bluuebunny/crossref_metadata_2025 huggingface dataset:
Can purchasing information be used to predict adherence to cardiovascular medications? An analysis of linked retail pharmacy and insurance claims data
Authors: Krumme Alexis A , Sanfélix-Gimeno Gabriel , Franklin Jessica M , Isaman Danielle L , Mahesri Mufaddal , Matlin Olga S , Shrank William H , Brennan Troyen A , Brill Gregory , Choudhry Niteesh K
Published: November 2016

Objective

The use of retail purchasing data may improve adherence prediction over approaches using healthcare insurance claims alone.

Design

Retrospective.

Setting and participants

A cohort of patients who received prescription medication benefits through CVS Caremark, used a CVS Pharmacy ExtraCare Health Care (ECHC) loyalty card, and initiated a statin medication in 2011.

Outcome

We evaluated associations between retail purchasing patterns and optimal adherence to statins in the 12 subsequent months.

Results

Among 11 010 statin initiators, 43% were optimally adherent at 12 months of follow-up. Greater numbers of store visits per month and dollar amount per visit were positively associated with optimal adherence, as was making a purchase on the same day as filling a prescription (p<0.0001 for all). Models to predict adherence using retail purchase variables had low discriminative ability (C-statistic: 0.563), while models with both clinical and retail purchase variables achieved a C-statistic of 0.617.

Conclusions

While the use of retail purchases may improve the discriminative ability of claims-based approaches, these data alone appear inadequate for adherence prediction, even with the addition of more complex analytical approaches. Nevertheless, associations between retail purchasing behaviours and adherence could inform the development of quality improvement interventions.
Descriptive analysis of a 1:1 physiotherapy outpatient intervention post primary lumbar discectomy: one arm of a small-scale parallel randomised controlled trial across two UK sites
Authors: Rushton A , Calcutt A , Heneghan N , Heap A , White L , Calvert M , Goodwin P
Published: November 2016

Objective

There is a lack of high-quality evidence for physiotherapy post lumbar discectomy. Substantial heterogeneity in treatment effects may be explained by variation in quality, administration and components of interventions. An optimised physiotherapy intervention may reduce heterogeneity and improve patient benefit. The objective was to describe, analyse and evaluate an optimised 1:1 physiotherapy outpatient intervention for patients following primary lumbar discectomy, to provide preliminary insights.

Design

A descriptive analysis of the intervention embedded within an external pilot and feasibility trial.

Setting

Two UK spinal centres.

Participants

Participants aged ≥18; post primary, single level, lumbar discectomy were recruited.

Intervention

The intervention encompassed education, advice, mobility and core stability exercises, progressive exercise, and encouragement of early return to work/activity. Patients received ≤8 sessions for ≤8 weeks, starting 4 weeks post surgery (baseline).

Outcomes

Blinded outcome assessment at baseline and 12 weeks (post intervention) included the Roland Morris Disability Questionnaire. STarT Back data were collected at baseline. Statistical analyses summarised participant characteristics and preplanned descriptive analyses. Thematic analysis grouped related data.

Findings

Twenty-two of 29 allocated participants received the intervention. STarT Back categorised n=16 (55%) participants ‘not at low risk’. Physiotherapists identified reasons for caution for 8 (36%) participants, commonly risk of overdoing activity (n=4, 18%). There was no relationship between STarT Back and physiotherapists’ evaluation of caution. Physiotherapists identified 154 problems (mean (SD) 5.36 (2.63)). Those ‘not at low risk’, and/or requiring caution presented with more problems, and required more sessions (mean (SD) 3.14 (1.16)).

Conclusions

Patients present differently and therefore require tailored interventions. These differences may be identified using clinical reasoning and outcome data.

Trial registration number

ISRCTN33808269; post results.
An online questionnaire survey of UK general practitioners’ knowledge and management of familial hypercholesterolaemia
Authors: Kwok See , Pang Jing , Adam Safwaan , Watts Gerald F , Soran Handrean
Published: November 2016

Objective

Early diagnosis and treatment of heterozygous familial hypercholesterolaemia (HeFH) is known to be associated with reduced mortality from premature coronary artery disease, but HeFH remains underdiagnosed. This survey aims to determine knowledge and current management of HeFH in general practice.

Setting

An online questionnaire was administered to general practitioners’ (GPs’) in the North West of England to assess their knowledge and management of HeFH.

Participants

Practising GPs in the North West of England were contacted by email and invited to complete an online questionnaire. Recruitment discontinued when the target of 100 was reached.

Primary outcome

An assessment of the knowledge and current management of HeFH in GPs.

Results

100 GP responses were analysed. Although only 39% considered themselves to have reasonable knowledge of HeFH, 89% knew that HeFH was a genetic disorder and 74% selected the correct lipid profile for diagnosing the condition. More than half (61%) were aware of current guidelines on HeFH. Gaps in knowledge were evident when only 30% correctly identified the prevalence of HeFH and half were not aware of the pattern of inheritance. Increased cardiovascular risk was underestimated by majority. 33% thought that they had HeFH patients in their practice confirming underdiagnosis of the condition. Statin therapy was recognised by 94% to be the right medication for treating HeFH. The majority (82%) regarded GPs to be the most effective healthcare professional for early recognition of HeFH.

Conclusions

GPs have an above-average knowledge of familial hypercholesterolaemia (FH) and almost universally consider that they have a key role in the early recognition of undiagnosed HeFH patients in the community. However, there are gaps in awareness that need to be addressed to further enhance the care of FH in the community.
Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: a cross-sectional study
Authors: Liu Gang , Zong Geng , Doty Richard L , Sun Qi
Published: November 2016

Objectives

To estimate the prevalence of, and explore potential risk factors for, taste and smell dysfunction in the general population of the USA.

Design

A cross-sectional study.

Setting

A cross-sectional analysis of data collected in the National Health and Nutrition Examination Survey (NHANES 2013–2014).

Participants

A total of 3519 men and women aged 40 years and older who participated in NHANES 2013–2014.

Main outcome measures

Using the NHANES Pocket Smell Test, smell impairment was defined as failing to correctly identify 6 or more of the 8 odours. Taste impairment was defined as failing to correctly identify quinine or sodium chloride.

Results

The estimated prevalence was 13.5% for smell impairment, 17.3% for taste impairment and 2.2% for taste and smell impairment. For smell, but not taste, prevalence estimates increased with age and were higher in men and ethnic minorities. In backward stepwise logistic regression, low educational attainment, low family income and a history of asthma or cancer were independently associated with a higher prevalence of smell impairment, whereas light-to-moderate alcohol consumption (1–3 drinks/day) was associated with a lower prevalence of this condition. After multivariate adjustment, being non-Hispanic Black Americans, consuming ≥4 drinks of alcohol per day and having a history of cardiovascular disease (CVD) were independently associated with a higher prevalence of taste impairment.

Conclusions

Based on a nationally representative multistage probability survey among the US population aged 40 years and older, smell and taste dysfunction affected ∼20.5 million (13.5%) and 26.3 million (17.3%) individuals, respectively. Age, gender, ethnicity, educational attainment, family income, light-to-moderate alcohol consumption and history of asthma or cancer were significant risk factors for smell dysfunction, whereas only ethnicity, heavy alcohol consumption and CVD history were associated with a higher prevalence of taste dysfunction.
Nutritional support in the intensive care unit
Authors: Kathrani Aarti
Published: November 2016

Nutritional assessment of companion animals is considered to be the fifth vital sign and nutritional support is an important aspect of care for animals in the intensive care unit (ICU). Malnutrition can develop quickly, even in adequately nourished but critically ill animals, and typically results from the type, severity and metabolic demands of the disease affecting the animal, demands from healing, and rapid fluid and electrolyte shifts, which could potentially result in deficiencies in micronutrients such as potassium and magnesium, and loss of specific vitamins and minerals. Adequate nutritional support can preserve lean body mass, facilitate wound healing, reverse the maladaptive metabolic response to injury, maintain organ function and reduce morbidity in critically ill animals. However, nutritional support, whether administered enterally or parenterally, can result in mechanical, infectious and metabolic complications. Therefore, the aims of nutritional support in the ICU include preserving lean body mass, correcting or preventing macro‐ or micronutrient deficiencies and preventing complications associated with the provision of nutritional support. This article discusses the whole procedure of nutritional intervention, from deciding which route to use to the selection of diets that can be fed and the support required for specific diseases and conditions.
Functional assessment of MeCP2 in Rett syndrome and cancers of breast, colon, and prostate
Authors: Pandey Somnath , Pruitt Kevin
Published: November 2016

Ever since the first report that mutations in methyl-CpG-binding protein 2 (MeCP2) causes Rett syndrome (RTT), a severe neurological disorder in females world-wide, there has been a keen interest to gain a comprehensive understanding of this protein. While the classical model associated with MeCP2 function suggests its role in gene suppression via recruitment of co-repressor complexes and histone deacetylases to methylated CpG-sites, recent discoveries have brought to light its role in transcription activation, modulation of RNA splicing, and chromatin compaction. Various post-translational modifications (PTMs) of MeCP2 further increase its functional versatility. Involvement of MeCP2 in pathologies other than RTT, such as tumorigenesis however, remains poorly explored and understood. This review provides a survey of the literature implicating MeCP2 in breast, colon and prostate cancer.
Predictive mapping of reproductive fish habitats to aid marine conservation planning
Authors: Schmiing Mara , Fontes Jorge , Afonso Pedro
Published: November 2016

Postsettlement spillover from marine protected areas (MPAs) can support adjacent fished populations and has been subject of many scientific studies. The larval subsidy effect, on the contrary, is more challenging to study and less demonstrated, although it, arguably, provides key benefits for fisheries. We modeled and predicted the spatial distribution of fish spawning biomass and fecundity across a temperate insular MPA network (Azores archipelago, Northeast Atlantic) and identified potential single- and multispecies reproductive habitats (RHs) in shallow reefs. Reproductive strategies or skewed sex ratios influenced spatial patterns of potential spawning biomass and fecundity. Predicted multispecies RHs covered 5%–20% of the studied reef habitat. Given their potentially high reproductive output, we argue that such sites should be considered in marine conservation planning to increase chances of achieving fisheries and conservation benefits. Spatial patterns of the reproductive output may function as surrogates for larval subsidy when limited or no larval connectivity information is available and also may assist in identifying potential larval sources and priority sites for conservation.
Recovery trends and predictions of Fraser fir (Abies fraseri) dynamics in the Southern Appalachian Mountains
Authors: Kaylor S. Douglas , Hughes M. Joseph , Franklin Jennifer A.
Published: November 2016

The endemic Fraser fir (Abies fraseri (Pursh) Poir.) is found in only seven montane regions in the southern Appalachians above ca. 1500 m elevation. Due to widespread insect-caused mortality from the invasive balsam woolly adelgid (Adelges piceae Ratzeburg), as well as possible impacts from climate change and atmospheric pollution, the future of Fraser fir populations remains uncertain. Long-term monitoring programs have been in place since the 1980s, and here we present the first predictive population models for endemic Fraser fir populations using the inventory data from Great Smoky Mountains National Park, which contains 74% of extant Fraser fir forests. Using two kinds of population data (understory density counts and overstory census data), we model Fraser fir population dynamics on five different mountaintops as a stage-structured matrix model with transition parameters estimated using hierarchical Bayesian inference. We predict robust recovery over the next several decades for some Fraser fir populations, particularly where mature overstory fir has persisted throughout the last two decades, and continued decline for populations at the lowest elevations. Fraser fir densities are already low at these lower elevations, suggesting that this population is vulnerable to local extirpation.
Avian predators transmit fear along the air–water interface influencing prey and their parental care
Authors: Gallagher Austin J. , Lawrence Michael J. , Jain-Schlaepfer Sofia M.R. , Wilson Alexander D.M. , Cooke Steven J.
Published: November 2016

The nonconsumptive consequences of predators on prey behavior, survival, and demography have recently garnered significant attention by ecologists. However, the impacts of top predators on free-ranging prey are challenging to evaluate because the most common fright response for prey is to leave the area of risk. Additionally, the top-down impacts of avian predators on aquatic environments are surprisingly overlooked. Here we investigated the nonconsumptive effects of avian predators on parental care in pumpkinseed (Lepomis gibbosus (L., 1758)) through use of a realistic model of a predatory bird, the Osprey (Pandion haliaetus (L., 1758)). Our predator model exacted dramatic metabolic fright responses and inducible defenses in experimental fish resulting in significant behavioral changes with respect to their parental care. Key parental behaviors including in-nest rotations and egg and nest maintenance were noticeably altered by predator treatments demonstrating as much as an order of magnitude difference in parental performance, suggesting that even transient predation risk might decrease reproductive fitness. Our data provide important new insights on how the landscape of fear operates along the air–water interface and suggests that avian predators may have greater controlling effects on fish populations than previously thought.
Third order optical nonlinear studies and its use to estimate thickness of sandwiched films of tetra-phenyl porphyrin derivatives
Authors: Rao A.Srinivasa , Dar Mudasir H. , Venkatramaiah N. , Venkatesan R. , Sharan Alok
Published: November 2016

Third-order nonlinear optical properties of tetra-phenyl porphyrin (H[Formula: see text]TPP) derivatives viz., H[Formula: see text]TPP(OH)[Formula: see text] and Zn(II)TPP doped in boric acid glass thin films were measured using single beam Z-scan and forward degenerate four-wave mixing (DFWM) techniques. Excited state lifetimes and absorption cross-sections were estimated from these experiments. Thickness of the porphyrin doped sandwich glass films were determined using DFWM technique for the first time. The values of nonlinear refractive index ([Formula: see text]) obtained for these systems are are found to be sensitive to the nature of substituents in porphyrin molecule. These results are interpreted in terms of delocalized [Formula: see text] electrons contributing to the third-order optical nonlinearity.
A fuzzy classification routine for fine-grained soils
Authors: Toksoz Derya , Yilmaz Isik , Nefeslioglu Hakan A. , Marschalko Marian
Published: November 2016

Soil classification is one of the most important stages in preliminary studies for design applications in geotechnical engineering. The classification of fine-grained soils is mostly determined using Casagrande's plasticity chart. However, owing to the factors affecting determination of liquid and plastic limits, uncertainties can arise in fine-grained soil classification when using this approach. The uncertainty increases particularly when the points on the chart fall on the lines that separate certain soil classes (A-line and/or 50% liquid limit line) or very close to these lines. In this study, a fuzzy classification routine is proposed to minimize these uncertainties. For this purpose, the spatial distances of the evaluation points on the chart from the lines were used as a controlling unit. The membership degrees that define the fuzzified soil (clay and/or silt), and plasticity (low and/or high plasticity), were evaluated by considering sigmoid functions. As a consequence, the soil types were established by aggregating fuzzified soil and plasticity using the fuzzy operators.
BDNF effects on functional recovery across motor behaviors after cervical spinal cord injury
Authors: Hernandez-Torres Vivian , Gransee Heather M. , Mantilla Carlos B. , Wang Yao , Zhan Wen-Zhi , Sieck Gary C.
Published: November 2016

Unilateral C2cervical spinal cord hemisection (SH) disrupts descending excitatory drive to phrenic motor neurons, thereby paralyzing the ipsilateral diaphragm muscle (DIAm) during ventilatory behaviors. Recovery of rhythmic DIAm activity ipsilateral to injury occurs over time, consistent with neuroplasticity and strengthening of spared synaptic inputs to phrenic motor neurons. Localized intrathecal delivery of brain-derived neurotrophic factor (BDNF) to phrenic motor neurons after SH enhances recovery of eupneic DIAm activity. However, the impact of SH and BDNF treatment on the full range of DIAm motor behaviors has not been fully characterized. We hypothesized that all DIAm motor behaviors are affected by SH and that intrathecal BDNF enhances the recovery of both ventilatory and higher force, nonventilatory motor behaviors. An intrathecal catheter was placed in adult, male Sprague-Dawley rats at C4to chronically infuse artificial cerebrospinal fluid (aCSF) or BDNF. DIAm electromyography (EMG) electrodes were implanted bilaterally to record activity across motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2and 5% CO2), sighs, airway occlusion, and sneezing. After SH, ipsilateral DIAm EMG activity was evident in only 43% of aCSF-treated rats during eupnea, and activity was restored in all rats after BDNF treatment. The amplitude of DIAm EMG (root mean square, RMS) was reduced following SH during eupnea and hypoxia-hypercapnia in aCSF-treated rats, and BDNF treatment promoted recovery in both conditions. The amplitude of DIAm RMS EMG during sighs, airway occlusion, and sneezing was not affected by SH or BDNF treatment. We conclude that the effects of SH and BDNF treatment on DIAm activity depend on motor behavior.

NEW & NOTEWORTHY This study demonstrates that after unilateral C2spinal cord hemisection (SH), there are differences in the spontaneous recovery of diaphragm (DIAm) electromyographic activity during ventilatory compared with more forceful, nonventilatory motor behaviors. Furthermore, we show that intrathecal delivery of brain-derived neurotrophic factor (BDNF) at the level of the phrenic motor neuron pool enhances recovery of ipsilateral DIAm activity following SH, exerting main effects on recovery of ventilatory but not higher force, nonventilatory behaviors.
A Case of a Gastrointestinal Stromal Tumor Diagnosed at the Postpartum Period
Authors: Kurt Sefa , Canda Aras Emre , Karadeniz Emre , Yavuzsen Tugba , Sagol Ozgul , Obuz Funda , Canda Mehmet Serefettin
Published: November 2016

Introduction. We discuss a rare gastrointestinal stromal tumor (GIST) case detected at the 10th postpartum week and we want to pay attention to the challenges and improvements in the diagnosis, surgery, chemotherapy, and follow-up of this rare tumor accompanied with the review of the current literature. Case Presentation. A 32-year-old multiparous woman presented with abdominal swelling 10 weeks after her second vaginal birth. Abdominal examination revealed a mass starting from the pelvic level and extending to the right upper quadrant. Radiological examinations showed a solid, multiloculated, and hypervascular mass starting from the pelvis and extending to the transverse colon. En bloc mass with a 20 cm jejunal segment resection and a left pelvic side wall peritonectomy with omentectomy was performed. The pathologic examination revealed a high-risk GIST which originated from the jejunum and disseminated to the peritoneum. The patient has been given imatinib 400 mg/day since then. She did not reveal any progression during the 15-month follow-up postoperatively. Conclusion. GIST tumors are rare and there is not sufficient information in the literature regarding its management. In this patient having high risk GIST and GIST sarcomatosis we successfully treated the patient by surgery and adjuvant imatinib chemotherapy.
Increased Activity of the Intracardiac Oxytocinergic System in the Development of Postinfarction Heart Failure
Authors: Wsol Agnieszka , Kasarello Kaja , Kuch Marek , Gala Kamila , Cudnoch-Jedrzejewska Agnieszka
Published: November 2016

Aim.The present study was designed to test the hypothesis that the development of postinfarction heart failure is associated with a change of activity of the intracardiac oxytocinergic system.Methods.Experiments were performed on male Sprague-Dawley rats subjected to myocardial infarction or sham surgery. Four weeks after the surgery, blood samples were collected and the samples of the left ventricle (LV) and right ventricle (RV) were harvested for evaluation of the mRNA expression (RT-PCR) of oxytocin (OT), oxytocin receptor (OTR), natriuretic peptides, and the level of OT and OTR protein (ELISA). The concentration of N-terminal B-type natriuretic peptide was measured to determine the presence of heart failure.Results.Plasma NT-proBNP concentration was higher in the infarcted rats. In the infarcted rats, the expression of OT mRNA and the OT protein level were higher in the RV. There were no significant differences between infarcted and noninfarcted rats in the expression of OT mRNA and in the OT protein level in the fragments of the LV. In both the left and the right ventricles, OTR mRNA expression was lower but the level of OTR protein was higher in the infarcted rats.Conclusions.In the present study, we indicate that postinfarction heart failure is associated with an increased activity of the intracardiac oxytocinergic system.
Rare Case of Posterior Reversible Leukoencephalopathy Syndrome Secondary to Acute Chest Syndrome
Authors: Aiyer Rohit , Klein Daniel , El-Sherif Yasir
Published: November 2016

We present a case of 29/m with a history of sickle cell disease who presented to the emergency department with sudden onset of chest, trunk, extremity, and back pain, consistent in quality and severity with the patient’s usual pain crises. Soon after admission to the medical unit for acute chest syndrome (ACS), the patient developed sudden onset of hypertension associated with left sided hemiplegia, lethargy, dysarthria, aphasia, and left sided facial droop. Neuroimaging revealed that on MRI Brain there was multifocal extensive signal abnormality and a small focal areas of hemorrhage compatible with posterior reversible leukoencephalopathy syndrome (PRES). Patient was treated with levetiracetam and phenytoin and improved soon afterwards, with resolution seen on follow-up MRI two months later.
Strong h-Convexity and Separation Theorems
Authors: Lara Teodoro , Merentes Nelson , Nikodem Kazimierz
Published: November 2016

Jensen inequality for strongly h-convex functions and a characterization of pairs of functions that can be separated by a strongly h-convex function are presented. As a consequence, a stability result of the Hyers-Ulam type is obtained.
Stability Analysis of the Periodic Solutions of Some Kinds of Predator-Prey Dynamical Systems
Authors: Pelen Neslihan Nesliye
Published: November 2016

Analysis of predator-prey dynamical systems that have the functional response which generalizes the other types of functional responses in two dimensions is mainly studied in this paper. The main problems for this study are to detect the if and only if conditions for attaining the periodic solution of the considered system and to find the condition for global asymptotic stability of this solution for some different types of predator-prey systems that are obtained from that system. To get the desired results, some aspects of semigroup theory for stability analysis and coincidence degree theory are used.
Tolerance in Kidney Transplantation: What Is on the B Side?
Authors: Carreras-Planella Laura , Borràs Francesc E. , Franquesa Marcella
Published: November 2016

Regulatory B cells (Breg) are in the spotlight for their role in immune homeostasis maintenance and tolerance achievement as in the last years the correlation with functional and increased Breg numbers in autoimmune diseases and transplantation has been extensively proven. Their study is, however, in its infancy with still little knowledge and consensus on their origin, phenotype, and mechanism of action. All this hampers the pursuit of an effective Breg induction method for therapeutic purposes. In this review we aim to summarize the studies on human Breg and their implication in kidney transplantation and to further discuss the issues surrounding therapeutic applications of this cell subset.
Mycoplasma hominis Induces Mediastinitis after a Tonsillar Abscess
Authors: Grancini Anna , Colosimo Manuela , Restelli Antonella , Colombo Rosaria , Maraschini Anna , Pozzi Cristina , Breda Giuseppe , Protti Alessandro , Arghittu Milena , Gallelli Luca , Maiavacca Rita
Published: November 2016

Mycoplasma hominis is commonly involved in genitourinary tract infections. We report a 59-year-old man who developed a M. hominis-associated mediastinitis following acute tonsillar infection.
Assessment of Temperature Rise and Time of Alveolar Ridge Splitting by Means of Er:YAG Laser, Piezosurgery, and Surgical Saw: An Ex Vivo Study
Authors: Matys Jacek , Flieger Rafał , Dominiak Marzena
Published: November 2016

The most common adverse effect after bone cutting is a thermal damage. The aim of our study was to evaluate the bone temperature rise during an alveolar ridge splitting, rating the time needed to perform this procedure and the time to raise the temperature of a bone by 10°C, as well as to evaluate the bone carbonization occurrence. The research included 60 mandibles (n=60) of adult pigs, divided into 4 groups (n=15). Two vertical and one horizontal cut have been done in an alveolar ridge using Er:YAG laser with set power of 200 mJ (G1), 400 mJ (G2), piezosurgery unit (G3), and a saw (G4). The temperature was measured by K-type thermocouple. The highest temperature gradient was noted for piezosurgery on the buccal and lingual side of mandible. The temperature rises on the bone surface along with the increase of laser power. The lower time needed to perform ridge splitting was measured for a saw, piezosurgery, and Er:YAG laser with power of 400 mJ and 200 mJ, respectively. The temperature rise measured on the bone over 10°C and bone carbonization occurrence was not reported in all study groups. Piezosurgery, Er:YAG laser (200 mJ and 400 mJ), and surgical saw are useful and safe tools in ridge splitting surgery.
Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop
Authors: Chang Cindy M. , Edwards Selvin H. , Arab Aarthi , Del Valle-Pinero Arseima Y. , Yang Ling , Hatsukami Dorothy K.
Published: November 2016

Since 2009, the FDA Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified-risk tobacco products and identifying and evaluating potential product standards. On August 3–4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: (i) approaches to evaluating and selecting biomarkers; (ii) biomarkers of exposure and relationship to disease risk; (iii) currently used biomarkers of exposure and biomarkers in development; and (iv) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems. This article synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. Cancer Epidemiol Biomarkers Prev; 26(3); 291–302. ©2016 AACR.
Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-cell Acute Lymphoblastic Leukemia
Authors: Pikman Yana , Alexe Gabriela , Roti Giovanni , Conway Amy Saur , Furman Andrew , Lee Emily S. , Place Andrew E. , Kim Sunkyu , Saran Chitra , Modiste Rebecca , Weinstock David M. , Harris Marian , Kung Andrew L. , Silverman Lewis B. , Stegmaier Kimberly
Published: November 2016

Purpose: Although significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease.

Experimental Design: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment. We then tested the combination of LEE011 with dexamethasone or everolimus in three orthotopic mouse models and measured on-target drug activity.

Results: We first determined that both NOTCH1-mutant and wild-type T-ALL are highly sensitive to pharmacologic inhibition of CDK4/6 when wild-type RB is expressed. Next, we determined that CDK4/6 inhibitors are antagonistic when used either concurrently or in sequence with many of the drugs used to treat relapsed T-ALL (methotrexate, mercaptopurine, asparaginase, and doxorubicin) but are synergistic with glucocorticoids, an mTOR inhibitor, and gamma secretase inhibitor. The combinations of LEE011 with the glucocorticoid dexamethasone or the mTOR inhibitor everolimus were tested in vivo and prolonged survival in three orthotopic mouse models of T-ALL. On-target activity was measured in peripheral blood and tissue of treated mice.

Conclusions: We conclude that LEE011 is active in T-ALL and that combination therapy with corticosteroids and/or mTOR inhibitors warrants further investigation. Clin Cancer Res; 23(4); 1012–24. ©2016 AACR.

See related commentary by Carroll et al., p. 873
Identifying Predictors of Anti-VEGF Treatment Response in Patients with Neovascular Age-Related Macular Degeneration through Discriminant and Principal Component Analysis
Authors: Holz Frank G. , Tadayoni Ramin , Beatty Stephen , Berger Alan R. , Cereda Matteo G. , Hykin Philip , Hoyng Carel B. , Wittrup-Jensen Kim , Altemark Andreas , Nilsson Jonas , Kim Kun , Sivaprasad Sobha
Published: November 2016

Objective: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. Methods: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). Results: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. Conclusion: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.
Assessment of Migraine History in Patients with a Transient Ischemic Attack or Stroke; Validation of a Migraine Screener for Stroke
Authors: van der Willik Daphne , Pelzer Nadine , Algra Ale , Terwindt Gisela M. , Wermer Marieke J.H.
Published: November 2016

Background: To investigate the connection between migraine and stroke, a reliable screening tool to gather information about a person's migraine history is crucial. We studied the test-characteristics of a 5-question Migraine Screener for Stroke (MISS). Methods: We included a random sample of patients with a transient ischemic attack or stroke who answered the MISS questionnaire when they were admitted to our hospital. After discharge, a semi-structured telephone interview was conducted to validate the migraine diagnosis with the International Classification of Headache Disorders, second-edition criteria as gold standard. Results: Forty-nine (22.2%) of the 221 included patients were diagnosed with life-time migraine (38.5% women, 7.7% men). The sensitivity of all questions combined was 0.47 (95% CI 0.31-0.62), the specificity was 0.97 (95% CI 0.93-0.99), the positive predictive value (PPV) was 0.80 (95% CI 0.59-0.93) and the negative predictive value (NPV) was 0.87 (95% CI 0.82-0.92). One question related to the presence of headache accompanied by hypersensitivity to lights and sounds had a better sensitivity (0.96, 95% CI 0.85-1.00) and NPV (0.99, 95% CI 0.95-1.00) than all questions put together. For assessing migraine with aura, the question about visual disturbances had a good NPV (0.99, 95% CI 0.96-1.00), but a low PPV (0.38, 95% CI 0.24-0.53). Conclusions: The MISS questionnaire can be used by researchers to rule out migraine history in stroke patients. To prevent misclassification, especially for the aura symptoms, patients with a positive screener should be interviewed more extensively to confirm the migraine diagnosis.
Roles of Non-Coding RNAs in Acute Kidney Injury
Authors: Zhou Ping , Chen Zhi , Zou Yan , Wan Xiaoxiao
Published: November 2016

Acute kidney injury (AKI) is a complex kidney disorder that leads to numerous complications, such as elevated nitrogenous wastes, metabolic acidosis, high potassium levels and even death. The pathogenesis of AKI is very complicated, and its causes are commonly categorized as prerenal, intrinsic or postrenal. In the past few years, evidence has accumulated showing that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have significant potential to aid the development of diagnostic and therapeutic strategies of AKI. In this review, we briefly summarize the current understanding of the mechanisms underlying AKI and the main functions of ncRNAs. We mainly focus on revealing the functions of miRNAs (e.g., miR-21, miR-24, miR-30 family, miR-126, miR-127, miR-150, miR-494 and miR-687) and lncRNAs (e.g., TapSAKI, AK139328 and lncRNA-PRINS) in the pathogenesis of AKI.
Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation
Authors: Basic-Jukic Nikolina , Gulin Marijana , Hudolin Tvrtko , Kastelan Zeljko , Katalinic Lea , Coric Marijana , Veda Marija Varnai , Ivkovic Vanja , Kes Petar , Jelakovic Bojan
Published: November 2016

Background/Aims: Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF.
Perifocal Inflammatory Reaction with Volume Fluctuation Caused by Diagnostic Radiation-Induced Regression in Germinoma Makes Histological Diagnosis Difficult despite Its Disappearance following Treatment: A Significant Pitfall and Countermeasures to It
Authors: Yoneoka Yuichiro , Yoshimura Junichi , Okada Masayasu , Fujii Yukihiko
Published: November 2016

We present a pediatric case of neurohypophyseal germinoma with a perifocal inflammatory reaction (PIR) with volume fluctuation caused by diagnostic radiation-induced regression (DRIR). On-target biopsy failed to confirm the histology because PIR hardly contained any germinoma cells. DRIR-related fluctuation of the tumor volume disguised germinoma as inflammation. We analyzed the cerebrospinal fluid (CSF) and detected a high level of placental alkaline phosphatase (PLAP), which demonstrated the neurohypophyseal lesion to be germinoma and brought the patient from successful radiochemotherapy up to complete remission. PIR adjacent to the germinoma (PIRAG) disappeared completely following radiochemotherapy, although it contained almost no germinoma cells. Examination of the CSF-PLAP level can complement the diagnosis of germinoma and will decrease the risk of misdiagnosis. Neurosurgeons should keep in mind PIRAG, DRIR, and the diagnostic value of CSF-PLAP when germinoma is suspected.
Regulation of Gene Expression by Exercise-Related Micrornas
Authors: Masi Laureane Nunes , Serdan Tamires Duarte Afonso , Levada-Pires Adriana Cristina , Hatanaka Elaine , Silveira Leonardo dos Reis , Cury-Boaventura Maria Fernanda , Pithon-Curi Tania Cristina , Curi Rui , Gorjão Renata , Hirabara Sandro Massao
Published: November 2016

Gene expression control by microRNAs (miRs) is an important mechanism for maintenance of cellular homeostasis in physiological and pathological conditions as well as in response to different stimuli including nutritional factors and exercise. MiRs are involved in regulation of several processes such as growth and development, fuel metabolism, insulin secretion, immune function, miocardium remodeling, cell proliferation, differenciation, survival, and death. These molecules have also been proposed to be potential biomarkers and/or therapeutical targets in obesity, type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, and cancer. MiRs are released by most cells and potentially act on intercellular communication to borderer or distant cells. Various studies have been performed to elucidate the involvement of miRs in exercise-induced effects. The aims of this review are: 1) to bring up the main advances for the comprehension of the mechanisms of action of miRs; 2) to present the main results on miR involvement in physical exercise; 3) to discuss the physiological effects of miRs modified by exercise. The state of the art and the perspectives on miRs associated with physical exercise will be presented. Thus, this review is important for updating recent advances and driving further strategies and studies on the exercise-related miR research.
Illegalising Licitness?
Authors: Yeo Woonkyung
Published: November 2016

In the mid-20th Century, the practice of bartering was one of the most prevalent forms of economic transaction around the Indonesian Archipelago. The most prevalent and crucial for Indonesian society was the trade conducted along the border between Singapore and Sumatra. The government centred in Jakarta often approved and even encouraged barter with Singapore at the regional and national level. In many cases, however, bartering along the borders was done autonomously by the regional government and traders, and often out of state control. In these circumstances, the central government sometimes “illegalised” barter trade, while the regional government and societies, arguing that their barter transactions were “licit”, issued a challenge to the government’s order. Such tension and conflict over barter in the region was exacerbated by political upheavals such as regional rebellions in the 1950s and the Konfrontasi in the 1960s. This article traces changing policies and discourses regarding “barter” between Singapore and the Indonesian islands (mostly Sumatra) in the mid-20th Century, and highlight how an economic transaction was politicised, and how the ideas of licitness and legality were in confrontation in certain political backgrounds.
Quality Registries in Sweden, Healthcare Improvements and Elderly Persons with Cognitive Impairments
Authors: Mattsson Titti
Published: November 2016

Policy-makers, the medical industry and researchers are demonstrating a keen interest in the potential of large registries of patient data, both nationally and internationally. The registries offer promising ways to measure and develop operational quality within health and medical care services. As a result of certain favourable patient data regulations and government funding, the development of quality registries is advanced in Sweden. The combination of increasing demand for more cost-efficient healthcare that can accommodate the demographic development of a rapidly ageing population, and the emergence of eHealth with an increasing digitalisation of patient data, calls attention to quality registries as a possible way for healthcare improvements. However, even if the use of registries has many advantages, there are some drawbacks from a patient privacy point of view. This article aims to analyse this growing interdependence of quality registries for the healthcare sector. It discusses some lessons from the Swedish case, with particular focus on the collection of data from elderly persons with cognitive impairments.
Converse Translation in Targum Pseudo-Jonathan Genesis 19.33: Did Lot Really Not Know That His Older Daughter Lay with Him?
Authors: Zhakevich Iosif J.
Published: November 2016

While Gen. 19.33–35 in the Hebrew Bible indicates that Lot did not know that his daughters lay with him, the manuscript of TgPsJ suggests that Lot did know when the older daughter arose after the act of intercourse was completed. The printed editions of TgPsJ disagree with the manuscript, but agree with the Hebrew Bible and state that Lot did not know when either daughter lay down or arose. This raises the question: Is the manuscript accurate or does it contain a textual error? Scholars disagree. Some affirm the manuscript; others prefer the printed editions. This article argues that the text of the manuscript is accurate: the targumist did indeed state that Lot knew when his older daughter arose after she lay with him.
An Analysis of the Syro-Hexapla of Job and Its Relationship to Other Ancient Sources
Authors: Meade John D.
Published: November 2016

The Syro-Hexapla is a valuable witness to the text of Origen’s Hexapla. This article describes the marginal material in the Syro-Hexapla of Job under the following headings: (1) hexaplaric notes, (2) longer scholia (from patristic works), (3) textual variants and other versions, (4) Greek words, and (5) exegetical notes / glosses. By examining all of the materials within the manuscript more insight into its history and provenance was made possible. According to the evidence, Syro-Hexapla Job probably originated in or around Alexandria and was probably translated from the Tetrapla or a text that preserved four Greek versions of Job along with other marginal material.
Key to the species of the genus Scleria (Cyperaceae) in Costa Rica based on the morphology of achenes
Authors: ESPINOZA PATRICIA , CHACÓN-MADRIGAL EDUARDO , SÁNCHEZ ETHEL , GÓMEZ-LAURITO JORGE
Published: November 2016

We described the achenes of 21 species of the genus Scleria reported in Costa Rica using 16 morphological characters and developed a key based only on achene characteristics. Specimens deposited in herbaria in Costa Rica were analyzed. We observed the achenes using a stereoscope and light microscope and took digital images that were used to measure the achenes. Besides, the achenes were observed using a Scanning Electron Microscope. A cluster analysis using achene characteristics was performed in order to know which species are morphologically similar. The intra-specific variation of the characteristics analyzed in the achenes studied is very small for all the species. Using characteristics of the achene, we could differentiate species among four of the five traditional sections of the genus used to classify the species: Hypoporum, Ophryoscleria, Schizolepis and Scleria. The key allows differentiating among 21 species of the genus Scleria previously reported in Costa Rica using only achenes. Besides the key, we prepared an illustrative guide for the genus using pictures taken with SEM and a stereoscope. The descriptions offer better information about the species that grow in Costa Rica.
Reinstatement of the Chinese species Cremanthodium gypsophilum (Asteraceae, Senecioneae)
Authors: WANG LONG , REN CHEN , YANG QIN-ER
Published: November 2016

Examination of herbarium specimens (including type material) of Cremanthodium principis and C. gypsophilum has revealed that the two species are morphologically very distinct from each other. We therefore reinstate the independent specific status of C. gypsophilum which has been placed in synonymy with C. principis. The latter species is currently known only from the holotype, and all the other specimens previously identified as C. principis should belong to C. gypsophilum.
Redescription of four species of Cytaea Keyserling, 1882 (Araneae: Salticidae)
Authors: TRĘBICKI ŁUKASZ , PATOLETA BARBARA M. , GARDZIŃSKA JOANNA
Published: November 2016

Four species of Cytaea Keyserling, 1882 are diagnosed, redescribed, and illustrated: C. laticeps (Thorell, 1878), C. nimbata (Thorell, 1881), C. rubra (Walckenaer, 1837), and C. sinuata (Doleschall, 1859).