abstracted from electronic medical records. The cohort included 72 male and 60 female patients with a median age of 60 years. LN metastasis, MTDs, and liver metastasis were present in 80%, 68%, and 58% of patients, respectively. Female sex and presence of MTDs were independent predictors of liver metastasis. The odds ratio for hepatic metastasis in the presence of MTDs was 16.68 (95% confidence interval [CI], 4.66-59.73) and 0.81 (95% CI, 0.20-3.26) for LN metastasis. Age, MTDs, and hepatic metastasis were associated with disease-specific survival (DSS) in univariate analysis. Primary tumor histologic grade, pT3/T4 stage, and LN metastasis were not associated with DSS. Multivariate analysis of liver metastasis-free survival stratified by tumor grade showed that MTDs were associated with adverse outcomes. The hazard ratio for MTDs was 4.58 (95% CI, 1.89-11.11), compared with 0.98 (95% CI, 0.47-2.05) for LN metastasis. MTDs, but not LN metastasis, in midgut NETs are a strong predictor for hepatic metastasis and are associated with poor DSS.
Public Health Staff Development Needs in Informatics: Findings From a National Survey of Local Health Departments
Authors: Massoudi Barbara L. , Chester Kelley , Shah Gulzar H.
Published: September 2016

Context:

Public health practice is information-intensive and information-driven. Public health informatics is a nascent discipline, and most public health practitioners lack necessary skills in this area.

Objective:

To describe the staff development needs of local health departments (LHDs) related to informatics.

Design:

Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County & City Health Officials.

Participants:

A total of 324 LHDs from all 50 states completed the survey (response rate: 50%).

Main Outcome Measure(s):

Outcome measures included LHDs' specific staff development needs related to informatics. Predictors of interest included jurisdiction size and governance type.

Results:

Areas of workforce development and improvement in informatics staff of LHDs included using and interpreting quantitative data, designing and running reports from information systems, using and interpreting qualitative data, using statistical or other analytical software, project management, and using geographical information systems. Significant variation in informatics training needs exists depending on the size of the LHD population and governance type.

Conclusion:

Substantial training needs exist for LHDs across many areas of informatics ranging from very basic to specialized skills and are related to the size of LHD population and governance type.
Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn
Authors: Freede Margaret , Leasure A. Renee , Proskin Howard M. , Hatch Daniel , Edwards Karethy , Pascucci MaryAnn , Smith Patsy R.
Published: September 2016

This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.
Evaluation of a Self-Management Program for Gastroesophageal Reflux Disease in China
Authors: Xu Wenhong , Sun Changxian , Lin Zheng , Lin Lin , Wang Meifeng , Zhang Hongjie , Song Yulei
Published: September 2016

Gastroesophageal reflux disease is a chronic disease with a high incidence worldwide. The various symptoms have substantial impact on the quality of life of affected individuals. A long-term self-management program can increase the ability of patients to make behavioral changes, and health outcomes can improve as a consequence. This study's aim was to evaluate the effectiveness of a self-management program for gastroesophageal reflux disease. A total of 115 patients with gastroesophageal reflux disease were allocated to the experimental group and the control group. The former received self-management intervention along with conventional drug therapy, whereas the latter received standard outpatient care and conventional drug therapy. After the clinical trial, the control group also received the same self-management intervention. The levels of self-management behaviors, self-efficacy, gastroesophageal reflux disease symptoms, and psychological condition were compared. Those in the experimental group demonstrated significantly higher self-efficacy for managing their illness, showed positive changes in self-management behaviors, and had comparatively better remission of symptoms and improvement in psychological distress. The program helped patients with gastroesophageal reflux disease self-manage their illness as possible.
Methionine-mediated gene expression and characterization of the CmhR regulon in Streptococcus pneumoniae
Authors: Afzal Muhammad , Shafeeq Sulman , Kuipers Oscar P.
Published: September 2016

This study investigated the transcriptomic response of Streptococcus pneumoniae D39 to methionine. Transcriptome comparison of the S. pneumoniae D39 wild-type grown in chemically defined medium with 0–10 mM methionine revealed the elevated expression of various genes/operons involved in methionine synthesis and transport (fhs, folD, gshT, metA, metB-csd, metEF, metQ, tcyB, spd-0150, spd-0431 and spd-0618). Furthermore, β-galactosidase assays and quantitative RT-PCR studies demonstrated that the transcriptional regulator, CmhR (SPD-0588), acts as a transcriptional activator of the fhs, folD, metB-csd, metEF, metQ and spd-0431 genes. A putative regulatory site of CmhR was identified in the promoter region of CmhR-regulated genes and this CmhR site was further confirmed by promoter mutational experiments.
Case study: Paralog diverged features may help reduce off-target effects of drugs
Authors: Sa Zhining , Zhou Jingqi , Zou Yangyun , Gu Xun
Published: September 2016

Side effects from targeted drugs is a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and exhibit similar structures and drug-binding pockets. In this study, we analyzed amino acid residues with type-II functional divergence, i.e., sites that are conserved in sequence constraints but differ in physicochemical properties between paralogs, to identify targetable differences between two paralogs. We analyzed paralogous protein receptors in the glucagon-like subfamily, glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), which are clinically validated drug targets in patients with type 2 diabetes and exhibit divergence in ligands, showing opposing roles in regulating glucose homeostasis. We identified 8 residues related to type-II functional divergence, which are conserved in functional constraints but differ in physicochemical properties between GCGR and GLP-1R. We detected significant enrichment of predicted residues in binding sites of the antagonist MK-0893 to GCGR. We also identified a type-II functional divergence-related residue involved in ligand-specific effects that was critical for agonist-mediated activation of GLP-1R. We describe the important role of type-II functional divergence-related sites in paralog discrimination, enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.
Unique properties of Zika NS2B-NS3pro complexes as decoded by experiments and MD simulations
Authors: Roy Amrita , Lim Liangzhong , Srivastava Shagun , Song Jianxing
Published: September 2016

Zika virus can be passed from a pregnant woman to her fetus, thus leading to birth defects including more than microcephaly. It has been recently estimated that one-third of the world population will be infected by Zika, but unfortunately no vaccine or medicine is available so far. Zika NS2B-NS3pro is essential for its replication and thus represents an attractive target for drug discovery/design. Here we characterized conformation, catalysis, inhibition and dynamics of linked and unlinked Zika NS2B-NS3pro complexes by both experiments and MD simulations. The results unveil the unique properties of Zika NS2B-NS3pro which are very different from Dengue one. Particularly, CD and NMR studies indicate that unlike Dengue, the C-terminal region of Zika NS2B with a significant sequence variation is highly disordered in the open conformation. Indeed, MD simulations reveal that up to 100 ns, the Dengue NS2B C-terminus constantly has close contacts with its NS3pro domain. By a sharp contrast, the Zika NS2B C-terminus loses the contacts with its NS3pro domain after 10 ns, further forming a short β-sheet characteristic of the closed conformation at 30 ns. Furthermore, we found that a small molecule, previously identified as an active site inhibitor for other flaviviral NS2B-NS3pro, inhibited Zika NS2B-NS3pro potently in an allosteric manner. Our study provides the first insight into the dynamics of Zika NS2B-NS3pro and further deciphers that it is susceptible to allosteric inhibition, which thus bears critical implications for the future development of therapeutic allosteric inhibitors.
A Pif1-dependent threshold separates DNA double-strand breaks and telomeres
Authors: Strecker Jonathan , Durocher Daniel
Published: September 2016

The natural ends of chromosomes resemble DNA double-strand breaks (DSBs) and telomeres are therefore necessary to prevent recognition by the DNA damage response. The enzyme telomerase can also generate new telomeres at DSBs, resulting in the loss of genetic information distal to the break. How cells deal with different DNA ends is therefore an important decision. One critical point of regulation is to limit telomerase activity at DSBs and this is primarily accomplished in budding yeast by the telomerase inhibitor Pif1. Here we use Pif1 as a sensor to gain insight into the cellular decision at DSB ends with increasing telomeric character. We uncover a striking transition point in which 34 bp of telomeric (TG1-3)nrepeat sequence is sufficient to render a DNA end insensitive to Pif1, thereby facilitating extension by telomerase. This phenomenon is unlikely to be due to Pif1 modification and we propose that Cdc13 confers a unique property to the TG34end that prevents Pif1 action. We identify novel Cdc13 mutations that resensitize DNA ends to Pif1 and discover that many Cdc13 telomerase-null mutations are dependent on Pif1 status. Finally, the observed threshold of Pif1 activity recapitulates several properties of both DSBs and telomeres and we propose that this is the dividing line between these entities.
Complex precipitation phenomena in strip cast steels with high sulfur and copper contents
Authors: Dorin T. , Taylor A. , Wood K. , Wang J. , Hodgson P. D. , Stanford N.
Published: September 2016

A series of three steel alloys with increasing Cu and S concentrations has been prepared by simulated direct strip casting. It was found that the rapid solidification that occurs during direct strip casting results in the formation of a high number density of fine MnS precipitates, while Cu was retained in solid solution above equilibrium concentration. Upon ageing the MnS particles were found to coarsen and increase in volume fraction, indicating that some S was retained in solid solution in the as-cast condition. Ageing also resulted in the precipitation of Cu-rich precipitates. A new method to determine precipitate composition from small-angle neutron scattering is presented. This methodology, in conjunction with atom-probe tomography, has been used to show that the composition of the Cu-rich precipitates depends on the alloy's bulk Cu content.
ISOSUBGROUP: an internet tool for generating isotropy subgroups of crystallographic space groups
Authors: Stokes Harold T. , van Orden Seth , Campbell Branton J.
Published: September 2016

ISOSUBGROUP, the newest member of the ISOTROPY Software Suite (http://iso.byu.edu), generates isotropy subgroups of crystallographic space groups based on superpositions of multiple irreducible representations, along with a wealth of information about each one. Like the original ISOTROPY program, its scope is general rather than being restricted to common types of order parameters of a user-specified parent structure. But like the newer ISODISTORT program, its user-friendly interface has menu-driven selections. This combination of features has been oft requested but unavailable until now. Program output includes information about the subgroup symmetry, ferroic species, phase-transition continuity, active k vectors, domains and secondary order parameters.
Topological characterization of electron density, electrostatic potential and intermolecular interactions of 2-nitroimidazole: an experimental and theoretical study
Authors: Kalaiarasi Chinnasamy , Pavan Mysore S , Kumaradhas Poomani
Published: September 2016

An experimental charge density distribution of 2-nitroimidazole was determined from high-resolution X-ray diffraction and the Hansen–Coppens multipole model. The 2-nitroimidazole compound was crystallized and a high-angle X-ray diffraction intensity data set has been collected at low temperature (110 K). The structure was solved and further, an aspherical multipole model refinement was performed up to octapole level; the results were used to determine the structure, bond topological and electrostatic properties of the molecule. In the crystal, the molecule exhibits a planar structure and forms weak and strong intermolecular hydrogen-bonding interactions with the neighbouring molecules. The Hirshfeld surface of the molecule was plotted, which explores different types of intermolecular interactions and their strength. The topological analysis of electron density at the bond critical points (b.c.p.) of the molecule was performed, from that the electron density ρbcp(r) and the Laplacian of electron density ∇2ρbcp(r) at the b.c.p.s of the molecule have been determined; these parameters show the charge concentration/depletion of the nitroimidazole bonds in the crystal. The electrostatic parameters like atomic charges and the dipole moment of the molecule were calculated. The electrostatic potential surface of the molecule has been plotted, and it displays a large electronegative region around the nitro group. All the experimental results were compared with the corresponding theoretical calculations performed usingCRYSTAL09.
Mutual transformation between crystalline phases in silicon after treatment in a planetary mill: HRTEM studies
Authors: Kulnitskiy Boris , Annenkov Mikhail , Perezhogin Igor , Popov Mikhail , Ovsyannikov Danila , Blank Vladimir
Published: September 2016

High-resolution transmission electron microscopy (HRTEM) studies of silicon after treatment in a planetary mill have been performed. It is shown that along with the initial phase of silicon, Si-I, the sample also contains some high-pressure phases: Si-III (Kasper phase) and Si-IV (lonsdaleite). We studied the orientation relationship between the particles of different phases, finding that there are, in general, two mechanisms of formation of Si-IV: (1) through the stacking faults formation; (2) through the transformation first to the Kasper phase (Si-III), and then from the Kasper phase to Si-IV. Estimations of temperature and pressure conditions in the planetary ball mill made previously are in accordance with the conditions of formation of the above-mentioned phases.