bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of a Commercially Sexually Abused Girl Using Trauma-Focused Cognitive Behavioral Therapy and Legal Interventions
Authors: Kenny Maureen C. , Helpingstine Claire E. , Weber Maya
Published: September 2018

This case study describes the use of trauma-focused cognitive behavioral therapy (TF-CBT) and legal interventions for a 16-year-old girl who was the victim of commercial sexual exploitation (CSE) and suffered from substance abuse, anxiety, and body image issues. Over the course of 1 year, the client was able to discontinue involvement in sexual exploitation, cease substance use, decrease her anxiety level, improve her self-concept, and reduce posttrauma symptoms. The case calls attention to the need for extended rapport building, flexibility in treatment, and tailoring manualized treatments. It highlights the path to CSE for one teenager as well as the resultant emotional and behavioral consequences. Given the extensive nature of her past traumas, case management was continued following the clients’ discharge from treatment to support her adjustment. These follow-up sessions were conducted about once a month and assisted with maintenance of treatment goals.
To What Extent Are Title V Grants and Educational Expenditures Associated With Educational Attainment of Latinxs at Hispanic-Serving Institutions?
Authors: Perez Ligia
Published: September 2018

Employing the institutional action framework, this study finds that Title V grants and expenditures in academic support and student services at 4-year Hispanic-Serving Institutions (HSI) are positively associated with educational attainment of Latinxs. Future research should investigate HSIs expenditures in instruction and their association with academic achievement. HSIs must strengthen their advocacy for Latinx students and pressure policy leaders for continued funding to reinforce their role in the educational attainment of Latinxs.
Relationship between GSTP1 rs1695 gene polymorphism and myelosuppression induced by platinum-based drugs: a meta-analysis
Authors: Lv Fei , Ma Yanju , Zhang Ye , Li Zhi
Published: September 2018

Although many previous studies have reported the relationship between GSTP1 rs1695 gene polymorphism and myelosuppression induced by platinum-based drugs, the conclusions are not consistent. The aim of the study is to evaluate the association between granulocytopenia and thrombocytopenia induced by platinum-based drugs and GSTP1 rs1695 gene polymorphism by meta-analysis. A literature search was performed using the Pubmed, Embase, CNKI, and Wanfang databases, and the odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the correlation. Finally,12 case-control studies comprising 1657 patients were included in our study. GSTP1 rs1695 gene polymorphism showed a significant correlation with granulocytopenia induced by platinum-based drugs (dominant genetic model: OR=1.60, 95% CI=1.19. 2.15, P=0.002; recessive genetic model: OR=3.72, 95% CI=1.73, 8.00, P=0.001; allelic genetic model: OR=1.76, 95% CI=1.34, 2.33, P=0.001). This gene polymorphism is not associated with thrombocytopenia (OR=0.87, 95% CI=0.47, 1.60, P=0.649). False-positive report probability showed that the association between polymorphism and adverse reactions is true. Sensitivity analysis showed that the results were stable. However, there was a certain publication bias in the included studies. In conclusion, the GSTP1 rs1695 gene polymorphism is associated with granulocytopenia induced by platinum-based drugs.
Usability of theophylline extended-release dry syrups
Authors: Chono Sumio , Ishikawa Shiori , Ikeda Akari , Togami Kohei
Published: September 2018

Objectives

We examined the usability of theophylline extended-release dry syrups, including their powder fluidity and ingestibility using one branded and six generic formulations (formulations A, B, C, D, E, F, and G, respectively).

Methods

To evaluate the ease of handling by pharmacists, powder fluidity was evaluated by measuring the repose angle, whereas to determine ingestibility, the viewpoints of patients or caregivers were evaluated using a questionnaire survey. Results and discussion: The repose angles of formulations A, B, C, D, E, and F were approximately 30°–40°. These formulations had sufficient powder fluidity, indicating the ease of weighing for most pharmacists. However, the repose angle of formulation G was <30°. Formulation G had high fluidity, suggesting its high rolling property. Thus, powder handling for formulation G may be more difficult than that for other six formulations. The ingestibility, such as the ease of mixing the dry syrup with water and odor intensity, was different between the formulations.

Conclusions

The present study provides useful information for selecting branded or generic theophylline extended-release dry syrups.
The ‘Necessity–Concerns Framework’ as a means of understanding non-adherence by applying polynomial regression in three chronic conditions
Authors: West Lorna M , Borg Theuma Ruth , Cordina Maria
Published: September 2018

Objective

The ‘Necessity–Concerns Framework’ is an important framework which can support healthcare professionals in targeting patients’ medication beliefs and decisions on adherence. Our aim was to determine how the interdependence of ‘necessity’ and ‘concerns’ beliefs for medication adherence compares across three chronic conditions.

Methods

Patients diagnosed with asthma, cardiovascular conditions or diabetes attending out-patient clinics completed a self-administered questionnaire. The questionnaire gathered information regarding demographics, medication adherence using the ‘Tool for Adherence Behaviour Screening’, presence of unused medication in households and medication beliefs using the ‘Beliefs about Medicines Questionnaire-Specific’. Polynomial regression was applied to determine the multidimensional interdependence of ‘necessity’ and ‘concerns’ beliefs for adherence. P-values ≤ 0.05 were taken to be significant.

Results

Confirmatory polynomial regression rejected the differential score model in all three groups. For each condition, exploratory polynomial regression found that linear terms indicated the best fitting model for predicting adherence. In all groups, adherence increased as necessity beliefs increased and concerns decreased. Patients suffering from cardiovascular conditions and diabetes with low necessity and low concerns beliefs reported higher medication adherence compared to those with high necessity and high concerns beliefs.

Discussion

Alleviating patients’ concerns can enhance medication adherence and potentially curb the issue of medication wastage.
When and how NK cell-induced programmed cell death benefits immunological protection against intracellular pathogen infection
Authors: Belizário José E , Neyra Jennifer M , Setúbal Destro Rodrigues Maria Fernanda
Published: September 2018

NK cells are innate lymphoid cells that exert a key role in immune surveillance through the recognition and elimination of transformed cells and viral, bacterial, and protozoan pathogen-infected cells without prior sensitization. Elucidating when and how NK cell-induced intracellular microbial cell death functions in the resolution of infection and host inflammation has been an important topic of investigation. NK cell activation requires the engagement of specific activating, co-stimulatory, and inhibitory receptors which control positively and negatively their differentiation, memory, and exhaustion. NK cells secrete diverse cytokines, including IFN-γ, TNF-α/β, CD95/FasL, and TRAIL, as well as cytoplasmic cytotoxic granules containing perforin, granulysin, and granzymes A and B. Paradoxically, NK cells also kill other immune cells like macrophages, dendritic cells, and hyper-activated T cells, thus turning off self-immune reactions. Here we first provide an overview of NK cell biology, and then we describe and discuss the life–death signals that connect the microbial pathogen sensors to the inflammasomes and finally to cell death signaling pathways. We focus on caspase-mediated cell death by apoptosis and pro-inflammatory and non-caspase-mediated cell death by necroptosis, as well as inflammasome- and caspase-mediated pyroptosis.
Matrine induces apoptosis via targeting CCR7 and enhances the effect of anticancer drugs in non-small cell lung cancer in vitro
Authors: Pu Jiangtao , Tang Xiaojun , Zhuang Xiang , Hu Zhi , He Kaiming , Wu Yunfei , Dai Tianyang
Published: September 2018

This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells. The results were further validated in LK2 cells that matrine regulated apoptosis gene expressions, which were reversed by CCL21 treatment. Furthermore, matrine enhances the effects of cisplatin, 5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced the effects of anticancer drugs in NSCLC cells; the mechanism might be associated with the CCR7 signal.
Deploying unqualified personnel in health records practice: Role substitution or quackery? Implications for health services delivery in Nigeria
Authors: Adeleke Ibrahim Taiwo , Suleiman-Abdul Qudrotullaah Bolanle , Aliyu Amina , Ishaq Ismaeel A , Adio Razzaq A
Published: September 2018

Healthcare professionals are obliged to work collaboratively regardless of their professional differences in order to provide the highest possible standard of care to patients. However, this type of collaboration can also lead to role substitution and, in effect, engagement of unqualified personnel in all health professions, including the health information management profession. This is a particular problem in developing nations such as Nigeria, where this trend has the potential to undermine the delivery of health services, the quality and the confidentiality of health information and trust between patients and healthcare professionals. To clarify and protect the professional identity of qualified health information management professionals in Nigeria and to prevent other experts who also work in health facilities (e.g. IT specialists, librarians) from claiming membership of the profession, the nomenclature for the health information management profession has been changed to health records and information management profession.
False Memories and True Memories of Childhood Trauma: Balancing the Risks
Authors: Goodman Gail S. , Gonzalves Lauren , Wolpe Samara
Published: September 2018

How often do clinical psychologists discuss with their adult clients the possibility that the clients might have been abused as children but had repressed the memory? If during the course of therapy clients remember being abused as children when the clients had no previous memories of such abuse, how likely is it that the memories are false? These questions underlie Patihis and Pendergrast’s Mechanical Turk survey study (this issue, p. 3). We discuss relevant scientific findings, including from longitudinal research on adults who as children experienced documented child maltreatment. We question inferences and generalizations resulting from the methodology Patihis and Pendergrast employed. We argue that clinicians are often justified in asking about past child abuse, remembered and forgotten, and that clinicians and researchers should strive to balance the risk of adults forming false memories with the need for adults to overcome childhood trauma.
Attention Bias in Rumination and Depression: Cognitive Mechanisms and Brain Networks
Authors: Kaiser Roselinde H. , Snyder Hannah R. , Goer Franziska , Clegg Rachel , Ironside Manon , Pizzagalli Diego A.
Published: September 2018

Depressed individuals exhibit biased attention to negative emotional information. However, much remains unknown about (a) the neurocognitive mechanisms of attention bias (e.g., qualities of negative information that evoke attention bias or functional brain network dynamics that may reflect a propensity for biased attention) and (b) distinctions in the types of attention bias related to different dimensions of depression (e.g., ruminative depression). Here, in 50 women, clinical depression was associated with facilitated processing of negative information only when such information was self-descriptive and task-relevant. However, among depressed individuals, trait rumination was associated with biases toward negative self-descriptive information regardless of task goals, especially when negative self-descriptive material was paired with self-referential images that should be ignored. Attention biases in ruminative depression were mediated by dynamic variability in frontoinsular resting-state functional connectivity. These findings highlight potential cognitive and functional network mechanisms of attention bias specifically related to the ruminative dimension of depression.
In vitro and in vivo assessment of biomedical Mg–Ca alloys for bone implant applications
Authors: Makkar Preeti , Sarkar Swapan Kumar , Padalhin Andrew R. , Moon Byoung-Gi , Lee Young Seon , Lee Byong Taek
Published: September 2018

Background:

Magnesium (Mg)-based alloys are considered to be promising materials for implant application due to their excellent biocompatibility, biodegradability, and mechanical properties close to bone. However, low corrosion resistance and fast degradation are limiting their application. Mg–Ca alloys have huge potential owing to a similar density to bone, good corrosion resistance, and as Mg is essential for Ca incorporation into bone. The objective of the present work is to determine the in vitro degradation and in vivo performance of binary Mg– xCa alloy ( x = 0.5 or 5.0 wt%) to assess its usability for degradable implant applications.

Methods:

Microstructural evolutions for Mg– xCa alloys were characterized by optical, SEM, EDX, and XRD. In vitro degradation tests were conducted via immersion test in phosphate buffer saline solution. In vivo performance in terms of interface, biocompatibility, and biodegradability of Mg– xCa alloys was examined by implanting samples into rabbit femoral condyle for 2 and 4 weeks.

Results:

Microstructural results showed the enhancement in intermetallic Mg2Ca phase with increase in Ca content. Immersion tests revealed that the dissolution rate varies linearly, with Ca content exhibiting more hydrogen gas evolution, increased pH, and higher degradation for Mg–5.0Ca alloy. In vivo studies showed good biocompatibility with enhanced bone formation for Mg–0.5Ca after 4 weeks of implantation compared with Mg–5.0Ca alloy. Higher initial corrosion rate with prolonged inflammation and rapid degradation was noticed in Mg–5.0Ca compared with Mg–0.5Ca alloy.

Conclusions:

The results suggest that Mg–0.5Ca alloy could be used as a temporary biodegradable implant material for clinical applications owing to its controlled in vivo degradation, reduced inflammation, and high bone-formation capability.
Load transfer of nanocomposite film on aluminum substrate
Authors: Her Shiuh-Chuan , Chien Pao-Chu
Published: September 2018

Introduction:

Nanocomposite films have attracted much attention in recent years. Depending on the composition of the film and fabrication method, a large range of applications has been employed for nanocomposite films.

Method:

In this study, nanocomposite films reinforced with multi-walled carbon nanotubes (MWCNTs) were deposited on the aluminum substrate through hot press processing. A shear lag model and Euler beam theory were employed to evaluate the stress distribution and load carrying capability of the nanocomposite film subjected to tensile load and bending moment.

Results:

The influence of MWCNT on the Young’s modulus and load carrying capability of the nanocomposite film was investigated through a parametric study. The theoretical predictions were verified by comparison with experimental tests. A close agreement with difference less than 6% was achieved between the theoretical prediction and experimental measurements.

Conclusions:

The Young’s modulus and load transfer of the nanocomposite film reinforced with MWCNTs increases with the increase of the MWCNT loading. Compared to the neat epoxy film, nanocomposite film with 1 wt % of MWCNT exhibits an increase of 20% in both the Young’s modulus and load carrying capability.
Mix design of asphalt mixture used for the waterproof and anti-cracking layer in the rainy area of South China
Authors: Liu Fuming , Dong Aixia , Liu Chaoqun , Wu Wenqing
Published: September 2018

Introduction:

In this study, the asphalt mixture (porosity <2%) was tested for use between the upper and middle layers of the asphalt pavement to improve its interlayer structure and to enhance its related waterproof and anti-cracking ability.

Methods:

Considering the weather characteristics and traffic conditions in Jiangxi Province, appropriate raw materials were selected. Based on the technical indexes of the raw materials, expected porosity (<2%), and AC-5 standard for the asphalt mixture, experiments were conducted to determine the best gradation range of the waterproof and anti-cracking layer, and to obtain the optimum amount of the asphalt and fiber used based on Marshall tests.

Results:

The high-temperature rutting test, low-temperature cracking test, and water stability test were conducted to evaluate the pavement performance of the waterproof and anti-cracking layer.

Conclusions:

A waterproof and anti-cracking layer was added between the upper and middle layers of the asphalt pavement, which has excellent performance for avoiding cracks and water damage.
The influence of Ca substitution on LaFeO3 nanoparticles in terms of structural and magnetic properties
Authors: Lin Qing , Xu Jianmei , Yang Fang , Yang Xingxing , He Yun
Published: September 2018

Background:

The nanocrystalline structure of La1 -xCa xFeO3 was prepared by a sol–gel method involving an auto-combustion process. The incorporation of rare-earths in LaFeO3 induces strain in magnetic properties, especially in terms of the following parameters: replacement amount, oxygen partial pressure, and calcination temperature.

Methods:

To determine the effects of the amount of Ca2+ ion doping agent and the calcination temperature on the microstructure, particle morphology, and magnetic properties of LaFeO3 crystal, we performed the following respective analytical methods: X-ray powder diffraction, Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy, and vibrating sample magnetometer tests.

Results:

The orthorhombic structure of LaFeO3 perovskite did not change even when it was doped with Ca2+ ions, and its space group continued to be Pnma (No.62). FT-IR spectra confirmed that the main band appearing at 568 cm−1 is due to the antisymmetric stretching vibration of Fe–O–Fe bonds in FeO6. The introduction of Ca inhibits the growth of grains but the morphology of particles is improved. With an increasing concentration of Ca2+ ions, magnetic behavior of the samples also witnessed an increasing trend in a proportionate manner. With an increase in calcination temperature, the enclosed area of the magnetic hysteresis curve of the sample reduced remarkably.

Conclusions:

The growth of nanoparticles can be restrained with an increase of Ca content that is used as doping agent. The magnetic behavior of La1 -xCa xFeO3 tilts towards G-type antiferromagnetism; the magnetic orientation is achieved from the super exchange interaction of Fe3+ ions with oxygen ions.
Study on electromagnetic characteristics of the magnetic coupling resonant coil for the wireless power transmission system
Authors: Wang Zhongxian , Liu Yiping , Wei Yonggeng , Song Yilin
Published: September 2018

Background:

The resonant coil design is taken as the core technology in the magnetic coupling resonant wireless power transmission system, which achieves energy transmission by the coupling of the resonant coil. This paper studies the effect of the resonant coil on energy transmission and the efficiency of the system. Combining a two-coil with a three-coil system, the optimum design method for the resonant coil is given to propose a novel coil structure.

Methods:

First, the co-simulation methods of Pspice and Maxwell are used. When the coupling coefficient of the resonant coil is different, the relationship between system transmission efficiency, output power, and frequency is analyzed. When the self-inductance of the resonant coil is different, the relationship between the performance and frequency of the system transmission is analyzed. Then, two-coil and three-coil structure models are built, and the parameters of the magnetic field of the coils are calculated and analyzed using the finite element method. In the end, a dual E-type simulation circuit model is used to optimize the design of the novel resonance coil.

Results:

The co-simulation results show that the coupling coefficients of the two-coil, three-coil, and novel coil systems are 0.017, 0.17 and 0.0126, respectively. The power loss of the novel coil is 16.4 mW.

Conclusions:

There is an obvious improvement in the three-coil system, which shows that the magnetic leakage of the field and the energy coupling are relatively small. The new structure coil has better performance, and the load loss is lower; it can improve the system output power and transmission efficiency.
The examination of vegetable- and mineral oil-based inks’ effects on print quality: Green printing effects with different oils
Authors: Aydemir Cem , Yenidoğan Semiha , Karademir Arif , Arman Kandirmaz Emine
Published: September 2018

Introduction:

Printing inks oil selection is related to the desired nature of the varnish in the ink production. Petroleum-derived mineral oils and vegetable oils can be used in offset inks.

Methods:

In this study, the behaviors of vegetable- and mineral oil-based inks on uncoated and coated paper surfaces were investigated in terms of printability. Solid tone test prints were done with offset printing of these inks. Print gloss of the printed samples was measured and a light fastness test was implemented on these samples in order to determine the resistance to fading. Absorption behavior and contact angles of the ink-printed films on the test papers were measured with the sessile water drop method depending on time, and surface energies were calculated.

Results:

On both paper types, linseed–soybean oil-based vegetable ink gave the highest brightness value. The lowest print gloss results on the paper were obtained from soybean oil-based inks. The lowest color change was recorded with mineral oil-based inks on gloss-coated papers. According to the ink-film–surface relation, when the contact angle is high, surface energy decreases and the absorbency of the ink-film is lower.

Conclusions:

In this study, the behaviors of vegetable- and mineral oil-based inks on different paper surfaces, and the effect on the quality of printability as well as differences, have been evaluated, taking environmental and health factors into consideration.
In vivo comparison of a fixed loop (EndoButton CL) with an adjustable loop (TightRope RT) device for femoral fixation of the graft in ACL reconstruction: A prospective randomized study and a literature review
Authors: Ranjan Rahul , Gaba Sahil , Goel Lakshay , Asif Naiyer , Kalra Mukesh , Kumar Ramesh , Kumar Arvind
Published: September 2018

Introduction:

There is a lack of in vivo studies comparing the functional outcome and knee stability after anterior cruciate ligament reconstruction (ACLR) using fixed loop (EndoButton (EB) CL) and adjustable loop (TightRope (TR) RT) devices for femoral fixation of soft tissue grafts.

Materials and methods:

Functional outcomes were assessed in terms of the International Knee Documentation Committee (IKDC) and Lysholm scores, knee stability by anteroposterior laxity and side-to-side difference (SSD) using KT-1000 arthrometer. The evaluation was performed preoperatively and post-operatively at 6 months and 2 years.

Results:

Both groups were matched in terms of demographic, preoperative, intraoperative and post-operative covariates. EB ( n = 52) appeared to have better IKDC and Lysholm scores at 6 months post-operative when compared to TR ( n = 50). However, at a final follow-up of 2 years, the results were similar. The anterior tibial translation and SSD were statistically insignificant between the two groups at 6 months and 2 years.

Conclusion:

ACLR using EB or TR for femoral fixation gives substantially equivalent functional results and knee stability at mid-term follow-up.
Transforming Dubai: Oasis to Tourist’s Paradise
Authors: Choudhary Bikramaditya K. , Paul Nian
Published: September 2018

Owing to fast pace of urbanization and associated development, Dubai rose to global prominence in a matter of a few years. Dubai has transformed its geographical incapacities to phantasmagorical way of living; from building the superlative structures to its magnificent architectural fantasies, to the reconfiguring of a desert into an urban hub of business, logistics, tourism, and retail shopping paradise. In the race to achieve global competence, it has changed its ecological realities into pursuits driven by enigma of capital and desire of hyper-consumerism. The creation of the cityscape paralleled by vanishing natural and cultural spaces of the recent past, retrofitted with global desires like shopping complexes, beach resorts, luxurious hotels, ski clubs, art museums, operas, etc. The article is situated in the context of the urban spatial transformation of Dubai, driven by neoliberal politics and the changing human–nature relationships riding on the accelerating capital circulation.
The prevalence of localised scleroderma in childhood assessed in the administrative claims data from the United States
Authors: Beukelman Timothy , Xie Fenglong , Foeldvari Ivan
Published: September 2018

Juvenile localised scleroderma is believed an orphan autoimmune disease, which occurs 10 times more often than systemic sclerosis in childhood and is believed to have a prevalence of 1 per 100,000 children. To gain data regarding the prevalence of juvenile localised scleroderma, we assessed the administrative claims data in the United States using the International Classification of Diseases, Ninth Revision diagnosis codes. We found an estimated prevalence in each year ranging from 3.2 to 3.6 per 10,000 children. This estimate is significantly higher as found in previous studies.
miR-125a and miR-34a expression predicts Richter syndrome in chronic lymphocytic leukemia patients
Authors: Balatti Veronica , Tomasello Luisa , Rassenti Laura Z. , Veneziano Dario , Nigita Giovanni , Wang Huan-You , Thorson John A. , Kipps Thomas J. , Pekarsky Yuri , Croce Carlo M.
Published: September 2018

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is characterized by the accumulation of CD19+/CD5+ lymphocytes and can have variable outcomes. Richter syndrome (RS) is a lethal complication in CLL patients that results in aggressive B-cell lymphomas, and there are no tests to predict its occurrence. Because alterations in microRNA expression can predict the development and progression of several cancers, we investigated whether dysregulation of specific microRNAs can predict RS in CLL patients. Thus, we compared microRNA expression levels in samples from 49 CLL patients who later developed RS with samples from 59 CLL patients who did not. We found that high expression of miR-125a-5p or low expression of miR-34a-5p can predict ∼50% of RS with a false positive rate of ∼9%. We found that CLL patients predicted to develop RS show either an increase of miR-125a-5p expression (∼20-fold) or a decrease of miR-34a-5p expression (∼21-fold) compared with CLL patients that are not predicted to develop RS. Thus, miR-125a-5p and miR-34a-5p can be valuable predictor markers of RS and have the potential to provide physicians with information that can indicate the best therapeutic strategy for CLL patients.
Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine platelet GPIIb-IIIa activation
Authors: Lagarrigue Frederic , Gingras Alexandre R. , Paul David S. , Valadez Andrew J. , Cuevas Monica N. , Sun Hao , Lopez-Ramirez Miguel A. , Goult Benjamin T. , Shattil Sanford J. , Bergmeier Wolfgang , Ginsberg Mark H.
Published: September 2018

Activation of platelet glycoprotein IIb-IIIa (GPIIb-IIIa; integrin αIIbβ3) leads to high-affinity fibrinogen binding and platelet aggregation during hemostasis. Whereas GTP-bound Rap1 GTPase promotes talin 1 binding to the β3 cytoplasmic domain to activate platelet GPIIb-IIIa, the Rap1 effector that regulates talin association with β3 in platelets is unknown. Rap1 binding to the talin 1 F0 subdomain was proposed to forge the talin 1–Rap1 link in platelets. Here, we report a talin 1 point mutant (R35E) that significantly reduces Rap1 affinity without a significant effect on its structure or expression. Talin 1 head domain (THD) (R35E) was of similar potency to wild-type THD in activating αIIbβ3 in Chinese hamster ovary cells. Coexpression with activated Rap1b increased activation, and coexpression with Rap1GAP1 reduced activation caused by transfection of wild-type THD or THD(R35E). Furthermore, platelets from Tln1R35E/R35E mice showed similar GPIIb-IIIa activation to those from wild-type littermates in response to multiple agonists. Tln1R35E/R35E platelets exhibited slightly reduced platelet aggregation in response to low doses of agonists; however, there was not a significant hemostatic defect, as judged by tail bleeding times. Thus, the Rap1–talin 1 F0 interaction has little effect on platelet GPIIb-IIIa activation and hemostasis and cannot account for the dramatic effects of loss of Rap1 activity on these platelet functions.
Comparison of low calorie high protein and low calorie standard protein diet on waist circumference of adults with visceral obesity and weight cycling
Authors: Witjaksono Fiastuti , Jutamulia Joan , Annisa Nagita Gianty , Prasetya Septian Ika , Nurwidya Fariz
Published: September 2018

Objectives

Many individuals with visceral obesity who previously had succeeded in reducing body weight regain and this loss–gain cycle repeats several times which is called as weight cycling. We aimed to evaluate the effect of a low calorie high protein diet (HP) compared to a low calorie standard protein diet (SP) on waist circumference of visceral obese adults with history of weight cycling.

Results

In this open-randomized clinical trial, participants were asked to follow dietary plan with reduction in daily caloric intake ranging from 500 to 1000 kcal from usual daily amount with minimum daily amount of 1000 kcal for 8 weeks and were divided in two groups: HP group with protein as 22–30% total calorie intake; and SP group with protein as 12–20% total calorie intake. There was a statistically significant difference (P < 0.001) between waist circumference before and after the dietary intervention among both groups. Meanwhile, there was no statistically significant difference in the mean reduction of waist circumference between HP and SP groups (P = 0.073). Taken together, the protein proportion does not significantly affected waist circumference.

Trial registration ClinicalTrials.gov NCT03374150, 11 December 2017
Deaths in custody in the Irish prison service: 5-year retrospective study of drug toxicology and unnatural deaths
Authors: Iqtidar Madeeha , Sharma Kapil , Mullaney Ronan , Kelly Enda , Keevans Mary , Cullinane Myra , Kennedy Harry , Mohan Damian
Published: September 2018

Mental health and substance misuse disorders are associated with unnatural deaths in prisoners. Deaths in Irish prisons between 2009 and 2014 were retrospectively analysed using coroner's findings, including post-mortem toxicology. There were 69 deaths in custody, 38 of which met inclusion criteria. All deaths by overdose (16) were positive for illicit drugs; 53% of deaths (8 of 15) due to hanging were also positive for illicit drugs, and 29% of deaths (2 of 7) from other causes were toxicology positive. In conclusion, 26 unnatural deaths (68%) were associated with use of illicit drugs, which are a major contributory factor to deaths of prisoners.

Declaration of interest

None.
It is ethical to diagnose a public figure one has not personally examined
Authors: Gartner John , Langford Alex , O'Brien Aileen
Published: September 2018

Should psychiatrists be able to speculate in the press or social media about their theories? John Gartner argues the risk to warn the public of concerns about public figures overrides the duty of confidentiality; whereas Alex Langford suggests this is beyond the ethical remit of psychiatric practice.

Declaration of interest

A.O'B is joint debates and analysis Editor of the British Journal of Psychiatry. J.G. is the founder of Duty To Warn, an association of mental health professionals who advocate the president's removal under the 25th Amendment on the grounds that he is psychologically unfit and dangerous.
Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy
Authors: Cruz Cristina , Llop-Guevara Alba , Garber Judy E. , Arun Banu K. , Pérez Fidalgo José A. , Lluch Ana , Telli Melinda L. , Fernández Cristian , Kahatt Carmen , Galmarini Carlos M. , Soto-Matos Arturo , Alfaro Vicente , Pérez de la Haza Aitor , Domchek Susan M. , Antolin Silvia , Vahdat Linda , Tung Nadine M. , Lopez Rafael , Arribas Joaquín , Vivancos Ana , Baselga José , Serra Violeta , Balmaña Judith , Isakoff Steven J.
Published: September 2018

Purpose

This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance.

Patients and Methods

Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35). Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m2 in arm A. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST). The translational substudy of resistance mechanisms included exome sequencing (n = 13) and in vivo experiments with patient-derived xenografts (n = 11) from BRCA1/2-mutated tumors.

Results

ORR was 41% (95% CI, 28% to 55%) in arm A and 9% (95% CI, 2% to 24%) in arm B. In arm A, median progression-free survival was 4.6 months (95% CI, 3.0 to 6.0 months), and median overall survival was 20.0 months (95% CI, 11.8 to 26.6 months). Patients with BRCA2 mutations showed an ORR of 61%, median progression-free survival of 5.9 months, and median overall survival of 26.6 months. The safety profile improved with lurbinectedin dose adjustment to body surface area. The most common nonhematologic adverse events seen at 3.5 mg/m2 were nausea (74%; grade 3, 5%) and fatigue (74%; grade 3, 21%). Neutropenia was the most common severe hematologic adverse event (grade 3, 47%; grade 4, 10%). Exome sequencing showed mutations in genes related to the nucleotide excision repair pathway in four of seven tumors at primary or acquired resistance and in one patient with short-term stable disease. In vivo, sensitivity to cisplatin and lurbinectedin was evidenced in lurbinectedin-resistant (one of two) and cisplatin-resistant (two of three) patient-derived xenografts.

Conclusion

Lurbinectedin showed noteworthy activity in patients with BRCA1/2 mutations. Response and survival was notable in those with BRCA2 mutations. Additional clinical development in this subset of patients with metastatic breast cancer is warranted.
An interview with James Sharpe
Authors: Grewal Seema
Published: September 2018

James Sharpe is a developmental biologist who studies the process of limb development using a multi-disciplinary approach, combining experimental systems, imaging and computer modelling. Formerly based at the Centre for Genomic Regulation in Barcelona, James was recently appointed Head of EMBL Barcelona. We caught up with James at the British Society for Developmental Biology Spring Meeting to ask him about his research, his thoughts on computational modelling, and his vision for the new EMBL Barcelona site.
Aberrant cerebellar Purkinje cell activity as the cause of motor attacks in a mouse model of episodic ataxia type 2
Authors: Tara Esra , Vitenzon Ariel , Hess Ellen , Khodakhah Kamran
Published: September 2018

Many cerebellar-induced neurological disorders, such as ataxias and cerebellar-induced dystonias, are associated with abnormal Purkinje cell activity. In tottering mice, a well-established mouse model of episodic ataxia type 2 (EA2), cerebellar Purkinje cells are required for the initiation of motor attacks. How Purkinje cells contribute to the initiation of attacks is not known, and to date there are no reports on the activity of Purkinje cells during motor attacks in the tottering mice. Here, we show that tottering Purkinje cells exhibit high-frequency burst firing during attacks, reminiscent of other mouse models of cerebellar-induced motor dysfunction. We recorded the activity of Purkinje cells in awake head-restrained tottering mice at baseline, or during caffeine-induced attacks. During motor attacks, firing of Purkinje cells transformed to high-frequency burst firing. Interestingly, the extent to which the activity of Purkinje cells was erratic was correlated with the severity of the motor dysfunction. In support of a causal role for erratic activity in generating motor dysfunction, we found that direct infusion of the small conductance calcium-activated potassium (SK) channel activator NS309 into the cerebellum of tottering mice in the midst of an attack normalized the firing of Purkinje cells and aborted attacks. Conversely, we found that inducing high-frequency burst firing of Purkinje cells in wild-type animals is sufficient to produce severe motor signs. We report that erratic activity of wild-type Purkinje cells results in ataxia and dystonic postures. Moreover, this aberrant activity is the cause of motor attacks in the tottering mice.
Recent advances in ankylosing spondylitis: understanding the disease and management
Authors: Garcia-Montoya Leticia , Gul Hanna , Emery Paul
Published: September 2018

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.
Young key affected population in Myanmar: are there any challenges in seeking information and care for HIV/sexually transmitted infections and reproductive health?
Authors: Htut Kyaw Min , Mon Myo Myo , Aye Zin Mar , Ni Lwin Lwin
Published: September 2018

Background: Unmet needs and barriers in seeking HIV/STI and RH information and care are present especially among young key affected population (YKAP). Therefore, the study was conducted to determine the health seeking behaviors of YKAP regarding HIV/STI and RH, and challenges in seeking health information and care.

Methods: A cross-sectional, mixed-methods study was conducted at two large cities in Myanmar. Face-to-face interviews were conducted with YKAP aged 15-24 years. In-depth interviews and key informant interviews were done with YKAP and health care providers. Descriptive statistics and bivariate analyses were done for quantitative data and thematic analysis was applied for qualitative data.

Results: A total of 119 young men who have sex with men (YMSM) and 123 young female sex workers (YFSW) included in the study. Mean age of YMSM and YFSW were 20.9±2.4 and 21.7±2.2 years. Over 30% of YMSM and 49.3% of YFSW had experience of any STI symptom. Particularly, 17% of YMSM and 10% of YFSW had genital ulcer, and majority sought health care at NGO clinics. About 37% of YMSM and 40% of YFSW visited Drop-in-center (DIC) within one to six months. Over 13% of YMSM and 14.6% of YFSW had challenges in seeking HIV/STI and RH information.  YMSM/YFSW type and age of YMSM were associated with visit to DIC. Lesser proportions of Tha-nge (43.5%), younger age YMSM (66.7%), brothel-based YFSW (47.9%) visited DIC than others (p<0.05). Challenges and unmet needs expressed by YKAP were reluctance in asking health information, worry for future fertility, consequences of anal sex and contraception. Challenges expressed by providers were limited time during outreach service and difficulty in reaching entertainment-based sex workers.

Conclusions: Special attention in provision of health information should be paid to YKAP since there is a considerable proportion of YKAP with unmet need in seeking HIV/STI/RH information and care.
Investigating the dynamics of Leishmania antigen in the urine of patients with visceral leishmaniasis: a pilot study
Authors: Ghosh Prakash , Cruz Israel , Picado Albert , Edwards Thomas , Khan Md. Anik Ashfaq , Hossain Faria , Chowdhury Rajashree , Adams Emily R. , Nath Rupen , Ndung'u Joseph M. , Mondal Dinesh
Published: September 2018

Background: Detection of Leishmania antigens in the urine provides a non-invasive means of diagnosis and treatment monitoring of cases of visceral leishmaniasis (VL). Leishmania antigen load in the urine may vary between different time-points within a day, thus influencing the performance of antigen-detection tests.

Methods: We investigated the dynamics of Leishmania antigen in urine collected at three different time points (08:00, 12:00 and 16:00 hours). All urine samples collected were tested with the Leishmania Antigen ELISA (VL ELISA) kit, produced by Kalon Biological Ltd., UK.

Results: The median concentration of Leishmania antigen in urine collected at 08:00 (2.7 UAU-urinary antigen units/ml) was higher than at 12:00 (1.7 UAU/ml) and at 16:00 (1.9 UAU/ml). These differences were found to be statistically significant (08:00 vs. 12:00, p=0.011; 08:00 vs. 16:00, p=0.041).

Conclusion: This pilot study indicates that the Leishmania antigen concentration is higher in urine samples collected in the morning, which has important implications when the VL ELISA kit or other tests to detect Leishmania antigen in urine are used for diagnosis of VL and treatment monitoring.
A novel nano-iron supplement to safely combat iron deficiency and anaemia in young children: The IHAT-GUT double-blind, randomised, placebo-controlled trial protocol
Authors: Pereira Dora I.A. , Mohammed Nuredin I. , Ofordile Ogochukwu , Camara Famalang , Baldeh Bakary , Mendy Thomas , Sanyang Chilel , Jallow Amadou T. , Hossain Ilias , Wason James , Prentice Andrew M.
Published: September 2018

Background: Iron deficiency and its associated anaemia (IDA) are the leading forms of micronutrient malnutrition worldwide. Conventional oral iron supplements have limited efficacy and have been associated with increased infection, diarrhoea, and detrimental changes to the gut microbiome, particularly in young children. Here we describe the rationale and design of the first clinical trial evaluating the efficacy and safety of a novel nano iron supplement, iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in young children (IHAT-GUT trial).

Methods:IHAT-GUT is a three-arm, double-blind, randomised, placebo-controlled trial conducted in Gambian children 6-35 months of age. The intervention consists of a 12-week supplementation with either IHAT, ferrous sulphate (both at doses bioequivalent to 12.5 mgFe/day) or placebo. Assessments are conducted at baseline, Day 15, and Day 85 of the supplementation period. The trial aims to include 600 children with IDA who will be randomly assigned (1:1:1) to each arm. The primary objectives are to test non-inferiority of IHAT in relation to ferrous sulphate at treating IDA, and to test superiority of IHAT in relation to ferrous sulphate and non-inferiority in relation to placebo in terms of diarrhoea incidence and prevalence. Secondary objectives are to test whether IHAT reduces the burden of enteric pathogens, morbidity, and intestinal inflammation, and that it does not cause detrimental changes to the gut microbiome, particularly in relation toLactobacillaceae,BifidobacteriaceaeandEnterobacteriaceae.

Discussion:This trial will test the hypothesis that supplementation with IHAT eliminates iron deficiency and improves haemoglobin levels without inducing gastrointestinal adverse effects. If shown to be the case, this would open the possibility for further testing and use of IHAT as an alternative iron source for micronutrient intervention strategies in resource-poor countries, with the ultimate aim to help reduce the IDA global burden.

Registration:This trial is registered at clinicaltrials.gov (NCT02941081).
Ensuring the durability of the working bodies of tillage machines
Authors: Новиков Владимир , Novikov Vladimir
Published: September 2018

The book sets out the criteria for the limiting state of the working bodies of tillage machines as a result of wear, analytical expressions for determining their durability based on the wear resistance of the materials from which they are made, and the wear ability of the soil.
The results of studies of the relative wear resistance of steels, surfacing materials, technical ceramics. Recommendations on the choice of steel grades for the production of working bodies are given.
Methods of calculation of strength of working bodies (on the example of ploughshare) from deformation and fracture are presented.
Various technologies of strengthening of working bodies and results of their tests are given.
The example of justification materials, technologies and designs during the development of the working bodies (on the example of the blade of the plow) for maximum durability and minimum cost in their manufacture.
The book is intended for engineers and technicians involved in the production and operation of agricultural machinery. It can also be useful for students of agricultural universities studying in the direction of "Agroengineering".
An Extended Mixed-Integer Programming Formulation and Dynamic Cut Generation Approach for the Stochastic Lot-Sizing Problem
Authors: Tunc Huseyin , Kilic Onur A. , Tarim S. Armagan , Rossi Roberto
Published: September 2018

We present an extended mixed-integer programming formulation of the stochastic lot-sizing problem for the static-dynamic uncertainty strategy. The proposed formulation is significantly more time efficient as compared to existing formulations in the literature and it can handle variants of the stochastic lot-sizing problem characterized by penalty costs and service level constraints, as well as backorders and lost sales. Also, besides being capable of working with a predefined piecewise linear approximation of the cost function—as is the case in earlier formulations—it has the functionality of finding an optimal cost solution with an arbitrary level of precision by means of a novel dynamic cut generation approach.

The online appendix is available at https://doi.org/10.1287/ijoc.2017.0792 .